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  • 751.
    Schizas, Nikos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Perry, Sharn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Andersson, Brittmarie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wählby, Carolina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Kullander, Klas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Hailer, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Differential neuroprotective effects of interleukin-1 receptor antagonist on spinal cord neurons after excitotoxic injury2017Ingår i: Neuroimmunomodulation, ISSN 1021-7401, E-ISSN 1423-0216, Vol. 24, s. 220-230Artikel i tidskrift (Refereegranskat)
  • 752.
    Schizas, Nikos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Rojas, Ramiro
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Kootala, Sujit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Andersson, Brittmarie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Pettersson, Jennie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hailer, Nils P
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice2014Ingår i: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 28, nr 6, s. 825-836Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Numerous biomaterials based on extracellular matrix-components have been developed. It was our aim to investigate whether a hyaluronic acid-based hydrogel improves neuronal survival and tissue preservation in organotypic spinal cord slice cultures. Organotypic spinal cord slice cultures were cultured for 4 days in vitro (div), either on hyaluronic acid-based hydrogel (hyaluronic acid-gel group), collagen gel (collagen group), directly on polyethylene terephthalate membrane inserts (control group), or in the presence of soluble hyaluronic acid (soluble hyaluronic acid group). Cultures were immunohistochemically stained against neuronal antigen NeuN and analyzed by confocal laser scanning microscopy. Histochemistry for choline acetyltransferance, glial fibrillary acidic protein, and Griffonia simplicifolia isolectin B4 followed by quantitative analysis was performed to assess motorneurons and different glial populations. Confocal microscopic analysis showed a 4-fold increase in the number of NeuN-positive neurons in the hyaluronic acid-gel group compared to both collagen (p < 0.001) and control groups (p < 0.001). Compared to controls, organotypic spinal cord slice cultures maintained on hyaluronic acid-based hydrogel showed 5.9-fold increased survival of choline acetyltransferance-positive motorneurons (p = 0.008), 2-fold more numerous resting microglial cells in the white matter (p = 0.031), and a 61.4% reduction in the number of activated microglial cells within the grey matter (p = 0.05). Hyaluronic acid-based hydrogel had a shear modulus (G') of ≈1200 Pascals (Pa), which was considerably higher than the ≈25 Pa measured for collagen gel. Soluble hyaluronic acid failed to improve tissue preservation. In conclusion, hyaluronic acid-based hydrogel improves neuronal and - most notably - motorneuron survival in organotypic spinal cord slice cultures and microglial activation is limited. The positive effects of hyaluronic acid-based hydrogel may at least in part be due to its mechanical properties.

  • 753. Schmidt, Oliver I.
    et al.
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Gahr, Ralf H.
    Dvorak, Marcel F
    Surgical Management of Osteoporotic Thoracolumbar Spinal Fractures2011Ingår i: Spine and Spinal Cord Trauma: Evidence-Based Management / [ed] Vaccaro, Alexander R.; Fehlings, Michael G.; Dvorak, Marcel F., New York: Thieme Medical Publishers, 2011, 1st ed, s. 414-426Kapitel i bok, del av antologi (Refereegranskat)
  • 754. Schmit, Stephanie L
    et al.
    Edlund, Christopher K
    Schumacher, Fredrick R
    Gong, Jian
    Harrison, Tabitha A
    Huyghe, Jeroen R
    Qu, Chenxu
    Melas, Marilena
    Van Den Berg, David J
    Wang, Hansong
    Tring, Stephanie
    Plummer, Sarah J
    Albanes, Demetrius
    Alonso, M Henar
    Amos, Christopher I
    Anton, Kristen
    Aragaki, Aaron K
    Arndt, Volker
    Barry, Elizabeth L
    Berndt, Sonja I
    Bezieau, Stéphane
    Bien, Stephanie
    Bloomer, Amanda
    Boehm, Juergen
    Boutron-Ruault, Marie-Christine
    Brenner, Hermann
    Brezina, Stefanie
    Buchanan, Daniel D
    Butterbach, Katja
    Caan, Bette J
    Campbell, Peter T
    Carlson, Christopher S
    Castelao, Jose E
    Chan, Andrew T
    Chang-Claude, Jenny
    Chanock, Stephen J
    Cheng, Iona
    Cheng, Ya-Wen
    Chin, Lee Soo
    Church, James M
    Church, Timothy
    Coetzee, Gerhard A
    Cotterchio, Michelle
    Cruz Correa, Marcia
    Curtis, Keith R
    Duggan, David
    Easton, Douglas F
    English, Dallas
    Feskens, Edith J M
    Fischer, Rocky
    FitzGerald, Liesel M
    Fortini, Barbara K
    Fritsche, Lars G
    Fuchs, Charles S
    Gago-Dominguez, Manuela
    Gala, Manish
    Gallinger, Steven J
    Gauderman, W James
    Giles, Graham G
    Giovannucci, Edward L
    Gogarten, Stephanie M
    Gonzalez-Villalpando, Clicerio
    Gonzalez-Villalpando, Elena M
    Grady, William M
    Greenson, Joel K
    Gsur, Andrea
    Gunter, Marc
    Haiman, Christopher A
    Hampe, Jochen
    Harlid, Sophia
    Harju, John F
    Hayes, Richard B
    Hofer, Philipp
    Hoffmeister, Michael
    Hopper, John L
    Huang, Shu-Chen
    Huerta, Jose Maria
    Hudson, Thomas J
    Hunter, David J
    Idos, Gregory E
    Iwasaki, Motoki
    Jackson, Rebecca D
    Jacobs, Eric J
    Jee, Sun Ha
    Jenkins, Mark A
    Jia, Wei-Hua
    Jiao, Shuo
    Joshi, Amit D
    Kolonel, Laurence N
    Kono, Suminori
    Kooperberg, Charles
    Krogh, Vittorio
    Kuehn, Tilman
    Küry, Sébastien
    LaCroix, Andrea
    Laurie, Cecelia A
    Lejbkowicz, Flavio
    Lemire, Mathieu
    Lenz, Heinz-Josef
    Levine, David
    Li, Christopher I
    Li, Li
    Lieb, Wolfgang
    Lin, Yi
    Lindor, Noralane M
    Liu, Yun-Ru
    Loupakis, Fotios
    Lu, Yingchang
    Luh, Frank
    Ma, Jing
    Mancao, Christoph
    Manion, Frank J
    Markowitz, Sanford D
    Martin, Vicente
    Matsuda, Koichi
    Matsuo, Keitaro
    McDonnell, Kevin J
    McNeil, Caroline E
    Milne, Roger
    Molina, Antonio J
    Mukherjee, Bhramar
    Murphy, Neil
    Newcomb, Polly A
    Offit, Kenneth
    Omichessan, Hanane
    Palli, Domenico
    Cotoré, Jesus P Paredes
    Pérez-Mayoral, Julyann
    Pharoah, Paul D
    Potter, John D
    Qu, Conghui
    Raskin, Leon
    Rennert, Gad
    Rennert, Hedy S
    Riggs, Bridget M
    Schafmayer, Clemens
    Schoen, Robert E
    Sellers, Thomas A
    Seminara, Daniela
    Severi, Gianluca
    Shi, Wei
    Shibata, David
    Shu, Xiao-Ou
    Siegel, Erin M
    Slattery, Martha L
    Southey, Melissa
    Stadler, Zsofia K
    Stern, Mariana C
    Stintzing, Sebastian
    Taverna, Darin
    Thibodeau, Stephen N
    Thomas, Duncan C
    Trichopoulou, Antonia
    Tsugane, Shoichiro
    Ulrich, Cornelia M
    van Duijnhoven, Franzel J B
    van Guelpan, Bethany
    Vijai, Joseph
    Virtamo, Jarmo
    Weinstein, Stephanie J
    White, Emily
    Win, Aung Ko
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Woods, Michael
    Wu, Anna H
    Wu, Kana
    Xiang, Yong-Bing
    Yen, Yun
    Zanke, Brent W
    Zeng, Yi-Xin
    Zhang, Ben
    Zubair, Niha
    Kweon, Sun-Seog
    Figueiredo, Jane C
    Zheng, Wei
    Marchand, Loic Le
    Lindblom, Annika
    Moreno, Victor
    Peters, Ulrike
    Casey, Graham
    Hsu, Li
    Conti, David V
    Gruber, Stephen B
    Novel Common Genetic Susceptibility Loci for Colorectal Cancer.2018Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.

    Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.

    Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.

    Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

  • 755. Schoemaker, Minouk J
    et al.
    Nichols, Hazel B
    Wright, Lauren B
    Brook, Mark N
    Jones, Michael E
    O'Brien, Katie M
    Adami, Hans-Olov
    Baglietto, Laura
    Bernstein, Leslie
    Bertrand, Kimberly A
    Boutron-Ruault, Marie-Christine
    Braaten, Tonje
    Chen, Yu
    Connor, Avonne E
    Dorronsoro, Miren
    Dossus, Laure
    Eliassen, A Heather
    Giles, Graham G
    Hankinson, Susan E
    Kaaks, Rudolf
    Key, Timothy J
    Kirsh, Victoria A
    Kitahara, Cari M
    Koh, Woon-Puay
    Larsson, Susanna C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Linet, Martha S
    Ma, Huiyan
    Masala, Giovanna
    Merritt, Melissa A
    Milne, Roger L
    Overvad, Kim
    Ozasa, Kotaro
    Palmer, Julie R
    Peeters, Petra H
    Riboli, Elio
    Rohan, Thomas E
    Sadakane, Atsuko
    Sund, Malin
    Tamimi, Rulla M
    Trichopoulou, Antonia
    Ursin, Giske
    Vatten, Lars
    Visvanathan, Kala
    Weiderpass, Elisabete
    Willett, Walter C
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Yuan, Jian-Min
    Zeleniuch-Jacquotte, Anne
    Sandler, Dale P
    Swerdlow, Anthony J
    Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women.2018Ingår i: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, nr 11, artikel-id e181771Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Importance: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation.

    Objective: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics.

    Design, Setting, and Participants: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017.

    Exposures: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years.

    Main Outcomes and Measures: Invasive or in situ premenopausal breast cancer.

    Results: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall.

    Conclusions and Relevance: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.

  • 756.
    Schumacher, Fredrick R.
    et al.
    Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA;Univ Hosp, Seidman Canc Ctr, Cleveland, OH USA;Royal Marsden NHS Fdn Trust, London, England.
    Al Olama, Ali Amin
    Univ Cambridge, Dept Clin Neurosci, Cambridge, England;Royal Marsden NHS Fdn Trust, London, England;Univ Cambridge, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
    Berndt, Sonja I.
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA;Royal Marsden NHS Fdn Trust, London, England.
    Benlloch, Sara
    Inst Canc Res, London, England;Univ Cambridge, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
    Ahmed, Mahbubl
    Inst Canc Res, London, England.
    Saunders, Edward J.
    Inst Canc Res, London, England.
    Dadaev, Tokhir
    Inst Canc Res, London, England.
    Leongamornlert, Daniel
    Inst Canc Res, London, England.
    Anokian, Ezequiel
    Inst Canc Res, London, England.
    Cieza-Borrella, Clara
    Inst Canc Res, London, England.
    Goh, Chee
    Inst Canc Res, London, England.
    Brook, Mark N.
    Inst Canc Res, London, England.
    Sheng, Xin
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
    Fachal, Laura
    Fdn Publ Galega Med Xenom SERGAS, CIBERER, Grp Med Xenom, IDIS, Santiago De Compostela, Spain;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge, England.
    Dennis, Joe
    Univ Cambridge, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
    Tyrer, Jonathan
    Univ Cambridge, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
    Muir, Kenneth
    Univ Manchester, Div Populat Hlth, Hlth Serv Res & Primary Care, Manchester, Lancs, England;Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England.
    Lophatananon, Artitaya
    Univ Manchester, Div Populat Hlth, Hlth Serv Res & Primary Care, Manchester, Lancs, England;Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England.
    Stevens, Victoria L.
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
    Gapstur, Susan M.
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
    Carter, Brian D.
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
    Tangen, Catherine M.
    Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
    Goodman, Phyllis J.
    Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
    Thompson, Ian M., Jr.
    CHRISTUS Santa Rosa Hosp Med Ctr, San Antonio, TX USA.
    Batra, Jyotsna
    Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia;Australian Prostate Canc Res Ctr Qld, Translat Res Inst, Brisbane, Qld, Australia;Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia.
    Chambers, Suzanne
    Griffith Univ, Menzies Hlth Inst Queensland, Nathan, Qld, Australia;Canc Council Queensland, Fortitude Valley, Qld, Australia.
    Moya, Leire
    Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia;Australian Prostate Canc Res Ctr Qld, Translat Res Inst, Brisbane, Qld, Australia;Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia.
    Clements, Judith
    Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia;Australian Prostate Canc Res Ctr Qld, Translat Res Inst, Brisbane, Qld, Australia;Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia.
    Horvath, Lisa
    Chris OBrien Lifehouse COBLH, Camperdown, NSW, Australia;Garvan Inst Med Res, Sydney, NSW, Australia.
    Tilley, Wayne
    Univ Adelaide, Dame Roma Mitchell Canc Res Ctr, Adelaide, SA, Australia.
    Risbridger, Gail P.
    Monash Univ, Dept Anat & Dev Biol, Prostate Canc Res Program, Monash Biomed Discovery Inst Canc Program, Clayton, Vic, Australia;Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia.
    Gronberg, Henrik
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Aly, Markus
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden.
    Nordstrom, Tobias
    Karolinska Inst, Danderyds Hosp, Dept Clin Sci, Stockholm, Sweden;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Pharoah, Paul
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge, England;Univ Cambridge, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
    Pashayan, Nora
    UCL, Dept Appl Hlth Res, London, England;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge, England.
    Schleutker, Johanna
    Univ Turku, Inst Biomed, Turku, Finland;Turku Univ Hosp, Dept Med Genet, Tyks Microbiol & Genet, Turku, Finland.
    Tammela, Teuvo L. J.
    Univ Tampere, Fac Med & Life Sci, Tampere, Finland;Tampere Univ Hosp, Dept Urol, Tampere, Finland.
    Sipeky, Csilla
    Univ Turku, Inst Biomed, Turku, Finland.
    Auvinen, Anssi
    Univ Tampere, Sch Hlth Sci, Dept Epidemiol, Tampere, Finland.
    Albanes, Demetrius
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
    Weinstein, Stephanie
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Hakansson, Niclas
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    West, Catharine M. L.
    Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England;Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester Canc Res Ctr, Div Canc Sci, Manchester, Lancs, England.
    Dunning, Alison M.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge, England.
    Burnet, Neil
    Univ Cambridge, Cambridge Univ Hosp NHS Fdn Trust, Ctr Oncol, Dept Oncol, Cambridge, England.
    Mucci, Lorelei A.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
    Giovannucci, Edward
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
    Andriole, Gerald L.
    Washington Univ, Sch Med, St Louis, MO USA.
    Cussenot, Olivier
    Tenon Hosp, CeRePP, Paris, France;UPMC, Sorbonne Univ, Tenon Hosp, GRC ONCOTYPE URO 5, Paris, France.
    Cancel-Tassin, Geraldine
    Tenon Hosp, CeRePP, Paris, France;UPMC, Sorbonne Univ, Tenon Hosp, GRC ONCOTYPE URO 5, Paris, France.
    Koutros, Stella
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
    Freeman, Laura E. Beane
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
    Sorensen, Karina Dalsgaard
    Aarhus Univ, Dept Clin Med, Aarhus, Denmark;Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark.
    Orntoft, Torben Falck
    Aarhus Univ, Dept Clin Med, Aarhus, Denmark;Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark.
    Borre, Michael
    Aarhus Univ, Dept Clin Med, Aarhus, Denmark;Aarhus Univ Hosp, Dept Urol, Aarhus, Denmark.
    Maehle, Lovise
    Oslo Univ Hosp, Dept Med Genet, Oslo, Norway.
    Grindedal, Eli Marie
    Oslo Univ Hosp, Dept Med Genet, Oslo, Norway.
    Neal, David E.
    Univ Oxford, Nuffield Dept Surg Sci, Oxford, England;Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge, England;Canc Res UK, Cambridge Res Inst, Cambridge, England;Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford, England.
    Donovan, Jenny L.
    Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
    Hamdy, Freddie C.
    Univ Oxford, Nuffield Dept Surg Sci, Oxford, England;Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford, England.
    Martin, Richard M.
    Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
    Travis, Ruth C.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England.
    Key, Tim J.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England.
    Hamilton, Robert J.
    Princess Margaret Canc Ctr, Dept Surg Oncol, Toronto, ON, Canada.
    Fleshner, Neil E.
    Princess Margaret Canc Ctr, Dept Surg Oncol, Toronto, ON, Canada.
    Finelli, Antonio
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA;Princess Margaret Canc Ctr, Div Urol, Toronto, ON, Canada.
    Ingles, Sue Ann
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
    Stern, Mariana C.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
    Rosenstein, Barry S.
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA;Icahn Sch Med Mt Sinai, Dept Radiat Oncol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Kerns, Sarah L.
    Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
    Ostrer, Harry
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA;Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
    Lu, Yong-Jie
    Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England.
    Zhang, Hong-Wei
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA;Second Mil Med Univ, Shanghai, Peoples R China.
    Feng, Ninghan
    Nanjing Med Univ, Wuxi Hosp 2, Wuxi, Peoples R China.
    Mao, Xueying
    Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England.
    Guo, Xin
    Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing, Peoples R China.
    Wang, Guomin
    Fudan Univ, Zhongshan Hosp, Dept Urol, Med Coll, Shanghai, Peoples R China.
    Sun, Zan
    China Med Univ, Peoples Hosp, Peoples Hosp Liaoning Prov, Shenyang, Peoples R China.
    Giles, Graham G.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostati, Melbourne, Vic, Australia.
    Southey, Melissa C.
    Monash Univ, Sch Clin Sci Monash Hlth, Precis Med, Clayton, Vic, Australia.
    MacInnis, Robert J.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostati, Melbourne, Vic, Australia.
    FitzGerald, Liesel M.
    Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia;Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia.
    Kibel, Adam S.
    Brigham & Womens Hosp, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA.
    Drake, Bettina F.
    Washington Univ, Sch Med, St Louis, MO USA.
    Vega, Ana
    Fdn Publ Galega Med Xenomica SERGAS, Grp Med Xenom, CIBERER, IDIS, Santiago De Compostela, Spain.
    Gomez-Caamano, Antonio
    SERGAS, Dept Radiat Oncol, Complexo Hosp Univ Santiago, Santiago De Compostela, Spain.
    Szulkin, Robert
    Scandinavian Dev Serv, Danderyd, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Eklund, Martin
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Kogevinas, Manolis
    Univ Pompeu Fabra, Barcelona, Spain;Hosp del Mar, Res Inst, IMIM, Barcelona, Spain;CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain;ISGlobal, Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
    Llorca, Javier
    Univ Cantabria, IDIVAL, Santander, Spain;CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain.
    Castano-Vinyals, Gemma
    Univ Pompeu Fabra, Barcelona, Spain;Hosp del Mar, Res Inst, IMIM, Barcelona, Spain;CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain;ISGlobal, Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
    Penney, Kathryn L.
    Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Stampfer, Meir
    Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Park, Jong Y.
    H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
    Sellers, Thomas A.
    H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
    Lin, Hui-Yi
    Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Biostat Program, New Orleans, LA USA.
    Stanford, Janet L.
    Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Cybulski, Cezary
    Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
    Wokolorczyk, Dominika
    Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
    Lubinski, Jan
    Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
    Ostrander, Elaine A.
    NHGRI, NIH, Bethesda, MD 20892 USA.
    Geybels, Milan S.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Weischer, Maren
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark.
    Bisbjerg, Rasmus
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Urol, Herlev, Denmark.
    Roder, Martin Andreas
    Copenhagen Univ Hosp, Rigshosp, Dept Urol, Copenhagen Prostate Canc Ctr, Copenhagen, Denmark.
    Iversen, Peter
    Copenhagen Univ Hosp, Rigshosp, Dept Urol, Copenhagen Prostate Canc Ctr, Copenhagen, Denmark.
    Brenner, Hermann
    German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany;Natl Ctr Tumor Dis NCT, Heidelberg, Germany;German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany;German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
    Cuk, Katarina
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Holleczek, Bernd
    Saarland Canc Registry, Saarbrucken, Germany.
    Maier, Christiane
    Univ Hosp Ulm, Inst Human Genet, Ulm, Germany.
    Luedeke, Manuel
    Univ Hosp Ulm, Inst Human Genet, Ulm, Germany.
    Schnoeller, Thomas
    Univ Hosp Ulm, Dept Urol, Ulm, Germany.
    Kim, Jeri
    Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA.
    Logothetis, Christopher J.
    Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA.
    John, Esther M.
    Canc Prevent Inst Calif, Fremont, CA USA;Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA USA;Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA USA.
    Teixeira, Manuel R.
    Univ Porto, Biomed Sci Inst ICBAS, Porto, Portugal;Portuguese Oncol Inst Porto, Dept Genet, Porto, Portugal.
    Paulo, Paula
    Portuguese Oncol Inst Porto, Dept Genet, Porto, Portugal.
    Cardoso, Marta
    Portuguese Oncol Inst Porto, Dept Genet, Porto, Portugal.
    Neuhausen, Susan L.
    City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA.
    Steele, Linda
    City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA.
    Ding, Yuan Chun
    City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA.
    De Ruyck, Kim
    Univ Ghent, Fac Med & Hlth Sci, Basic Med Sci, Ghent, Belgium.
    De Meerleer, Gert
    Univ Ghent, Fac Med & Hlth Sci, Basic Med Sci, Ghent, Belgium.
    Ost, Piet
    Ghent Univ Hosp, Dept Radiotherapy, Ghent, Belgium.
    Razack, Azad
    Univ Malaya, Dept Surg, Fac Med, Kuala Lumpur, Malaysia.
    Lim, Jasmine
    Univ Malaya, Dept Surg, Fac Med, Kuala Lumpur, Malaysia.
    Teo, Soo-Hwang
    Subang Jaya Med Ctr, Outpatient Ctr, CRM, Selangor, Malaysia.
    Lin, Daniel W.
    Univ Washington, Dept Urol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Newcomb, Lisa F.
    Univ Washington, Dept Urol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Lessel, Davor
    Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany.
    Gamulin, Marija
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA;Univ Hosp Ctr Zagreb, Div Med Oncol, Urogenital Unit, Dept Oncol, Zagreb, Croatia.
    Kulis, Tomislav
    Univ Zagreb, Sch Med, Univ Hosp Ctr Zagreb, Dept Urol, Zagreb, Croatia.
    Kaneva, Radka
    Med Univ Sofia, Dept Med Chem & Biochem, Mol Med Ctr, Sofia, Bulgaria.
    Usmani, Nawaid
    Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB, Canada;Cross Canc Inst, Div Radiat Oncol, Edmonton, AB, Canada.
    Singhal, Sandeep
    Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB, Canada;Cross Canc Inst, Div Radiat Oncol, Edmonton, AB, Canada.
    Slavov, Chavdar
    Med Univ Sofia, Dept Urol, Sofia, Bulgaria;Med Univ Sofia, Alexandrovska Univ Hosp, Sofia, Bulgaria.
    Mitev, Vanio
    Med Univ Sofia, Dept Med Chem & Biochem, Mol Med Ctr, Sofia, Bulgaria.
    Parliament, Matthew
    Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB, Canada;Cross Canc Inst, Div Radiat Oncol, Edmonton, AB, Canada.
    Claessens, Frank
    Katholieke Univ Leuven, Dept Cellular & Mol Med, Mol Endocrinol Lab, Leuven, Belgium.
    Joniau, Steven
    Univ Hosp Leuven, Dept Urol, Leuven, Belgium.
    Van den Broeck, Thomas
    Katholieke Univ Leuven, Dept Cellular & Mol Med, Mol Endocrinol Lab, Leuven, Belgium;Univ Hosp Leuven, Dept Urol, Leuven, Belgium.
    Larkin, Samantha
    Univ Southampton, Southampton Gen Hosp, Southampton, Hants, England.
    Townsend, Paul A.
    Univ Manchester, Div Canc Sci,Hlth Innovat Manchester, Manchester Canc Res Ctr,NIHR Manchester Biomed Re, Fac Biol Med & Hlth,Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
    Aukim-Hastie, Claire
    Univ Surrey, Guildford, Surrey, England.
    Dominguez, Manuela Gago
    Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA;Galician Fdn Genom Med, Genom Med Grp,SERGAS, Inst Invest Sanitaria Santiago de Compostela IDIS, Complejo Hosp Univ Santiago,Serv Galego Saude, Santiago De Compostela, Spain.
    Castelao, Jose Esteban
    Complexo Hosp Univ Vigo, Inst Invest Biomed Galicia IISGS, CHUVI Hosp, Genet Oncol Unit, Vigo, Spain.
    Martinez, Maria Elena
    Univ Calif San Diego, Moores Canc Ctr, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
    Roobol, Monique J.
    Erasmus Univ, Med Ctr, Dept Urol, Rotterdam, Netherlands.
    Jenster, Guido
    Erasmus Univ, Med Ctr, Dept Urol, Rotterdam, Netherlands.
    van Schaik, Ron H. N.
    Erasmus Univ, Med Ctr, Dept Clin Chem, Rotterdam, Netherlands.
    Menegaux, Florence
    Univ Paris Saclay, Univ Paris Sud, INSERM, Canc & Environm Grp,Ctr Res Epidemiol & Populat H, Villejuif, France.
    Truong, Therese
    Univ Paris Saclay, Univ Paris Sud, INSERM, Canc & Environm Grp,Ctr Res Epidemiol & Populat H, Villejuif, France.
    Koudou, Yves Akoli
    Univ Paris Saclay, Univ Paris Sud, INSERM, Canc & Environm Grp,Ctr Res Epidemiol & Populat H, Villejuif, France.
    Xu, Jianfeng
    NorthShore Univ HealthSyst, Program Personalized Canc Care, Evanston, IL USA.
    Khaw, Kay-Tee
    Univ Cambridge, Clin Gerontol Unit, Cambridge, England.
    Cannon-Albright, Lisa
    George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA;Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA.
    Pandha, Hardev
    Univ Surrey, Guildford, Surrey, England.
    Michael, Agnieszka
    Univ Surrey, Guildford, Surrey, England.
    Thibodeau, Stephen N.
    Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
    McDonnell, Shannon K.
    Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
    Schaid, Daniel J.
    Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
    Lindstrom, Sara
    Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
    Turman, Constance
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
    Ma, Jing
    Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Hunter, David J.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
    Riboli, Elio
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
    Siddiq, Afshan
    Queen Mary Univ London, Genom England, London, England.
    Canzian, Federico
    German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
    Kolonel, Laurence N.
    Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. Geisel Sch Med Dartmouth, Dept Biomed Data Sci, Lebanon, NH USA. Geisel Sch Med Dartmouth, Dept Mol & Syst Biol, Hanover, NH USA.
    Le Marchand, Loic
    Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. Geisel Sch Med Dartmouth, Dept Biomed Data Sci, Lebanon, NH USA. Geisel Sch Med Dartmouth, Dept Mol & Syst Biol, Hanover, NH USA.
    Hoover, Robert N.
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
    Machiela, Mitchell J.
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
    Cui, Zuxi
    Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
    Kraft, Peter
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
    Conti, David V.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
    Easton, Douglas F.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge, England;Univ Cambridge, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
    Wiklund, Fredrik
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Chanock, Stephen J.
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
    Henderson, Brian E.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
    Kote-Jarai, Zsofia
    Inst Canc Res, London, England.
    Haiman, Christopher A.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
    Eeles, Rosalind A.
    Inst Canc Res, London, England;Royal Marsden NHS Fdn Trust, London, England.
    Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci2018Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 7, s. 928-936Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 x 10(-8)) with PrCa and one locus significantly associated with early-onset PrCa (<= 55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 x 10(-9); G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 x 10(-9); T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.

  • 757.
    Sdona, Emmanouela
    et al.
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden.
    Hallberg, Jenny
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden;Sachs Childrens Hosp, Sodersjukhuset, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Andersson, Niklas
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden.
    Ekström, Sandra
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden;Reg Stockholm, Ctr Occupat & Environm Med, Stockholm, Sweden.
    Rautiainen, Susanne
    Karolinska Inst, Dept Publ Hlth Sci, Global & Sexual Hlth, Stockholm, Sweden;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
    Håkansson, Niclas
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden.
    Kull, Inger
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden;Sachs Childrens Hosp, Sodersjukhuset, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Melen, Erik
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden;Sachs Childrens Hosp, Sodersjukhuset, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Bergström, Anna
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden;Reg Stockholm, Ctr Occupat & Environm Med, Stockholm, Sweden.
    Dietary antioxidant intake in school age and lung function development up to adolescence2020Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 55, nr 2, artikel-id 1900990Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dietary antioxidant intake has been hypothesised to influence lung function. The association between total antioxidant capacity (TAC) of the diet at age 8 years and lung function development up to 16 years in 2307 participants from the Swedish population-based birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiology) was investigated. Information on TAC was obtained from a food frequency questionnaire at 8 years. Lung function was measured by spirometry at 8 and 16 years, impulse oscillometry (IOS) and exhaled nitric oxide fraction (F-eNO) at 16 years. Low lung function was defined as forced expiratory volume in 1 s (FEV1) z-score below the 25th percentile. Longitudinal associations between TAC and lung function were analysed by mixed effect models adjusted for potential confounders. Stratification by asthma at 8 years was performed to examine effect modification. The median TAC intake was 10 067 mu mol Trolox equivalents (TE).g(-1), with males having a lower mean compared to females (9963 versus 10819 mu mol TE.g(-1)). In analyses of lung function change between 8 and 16 years, there were no statistically significant associations between TAC in tertiles and spirometry results for the total study population. Among children with asthma at 8 years (prevalence 7%), higher TAC was associated with higher mean FEV1 (0.46 SD, 95% CI 0.11-0.80) and decreased odds of low lung function at 16 years (OR 0.28, 95% CI 0.12-0.65). There were no associations between TAC and forced vital capacity or IOS/F-eNO results. High dietary antioxidant intake in school age may be associated with improved lung function development from school age to adolescence among children with asthma.

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  • 758.
    Selin, Jinjin Z.
    et al.
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, SE-17177 Stockholm, Sweden..
    Lindblad, Birgitta E.
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, SE-17177 Stockholm, Sweden.;Orebro Univ, Dept Ophthalmol, Sch Med Sci, SE-70182 Orebro, Sweden..
    Bottai, Matteo
    Karolinska Inst, Div Biostat, Inst Environm Med, SE-17177 Stockholm, Sweden..
    Morgenstern, Ralf
    Karolinska Inst, Div Biochem Toxicol, Inst Environm Med, SE-17177 Stockholm, Sweden..
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, SE-17177 Stockholm, Sweden..
    High-dose B-vitamin supplements and risk for age-related cataract: a population-based prospective study of men and women2017Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 118, nr 2, s. 154-160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous studies that have investigated the association between B-vitamin supplement use and risk for cataract yield conflicting results. The aim of this study was to examine the association between use of high-dose B-vitamin supplements (approximately 10 times recommended daily intake) and risk for age-related cataract in a population-based prospective study of 13 757 women from the Swedish Mammography Cohort and 22 823 men from the Cohort of Swedish Men. Dietary supplement use and potential confounders were assessed using a questionnaire at baseline. Information on cataract diagnosis and extraction was obtained through linkage to registers. During the follow-up period between January 1998 and December 2011, we identified 8395 cataract cases (3851 for women and 4544 for men). The use of B vitamins plus other supplements and B vitamins only was associated with 9% (95% CI 2, 17) and 27% (95% CI 12, 43) increased risk for cataract, respectively. The hazard ratios for use of B vitamins only and risk for cataract stratified by different age groups were as follows: < 60 years: 1.88 (95% CI 1.47, 2.39); 60-69 years: 1.21 (95% CI 0.96, 1.53); and >= 70 years: 1.09 (95% CI 0.91, 1.31) (P-interaction=0.002). Our results suggest that the use of high-dose B-vitamin supplements was associated with an increased risk for cataract. This association might be confined to younger participants.

  • 759. Selin, Jinjin Zheng
    et al.
    Lindblad, Birgitta Ejdervik
    Rautiainen, Susanne
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Morgenstern, Ralf
    Bottai, Matteo
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Wolk, Alicja
    Are Increased Levels of Systemic Oxidative Stress and Inflammation Associated with Age-Related Cataract?2014Ingår i: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 21, nr 5, s. 700-704Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Oxidative stress and inflammation may be involved in the etiology of age-related cataract. This study is the first to investigate the association between urinary levels of 8-iso-prostaglandin F-2 alpha (PGF(2 alpha); as a biomarker for systemic oxidative stress in vivo) and 15-keto-dihydro-PGF(2 alpha) (as a biomarker for systemic inflammation in vivo) and risk of age-related cataract. We observed in a nested case-control study, including 258 women with incident cataract diagnosis and/or cataract extraction and 258 women without cataract, matched on age and date of urine sample collection that, women with higher levels of urinary 8-iso-PGF(2 alpha) as compared with lower levels had an increased risk of age-related cataract. There was no difference in 15-keto-dihydro-PGF(2 alpha) levels between cases and controls. Our observations lead to the hypothesis that higher systemic oxidative stress increases the risk of developing age-related cataract.

  • 760.
    Sennerby, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Garmo, Hans
    Regional Oncologic Center, Uppsala University, Uppsala .
    Ahlbom, Anders
    Pedersen, Nancy L.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cardiovascular diseases and risk of hip fracture2009Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 302, nr 15, s. 1666-1673Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Recent studies indicate common etiologies for cardiovascular disease (CVD) and osteoporotic fractures. OBJECTIVES: To examine the relation between CVD and risk of hip fracture in twins and evaluate the relative importance of genetics and lifestyle factors in this association. DESIGN, SETTING, AND PARTICIPANTS: A cohort of all 31,936 Swedish twins born from 1914-1944 was followed up from the age of 50 years. The National Patient Registry identified twins with CVDs and fractures from 1964 through 2005. Time-dependent exposures using Cox proportional hazard regression models were evaluated. MAIN OUTCOME MEASURE: Time to hip fracture after diagnosis of CVD. RESULTS: The crude absolute rate of hip fractures was 12.6 per 1000 person-years after a diagnosis of heart failure, 12.6 per 1000 person-years after a stroke, 6.6 per 1000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1000 person-years after a diagnosis of ischemic heart disease compared with 1.2 per 1000 person-years for those without a CVD diagnosis. The multivariable-adjusted hazard ratio (HR) of hip fracture after a diagnosis of heart failure was 4.40 (95% confidence interval [CI], 3.43-5.63); after a stroke, the HR was 5.09 (95% CI, 4.18-6.20); after a diagnosis of peripheral atherosclerosis, the HR was 3.20 (95% CI, 2.28-4.50); and after an ischemic heart disease event, the HR was 2.32 (95% CI, 1.91-2.84). Identical twins without heart failure and stroke also had, after their co-twins had been exposed to these respective diseases, an increased rate of hip fracture. These sibling twins pseudoexposed for heart failure had a multivariable-adjusted HR of 3.74 (95% CI, 1.97-7.10) for hip fracture, whereas pseudoexposure for stroke had an HR of 2.29 (95% CI, 1.20-4.35). CONCLUSIONS: A diagnosis of CVD was significantly associated with risk of subsequent hip fracture. Increased risks in co-twins without an index diagnosis suggest genetic factors in the association between CVD and osteoporotic fractures.

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  • 761. Shakersain, Behnaz
    et al.
    Rizzuto, Debora
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Faxén-Irving, Gerd
    Fratiglioni, Laura
    Xu, Wei-Li
    The Nordic Prudent Diet Reduces Risk of Cognitive Decline in the Swedish Older Adults: A Population-Based Cohort Study.2018Ingår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, nr 2, artikel-id E229Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Appropriate dietary pattern for preserving cognitive function in northern Europe remains unknown. We aimed to identify a Nordic dietary pattern index associated with slower cognitive decline compared to the Mediterranean-DASH Intervention for Neurodegenerative Delay, Mediterranean Diet, Dietary Approaches to Stop Hypertension, and Baltic Sea Diet indices. A total of 2223 dementia-free adults aged ≥60 were followed for 6 years. Mini-Mental State Examination was administrated at baseline and follow-ups. Dietary intake was assessed by 98-item food frequency questionnaire, and the Nordic Prudent Dietary Pattern (NPDP) was identified. Data were analysed using mixed-effects and parametric survival models and receiver operating characteristic curves with adjustment for potential confounders. Moderate (β = 0.139, 95% CI 0.077-0.201) and high adherence (β = 0.238, 95% CI 0.175-0.300) to NPDP were associated with less cognitive decline compared to other four indices. High adherence to NPDP was also associated with the lowest risk of MMSE decline to ≤24 (HR = 0.176, 95% CI 0.080-0.386) and had the greatest ability to predict such decline (area under the curve = 0.70). Moderate-to-high adherence to the NPDP may predict a better-preserved cognitive function among older adults in Nordic countries. Regional dietary habits should be considered in developing dietary guidelines for the prevention of cognitive impairment and dementia.

  • 762. Shakersain, Behnaz
    et al.
    Santoni, Giola
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Faxén-Irving, Gerd
    Fastbom, Johan
    Fratiglioni, Laura
    Xu, Weili
    Prudent diet may attenuate the adverse effects of Western diet on cognitive decline2016Ingår i: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 12, nr 2, s. 100-109, artikel-id S1552-5260(15)02701-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: The influence of mixed dietary patterns on cognitive changes is unknown.

    METHODS: A total of 2223 dementia-free participants aged ≥60 were followed up for 6 years to examine the impact of dietary patterns on cognitive decline. Mini-mental state examination (MMSE) was administered. Diet was assessed by a food frequency questionnaire. By factor analysis, Western and prudent dietary patterns emerged. Mixed-effect models for longitudinal data with repeated measurements were used.

    RESULTS: Compared with the lowest adherence to each pattern, the highest adherence to prudent pattern was related to less MMSE decline (β = 0.106, P = .011), whereas the highest adherence to Western pattern was associated with more MMSE decline (β = -0.156, P < .001). The decline associated with Western diet was attenuated when accompanied by high adherence to prudent pattern.

    DISCUSSION: High adherence to prudent diet may diminish the adverse effects of high adherence to Western diet on cognitive decline.

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  • 763.
    Sigurdsson, Snaevar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Garnier, Sophie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Grundberg, Elin
    Kwan, Tony
    Nilsson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Sturfelt, Gunnar
    Bengtsson, Anders A.
    Jönsen, Andreas
    Truedsson, Lennart
    Rantapää-Dahlqvist, Solbritt
    Eriksson, Catharina
    Alm, Gunnar
    Göring, Harald H. H.
    Pastinen, Tomi
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF52008Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 17, nr 18, s. 2868-2876Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is the prototype autoimmune disease where genes regulated by type I interferon (IFN) are over-expressed and contribute to the disease pathogenesis. Because signal transducer and activator of transcription 4 (STAT4) plays a key role in the type I IFN receptor signaling, we performed a candidate gene study of a comprehensive set of single nucleotide polymorphism (SNPs) in STAT4 in Swedish patients with SLE. We found that 10 out of 53 analyzed SNPs in STAT4 were associated with SLE, with the strongest signal of association (P = 7.1 x 10(-8)) for two perfectly linked SNPs rs10181656 and rs7582694. The risk alleles of these 10 SNPs form a common risk haplotype for SLE (P = 1.7 x 10(-5)). According to conditional logistic regression analysis the SNP rs10181656 or rs7582694 accounts for all of the observed association signal. By quantitative analysis of the allelic expression of STAT4 we found that the risk allele of STAT4 was over-expressed in primary human cells of mesenchymal origin, but not in B-cells, and that the risk allele of STAT4 was over-expressed (P = 8.4 x 10(-5)) in cells carrying the risk haplotype for SLE compared with cells with a non-risk haplotype. The risk allele of the SNP rs7582694 in STAT4 correlated to production of anti-dsDNA (double-stranded DNA) antibodies and displayed a multiplicatively increased, 1.82-fold risk of SLE with two independent risk alleles of the IRF5 (interferon regulatory factor 5) gene.

  • 764.
    Siilin, Helene
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lundgren, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mellström, Dan
    Ohlsson, Claes
    Karlsson, Magnus
    Orwoll, Eric
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Prevalence of Primary Hyperparathyroidism and Impact on Bone Mineral Density in Elderly Men: MrOs Sweden2011Ingår i: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 35, nr 6, s. 1266-1272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Age and sex are of importance in the development of primary hyperparathyroidism (PHPT), and the disease is most common in postmenopausal women. Skeletal complications are well known at an advanced stage of PHPT, although the impact on bone mineral density (BMD) is evident in patients with mild disease. This study examines the prevalence of PHPT in elderly men and its impact on BMD. METHODS: Calcium homeostasis and BMD, measured by dual X-ray absorptiometry, were evaluated in 3014 men ages 69 to 81 years in the MrOS-Sweden cohort. Individuals with a low glomerular filtration rate (<21 ml/min/1.73 m(2)) and vitamin D deficiency (<50 nmol/l) were excluded. Among the remaining subjects, PHPT was assumed in subjects with above-normal albumin-adjusted serum (s)-calcium and plasma intact parathyroid hormone (p-iPTH) levels (PHPT group). BMD was compared between the PHPT group and men without PHPT. Subjects with inappropriately elevated iPTH (IEP group), based on both s-calcium (2.34 mmol/l) and iPTH (4.24 pmol/l) levels being above the median level, were compared to the rest of the cohort. RESULTS: The prevalence of PHPT was estimated to be 0.73%. The mean BMD in the total hip and femoral neck was lower in the PHPT group than in the PHPT controls. Significantly lower BMD (p < 0.05) was seen in the IEP group (total hip and lumbar spine). CONCLUSIONS: Elderly men appear to have a lower prevalence of PHPT than women at the same age. The impact of disturbed calcium homeostasis on BMD was also evident in this population group.

  • 765.
    Silfverswärd, Carl-Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Penno, Hendrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Frost, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nilsson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Expression of Markers of Activity in Cultured Human Osteoblasts: Effects of Interleukin-4 and Interleukin-132010Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, nr 5, s. 338-342Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cytokines regulate proliferation, differentiation and activation of osteoblasts. Interleukin-4 (IL-4) and interleukin-13 (IL-13) takes part in this regulation by inhibiting proliferation and by enhancement of interleukin-6 (IL-6) formation in cultured human osteoblasts (hOBs). In the present study we have investigated the effects of IL-4 and IL-13 on markers of osteoblastic activity in isolated hOBs. Treatment with either IL-4 or IL-13 (1–100 pM) stimulated the formation of alkaline phosphatase (ALP) dose-dependently, detected by enzyme reaction and histochemistry. IL-4 and IL-13 also induced an increase in the secretion of procollagen type I carboxypeptide (PICP) from cultured hOBs, measured by RIA. Osteocalcin secretion measured by ELISA-technique was unaffected. The rate of mineralization, assessed by von Kossa and Alizarin Red staining, was clearly enhanced in hOBs stimulated by IL-4 or IL-13. In conclusion IL-4 and IL-13 exert multiple effects on osteoblast activity in cultured hOBs. Stimulation of ALP secretion together with enhanced collagen secretion and mineralization suggests that IL-4 and IL-13 also have the capacity to maintain hOBs in a differentiated, productive phase.

  • 766.
    Silfverswärd, Carl-Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sisask, Gregor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ohlsson, Claes
    Frost, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nilsson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bone Formation in Interleukin-4 and Interleukin-13 depleted Mice2008Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, nr 3, s. 410-420Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose Cytokines play an important role in the complex process of bone formation. We have previously found an altered skeletal phenotype with reduction of cortical bone mass in mice depleted of the 2 cytokines interleukin-4 (IL-4) and interleukin-13 (IL 13). The present study was performed to investigate a potential role of IL-4 and IL-13 in fracture healing and bone induction by demineralized xenogenic bone matrix (DXBM). Methods Callus formation in IL-4(-/-)IL-13(-/-) (IL-4/13 knockout) and wild-type (WT) male mice was compared using a standardized fracture model. The capacity of IL-4(-/-)IL-13(-/-) and WT male and female mice to form heterotopic bone was compared using intramuscular implants of DXBM. Bone formation and mechanical properties were evaluated by pQCT, ash weight, 3-point bending, radiology, and immunohistology. Results In the fracture investigation substantial amounts of new bone formation by 5 weeks were found, but no differences in radiographical healing, callus volume, BMD, BMC, or mechanical properties were detected between IL-4(-/-)IL-13(-/-) and WT mice. In the DXBM investigation radiographic analysis confirmed mineralization of implants in both groups, but no difference in the amount of mineral deposition (net bone formation) between IL-4(-/-)IL-13(-/-) and WT mice was found. Immunohistology showed inhibition of autonomic nerves in the capsule of the IL-4(-/-)IL-13(-/-) group along with a lack of vascularization within the implants. Interpretation Depletion of IL-4 and IL-13 does not cause any major alteration in fracture healing or heterotopic bone formation in mice. The pattern of autonomous nerve expression and expression of markers of neovascularization is, however, altered to some extent by the absence of IL-4 and IL-13.

  • 767.
    Sisask, Gregor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bone Development and the Nervous System2009Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Innervation of bone influence bone modeling, growth and remodeling. Pro-inflammatory cytokines released after tissue trauma are recognized as neurotrophic factors as well as factors influencing bone formation. The Wnt signaling pathway, essential for cell migration during embryogenesis is found to influence bone formation during fracture healing. Alterations in growth and bone formation are seen in denervating disorders and in manipulated Wnt signaling. The aim of the present thesis was to study; sensory and autonomic innervation in the developing skeleton in rats and mice, a possible influence on bone formation in IL-4 and IL-13 depleted mice, and fracture healing in altered Wnt signaling by glycogen synthase-3β inhibition in rats.

    Bone innervation with sensory and autonomic nerves in modeling and growth follows a predictable and reproducible pattern both in the rat and in the mouse with sensory nerves occurring prior to autonomic nerves in areas with high chondrogenic and osteogenic activity. The time lag in occurrence between sensory and autonomic nerves indicates the importance of developmental timing between different nerve qualities in skeletal ontogeny. These findings give substantial morphologic support for important regulatory effects by the nervous system on bone development.

    Depletion of the anti-inflammatory cytokines IL-4 and IL-13 production in mice resulted in an inhibited autonomic innervation and lack of implant capillary ingrowth, studied by DXBM implants. In fracture healing no differences between IL-4/13 knockout mice and wild type mice were found concerning fracture callus parameters, biomechanical properties or histology except that sensory and autonomic nerves were found in the bone marrow in knockout mice but not in wild type mice.

    An altered canonical Wnt signaling was achieved by the GSK-3β inhibitor AR28. The increase in cytoplasmic β-catenin, due to inhibited degradation, resulted in a remarkable anabolic effect both on the fractured bone and on fracture healing. The histological analysis showed that the fractures healed without the usual formation of fibro-cartilage callus. This finding suggests that inhibition of GSK-3β inhibits the differentiation of chondrocytes and instead promotes the differentiation of mesenchymal progenitor cells into osteogenic cells.

    Delarbeten
    1. Ontogeny of sensory nerves in the developing skeleton
    Öppna denna publikation i ny flik eller fönster >>Ontogeny of sensory nerves in the developing skeleton
    1995 (Engelska)Ingår i: Anatomical Record, ISSN 0003-276X, E-ISSN 1097-0185, Vol. 243, nr 2, s. 234-240Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Previous studies have shown that the neuropeptide calcitonin gene-related peptide (CGRP) have an influence on osteoclastic bone resorption and that CGRP and substance P (SP), both wellknown markers for sensory neurons, behave as growth factors.Materials and Methods: The ontogeny of the sensory nerves in the hindlimb skeleton of the rat was studied from gestational day (GD) 15 to neonatal day (ND) 24 by immunohistochemistry. Neurofilaments and nerve terminals were labelled with protein gene-product 9.5 (PGP 9.5) and synaptophycin (SYN) respectively.Results: PGP 9.5 appeared at GD 15 and SYN at GD 19, both in the perichondrial tissue of the long bones. One week later, at ND 4 nerve fibre, immunoreactive to PGP 9.5 and SYN were observed within the bone organ. Sensory nerves, indicated by CGRP and SP, were first discerned at GD 18-19 in the periosteal tissue of the diaphyseal and metaphseal regions and in the bone organ at ND 4. Approximately at ND 6, vascular as well as non-vascular nerves extended into the metaphyses and at ND 8 into the epiphyses, concomitant with the first signs of mineralization.Conclusions: The study shows that a functional sensory nerve supply of the developing bone organ occurs immediatly prior to partus, apparently parallel with an increasing mineralization. The combined findings may indicate a sensory influence on developmental processes in the skeleton

    Nyckelord
    Immunohistochemistry, Substance P, Calcitonin gene-related peptide, Rat bone innervation, Skeletal development
    Nationell ämneskategori
    Kirurgi Cell- och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-99431 (URN)10.1002/ar.1092430210 (DOI)8554179 (PubMedID)
    Tillgänglig från: 2009-03-13 Skapad: 2009-03-13 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    2. The Development of Autonomic Innervation in Bone and Joints of the Rat
    Öppna denna publikation i ny flik eller fönster >>The Development of Autonomic Innervation in Bone and Joints of the Rat
    1996 (Engelska)Ingår i: Journal of the Autonomic Nervous System, ISSN 0165-1838, E-ISSN 1872-7476, Vol. 59, nr 1-2, s. 27-33Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The development of autonomic nerves in the hindlimb skeleton, was studied in rats from gestational day (G) 15 to postnatal day (P) 24 by immunoreactivity to neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). Control labelling with antisera to neurofilaments, protein gene-product 9.5 (PGP 9.5), and nerve terminals, synaptophysin (SYN), showed nerve fibres at G15 and nerve terminals at G19 in the perichondrial tissue. From P4, nerve fibres and terminals were observed within the bone organ. Noradrenergic sympathetic nerves, containing NPY, were first discerned at birth, G21, in the perichondrial tissue and within the bone organ at P4. Autonomic cholinergic nerve fibres, indicated by immunoreactivity to VIP, exhibited a similar temporal and regional occurrence. The diaphyseal parts were first supplied with autonomic nerves at P4. The nerve fibres extended into the metaphyses at P6-8 and finally into the epiphyses at P10, concomitant with the first signs of mineralization. Vascular as well as non-vascular nerve fibres were seen. The study shows that developing bone organ is supplied with autonomic nerves from birth, and the the growth of nerves parallels the mineralisation process. Previous studies have demonstrated that NPY potently inhibits parathyroid hormone (PTH) induced effects on osteoblastic bone cells and that VIP is a strong inductor of bone resorption. NPY and VIP also exert vasoregulatory effects. The combined findings suggest an autonomic influence on bone development.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-58779 (URN)10.1016/0165-1838(95)00139-5 (DOI)8816362 (PubMedID)
    Tillgänglig från: 2008-10-17 Skapad: 2008-10-17 Senast uppdaterad: 2017-12-01Bibliografiskt granskad
    3. Bone Formation in Interleukin-4 and Interleukin-13 depleted Mice
    Öppna denna publikation i ny flik eller fönster >>Bone Formation in Interleukin-4 and Interleukin-13 depleted Mice
    Visa övriga...
    2008 (Engelska)Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, nr 3, s. 410-420Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background and purpose Cytokines play an important role in the complex process of bone formation. We have previously found an altered skeletal phenotype with reduction of cortical bone mass in mice depleted of the 2 cytokines interleukin-4 (IL-4) and interleukin-13 (IL 13). The present study was performed to investigate a potential role of IL-4 and IL-13 in fracture healing and bone induction by demineralized xenogenic bone matrix (DXBM). Methods Callus formation in IL-4(-/-)IL-13(-/-) (IL-4/13 knockout) and wild-type (WT) male mice was compared using a standardized fracture model. The capacity of IL-4(-/-)IL-13(-/-) and WT male and female mice to form heterotopic bone was compared using intramuscular implants of DXBM. Bone formation and mechanical properties were evaluated by pQCT, ash weight, 3-point bending, radiology, and immunohistology. Results In the fracture investigation substantial amounts of new bone formation by 5 weeks were found, but no differences in radiographical healing, callus volume, BMD, BMC, or mechanical properties were detected between IL-4(-/-)IL-13(-/-) and WT mice. In the DXBM investigation radiographic analysis confirmed mineralization of implants in both groups, but no difference in the amount of mineral deposition (net bone formation) between IL-4(-/-)IL-13(-/-) and WT mice was found. Immunohistology showed inhibition of autonomic nerves in the capsule of the IL-4(-/-)IL-13(-/-) group along with a lack of vascularization within the implants. Interpretation Depletion of IL-4 and IL-13 does not cause any major alteration in fracture healing or heterotopic bone formation in mice. The pattern of autonomous nerve expression and expression of markers of neovascularization is, however, altered to some extent by the absence of IL-4 and IL-13.

    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-96657 (URN)10.1080/17453670710015337 (DOI)000257593200016 ()18622847 (PubMedID)
    Tillgänglig från: 2008-01-24 Skapad: 2008-01-24 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    4. Ontogeny of sensory and autonomic nerves in the developing mouse skeleton
    Öppna denna publikation i ny flik eller fönster >>Ontogeny of sensory and autonomic nerves in the developing mouse skeleton
    2013 (Engelska)Ingår i: Autonomic Neuroscience: Basic & Clinical, ISSN 1566-0702, E-ISSN 1872-7484, Vol. 177, nr 2, s. 237-243Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Bone innervation is implicated in bone modeling and remodeling. This study investigates skeletal nerve development in embryonic and newborn mice, focusing on sensory and autonomic nerves and their temporal occurrence. Materials and methods: The ontogeny of innervation and angiogenesis in the hindlimb skeleton of mice was studied from embryonic day (E) 15 to postnatal day (P) 20. Neuronal tissue was immunohistochemically labeled for detection of growth associated protein 43 (GAP-43), protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY). Vascular endothelium was labeled for platelet endothelium cell adhesion molecule-1 (PECAM-1). Morphology was evaluated with hematoxylin and eosin staining. Results: GAP-43, PGP 9.5, CGRP, and PECAM-1 were all present at E 15, adjacent to areas with high osteogenic and chondrogenic activity. In the primary ossification centers, GAP-43 was found at E 15, PGP 9.5 at E 17, CGRP at E 19, and NPY at P4. The same time lag in appearance was observed in the secondary ossification centers. The covering capillary network was initially dense, but became mature and sparse from P 12 onwards. Conclusion: A functional nerve supply co-localized with a rich capillary network is seen early in the developing mouse skeleton, especially in areas with high osteogenic activity. Sensory innervation occurs prior to partus, while autonomic innervation (revealed by the presence of NPY and TH) is established post partum. The findings indicate a time-related development of nerves with different qualities, according to skeletal development.

    Nyckelord
    Immunohistochemistry-bone, Calcitonin gene-related peptide, Neuropeptide Y, Tyrosine hydroxylase, PECAM-1, Skeletal development, Mouse bone innervation
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-99438 (URN)10.1016/j.autneu.2013.05.005 (DOI)000325665700024 ()
    Tillgänglig från: 2009-03-13 Skapad: 2009-03-13 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    5. AR28 a GSK3beta-inhibitor heal fractures rapidly without endochondral bone formation
    Öppna denna publikation i ny flik eller fönster >>AR28 a GSK3beta-inhibitor heal fractures rapidly without endochondral bone formation
    Visa övriga...
    (Engelska)Manuskript (Övrig (populärvetenskap, debatt, mm))
    Identifikatorer
    urn:nbn:se:uu:diva-99442 (URN)
    Tillgänglig från: 2009-03-13 Skapad: 2009-03-13 Senast uppdaterad: 2010-01-14
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  • 768.
    Sisask, Gregor
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Marsell, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sundgren-Andersson, Anna
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nilsson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Metabola bensjukdomar.
    Jonsson, Kenneth B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation2013Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 54, nr 1, s. 126-132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fracture healing is a complex interplay between endochondral and intramembranous bone formation processes. The canonical Wnt/β-catenin pathway enhances new bone formation and may play a role in fracture healing. Glycogen synthase kinase 3β (GSK3β) is a key regulator of β-catenin degradation. In this study, we investigate the effects of AZD2858, an orally bioactive GSK3 inhibitor, on fracture healing. Femoral fractures were produced in rats after the insertion of a femoral nail. The rats were treated with oral administration of AZD2858 at a dose of 30μmol/kg (20mg/kg) daily for up to 3weeks, while control animals were administered vehicle. At 4days, and at 1, 2 and 3weeks, histological analysis was performed, and at the 2 and 3week time points, we performed peripheral quantitative computed tomography (pQCT), X-rays, and four-point bending tests. Peripheral QCT showed an increase in both mineral density (of 28% at 2weeks and 38% at 3weeks) and mineral content (of 81% at 2weeks and 93% at 3weeks) in the calluses from AZD2858 treated animals as compared to vehicle treated animals. Histological analysis demonstrated that rats treated with GSK3 inhibitor healed their fractures rapidly, but without the pre-formation of cartilage tissue. Furthermore, four-point bending tests of fractured femora from animals treated for 2 and 3weeks showed an increase in strength in treated animals compared to their vehicle-treated controls. In conclusion, AZD2858, a potent GSK3 inhibitor, has a substantial impact on fracture healing. The fractures healed with a bony callus without an obvious endochondral component, suggesting that AZD2858 drives mesenchymal cells into the osteoblastic pathway. This leads to direct bone repair in an unstable fracture milieu.

  • 769.
    Sisask, Gregor
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Silfverswärd, Carl-Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Bjurholm, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Nilsson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ontogeny of sensory and autonomic nerves in the developing mouse skeleton2013Ingår i: Autonomic Neuroscience: Basic & Clinical, ISSN 1566-0702, E-ISSN 1872-7484, Vol. 177, nr 2, s. 237-243Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bone innervation is implicated in bone modeling and remodeling. This study investigates skeletal nerve development in embryonic and newborn mice, focusing on sensory and autonomic nerves and their temporal occurrence. Materials and methods: The ontogeny of innervation and angiogenesis in the hindlimb skeleton of mice was studied from embryonic day (E) 15 to postnatal day (P) 20. Neuronal tissue was immunohistochemically labeled for detection of growth associated protein 43 (GAP-43), protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY). Vascular endothelium was labeled for platelet endothelium cell adhesion molecule-1 (PECAM-1). Morphology was evaluated with hematoxylin and eosin staining. Results: GAP-43, PGP 9.5, CGRP, and PECAM-1 were all present at E 15, adjacent to areas with high osteogenic and chondrogenic activity. In the primary ossification centers, GAP-43 was found at E 15, PGP 9.5 at E 17, CGRP at E 19, and NPY at P4. The same time lag in appearance was observed in the secondary ossification centers. The covering capillary network was initially dense, but became mature and sparse from P 12 onwards. Conclusion: A functional nerve supply co-localized with a rich capillary network is seen early in the developing mouse skeleton, especially in areas with high osteogenic activity. Sensory innervation occurs prior to partus, while autonomic innervation (revealed by the presence of NPY and TH) is established post partum. The findings indicate a time-related development of nerves with different qualities, according to skeletal development.

  • 770.
    Sjögren, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Becker, Wulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Warensjö, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Olsson, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Gustafsson, Inga-Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Karlström, Brita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Mediterranean and carbohydrate-restricted diets and mortality among elderly men: a cohort study in Sweden2010Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, nr 4, s. 967-974Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Comparative studies on dietary patterns and long-term mortality are sparse. Objective: The objective was to examine the relations between 10-y mortality and adherence to the World Health Organization dietary guidelines [Healthy Diet Indicator (HDI)], a Mediterranean-like diet, and a carbohydrate-restricted (CR) diet in elderly Swedish men. Design: Dietary habits were determined by 7-d dietary records in a population-based longitudinal study of 924 Swedish men (age: 71 +/- 1 y). The HDI score (-1 to 8 points), the Mediterranean Diet Score (MDS; 0-8 points), and the CR score (2-20 points) were calculated for each participant. Nonadequate reporters of energy intake were identified (n = 413). Mortality was registered during a median follow-up of 10.2 y. Cox proportional hazards regression, with multivariable adjustments, was used to determine the effects of adherence to each dietary pattern. Results: Two hundred fifteen and 88 subjects died of all-cause and cardiovascular disease, respectively. In all individuals, risk relations to mortality for each SD increment in the scores were observed for only MDS, with an adjusted hazard ratio (HR) of 0.83 (95% CI: 0.70, 0.99). Among adequate dietary reporters (n = 511), adjusted HRs for each SD increment in scores were enhanced for MDS (ie, 0.71; 95% CI: 0.55, 0.92) for all-cause mortality and 0.63 (95% CI: 0.42, 0.96) for cardiovascular mortality. Corresponding HRs for CR diet score were 1.19 (95% CI: 0.97, 1.45) for all-cause mortality and 1.44 (95% CI: 1.03, 2.02) for cardiovascular mortality. Conclusion: Adherence to a Mediterranean-like dietary pattern reduced mortality, whereas adherence to a CR dietary pattern appeared to increase mortality in elderly Swedish men, especially when only adequate dietary reporters were considered.

  • 771.
    Sjöholm, Pontus
    et al.
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
    Otten, Volker
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
    Wolf, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Gordon, Max
    Karolinska Inst, Danderyd Hosp, Dept Orthoped, Stockholm, Sweden;Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Karsten, Gustav
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
    Sköldenberg, Olof
    Karolinska Inst, Danderyd Hosp, Dept Orthoped, Stockholm, Sweden;Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Mukka, Sebastian
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
    Posterior and anterior tilt increases the risk of failure after internal fixation of Garden I and II femoral neck fracture2019Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 90, nr 6, s. 537-541Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose - Preoperative posterior tilt of the femoral head as seen on lateral radiographs has been reported to affect the risk of fixation failure in cases of minimally displaced femoral neck fractures (Garden I-II). We investigated radiological risk factors of treatment failure. Patients and methods - We included 417 patients (68% women, median age: 78 years (50-108) with a minimally displaced femoral neck fracture (Garden I-II) treated with internal fixation in a retrospective cohort study. The patients were followed for 3.4 years (2-14). Data on age, sex, housing, cognitive impairment, implant angulation, pre- and postoperative tilt, hip complications, and reoperations were recorded. The risk of fixation failure was assessed using Cox proportional hazards regression analysis. Results - The overall reoperation rate was 17%, and the rate of treatment failure (fixation failure, nonunion, avascular necrosis, or posttraumatic osteoarthritis) was 13%. Cox proportional hazard analysis revealed an increased risk of treatment failure with a preoperative posterior tilt of at least 20 degrees and a preoperative anterior tilt greater than 10 degrees. A failure occurred in 13 of the 65 patients with a posterior tilt of at least 20 degrees and in 5 of the 9 patients with an anterior tilt greater than 10 degrees. Interpretation - A preoperative posterior tilt of 20 degrees and an anterior tilt greater than 10 degrees in cases of Garden I and II femoral neck fractures increase the risk of fixation failure necessitating additional surgery. In this group of patients, there is a need for future interventional studies regarding the feasibility of primary hip arthroplasty.

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  • 772. Skeppholm, M
    et al.
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Pain from donor site after anterior cervical fusion with bone graft: a prospective randomized study with 12 months of follow-up2013Ingår i: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 22, nr 1, s. 142-147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION:

    Harvesting bone graft from the iliac crest in spinal fusion surgery is a widely used technique. However, complications can occur and there are also reports of patients with persistent graft site pain after surgery. The aim of this study was to evaluate pain from the donor site (DS) over time, and register associated complications and if it affected health-related quality of life (HRQoL).

    MATERIAL AND METHODS:

    One hundred and seven patients participating in an RCT between two different methods of reconstruction after cervical decompression were included in this study. One group underwent surgery with bone graft (BG) from the iliac crest and the other with no bone graft (NBG). All patients were evaluated concerning pain at DS and HRQoL preoperatively, at 4  weeks, 3 months and 1 year. Pain was evaluated with visual analog scale (VAS) and HRQoL with EQ-5D.

    RESULTS:

    A statistically significant difference was found at all times of follow-up in the BG group compared to preoperative levels and the NBG group. The VAS levels at follow-ups at 3 months and 1 year were however of questionable clinical importance. Two patients in the BG group had superficial wound infections postoperatively and five patients still had sensory disturbance in the area of graft site at 12 months. No major complications were registered. No difference could be seen in EQ-5D at any time of follow-up between the groups.

    CONCLUSION:

    Harvesting of iliac crest bone graft is associated with significant pain. However, at 3 months postoperatively, the negative effect of clinical importance seemed to have disappeared compared to when no bone graft was harvested. The pain from bone graft harvesting does not seem to affect the quality of life at 4 weeks postoperatively and onward.

  • 773.
    Skeppholm, Martin
    et al.
    Lowenstromska Sjukhuset, Stockholm Spine Ctr, S-19489 Upplands Vasby, Sweden.; Karolinska Inst, Dept Learning Informat Management & Eth, Tomtebodavagen 18, S-17177 Stockholm, Sweden.
    Fransson, Roland
    Lowenstromska Sjukhuset, Stockholm Spine Ctr, S-19489 Upplands Vasby, Sweden.
    Hammar, Margareta
    Lowenstromska Sjukhuset, Stockholm Spine Ctr, S-19489 Upplands Vasby, Sweden.
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The association between preoperative mental distress and patient-reported outcome measures in patients treated surgically for cervical radiculopathy2017Ingår i: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 17, nr 6, s. 790-798Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND CONTEXT: Previous research indicates that there might exist a link between the experience of pain and mental distress. Pain can possibly trigger anxiety and chronic pain, as well as also depression. On the other hand, anxiety and depression might also be risk factors for painful conditions and more pronounced subsequent disability and thus, the pathways may be bidirectional. Expanded knowledge of how different factors affect pain and function may help surgeons in preoperative decision-making.

    PURPOSE: The aim of this study was to evaluate the impact of potential preoperative risk factors with special reference to mental distress.

    STUDY DESIGN/SETTING: This is a prospective outcome study in a cohort from a multicenter randomized controlled trial comparing anterior cervical decompression and fusion with disc replacement.

    PATIENT SAMPLE: The sample included 151 patients with cervical radiculopathy planned for surgery.

    OUTCOME MEASURES: Surgical outcome was evaluated with Neck Disability Index (NDI), health related quality-of-life with European Quality of Life-5 Dimensions, and pain with visual analogue scale for arm and neck. Mental distress was preoperatively measured with the Hospital Anxiety and Depression (HAD) scale.

    METHODS: Preoperative data regarding possible risk factors for poor outcome were analyzed in multiple linear regression models with postoperative NDI and change of NDI as dependent factors. Patients with high preoperative levels of anxiety or depression (H-HAD), indicating mental distress, were compared with patients scoring low/moderate levels (L-HAD) regarding patient-reported outcome measures (PROMs) preoperatively and at 1- and 2-year follow-up.

    RESULTS: Outcome data were available for 136 patients at the 2-year follow-up. No statistically significant difference in any outcome data could be demonstrated between the two surgical treatment groups. Mental distress was the variable most strongly associated with NDI at 2 years in the regression analysis. There were 42 patients classified as H-HAD and 94 as L-HAD. The average improvement in NDI was 16.9 in the H-HAD group and 26.3 in the L-HAD group, p=.02. The H-HAD patients showed a tendency for poorer baseline data and worse outcome overall in all PROMs at follow-up at both 1 and 2 years.

    CONCLUSIONS: Preoperative mental distress measured with HAD was associated with worse outcome overall. More research is needed to investigate whether patients with mental distress may achieve better results if other treatments are offered, either as non-surgical treatment alone or as an adjunct to surgery.

  • 774.
    Skeppholm, Martin
    et al.
    Stockholm Spine Center, Löwenströmska sjukhuset, Upplands Väsby.
    Frost, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Diskbråckskirurgi polikliniskt: Säkert och uppskattat alternativ för selekterade patienter [Ambulatory diskectomy. Safe and appreciated alternative for selected patients]2009Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, nr 10, s. 679-80Artikel i tidskrift (Refereegranskat)
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    FULLTEXT01
  • 775. Skeppholm, Martin
    et al.
    Ingebro, Catarina
    Engstrom, Therese
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The Dysphagia Short Questionnaire: An Instrument for Evaluation of Dysphagia: A Validation Study With 12 Months' Follow-up After Anterior Cervical Spine Surgery2012Ingår i: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 37, nr 11, s. 996-1002Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study Design. Prospective clinical validation study of questionnaire to assess dysphagia.

    Objective. To test validity and reliability of Dysphagia Short Questionnaire (DSQ), and also to determine levels of dysphagia over time after anterior cervical spine surgery (ACSS).

    Summary of Background Data. Dysphagia is common after ACSS but reports on the incidence vary widely between 1% and 79%, indicating an evaluation problem. Several tools for evaluation of dysphagia exist but common features are that they are cumbersome to use and usually are designed for patients with neurological or malignant diseases in the neck region. Others are not validated, for example, the Bazaz score. There is, thus, a need for a more adapted tool to evaluate dysphagia in patients undergoing ACSS.

    Methods. The DSQ was constructed in collaboration with a group of ear-nose-and-throat specialists. In a first validation study, 45 patients with stationary dysphagia for various reasons completed the DSQ twice 2 weeks apart, the M. D. Anderson Dysphagia Inventory (MDADI), the Bazaz score, and a quality-of-life score, the EQ-5D. To evaluate the utility of the DSQ, a second validation study was performed, where 111 subjects undergoing ACSS for degenerative disk disease completed the form preoperatively and at 4 weeks, 3 months, and 1 year after surgery.

    Results. In the first study, the DSQ correlated to MDADI (r = 0.59) and showed good reproducibility. The Bazaz score did not correlate to the DSQ, the MDADI, or the EQ-5 D. In the second study, dysphagia was present in a few patients already preoperatively. At 4 weeks, 85% of the patients reported dysphagia. The level had dropped significantly at 3 months and had returned to baseline levels at 1 year.

    Conclusion. We consider the DSQ to be a validated tool for the assessment of dysphagia in ACSS patients. Dysphagia after ACSS for cervical spondylosis is common but the symptoms on a group level are not very severe and are also temporary.

  • 776. Skeppholm, Martin
    et al.
    Lindgren, Lars
    Henriques, Thomas
    Vavruch, Ludek
    Lofgren, Hakan
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The Discover artificial disc replacement versus fusion in cervical radiculopathy-a randomized controlled outcome trial with 2-year follow-up2015Ingår i: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 15, nr 6, s. 1284-1294Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND CONTEXT: Several previous studies comparing artificial disc replacement (ADR) and fusion have been conducted with cautiously positive results in favor of ADR. This study is not, in contrast to most previous studies, an investigational device exemption study required by the Food and Drug Administration for approval to market the product in the United States. This study was partially funded with unrestricted institutional research grants by the company marketing the artificial disc used in this study. PURPOSE: To compare outcomes between the concepts of an artificial disc to treatment with anterior cervical decompression and fusion (ACDF) and to register complications associated to the two treatments during a follow-up time of 2 years. STUDY DESIGN/SETTING: This is a randomized controlled multicenter trial, including three spine centers in Sweden. PATIENT SAMPLE: The study included patients seeking care for cervical radiculopathy who fulfilled inclusion criteria. In total, 153 patients were included. OUTCOME MEASURES: Self-assessment with Neck Disability Index (NDI) as a primary outcome variable and EQ-5D and visual analog scale as secondary outcome variables. METHODS: Patients were randomly allocated to either treatment with the Depuy Discover artificial disc or fusion with iliac crest bone graft and plating. Randomization was blinded to both patient and caregivers until time for implantation. Adverse events, complications, and revision surgery were registered as well as loss of follow-up. RESULTS: Data were available in 137 (91%) of the included and initially treated patients. Both groups improved significantly after surgery. NDI changed from 63.1 to 39.8 in an intention-to-treat analysis. No statistically significant difference between the ADR and the ACDF groups could be demonstrated with NDI values of 39.1 and 40.1, respectively. Nor in secondary outcome measures (EQ-5D and visual analog scale) could any statistically significant differences be demonstrated between the groups. Nine patients in the ADR group and three in the fusion group underwent secondary surgery because of various reasons. Two patients in each group underwent secondary surgery because of adjacent segment pathology. Complication rates were not statistically significant between groups. CONCLUSIONS: Artificial disc replacement did not result in better outcome compared to fusion measured with NDI 2 years after surgery.

  • 777. Skeppholm, Martin
    et al.
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Comparison of dysphagia between cervical artificial disc replacement and fusion: data from a randomized controlled study with two years of follow-up2013Ingår i: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 38, nr 24, s. E1507-E1510Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY DESIGN

    Prospective randomized controlled trial.

    OBJECTIVE

    To determine and explain any differences in self-reported dysphagia between patients treated with artificial disc replacement and anterior cervical decompression and fusion (ACDF).

    SUMMARY OF BACKGROUND DATA

    Dysphagia after anterior cervical spine surgery has in previous studies been evaluated regarding different influencing factors. Surgical technique, number of treated levels, and type of implant has been shown to be of possible importance.

    METHODS

    One hundred thirty-six patients from a randomized controlled trial between artificial disc replacement and ACDF in 1 or 2 surgical levels were evaluated regarding dysphagia. Evaluation was done with the dysphagia short questionnaire preoperatively, at 4 weeks, 3 months, and 1 and 2 years postoperatively. Reconstruction in the artificial disc replacement group was performed with the Discover artificial disc. Bone graft and anterior plating was used in the ACDF group. Type of implant was blinded to the patients and the surgeon until time of implantation.

    RESULTS

    Demographics and dysphagia short questionnaire levels were similar in both groups preoperative. At 4 weeks of follow-up postoperatively, dysphagia was significantly higher in both groups than baseline levels, P < 0.01. No significant differences were seen between the groups until follow-up at 2 years, which showed significantly higher dysphagia short questionnaire levels in the ACDF group, P = 0.04. The difference was statistically significant in both patients treated with 1- and 2-level surgery, P = 0.029 and P = 0.032, respectively. A logistic regression model showed a stronger association to type of implant than to number of surgical levels. Duration of surgery was highly associated to number of surgical levels but did not differ significantly between types of implant.

    CONCLUSION

    Long-term postoperative dysphagia could be explained by bulk of implant or decreased motion in the cervical spine. However, it is doubtful if differences between the groups in this study can be interpreted as a clinically important difference.

  • 778. Skeppholm, Martin
    et al.
    Svedmark, Per
    Noz, Marilyn E.
    Maguire, Gerald Q., Jr.
    Olivecrona, Henrik
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Evaluation of mobility and stability in the Discover artificial disc: an in vivo motion study using high-accuracy 3D CT data2015Ingår i: Journal of Eurosurgery : Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 23, nr 3, s. 383-389Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECT Artificial disc replacement (ADR) devices are unlike implants used in cervical fusion in that they are continuously exposed to stress not only within the implant site but also at their site of attachment to the adjacent vertebra. An imaging technique with higher accuracy than plain radiography and with the possibility of 3D visualization would provide more detailed information about the motion quality and stability of the implant in relation to the vertebrae. Such high-accuracy studies have previously been conducted with radiostereometric analysis (RSA), which requires implantation of tantalum markers in the adjacent vertebrae. The aim of this study was to evaluate in vivo motion and stability of implanted artificial discs. A noninvasive analysis was performed with CT, with an accuracy higher than that of plain radiographs and almost as high as RSA in cervical spine. METHODS Twenty-eight patients with ADR were included from a larger cohort of a randomized controlled trial comparing treatment of cervical radiculopathy with ADR or anterior cervical decompression and fusion. Surgical levels included C4-7; 18 patients had 1-level surgery and 10 patients had 2-level surgery. Follow-up time ranged from 19 to 50 months, with an average of 40 months. Two CT volumes of the cervical spine, 1 in flexion and 1 in extension, were obtained in each patient and then spatially registered using a customized imaging tool, previously used and validated for the cervical spine. Motion between the components in the artificial disc, as well as motion between the components and adjacent vertebrae, were calculated in 3 planes. Intraclass correlation (ICC) between independent observers and repeatability of the method were also calculated. RESULTS Intrinsic motion, expressed as degrees in rotation and millimeters in translation, was detectable in a majority of the ADRs. In the sagittal plane, in which the flexion/extension was performed, sagittal rotation ranged between 0.2 and 15.8 and translation between 0.0 and 5.5 mm. Eight percent of the ADRs were classified as unstable, as motion between at least 1 of the components and the adjacent vertebra was detected. Five percent were classified as ankylotic, with no detectable motion, and another 8% showed very limited motion due to heterotopic ossification. Repeatability for the motion in the sagittal plane was calculated to be 1.300 for rotation and 1.29 mm for translation (95% confidence level), ICC 0.99 and 0.84, respectively. All 3 patients with unstable devices had undergone 1-level ADRs at C5-6. They all underwent revision surgery due to increased neck pain, and instability was established during the surgery. CONCLUSIONS The majority of the artificial discs in this study showed intrinsic mobility several years after implantation and were also shown to be properly attached. Implant instability was detected in 8% of patients and, as all of these patients underwent revision surgery due to increasing neck pain, this might be a more serious problem than heterotopic bone formation.

  • 779.
    Sköld, Caroline
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Tropp, Hans
    Berg, Svante
    Five-year follow-up of total disc replacement compared to fusion: a randomized controlled trial2013Ingår i: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 22, nr 10, s. 2288-2295Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To evaluate long-term clinical results of lumbar total disc replacement (TDR) compared with posterior lumbar fusion. This prospective randomized controlled trial comprised 152 patients; 80 were randomized to TDR and 72 to fusion. All patients had chronic low back pain (CLBP) and had not responded to nonsurgical treatment. Primary outcome measure was global assessment of back pain (GA), secondary outcome measures were back and leg pain, Oswestry Disability Index (ODI), EQ5D, and SF-36. All measures were collected from SweSpine (Swedish national register for spinal surgery) at 1, 2, and 5 years. Follow-up rate at 5 years was 99.3 %. Both groups showed clinical improvement at 5-year follow-up. For GA, 38 % (30/80) in the TDR group were totally pain free vs. 15 % (11/71) in the fusion group (p < 0.003). Back pain and improvement of back pain were better in the TDR group: VAS back pain at 5 years 23 +/- A 29 vs. 31 +/- A 27, p = 0.009, and VAS improvement of back pain at 5 years 40 +/- A 32 vs. 28 +/- A 32, p = 0.022. ODI and improvement in ODI were also better in the TDR group: ODI at 5 years 17 +/- A 19 vs. 23 + 17, p = 0.02 and ODI improvement at 5 years 25 +/- A 18 vs. 18 +/- A 19 (p = 0.02). There was no difference in complications and reoperations between the two groups. Global assessment of low back pain differed between the two surgical groups at all follow-up occasions. Significant differences between groups concerning back pain, pain improvement, and ODI were present at 1 year and disappeared at 2 years, but reappeared at the 5-year follow-up.

  • 780.
    Snellman, Greta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Boning up on Vitamin D: Observational Studies on Bone and Health2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The primary function of vitamin D in humans is to maintain sufficient circulating calcium concentrations. Low vitamin D levels could result in excessive calcium resorption from bone. Vitamin deficiency may therefore decrease bone mineral density (BMD), resulting in an increased risk of fracture. This thesis sought to determine the association between vitamin D intake and bone health and to estimate circulating levels of vitamin D optimal for bone health without increasing the risk for non-bone disease. Furthermore, the thesis assessed the difference in performance between common serum vitamin D assays and the genetic influence of vitamin D status.

    In prospective population-based cohorts, blood concentrations <40 nmol/L (lowest 5%) increased the risk of fracture in elderly men. Low levels were further associated with a slight decrease in lumbar spine BMD. Both high (>98 nmol/L) and low (<46 nmol/L) vitamin D levels were associated with higher cancer and overall mortality. In another cohort, also of older men and women, no association was found between vitamin D levels and fracture. Low vitamin D levels were weakly associated with decreased total body BMD in men but not in women.

    Dietary intake of vitamin D over a 20-year period in more than 60,000 Swedish women was not associated with osteoporosis or fracture, regardless of calcium intake. During summer, dietary vitamin D intake and other life style habits are of minor importance for the variation in vitamin D levels relative to sun exposure and genes. In summer time, genes explain about half  of the variation in vitamin D levels, but none of the variance in winter time. The variability between vitamin D assays was substantial. Three assays classified 8, 22 and 43% of the same study population as vitamin D insufficient if <50 nmol/L was set as the insufficiency level.

    Based on the results in this thesis, low 25(OH)D levels and low dietary vitamin D intake are not a major cause of fractures in community-dwelling elderly Swedish women and men. Differences in assay performance and potential negative health outcomes of high 25(OH)D levels need to be considered.

    Delarbeten
    1. Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study
    Öppna denna publikation i ny flik eller fönster >>Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study
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    2009 (Engelska)Ingår i: PloS one, ISSN 1932-6203, Vol. 4, nr 11, s. e7747-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 204 same-sex twins, aged 39-85 years and living at northern latitude 60 degrees, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0-88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3-32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48-86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season. CONCLUSIONS/SIGNIFICANCE: There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.

    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Ortopedi
    Identifikatorer
    urn:nbn:se:uu:diva-110673 (URN)10.1371/journal.pone.0007747 (DOI)000271721900006 ()19915719 (PubMedID)
    Tillgänglig från: 2009-11-23 Skapad: 2009-11-23 Senast uppdaterad: 2018-11-30
    2. Determining Vitamin D Status: A Comparison between Commercially Available Assays
    Öppna denna publikation i ny flik eller fönster >>Determining Vitamin D Status: A Comparison between Commercially Available Assays
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    2010 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, Vol. 5, nr 7, s. e11555-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays. Methodology/Principal Findings: Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLCAPCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81-89), intermediate for RIA (70 nmol/L, 95% CI 66-74) and lowest with CLIA (60 nmol/L, 95% CI 56-64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D. Conclusions/Significance: There are substantial inter-assay differences in performance. The most valid method was HPLCAPCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.

    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Ortopedi
    Identifikatorer
    urn:nbn:se:uu:diva-135969 (URN)10.1371/journal.pone.0011555 (DOI)000279822300010 ()20644628 (PubMedID)
    Tillgänglig från: 2010-12-09 Skapad: 2010-12-09 Senast uppdaterad: 2018-08-24
    3. Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden
    Öppna denna publikation i ny flik eller fönster >>Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden
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    2010 (Engelska)Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, nr 6, s. 2637-2645Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Context: Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. Objective: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. Design and Participants: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. Setting: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. Main Outcome Measure: Time to fracture was measured. Results: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09-2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. Conclusions: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60 degrees , only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

    Nationell ämneskategori
    Medicin och hälsovetenskap Kirurgi
    Forskningsämne
    Ortopedi
    Identifikatorer
    urn:nbn:se:uu:diva-123253 (URN)10.1210/jc.2009-2699 (DOI)000278444000017 ()20332246 (PubMedID)
    Tillgänglig från: 2010-04-27 Skapad: 2010-04-27 Senast uppdaterad: 2018-08-24Bibliografiskt granskad
    4. Serum 25-hydroxyvitamin D in relation to BMD and fractures in a Swedish cohort of women and men
    Öppna denna publikation i ny flik eller fönster >>Serum 25-hydroxyvitamin D in relation to BMD and fractures in a Swedish cohort of women and men
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background/aim

    Vitamin D insufficiency has been suggested to be common and to cause osteoporotic fractures. Results from previous studies are inconsistent. The aim of our study was to assess if circulating vitamin D is associated with incident fractures and bone mineral density (BMD) among elderly Swedish men and women.

    Method

    A population-based cohort consisting of 1002 Swedish men and women, aged 70-years at baseline with a setting at latitude 60o north, was followed for 7 years. Serum vitamin D (25(OH)D) at baseline was analysed by an immunoassay. Fractures during follow-up were identified from registry data and BMD was measured with DXA. Association between 25(OH)D levels and time to fracture was our primary endpoint and BMD our secondary outcome.

    Result

    Mean S-25(OH)Dlevel was 58 (SD 20) nmol/L and 38% of the participants had levels <50 nmol/L. After multivariable adjustment, S-25(OH)D was only associated with total body BMD among men (P=0.03) but the relation was weak. Each SD increase in S-25(OH)D (approximately 20 nmol/L) conferred a 1% increase in total body BMD. Low vitamin D levels were not associated with lower BMD at the total hip or the lumbar spine in men or women. During follow-up, 155 (15%) of the participants sustained a fracture. No association between 25(OH)D and the rate of fracture was evident. The lowest quintile compared to highest quintile of 25(OH)D conferred a HR of 1.13 (95% CI 0.65-1.94).

    Conclusion

    In a general population of elderly Swedish men and women, serum vitamin D is not a strong determinant of fractures or of low bone mineral density.

    Nyckelord
    Vitamin D, fracture, BMD, observational study
    Nationell ämneskategori
    Ortopedi
    Forskningsämne
    Epidemiologi; Ortopedi
    Identifikatorer
    urn:nbn:se:uu:diva-159837 (URN)
    Tillgänglig från: 2011-10-10 Skapad: 2011-10-10 Senast uppdaterad: 2018-08-24
    5. Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women
    Öppna denna publikation i ny flik eller fönster >>Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women
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    2012 (Engelska)Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, nr Suppl 1, s. S65-S65Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
    Abstract [en]

    Context: Vitamin D deficiency may lead to osteoporosis and fracture but the importance of dietary vitamin D intake for skeletal health in adults is uncertain.

    Objective: To investigate associations between long-term dietary intake of vitamin D with risk of fractures and osteoporosis.

    Design: A prospective longitudinal cohort study.

    Setting: The population-based Swedish Mammography Cohort and the subcohort SMC Clinical.

    Participants: 61,433 women (age range 38 to 76 years) were followed for 19 years. Of these, 5,022 participated in the subcohort. Diet was assessed by repeated food frequency questionnaires.   

    Main outcome measures: Incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort.

    Results: 14,738 women experienced any type of first fracture during follow-up, with 3,871 of these being hip fractures. Twenty percent of the women in the subcohort were classified as osteoporotic. A multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for any first fracture was 0.96 (95% CI 0.92-1.01) for the lowest and 1.02 (95% CI 0.96-1.07) for the highest quintile when compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (95% CI, 0.96-1.08) for the lowest and 1.14 (95% CI, 1.03-1.26) for the highest quintile. The odds ratio of osteoporosis by quintiles of vitamin D intake was 1.20 (95% CI, 0.85-1.71) for the lowest and 0.99 (95% CI, 0.78-1.25) for the highest quintile. Bone mineral density, however, were 2% higher at the lumbar spine and 0.3% higher at the total hip in women with highest vs. women with lowest intake of vitamin D (p<0.0001).

    Conclusions: Dietary intake of vitamin D seems to be of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish middle-aged and elderly women.

    Nyckelord
    Vitamin D, fraktur, BMD, observationsstudie
    Nationell ämneskategori
    Ortopedi
    Forskningsämne
    Epidemiologi; Ortopedi
    Identifikatorer
    urn:nbn:se:uu:diva-159833 (URN)10.1016/j.bone.2012.02.182 (DOI)000304503500157 ()
    Konferens
    39th Annual Congress of the European-Calcified-Tissue-Society (ECTS), MAY 19-23, 2012, Stockholm, SWEDEN
    Anmärkning
    Also published in the same volume of Bone on pages S136-S137 with DOI 10.1016/j.bone.2012.02.421Tillgänglig från: 2011-10-10 Skapad: 2011-10-10 Senast uppdaterad: 2018-08-24Bibliografiskt granskad
    6. Plasma vitamin D and mortality in older men: a community-based prospective cohort study
    Öppna denna publikation i ny flik eller fönster >>Plasma vitamin D and mortality in older men: a community-based prospective cohort study
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    2010 (Engelska)Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, nr 4, s. 841-848Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. Objective: We aimed to examine how vitamin D status relates to overall and cause-specific mortality. Design: The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). Results: During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk. Conclusions: Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.

    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Ortopedi
    Identifikatorer
    urn:nbn:se:uu:diva-134811 (URN)10.3945/ajcn.2010.29749 (DOI)000282234100022 ()20720256 (PubMedID)
    Tillgänglig från: 2010-12-01 Skapad: 2010-12-01 Senast uppdaterad: 2018-08-24
    Ladda ner fulltext (pdf)
    fulltext
  • 781.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lemming, Eva Warensjo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Michaelsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Long-Term Dietary Vitamin D Intake and Risk of Fracture and Osteoporosis: A Longitudinal Cohort Study of Swedish Middle-aged and Elderly Women2014Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, nr 3, s. 781-790Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: The importance of dietary vitamin D for osteoporotic fracture prevention is uncertain. Objective: Our objective was to investigate associations between dietary vitamin D intake with risk of fracture and osteoporosis. Design and Participants: In the population-based Swedish Mammography Cohort (including 61 433 women followed for 19 years), diet was assessed by repeated food frequency questionnaires. Setting: The study was conducted in 2 municipalities in central Sweden. Main Outcome Measure: Incident fractures were identified from registry data. In a subcohort (n = 5022), bone mineral density was determined by dual-energy x-ray absorptiometry and serum 25-hydroxyvitamin D was measured using HPLC-tandem mass spectrometry. Results: A total of 14 738 women experienced any type of first fracture during follow-up, and 3871 had a hip fracture. Multivariable-adjusted hazard ratio (HR) for any first fracture was 0.96 (95% confidence interval, 0.92-1.01) for the lowest (mean, 3.1 mu g/d) and 1.02 (0.96-1.07) for the highest (mean, 6.9 mu g/d) quintile compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (0.96-1.08) for the lowest and 1.14 (1.03-1.26) for the highest quintile. Intakes >10 mu g/d, compared with <5 mu g/d, conferred an HR of 1.02 (0.92-1.13) for any fracture and an HR of 1.27 (1.03-1.57) for hip fracture. The intake of vitamin D did not affect the odds for osteoporosis, although higher levels were associated with higher bone mineral density (0.3%-2%, P < .0001). A positive association was observed between vitamin D intake and serum 25-hydroxyvitamin D. Conclusions: Dietary intakes of vitamin D seem of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish women.

  • 782.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Serum 25-hydroxyvitamin D in relation to BMD and fractures in a Swedish cohort of women and menManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background/aim

    Vitamin D insufficiency has been suggested to be common and to cause osteoporotic fractures. Results from previous studies are inconsistent. The aim of our study was to assess if circulating vitamin D is associated with incident fractures and bone mineral density (BMD) among elderly Swedish men and women.

    Method

    A population-based cohort consisting of 1002 Swedish men and women, aged 70-years at baseline with a setting at latitude 60o north, was followed for 7 years. Serum vitamin D (25(OH)D) at baseline was analysed by an immunoassay. Fractures during follow-up were identified from registry data and BMD was measured with DXA. Association between 25(OH)D levels and time to fracture was our primary endpoint and BMD our secondary outcome.

    Result

    Mean S-25(OH)Dlevel was 58 (SD 20) nmol/L and 38% of the participants had levels <50 nmol/L. After multivariable adjustment, S-25(OH)D was only associated with total body BMD among men (P=0.03) but the relation was weak. Each SD increase in S-25(OH)D (approximately 20 nmol/L) conferred a 1% increase in total body BMD. Low vitamin D levels were not associated with lower BMD at the total hip or the lumbar spine in men or women. During follow-up, 155 (15%) of the participants sustained a fracture. No association between 25(OH)D and the rate of fracture was evident. The lowest quintile compared to highest quintile of 25(OH)D conferred a HR of 1.13 (95% CI 0.65-1.94).

    Conclusion

    In a general population of elderly Swedish men and women, serum vitamin D is not a strong determinant of fractures or of low bone mineral density.

  • 783.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Warensjö-Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Institutet för miljömedicin, Karolinska Institutet.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women2012Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, nr Suppl 1, s. S65-S65Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Context: Vitamin D deficiency may lead to osteoporosis and fracture but the importance of dietary vitamin D intake for skeletal health in adults is uncertain.

    Objective: To investigate associations between long-term dietary intake of vitamin D with risk of fractures and osteoporosis.

    Design: A prospective longitudinal cohort study.

    Setting: The population-based Swedish Mammography Cohort and the subcohort SMC Clinical.

    Participants: 61,433 women (age range 38 to 76 years) were followed for 19 years. Of these, 5,022 participated in the subcohort. Diet was assessed by repeated food frequency questionnaires.   

    Main outcome measures: Incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort.

    Results: 14,738 women experienced any type of first fracture during follow-up, with 3,871 of these being hip fractures. Twenty percent of the women in the subcohort were classified as osteoporotic. A multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for any first fracture was 0.96 (95% CI 0.92-1.01) for the lowest and 1.02 (95% CI 0.96-1.07) for the highest quintile when compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (95% CI, 0.96-1.08) for the lowest and 1.14 (95% CI, 1.03-1.26) for the highest quintile. The odds ratio of osteoporosis by quintiles of vitamin D intake was 1.20 (95% CI, 0.85-1.71) for the lowest and 0.99 (95% CI, 0.78-1.25) for the highest quintile. Bone mineral density, however, were 2% higher at the lumbar spine and 0.3% higher at the total hip in women with highest vs. women with lowest intake of vitamin D (p<0.0001).

    Conclusions: Dietary intake of vitamin D seems to be of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish middle-aged and elderly women.

  • 784.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Berglund, Lars
    Wernroth, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Determining Vitamin D Status: A Comparison between Commercially Available Assays2010Ingår i: PLoS ONE, ISSN 1932-6203, Vol. 5, nr 7, s. e11555-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays. Methodology/Principal Findings: Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLCAPCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81-89), intermediate for RIA (70 nmol/L, 95% CI 66-74) and lowest with CLIA (60 nmol/L, 95% CI 56-64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D. Conclusions/Significance: There are substantial inter-assay differences in performance. The most valid method was HPLCAPCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.

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  • 785.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Olofsson, Sylvia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wolk, Alicja
    Pedersen, Nancy L.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study2009Ingår i: PloS one, ISSN 1932-6203, Vol. 4, nr 11, s. e7747-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 204 same-sex twins, aged 39-85 years and living at northern latitude 60 degrees, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0-88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3-32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48-86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season. CONCLUSIONS/SIGNIFICANCE: There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.

  • 786.
    Sobestiansky, Sigvard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Uppsala Univ Hosp, Dept Geriatr Med, Uppsala, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Uppsala Univ Hosp, Dept Geriatr Med, Uppsala, Sweden; Karolinska Univ Hosp, Theme Ageing, Stockholm, Sweden.
    Sarcopenia prevalence and associations with mortality and hospitalisation by various sarcopenia definitions in 85-89 year old community-dwelling men: a report from the ULSAM study2019Ingår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 19, artikel-id 318Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Operational definitions of sarcopenia, i.e. loss of muscle function and mass, have been proposed by the European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). The aim of this study was to analyse the prevalence and outcome, i.e. all-cause mortality and hospitalisation, of sarcopenia and its diagnostic components in octogenarian community-dwelling men.

    METHODS: In total 287 men, aged 85-89 y, participating in the Uppsala Longitudinal Study of Adult Men (ULSAM) underwent Dual X-ray Absorptiometry (DXA), measurement of hand grip strength (HGS), gait speed (GS), and a five-times chair stand test (CS). Sarcopenia and probable sarcopenia were defined according to EWGSOP (2010), EWGSOP2 (2018), and FNIH (2014). All-cause mortality and hospitalisations over 3 years were registered.

    RESULTS: Sarcopenia according to EWGSOP, EWGSOP2 and FNIH was observed in 21%, 20%, and 8% of the men, respectively, while probable sarcopenia (EWGSOP2; eq. reduced muscle strength only) was seen in 73%. "Sarcopenia (EWGSOP)" and "probable sarcopenia (EWGSOP2)" were associated with increased mortality (HR 1.95, 95% CI 1.12-3.40 and HR 3.26, 95% CI 1.38-7.70, respectively). "Probable sarcopenia (EWGSOP2)" was associated with days of hospitalisation (RR 2.12, 95% CI 1.36-3.30), whereas sarcopenia according to FNIH showed an association with the number of hospitalisations (RR 1.75, 95% CI 1.10-2.81).

    CONCLUSIONS: In very old men, reduced muscle strength, i.e. probable sarcopenia, was common and associated with mortality and length of stay during hospitalisation. When combined with low muscle mass (according to DXA), i.e. sarcopenia, the various definitions were associated more weakly with the adverse outcomes. The findings support the emphasis on reduced muscle strength as the major determinant of sarcopenia.

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  • 787. Sodemann, B
    et al.
    Persson, P E
    Nilsson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Periarticular heterotopic ossification after total hip arthroplasty for primary coxarthrosis.1988Ingår i: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, nr 237, s. 150-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Periarticular heterotopic ossification (PHO) is a common roentgenographic finding, occurring in more than two-thirds of patients after total hip arthroplasty (THA) for coxarthrosis. In the present study, 56 patients treated with bilateral THA were analyzed to determine the correlation between heterotopic ossification on the two sides. A strong correlation was found between the grade of PHO on the two sides: patients who developed severe PHO after the first THA invariably developed considerable PHO after surgery on the other side. The incidence and grade of PHO were higher in men than in women.

  • 788. Sodemann, B
    et al.
    Persson, P E
    Nilsson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Prevention of heterotopic ossification by nonsteroid antiinflammatory drugs after total hip arthroplasty.1988Ingår i: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, nr 237, s. 158-63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The effect of three weeks of postoperative treatment with indomethacin or ibuprofen on the development of periarticular heterotopic ossification (PHO) after bilateral total hip arthroplasty (THA) was investigated. Widespread PHO did not occur in 31 patients who had been treated with indomethacin or ibuprofen after both operations. Thirty-eight patients had been treated after one but not the other THA. Widespread PHO occurred in 14 of 38 untreated THA, but was not found after THA on the treated side. These findings are indicative of an inhibitory effect of nonsteroid antiinflammatory drugs on the development of PHO, since the development of severe heterotopic ossification is strongly correlated between the two sides after bilateral THA.

  • 789. Sodemann, B
    et al.
    Persson, P E
    Nilsson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Prevention of periarticular heterotopic ossification following total hip arthroplasty. Clinical experience with indomethacin and ibuprofen.1988Ingår i: Archives of orthopaedic and traumatic surgery. Archiv für orthopädische und Unfall-Chirurgie, ISSN 0344-8444, Vol. 107, nr 6, s. 329-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prophylactic treatment with indomethacin or ibuprofen to prevent periarticular heterotopic ossification (PHO) was investigated in a consecutive series of 200 total hip replacements (THR) performed for primary coxarthrosis in 170 patients. No widespread PHO (grades III and IV) occurred in 166 THR treated with indomethacin or ibuprofen from the 1st to the 21st postoperative day. Only one patient exhibited moderate (grade-II) ossification. In contrast, the incidence of PHO grades III and IV was found to be high (23%) in the 35 THR for which the patients did not receive prophylaxis according to intention. It was concluded that 3 weeks' postoperative treatment with indomethacin or ibuprofen is sufficient to prevent the development of clinically significant heterotopic ossification.

  • 790. Sodemann, Bent
    et al.
    Persson, Per-Erik
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nilsson, Olle
    Periarticular heterotopic ossification after total hip arthroplasty for primary coxarthrosis1988Ingår i: Clin Orthop, ISSN 0009-921, nr 237, s. 150-157Artikel i tidskrift (Refereegranskat)
  • 791. Sodemann, Bent
    et al.
    Persson, Per-Erik
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nilsson, Olle
    Prevention of heterotopic ossification by nonsteroid antiinflammatory drugs after total hip arthroplasty1988Ingår i: Clin Orthop, ISSN 0009-921, nr 237, s. 158-163Artikel i tidskrift (Refereegranskat)
  • 792. Sodemann, Bent
    et al.
    Persson, Per-Erik
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nilsson, Olle
    Prevention of periarticular heterotopic ossification following total hip arthroplasty: Clinical experience with indomethacin and ibuprofen1988Ingår i: Arch Orthop Trauma Surg, ISSN 0936-8051, Vol. 107, nr 6, s. 329-333Artikel i tidskrift (Refereegranskat)
  • 793.
    Staaf, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Åkerström, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Ljungström, Viktor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Karlsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hög tid att söka till nya MD/PhD-programmet vid Uppsala universitet: Tidig bro mellan preklinisk forskning och klinik2012Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 17-18, s. 898-898Artikel i tidskrift (Refereegranskat)
  • 794.
    Stackelberg, Otto
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi. Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Box 210, SE-17177 Stockholm, Sweden.;Soder Sjukhuset, Dept Surg, Stockholm, Sweden..
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Box 210, SE-17177 Stockholm, Sweden..
    Eliasson, Ken
    Orebro Univ Hosp, Dept Cardiovasc Surg, Sect Vasc Surg, Orebro, Sweden..
    Hellberg, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Bersztel, Adam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Box 210, SE-17177 Stockholm, Sweden..
    Orsini, Nicola
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Box 210, SE-17177 Stockholm, Sweden..
    Wanhainen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Björck, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Lifestyle and Risk of Screening-Detected Abdominal Aortic Aneurysm in Men2017Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, nr 5, artikel-id e004725Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-Modifiable lifestyle-related factors associated with risk of abdominal aortic aneurysm (AAA) are rarely investigated with a prospective design. We aimed to study possible associations among such factors and comorbidities with mean abdominal aortic diameter (AAD) and with risk of AAA among men screened for the disease. Methods and Results-Self-reported lifestyle-related exposures were assessed at baseline (January 1, 1998) among 14 249 men from the population-based Cohort of Swedish Men, screened for AAA between 65 and 75 years of age (mean 13 years after baseline). Multivariable prediction of mean AAD was estimated with linear regression, and hazard ratios (HRs) of AAA (AAD >= 30 mm) with Cox proportional hazard regression. The AAA prevalence was 1.2% (n=168). Smoking, body mass index, and cardiovascular disease were associated with a larger mean AAD, whereas consumption of alcohol and diabetes mellitus were associated with a smaller mean AAD. The HR of AAA was increased among participants who were current smokers with >= 25 pack-years smoked compared with never smokers (HR 15.59, 95% CI 8.96-27.15), those with a body mass index >= 25 versus <25 ( HR 1.89, 95% CI, 1.22-2.93), and those with cardiovascular disease (HR 1.77, 95% CI, 1.13-2.77), and hypercholesterolemia (HR 1.59, 95% CI 1.08-2.34). Walking or bicycling for >40 minutes/day (versus almost never) was associated with lower AAA hazard (HR 0.59, 95% CI 0.36-0.97) compared with almost never walking or bicycling. Conclusions-This prospective study confirms that modifiable lifestyle-related factors are associated with AAD and with AAA disease.

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  • 795.
    Stattin, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Epidemiology of Physical Activity and Fragility Fractures2020Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Fragility fractures mainly affect elderly individuals and often cause long term pain, loss of function and higher mortality rates. Physical activity improves balance, increases muscle strength and bone mineral density, and may reduce the risk of fragility fractures. The aim of this thesis is to investigate the association between physical activity and fragility fractures.

    In Paper I the risk of hip and any fracture was investigated across levels of habitual walking/bicycling and exercise in participants from the population-based Cohort of Swedish Men (COSM) and Swedish Mammography Cohort (SMC). Individuals walking/bicycling a maximum of 20 minutes per day had a lower risk of hip and any fracture than individuals who did not walk or bicycle. The risk of hip and any fracture was gradually lower with increasing levels of exercise. In Paper II participants in the cross-country skiing race Vasaloppet were compared to non-participants from the general population, and were found to have a higher risk of any and forearm fracture but a lower risk of hip, proximal humerus and lower leg fracture. There was no difference in the risk of vertebral fracture. In Paper III, the association between physical activity and cardiovascular candidate plasma protein concentrations were analyzed in participants from the EpiHealth cohort and the Swedish Mammography Cohort Clinical. Of 184 assayed proteins, 75 associations with physical activity were discovered and 28 subsequently replicated in multivariable adjusted models. In Paper IV the COSM, SMC and the Vasaloppet cohort were combined to achieve as wide a range of physical activity as possible and a common measure of physical activity was created using generalized structural equation modeling (GSEM). Low levels of physical activity were associated with higher risk of any and hip fracture but lower risk of wrist fracture. Individuals with physical activity close to the median of the combined cohort had the lowest risk of fracture, and higher levels of physical activity was associated with a higher risk of any fracture.

    In conclusion, physical activity is associated with a lower risk of major fractures such as hip fractures, but may in large quantities increase the risk of wrist and any fracture. Physical activity is associated with more beneficial concentrations of 28 cardiovascular plasma proteins.

    Delarbeten
    1. Leisure-Time Physical Activity and Risk of Fracture: A Cohort Study of 66,940 Men and Women
    Öppna denna publikation i ny flik eller fönster >>Leisure-Time Physical Activity and Risk of Fracture: A Cohort Study of 66,940 Men and Women
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    2017 (Engelska)Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr 8, s. 1599-1606Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Physical activity has been associated with reduced risk of fracture, but it is not known how the intensity or frequency of physical activity influences this risk reduction. We aim to compare the risk of hip fracture and fracture of any locale between men and women with different levels of leisure-time walking/bicycling and exercise. A total of 37,238 women (born 1914-1948) from the Swedish Mammography Cohort and 45,906 men (born 1918-1952) from the Cohort of Swedish Men were followed for a maximum of 17 years. Exposure and covariate information was collected through a self-administered questionnaire in 1997. Incident fractures (5153 individuals with hip fracture and 15,043 with any type of fracture) and comorbidities were gathered from national and local patient registries. Hazard ratios (HRs) were calculated using Cox proportional hazards regression. Individuals who walked/bicycled less than 20 minutes per day had a lower rate of hip fracture (multivariable adjusted HR = 0.77; 95% confidence interval [CI] 0.70 to 0.85) and any fracture (HR = 0.87; 95% CI 0.82 to 0.92) compared with those who hardly ever walked/bicycled. These reduced rates were also evident in both sexes, in different age categories, for vertebral fractures and for non-hip, non-vertebral fractures. Those who reported exercise 1 hour per week had a lower rate of hip fracture (HR = 0.87; 95% CI 0.80 to 0.96) and any fracture (HR = 0.94; 95% CI 0.89 to 0.99) compared with those who exercised less than 1 hour per week. Only minor differences in HRs were observed in individuals with moderate compared with higher levels of walking/bicycling or exercise. Walking/bicycling and exercise showed almost equal reductions in rate of fracture when compared with those in a joint category with lowest activity. In conclusion, both moderate and high self-reported frequency of physical activity is associated with reduced future risk of fracture.

    Nyckelord
    EPIDEMIOLOGY, EXERCISE, FRACTURE PREVENTION, GENERAL POPULATION STUDY, OSTEOPOROSIS
    Nationell ämneskategori
    Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
    Identifikatorer
    urn:nbn:se:uu:diva-334469 (URN)10.1002/jbmr.3161 (DOI)000407438800002 ()28460152 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet
    Tillgänglig från: 2017-11-23 Skapad: 2017-11-23 Senast uppdaterad: 2020-01-19Bibliografiskt granskad
    2. Decreased Hip, Lower Leg, and Humeral Fractures but Increased Forearm Fractures in Highly Active Individuals
    Öppna denna publikation i ny flik eller fönster >>Decreased Hip, Lower Leg, and Humeral Fractures but Increased Forearm Fractures in Highly Active Individuals
    Visa övriga...
    2018 (Engelska)Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 10, s. 1842-1850Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    It is not known how physical exercise affects the risk of different types of fractures, especially in highly active individuals. To investigate this association, we studied a cohort of 118,204 men and 71,757 women who from 1991 to 2009 participated in Vasaloppet, a long-distance cross-country skiing race in Sweden, and 505,194 nonparticipants frequency-matched on sex, age, and county of residence from the Swedish population. Participants ranged from recreational exercisers to world-class skiers. Race participation, distance of race run, number of races participated in, and finishing time were used as proxies for physical exercise. Incident fractures from 1991 to 2010 were obtained from national Swedish registers. Over a median follow-up of 8.9 years, 53,175 fractures of any type, 2929 hip, 3107 proximal humerus, 11,875 lower leg, 11,733 forearm, and 2391 vertebral fractures occurred. In a Cox proportional hazard regression analysis using time-updated exposure and covariate information, participation in the race was associated with an increased risk of any type of fracture (hazard ratio [HR], 1.02; 95% CI, 1.00 to 1.05); forearm fractures had an HR, 1.11 with a 95% CI, 1.06 to 1.15. There was a lower risk of hip (HR, 0.75; 95% CI, 0.67 to 0.83), proximal humerus (HR, 0.90; 95% CI, 0.82 to 0.98), and lower leg fractures (HR, 0.93; 95% CI, 0.89 to 0.97), whereas the HR of vertebral fracture was 0.97 with a 95% CI, 0.88 to 1.07. Among participants, the risk of fracture was similar irrespective of race distance and number of races run. Participants close to the median finishing time had a lower risk of fracture compared with faster and slower participants. In summary, high levels of physical exercise were associated with a slightly higher risk of fractures of any type, including forearm fractures, but a lower risk of hip, proximal humerus, and lower leg fractures. © 2018 American Society for Bone and Mineral Research.

    Nyckelord
    EPIDEMIOLOGY, EXERCISE, FRACTURE PREVENTION, ORTHOPEDICS, OSTEOPOROSIS
    Nationell ämneskategori
    Ortopedi
    Identifikatorer
    urn:nbn:se:uu:diva-367531 (URN)10.1002/jbmr.3476 (DOI)000448078300011 ()29933501 (PubMedID)
    Tillgänglig från: 2018-11-30 Skapad: 2018-11-30 Senast uppdaterad: 2020-01-19Bibliografiskt granskad
    3. Physical activity is associated with a large number of cardiovascular-specific proteins: Cross-sectional analyses in two independent cohorts
    Öppna denna publikation i ny flik eller fönster >>Physical activity is associated with a large number of cardiovascular-specific proteins: Cross-sectional analyses in two independent cohorts
    Visa övriga...
    2019 (Engelska)Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 26, nr 17, s. 1865-1873, artikel-id UNSP 2047487319868033Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Aims:We aimed to discover and replicate associations between leisure-time physical activity and cardiovascular candidate plasma protein biomarkers and to examine whether the associations were independent of body fat. Methods:We used cross-sectional data from two population-based cohorts, the EpiHealth (discovery cohort; n = 2239) and the Swedish Mammography Cohort - Clinical (SMCC; replication cohort; n = 4320). Physical activity during leisure time was assessed using questionnaires, and plasma concentrations of 184 proteins were assayed using the Olink Proseek Multiplex Cardiovascular 2 and 3 kits. We applied adjusted linear regression models using the False Discovery Rate to control for multiple testing in discovery. Results:In EpiHealth, physical activity was associated with 75 cardiovascular plasma biomarkers, of which 28 associations were verified (replicated) in SMCC. Findings include seven novel associations in human: paraoxonase 3, cystatin B, cathepsin Z, alpha-L-iduronidase, prostasin, growth differentiation factor 2 and tumour necrosis factor alpha receptor superfamily member 11A. Estimates for associations were similar across tertiles of body fat and physical activity was associated with four biomarkers independent of body fat percentage: paraoxonase 3, cystatin B, fatty acid-binding protein 4 and interleukin-1 receptor antagonist. Conclusion: Leisure-time physical activity was associated with 28 cardiovascular-specific proteins; four associations were independent of body fat. Biomarkers in novel associations are involved in several atherosclerotic processes including regulation of low-density lipoprotein oxidation, protein degradation and immune cell adhesion and migration. Further research into these pathways may yield new insights into how physical activity affects cardiovascular health.

    Ort, förlag, år, upplaga, sidor
    SAGE PUBLICATIONS LTD, 2019
    Nyckelord
    Physical activity, exercise, cardiovascular disease, proteins, proteomics, biomarkers
    Nationell ämneskategori
    Kardiologi
    Identifikatorer
    urn:nbn:se:uu:diva-398862 (URN)10.1177/2047487319868033 (DOI)000483261400001 ()31409108 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 2017-00644Vetenskapsrådet, 2017-06100Vetenskapsrådet, 2015-03527Vetenskapsrådet
    Tillgänglig från: 2019-12-11 Skapad: 2019-12-11 Senast uppdaterad: 2020-01-19Bibliografiskt granskad
    4. The risk of different fracture types across a wide range of physical activity levels, from sedentary individuals to elite athletes
    Öppna denna publikation i ny flik eller fönster >>The risk of different fracture types across a wide range of physical activity levels, from sedentary individuals to elite athletes
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Abstract

    Background Physical activity has been associated with a lower risk of fragility fractures, but the shape of the association is not known.

    Methods Individuals aged 49-68 years were drawn from the population-based Swedish Mammography Cohort (n=22,256) and Cohort of Swedish Men (n=28,749) as well as from a cohort of highly physically active participants in the Vasaloppet skiing race (n=12,984). A common measure of physical activity was created from lifestyle questionnaires and race data using generalized structural equation modeling. The median physical activity corresponded to 2-3 hours of weekly exercise or 20-40 minutes of daily walking/bicycling.  The rate of any, wrist, proximal humerus, spine and hip fractures were estimated using restricted cubic splines in Cox proportional hazard models.

    Results During a maximal follow-up of 13 years, 8,506 fractures at any site, 2,164 wrist, 779 proximal humerus, 346 spine and 908 hip fractures occurred. The rate of any fracture was lowest close to the median physical activity and higher in both low and high levels of physical activity, hazard ratio (HR) 1.05 (95% confidence interval (CI) 1.01-1.08) and 1.11 (95% CI 1.05-1.17) for physical activity 1 SD below and 1.5 SD above the average, respectively. The rate of wrist fracture was lowest among individuals with low levels of physical activity, HR 0.92 (95% CI 0.86-0.99) for physical activity 1 SD below the average, and increased until the median level of physical activity. Proximal humerus fracture was not associated with physical activity. Spine fracture had a U-shaped association with physical activity with wide confidence intervals. Low physical activity was associated with higher rate of hip fracture, HR 1.24 (95% CI 1.12-1.36) for physical activity 1 SD below the average.

    Discussion In this combination of cohorts including individuals with a wide range of physical activity, from sedentary individuals to elite athletes, the associations between physical activity and fractures were non-linear and differed according to fracture site. For wrist and hip fractures, there appears to be a threshold value above which further physical activity is not associated with further changes in the rate of fracture.

    Nyckelord
    fracture, orthopedics, physical activity, fragility fracture, epidemiology, GSEM
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Epidemiologi
    Identifikatorer
    urn:nbn:se:uu:diva-402746 (URN)
    Tillgänglig från: 2020-01-19 Skapad: 2020-01-19 Senast uppdaterad: 2020-01-22
    Ladda ner fulltext (pdf)
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  • 796.
    Stattin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hållmarker, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Mora Lasarett, Dept Internal Med, Mora, Sweden.
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Dalarna, Sweden.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Decreased Hip, Lower Leg, and Humeral Fractures but Increased Forearm Fractures in Highly Active Individuals2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 10, s. 1842-1850Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is not known how physical exercise affects the risk of different types of fractures, especially in highly active individuals. To investigate this association, we studied a cohort of 118,204 men and 71,757 women who from 1991 to 2009 participated in Vasaloppet, a long-distance cross-country skiing race in Sweden, and 505,194 nonparticipants frequency-matched on sex, age, and county of residence from the Swedish population. Participants ranged from recreational exercisers to world-class skiers. Race participation, distance of race run, number of races participated in, and finishing time were used as proxies for physical exercise. Incident fractures from 1991 to 2010 were obtained from national Swedish registers. Over a median follow-up of 8.9 years, 53,175 fractures of any type, 2929 hip, 3107 proximal humerus, 11,875 lower leg, 11,733 forearm, and 2391 vertebral fractures occurred. In a Cox proportional hazard regression analysis using time-updated exposure and covariate information, participation in the race was associated with an increased risk of any type of fracture (hazard ratio [HR], 1.02; 95% CI, 1.00 to 1.05); forearm fractures had an HR, 1.11 with a 95% CI, 1.06 to 1.15. There was a lower risk of hip (HR, 0.75; 95% CI, 0.67 to 0.83), proximal humerus (HR, 0.90; 95% CI, 0.82 to 0.98), and lower leg fractures (HR, 0.93; 95% CI, 0.89 to 0.97), whereas the HR of vertebral fracture was 0.97 with a 95% CI, 0.88 to 1.07. Among participants, the risk of fracture was similar irrespective of race distance and number of races run. Participants close to the median finishing time had a lower risk of fracture compared with faster and slower participants. In summary, high levels of physical exercise were associated with a slightly higher risk of fractures of any type, including forearm fractures, but a lower risk of hip, proximal humerus, and lower leg fractures. © 2018 American Society for Bone and Mineral Research.

  • 797.
    Stattin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Höijer, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hållmarker, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Unit of Cardiovascular and Nutritional Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The risk of different fracture types across a wide range of physical activity levels, from sedentary individuals to elite athletesManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Abstract

    Background Physical activity has been associated with a lower risk of fragility fractures, but the shape of the association is not known.

    Methods Individuals aged 49-68 years were drawn from the population-based Swedish Mammography Cohort (n=22,256) and Cohort of Swedish Men (n=28,749) as well as from a cohort of highly physically active participants in the Vasaloppet skiing race (n=12,984). A common measure of physical activity was created from lifestyle questionnaires and race data using generalized structural equation modeling. The median physical activity corresponded to 2-3 hours of weekly exercise or 20-40 minutes of daily walking/bicycling.  The rate of any, wrist, proximal humerus, spine and hip fractures were estimated using restricted cubic splines in Cox proportional hazard models.

    Results During a maximal follow-up of 13 years, 8,506 fractures at any site, 2,164 wrist, 779 proximal humerus, 346 spine and 908 hip fractures occurred. The rate of any fracture was lowest close to the median physical activity and higher in both low and high levels of physical activity, hazard ratio (HR) 1.05 (95% confidence interval (CI) 1.01-1.08) and 1.11 (95% CI 1.05-1.17) for physical activity 1 SD below and 1.5 SD above the average, respectively. The rate of wrist fracture was lowest among individuals with low levels of physical activity, HR 0.92 (95% CI 0.86-0.99) for physical activity 1 SD below the average, and increased until the median level of physical activity. Proximal humerus fracture was not associated with physical activity. Spine fracture had a U-shaped association with physical activity with wide confidence intervals. Low physical activity was associated with higher rate of hip fracture, HR 1.24 (95% CI 1.12-1.36) for physical activity 1 SD below the average.

    Discussion In this combination of cohorts including individuals with a wide range of physical activity, from sedentary individuals to elite athletes, the associations between physical activity and fractures were non-linear and differed according to fracture site. For wrist and hip fractures, there appears to be a threshold value above which further physical activity is not associated with further changes in the rate of fracture.

  • 798.
    Stattin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Elmstahl, Solve
    Lund Univ, Dept Clin Sci, Div Geriatr Med, Lund, Sweden.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Unit Cardiovasc & Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Warensjö Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Physical activity is associated with a large number of cardiovascular-specific proteins: Cross-sectional analyses in two independent cohorts2019Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 26, nr 17, s. 1865-1873, artikel-id UNSP 2047487319868033Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims:We aimed to discover and replicate associations between leisure-time physical activity and cardiovascular candidate plasma protein biomarkers and to examine whether the associations were independent of body fat. Methods:We used cross-sectional data from two population-based cohorts, the EpiHealth (discovery cohort; n = 2239) and the Swedish Mammography Cohort - Clinical (SMCC; replication cohort; n = 4320). Physical activity during leisure time was assessed using questionnaires, and plasma concentrations of 184 proteins were assayed using the Olink Proseek Multiplex Cardiovascular 2 and 3 kits. We applied adjusted linear regression models using the False Discovery Rate to control for multiple testing in discovery. Results:In EpiHealth, physical activity was associated with 75 cardiovascular plasma biomarkers, of which 28 associations were verified (replicated) in SMCC. Findings include seven novel associations in human: paraoxonase 3, cystatin B, cathepsin Z, alpha-L-iduronidase, prostasin, growth differentiation factor 2 and tumour necrosis factor alpha receptor superfamily member 11A. Estimates for associations were similar across tertiles of body fat and physical activity was associated with four biomarkers independent of body fat percentage: paraoxonase 3, cystatin B, fatty acid-binding protein 4 and interleukin-1 receptor antagonist. Conclusion: Leisure-time physical activity was associated with 28 cardiovascular-specific proteins; four associations were independent of body fat. Biomarkers in novel associations are involved in several atherosclerotic processes including regulation of low-density lipoprotein oxidation, protein degradation and immune cell adhesion and migration. Further research into these pathways may yield new insights into how physical activity affects cardiovascular health.

  • 799.
    Stattin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Larsson, Susanna C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Stockholm, Sweden.
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Stockholm, Sweden.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Leisure-Time Physical Activity and Risk of Fracture: A Cohort Study of 66,940 Men and Women2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr 8, s. 1599-1606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Physical activity has been associated with reduced risk of fracture, but it is not known how the intensity or frequency of physical activity influences this risk reduction. We aim to compare the risk of hip fracture and fracture of any locale between men and women with different levels of leisure-time walking/bicycling and exercise. A total of 37,238 women (born 1914-1948) from the Swedish Mammography Cohort and 45,906 men (born 1918-1952) from the Cohort of Swedish Men were followed for a maximum of 17 years. Exposure and covariate information was collected through a self-administered questionnaire in 1997. Incident fractures (5153 individuals with hip fracture and 15,043 with any type of fracture) and comorbidities were gathered from national and local patient registries. Hazard ratios (HRs) were calculated using Cox proportional hazards regression. Individuals who walked/bicycled less than 20 minutes per day had a lower rate of hip fracture (multivariable adjusted HR = 0.77; 95% confidence interval [CI] 0.70 to 0.85) and any fracture (HR = 0.87; 95% CI 0.82 to 0.92) compared with those who hardly ever walked/bicycled. These reduced rates were also evident in both sexes, in different age categories, for vertebral fractures and for non-hip, non-vertebral fractures. Those who reported exercise 1 hour per week had a lower rate of hip fracture (HR = 0.87; 95% CI 0.80 to 0.96) and any fracture (HR = 0.94; 95% CI 0.89 to 0.99) compared with those who exercised less than 1 hour per week. Only minor differences in HRs were observed in individuals with moderate compared with higher levels of walking/bicycling or exercise. Walking/bicycling and exercise showed almost equal reductions in rate of fracture when compared with those in a joint category with lowest activity. In conclusion, both moderate and high self-reported frequency of physical activity is associated with reduced future risk of fracture.

  • 800.
    Stattin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sandin, Fredrik
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Bratt, Ola
    Lund Univ, Dept Translat Med, Urol Canc Res Unit, Lund, Sweden.;Cambridge Hosp, Dept Urol, Cambridge, England..
    Lambe, Mats
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    The Risk of Distant Metastases and Cancer Specific Survival in Men with Serum Prostate Specific Antigen Values above 100 ng/ml2015Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, nr 6, s. 1594-1600Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Current EAU (European Association of Urology) guidelines state that prostate specific antigen 100 ng/ml or greater at diagnosis indicates metastatic disease. We examined the association of prostate specific antigen 100 ng/ml or greater at diagnosis with distant metastasis and prostate cancer specific survival. Material and Methods: A total of 15,635 men with prostate cancer diagnosed between 1998 and 2009 who were identified in PCBaSe (Prostate Cancer Data Base Sweden 2.0) were included in a population based registry study. Prostate cancer specific survival was compared among 3 groups, including 1,879 men with prostate specific antigen 100 ng/ml or greater and negative imaging (MO), 5,642 with distant metastases on imaging (M1) and prostate specific antigen 100 ng/ml or greater, and 3,828 with M1 and prostate specific antigen less than 100 ng/ml. A fourth group consisted of 4,286 men with prostate specific antigen 100 ng/ml or greater who had not undergone imaging (Mx). The latter men were not included in the assessment of survival. Results: Of 7,521 men with prostate specific antigen 100 ng/ml or greater who underwent imaging for staging 75% were classified with M1 disease. Only 59% of 3,527 men with prostate specific antigen 100 to 300 mg/ml had distant metastases on imaging. Five-year prostate cancer specific survival was 72% (95% CI 70-74) in men with prostate specific antigen 100 ng/ml or greater and MO, 24% (95% CI 23-25) in men with prostate specific antigen 100 ng/ml or greater and Ml, and 39% (95% CI 37-40) in men with prostate specific antigen less than 100 ng/ml and Ml. Conclusions: A fourth of men with prostate specific antigen 100 ng/ml or greater did not have distant metastases. They had twofold to threefold higher 5-year survival than men with distant metastases on imaging. Our findings strongly suggest that using prostate specific antigen 100 ng/ml or greater as an indicator of metastatic disease should be reconsidered.

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