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  • 151.
    Ljunggren, Mirjam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Theorell-Haglöw, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lindahl, Bertil
    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.
    Lindberg, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Increased risk of heart failure in women with symptoms of sleep-disordered breathing2016Ingår i: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 17, s. 32-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: An association between obstructive sleep apnea and the incidence of heart failure has been reported in men but not in women. The aim of this study was to investigate whether a combination of snoring and excessive daytime sleepiness, the two main symptoms of obstructive sleep apnea syndrome, was able to predict incident heart failure in a population-based sample of women.

    METHODS: The population-based cohort study Sleep and Health in Women (SHE; n = 5990 women born between 1901 and 1980) was used, with baseline questionnaire data from April 2000 relating to snoring, excessive daytime sleepiness, and covariates. Using data retrieved from the Swedish National Patient Register and Cause of Death Register, the follow-up of incident heart failure continued until 31 December 2011.

    RESULTS: Among women with both snoring and excessive daytime sleepiness at baseline, 5.3% developed heart failure during follow-up compared with 0.9% in the reference group with neither snoring nor excessive daytime sleepiness. After adjustment for age, waist circumference, smoking, alcohol, hypertension, diabetes, previous myocardial infarction, physical inactivity, depressive symptoms, menopausal status, and hormone replacement therapy, women with the combination of snoring and excessive daytime sleepiness had a twofold increase in the risk of incident heart failure (hazard ratio [HR] 2.2 95% confidence interval [CI] 1.1-4.4).

    CONCLUSION: Symptoms of obstructive sleep apnea, that is, the combination of snoring and excessive daytime sleepiness, are associated with an increased risk of developing heart failure in women.

  • 152. Lu, Yingchang
    et al.
    Day, Felix R
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Buchkovich, Martin L
    Na, Jianbo
    Bataille, Veronique
    Cousminer, Diana L
    Dastani, Zari
    Drong, Alexander W
    Esko, Tõnu
    Evans, David M
    Falchi, Mario
    Feitosa, Mary F
    Ferreira, Teresa
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Haring, Robin
    Hysi, Pirro G
    Iles, Mark M
    Justice, Anne E
    Kanoni, Stavroula
    Lagou, Vasiliki
    Li, Rui
    Li, Xin
    Locke, Adam
    Lu, Chen
    Mägi, Reedik
    Perry, John R B
    Pers, Tune H
    Qi, Qibin
    Sanna, Marianna
    Schmidt, Ellen M
    Scott, William R
    Shungin, Dmitry
    Teumer, Alexander
    Vinkhuyzen, Anna A E
    Walker, Ryan W
    Westra, Harm-Jan
    Zhang, Mingfeng
    Zhang, Weihua
    Zhao, Jing Hua
    Zhu, Zhihong
    Afzal, Uzma
    Ahluwalia, Tarunveer Singh
    Bakker, Stephan J L
    Bellis, Claire
    Bonnefond, Amélie
    Borodulin, Katja
    Buchman, Aron S
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Choh, Audrey C
    Choi, Hyung Jin
    Curran, Joanne E
    de Groot, Lisette C P G M
    De Jager, Philip L
    Dhonukshe-Rutten, Rosalie A M
    Enneman, Anke W
    Eury, Elodie
    Evans, Daniel S
    Forsen, Tom
    Friedrich, Nele
    Fumeron, Frédéric
    Garcia, Melissa E
    Gärtner, Simone
    Han, Bok-Ghee
    Havulinna, Aki S
    Hayward, Caroline
    Hernandez, Dena
    Hillege, Hans
    Ittermann, Till
    Kent, Jack W
    Kolcic, Ivana
    Laatikainen, Tiina
    Lahti, Jari
    Mateo Leach, Irene
    Lee, Christine G
    Lee, Jong-Young
    Liu, Tian
    Liu, Youfang
    Lobbens, Stéphane
    Loh, Marie
    Lyytikäinen, Leo-Pekka
    Medina-Gomez, Carolina
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nalls, Mike A
    Nielson, Carrie M
    Oozageer, Laticia
    Pascoe, Laura
    Paternoster, Lavinia
    Polašek, Ozren
    Ripatti, Samuli
    Sarzynski, Mark A
    Shin, Chan Soo
    Narančić, Nina Smolej
    Spira, Dominik
    Srikanth, Priya
    Steinhagen-Thiessen, Elisabeth
    Sung, Yun Ju
    Swart, Karin M A
    Taittonen, Leena
    Tanaka, Toshiko
    Tikkanen, Emmi
    van der Velde, Nathalie
    van Schoor, Natasja M
    Verweij, Niek
    Wright, Alan F
    Yu, Lei
    Zmuda, Joseph M
    Eklund, Niina
    Forrester, Terrence
    Grarup, Niels
    Jackson, Anne U
    Kristiansson, Kati
    Kuulasmaa, Teemu
    Kuusisto, Johanna
    Lichtner, Peter
    Luan, Jian'an
    Mahajan, Anubha
    Männistö, Satu
    Palmer, Cameron D
    Ried, Janina S
    Scott, Robert A
    Stancáková, Alena
    Wagner, Peter J
    Demirkan, Ayse
    Döring, Angela
    Gudnason, Vilmundur
    Kiel, Douglas P
    Kühnel, Brigitte
    Mangino, Massimo
    Mcknight, Barbara
    Menni, Cristina
    O'Connell, Jeffrey R
    Oostra, Ben A
    Shuldiner, Alan R
    Song, Kijoung
    Vandenput, Liesbeth
    van Duijn, Cornelia M
    Vollenweider, Peter
    White, Charles C
    Boehnke, Michael
    Boettcher, Yvonne
    Cooper, Richard S
    Forouhi, Nita G
    Gieger, Christian
    Grallert, Harald
    Hingorani, Aroon
    Jørgensen, Torben
    Jousilahti, Pekka
    Kivimaki, Mika
    Kumari, Meena
    Laakso, Markku
    Langenberg, Claudia
    Linneberg, Allan
    Luke, Amy
    Mckenzie, Colin A
    Palotie, Aarno
    Pedersen, Oluf
    Peters, Annette
    Strauch, Konstantin
    Tayo, Bamidele O
    Wareham, Nicholas J
    Bennett, David A
    Bertram, Lars
    Blangero, John
    Blüher, Matthias
    Bouchard, Claude
    Campbell, Harry
    Cho, Nam H
    Cummings, Steven R
    Czerwinski, Stefan A
    Demuth, Ilja
    Eckardt, Rahel
    Eriksson, Johan G
    Ferrucci, Luigi
    Franco, Oscar H
    Froguel, Philippe
    Gansevoort, Ron T
    Hansen, Torben
    Harris, Tamara B
    Hastie, Nicholas
    Heliövaara, Markku
    Hofman, Albert
    Jordan, Joanne M
    Jula, Antti
    Kähönen, Mika
    Kajantie, Eero
    Knekt, Paul B
    Koskinen, Seppo
    Kovacs, Peter
    Lehtimäki, Terho
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Liu, Yongmei
    Orwoll, Eric S
    Osmond, Clive
    Perola, Markus
    Pérusse, Louis
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Rivadeneira, Fernando
    Rudan, Igor
    Salomaa, Veikko
    Sørensen, Thorkild I A
    Stumvoll, Michael
    Tönjes, Anke
    Towne, Bradford
    Tranah, Gregory J
    Tremblay, Angelo
    Uitterlinden, André G
    van der Harst, Pim
    Vartiainen, Erkki
    Viikari, Jorma S
    Vitart, Veronique
    Vohl, Marie-Claude
    Völzke, Henry
    Walker, Mark
    Wallaschofski, Henri
    Wild, Sarah
    Wilson, James F
    Yengo, Loïc
    Bishop, D Timothy
    Borecki, Ingrid B
    Chambers, John C
    Cupples, L Adrienne
    Dehghan, Abbas
    Deloukas, Panos
    Fatemifar, Ghazaleh
    Fox, Caroline
    Furey, Terrence S
    Franke, Lude
    Han, Jiali
    Hunter, David J
    Karjalainen, Juha
    Karpe, Fredrik
    Kaplan, Robert C
    Kooner, Jaspal S
    McCarthy, Mark I
    Murabito, Joanne M
    Morris, Andrew P
    Bishop, Julia A N
    North, Kari E
    Ohlsson, Claes
    Ong, Ken K
    Prokopenko, Inga
    Richards, J Brent
    Schadt, Eric E
    Spector, Tim D
    Widén, Elisabeth
    Willer, Cristen J
    Yang, Jian
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Mohlke, Karen L
    Hirschhorn, Joel N
    Pospisilik, John Andrew
    Zillikens, M Carola
    Lindgren, Cecilia
    Kilpeläinen, Tuomas Oskari
    Loos, Ruth J F
    New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk2016Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, artikel-id 10495Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

  • 153.
    Ludvigsson, Jonas F.
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Orebro Univ Hosp, Dept Paediat, Orebro, Sweden.;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England..
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Bonamy, Anna-Karin Edstedt
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, S-17177 Stockholm, Sweden.;Karolinska Hosp & Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Ljung, Rickard
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-17177 Stockholm, Sweden..
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Neovius, Martin
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, S-17177 Stockholm, Sweden..
    Stephansson, Olof
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, S-17177 Stockholm, Sweden.;Karolinska Hosp & Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Ye, Weimin
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Registers of the Swedish total population and their use in medical research2016Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, nr 2, s. 125-136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The primary aim of the Swedish national population registration system is to obtain data that (1) reflect the composition, relationship and identities of the Swedish population and (2) can be used as the basis for correct decisions and measures by government and other regulatory authorities. For this purpose, Sweden has established two population registers: (1) The Population Register, maintained by the Swedish National Tax Agency ("Folkbokforingsregistret"); and (2) The Total Population Register (TPR) maintained by the government agency Statistics Sweden ("Registret over totalbefolkningen"). The registers contain data on life events including birth, death, name change, marital status, family relationships and migration within Sweden as well as to and from other countries. Updates are transmitted daily from the Tax Agency to the TPR. In this paper we describe the two population registers and analyse their strengths and weaknesses. Virtually 100 % of births and deaths, 95 % of immigrations and 91 % of emigrations are reported to the Population Registers within 30 days and with a higher proportion over time. The over-coverage of the TPR, which is primarily due to underreported emigration data, has been estimated at up to 0.5 % of the Swedish population. Through the personal identity number, assigned to all residents staying at least 1 year in Sweden, data from the TPR can be used for medical research purposes, including family design studies since each individual can be linked to his or her parents, siblings and offspring. The TPR also allows for identification of general population controls, participants in cohort studies, as well as calculation of follow-up time.

  • 154.
    Ludvigsson, Jonas F.
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Orebro Univ Hosp, Dept Paediat, Orebro, Sweden;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England;Columbia Univ, New York, NY 10027 USA.
    Mahl, Martin
    Karolinska Univ Hosp, Inflammat & Infect Theme, Patient Area Gastroenterol Dermatovenerol & Rheum, Stockholm, Sweden;Karolinska Inst, Inst Med Solna, Unit Internal Med, Stockholm, Sweden.
    Sachs, Michael C.
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Björk, Jan
    Karolinska Univ Hosp, Inflammat & Infect Theme, Patient Area Gastroenterol Dermatovenerol & Rheum, Stockholm, Sweden;Karolinska Inst, Inst Med Solna, Unit Internal Med, Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ekbom, Anders
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Askling, Johan
    Sachs Children & Youth Hosp, Dept Pediat Gastroenterol & Nutr, Stockholm, Sweden.
    Backman, Ann-Sofie
    Karolinska Univ Hosp, Inflammat & Infect Theme, Patient Area Gastroenterol Dermatovenerol & Rheum, Stockholm, Sweden;Karolinska Inst, Inst Med Solna, Unit Internal Med, Stockholm, Sweden.
    Olen, Ola
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden;Sachs Children & Youth Hosp, Dept Pediat Gastroenterol & Nutr, Stockholm, Sweden;Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Fracture Risk in Patients With Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study From 1964 to 20142019Ingår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 114, nr 2, s. 291-304Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION:Most studies on fractures in inflammatory bowel disease (IBD) are based on patients from tertiary centers or patients followed up before the introduction of immunomodulators or biologics. In addition, the role of corticosteroids in fracture risk has rarely been examined.METHODS:We conducted a nationwide population-based cohort study of 83,435 patients with incident IBD (ulcerative colitis [UC]: n = 50,162, Crohn's disease [CD]: n = 26,763, and IBD unclassified: 6,510) and 825,817 reference individuals from 1964 to 2014. Using multivariable Cox regression, we estimated hazard ratios (HRs) for hip fracture and any fracture and the association with cumulative corticosteroid exposure.RESULTS:During 1,225,415 person-years of follow-up in patients with IBD, there were 2,491 first-time hip fractures (203/100,000 person-years) compared with 20,583 hip fractures during 12,405,642 person-years in reference individuals (159/100,000 person-years). This corresponded to an HR of 1.42 (95% confidence interval [CI] = 1.36-1.48). The risk for hip fracture was higher in CD compared with UC (P < 0.001). Inflammatory bowel disease was also associated with any fracture (IBD: HR = 1.18; 95% CI = 1.15-1.20). Hazard ratios for hip fracture had not changed since the introduction of immunomodulators or biologics. Increasing exposure to corticosteroids was associated with hip fracture in both IBD and non-IBD individuals (P < 0.001), but only in elderly (>60 years) patients with IBD. The association between IBD and hip fracture was nonsignificant among individuals without corticosteroids (HR = 1.11; 95% CI = 0.86-1.44).CONCLUSIONS:Inflammatory bowel disease (CD and UC) is associated with an increased risk of hip fracture and any fracture, but not in individuals without a history of corticosteroid treatment. The association between corticosteroids and hip fracture was restricted to elderly patients with IBD.

  • 155. Ludvigsson, Jonas F.
    et al.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ekbom, A.
    Montgomery, Scott M.
    Coeliac disease and the risk of fractures: A general population-based cohort study2007Ingår i: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 25, nr 3, s. 273-285Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Earlier studies have suggested that untreated coeliac disease may be associated with osteoporosis, but results are contradictory for the risk of long-term fractures. AIM: To study the association between coeliac disease and fractures. METHODS: We used Cox regresson to examine the future risk of hip fracture and fracture of any type in more than 13 000 individuals with coeliac disease and 65 000 age- and sex-matched reference individuals in a general population-based cohort. RESULTS: During follow-up, 1365 first hip fractures and 4847 fractures of any type occurred. Coeliac disease was positively associated with subsequent hip fracture (hazard ratio = 2.1; 95% CI = 1.8-2.4) (in children: hazard ratio = 2.6; 95% CI = 1.1-6.2) and fractures of any type (hazard ratio = 1.4; 95% CI = 1.3-1.5) (in children: hazard ratio = 1.1; 95% CI = 1.0-1.2). The absolute excess risk of hip fractures in children with coeliac disease was 4/100 000 person-years. Incidence ratios for hip fracture in individuals with CD were around two both prior to diagnosis of coeliac disease and afterwards; this risk increase remained 20 years after diagnosis of coeliac disease. CONCLUSIONS: Individuals with coeliac disease, including children with coeliac disease, may be at increased risk of hip fracture and fracture of any type. Coeliac disease may be positively associated with long-term hip fracture risk.

  • 156.
    MacDowall, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Canto Moreira, Nuno
    Department of Clinical Neuroscience (CNS), K8, Karolinska Universitetssjukhuset Solna, Stockholm.
    Marques, Catarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Skeppholm, Martin
    Karolinska Inst, Med Management Ctr, Hlth Econ & Hlth Evaluat Res Grp, Dept Learning Informat Management & Eth LIME, Stockholm, Sweden;Sophiahemmets Sjukhus, Ctr Spine Surg Stockholm, Stockholm, Sweden.
    Lindhagen, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Löfgren, Håkan
    Länssjukhuset Ryhov, Jönköping.
    Michaëlsson, Karl
    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.
    Artificial disc replacement versus fusion in patients with cervical degenerative disc disease and radiculopathy: a randomized controlled trial with 5-year outcomes2019Ingår i: Journal of Neurosurgery: Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 30, nr 3, s. 323-331Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE

    The method of artificial disc replacement (ADR) has been developed as an alternative treatment to fusion surgery after decompression for cervical degenerative disc disease (DDD) with radiculopathy. Preserving the motion of ADR devices aims to prevent immobilization side effects such as adjacent-segment pathology (ASP). However, long-term follow-up evaluations using MRI are needed to investigate if this intent is achieved.

    METHODS

    The authors performed a randomized controlled trial with 153 patients (mean age 47 years) undergoing surgery for cervical radiculopathy. Eighty-three patients received an ADR and 70 patients underwent fusion surgery. Outcomes after 5 years were assessed using patient-reported outcome measures using the Neck Disability Index (NDI) score as the primary outcome; motion preservation and heterotopic ossification by radiography; ASP by MRI; and secondary surgical procedures.

    RESULTS

    Scores on the NDI were approximately halved in both groups: the mean score after 5 years was 36 (95% confidence interval [CI] 31–41) in the ADR group and 32 (95% CI 27–38) in the fusion group (p = 0.48). There were no other significant differences between the groups in six other patient-related outcome measures. Fifty-four percent of the patients in the ADR group preserved motion at the operated cervical level and 25% of the ADRs were spontaneously fused. Seventeen ADR patients (21%) and 7 fusion patients (10%) underwent secondary surgery (p = 0.11), with 5 patients in each group due to clinical ASP.

    CONCLUSIONS

    In patients with cervical DDD and radiculopathy decompression as well as ADR, surgery did not result in better clinical or radiological outcomes after 5 years compared with decompression and fusion surgery.

  • 157.
    MacDowall, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Skeppholm, Martin
    Institutionen för lärande, informatik, management och etik. Department for learning, informatics, management and ethics.
    Lindhagen, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Löfgren, Håkan
    Department of Neuro-Orthopaedic Center, Jönköping, Sweden.
    Michaëlsson, Karl
    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.
    Artificial Disc Replacement versus Fusion in Patients with Cervical Degenerative Disc Disease with radiculopathy: 5-year Outcomes from the National Swedish Spine Register2019Ingår i: Journal of Neurosurgery: Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 30, nr 2, s. 159-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The long-term efficacy of artificial disc replacement (ADR) surgery compared with fusion after decompression for the treatment of cervical degenerative disc disease and radiculopathy has not previously been investigated in a population-based setting.

    METHODS: All patients with cervical degenerative disc disease and radiculopathy who were in the national Swedish Spine Registry (Swespine) beginning in January 1, 2006, were eligible for the study. Follow-up information was obtained up to November 15, 2017. The authors compared, using propensity score matching, patients treated with anterior decompression and insertion of an ADR with patients who underwent anterior decompression combined with fusion surgery. The primary outcome was the Neck Disability Index (NDI), a patient-reported function score ranging from 0% to 100%, with higher scores indicating greater disability and a minimum clinically important difference of > 15%.

    RESULTS: A total of 3998 patients (2018: 1980 women/men) met the inclusion criteria, of whom 204 had undergone arthroplasty and 3794 had undergone fusion. After propensity score matching, 185 patients with a mean age of 49.7 years remained in each group. Scores on the NDI were approximately halved in both groups after 5 years, but without a significant mean difference in NDI (3.0%; 95% CI -8.4 to 2.4; p = 0.28) between the groups. There were no differences between the groups in EuroQol-5 Dimensions or in pain scores for the neck and arm.

    CONCLUSIONS: In patients with cervical degenerative disc disease and radiculopathy, decompression plus ADR surgery did not result in a clinically important difference in outcomes after 5 years, compared with decompression and fusion surgery.

  • 158. Maddock, Jane
    et al.
    Zhou, Ang
    Cavadino, Alana
    Kuźma, Elżbieta
    Bao, Yanchun
    Smart, Melissa C
    Saum, Kai-Uwe
    Schöttker, Ben
    Engmann, Jorgen
    Kjærgaard, Marie
    Karhunen, Ville
    Zhan, Yiqiang
    Lehtimäki, Terho
    Rovio, Suvi P
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lahti, Jari
    Marques-Vidal, Pedro
    Sen, Abhijit
    Perna, Laura
    Schirmer, Henrik
    Singh-Manoux, Archana
    Auvinen, Juha
    Hutri-Kähönen, Nina
    Kähönen, Mika
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Räikkönen, Katri
    Melhus, Håkan
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Guessous, Idris
    Petrovic, Katja E
    Schmidt, Helena
    Schmidt, Reinhold
    Vollenweider, Peter
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Eriksson, Johan G
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Raitakari, Olli T
    Hägg, Sara
    Pedersen, Nancy L
    Herzig, Karl-Heinz
    Järvelin, Marjo-Riitta
    Veijola, Juha
    Kivimaki, Mika
    Jorde, Rolf
    Brenner, Hermann
    Kumari, Meena
    Power, Chris
    Llewellyn, David J
    Hyppönen, Elina
    Vitamin D and cognitive function: A Mendelian randomisation study.2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 13230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

  • 159. Maggio, Marcello
    et al.
    De Vita, Francesca
    Lauretani, Fulvio
    Ceda, Gian Paolo
    Volpi, Elena
    Giallauria, Francesco
    De Cicco, Giuseppe
    Cattabiani, Chiara
    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.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Vitamin D and Endothelial Vasodilation in Older Individuals: Data From the PIVUS Study2014Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, nr 9, s. 3382-3389Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT:

    Vitamin D plays a role in a wide range of extraskeletal processes, including vascular function. Endothelial dysfunction is a predictor of cardiovascular disease, especially in older subjects. However, the relationship between vitamin D levels and indexes of endothelial vasodilation has never been fully addressed in older individuals.

    OBJECTIVE:

    The objective of this study was to examine the association between vitamin D and endothelial function in a large community-based sample of older subjects.

    METHODS:

    This cross-sectional study involved 852 community-dwelling men and women aged 70 years from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), with complete data on vascular function and 25-hydroxyvitamin D. We evaluated endothelium-dependent vasodilation by an invasive forearm technique with acetylcholine, endothelium-independent vasodilation by sodium nitroprussiate, flow-mediated vasodilation, and the pulse wave analysis (reflectance index). Vitamin D levels were measured by chemiluminescence. We used multivariate regression models adjusted for body mass index (model 1) and for multiple confounders (high-sensitivity C-reactive protein, insulin, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, smoking, sex hormones, season of blood collection, hypertension, diabetes, cardiovascular medications and diseases, statin usage, plasma calcium and calcium intake, PTH, physical exercise, liver and kidney function tests, albumin; model 2).

    RESULTS:

    In women, but not in men, vitamin D levels were positively associated with endothelium-independent vasodilation in both model 1 (β ± SE = 1.41 ± 0.54; P = .001), and model 2 (β ± SE = 2.01 ± 0.68; P = .003).We found no significant relationship between vitamin D levels and endothelium-dependent vasodilation, flow-mediated vasodilation, and reflectance index in both sexes.

    CONCLUSIONS:

    In older women, but not in men, vitamin D is positively and independently associated with EIDV.

  • 160.
    Manousaki, Despoina
    et al.
    McGill Univ, Dept Human Genet, Montreal.
    Dudding, Tom
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Haworth, Simon
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Hsu, Yi-Hsiang
    Hebrew SeniorLife, Inst Aging Res, Boston.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston.
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, Rotterdam.
    Voortman, Trudy
    Erasmus MC, Dept Epidemiol, Rotterdam.
    van der Velde, Nathalie
    Erasmus MC, Dept Internal Med, Rotterdam.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Robinson-Cohen, Cassiane
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle.
    Cousminer, Diana
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia.
    Nethander, Maria
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Vanderput, Liesbeth
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Noordam, Raymond
    Leiden Univ, Sect Gerontol & Geriatr, Dept Internal Med, Med Ctr, Leiden.
    Forgetta, Vincenzo
    McGill Univ, Dept Human Genet, Montreal, PQ.
    Greenwood, Celia
    McGill Univ, Dept Human Genet, Montreal, PQ.
    Biggs, Mary Lou
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Biostat, Cardiovasc Hlth Res Unit, Seattle.
    Psaty, Bruce
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle.
    Rotter, Jerome
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance.
    Zemel, Babette
    Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia.
    Mitchell, Jonathan
    Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia.
    Taylor, Bruce
    Univ Tasmania, Menzies Res Inst Tasmania, Hobart.
    Lorentzon, Matthias
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med, Sahlgrenska Acad, Gothenburg.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.;Skane Univ Hosp, Dept Orthopaed, Malmö.
    Jaddoe, Vincent
    Erasmus MC, Generat Study Grp R, Rotterdam.
    Tiemeier, Henning
    Erasmus MC, Generat Study Grp R, Rotterdam.
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, Rotterdam.
    Franco, Oscar
    Erasmus MC, Dept Epidemiol, Rotterdam.
    Uitterlinden, Andre
    Erasmus MC, Dept Internal Med, Rotterdam.
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam.
    van Schoor, Natasja
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam.
    Ham, Annelies
    Erasmus MC, Dept Internal Med, Rotterdam.
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam.
    Karasik, David
    Hebrew SeniorLife, Inst Aging Res, Boston.
    de Mutsert, Renee
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    Rosendaal, Fritz
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    den Heijer, Martin
    Vrije Univ Amsterdam, Dept Endocrinol, Med Ctr, Amsterdam.
    Wang, Thomas
    Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kestenbaum, Bryan
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle.
    Ohlsson, Claes
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Mellstrom, Dan
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    de Groot, Lisette
    Wageningen Univ, Dept Human Nutr, Wageningen.
    Grant, Struan
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia.
    Kiel, Douglas
    Hebrew SeniorLife, Inst Aging Res, Boston.
    Zillikens, Carola
    Erasmus MC, Dept Internal Med, Rotterdam.
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, Rotterdam.
    Sawcer, Stephen
    Univ Cambridge, Dept Clin Neurosci, Cambridge Biomed Campus, Cambridge.
    Timpson, Nicholas
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Richards, Brent
    McGill Univ, Dept Human Genet, Montreal.
    Low Frequency Coding Variation in CYP2R1 has Large Effects on Vitamin D Level and Risk of Multiple Sclerosis2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr S1, s. S319-S320, artikel-id Meeting Abstract: MO0459Artikel i tidskrift (Övrigt vetenskapligt)
  • 161.
    Manousaki, Despoina
    et al.
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada..
    Dudding, Tom
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Haworth, Simon
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Hsu, Yi-Hsiang
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02142 USA..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Voortman, Trudy
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    van der Velde, Nathalie
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Acad Med Ctr, Dept Internal Med, Sect Geriatr, NL-1105 AZ Amsterdam, Netherlands..
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Robinson-Cohen, Cassianne
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA..
    Cousminer, Diana L.
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA..
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, S-41390 Gothenburg, Sweden..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden..
    Noordam, Raymond
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-2333 ZA Leiden, Netherlands..
    Forgetta, Vincenzo
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada..
    Greenwood, Celia M. T.
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Oncol, Montreal, PQ H4A 3T2, Canada..
    Biggs, Mary L.
    Univ Washington, Dept Med & Biostat, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.;Kaiser Permanente Washington Hlth Res Unit, Seattle, WA 98101 USA..
    Rotter, Jerome I.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Zemel, Babette S.
    Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA..
    Mitchell, Jonathan A.
    Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA..
    Taylor, Bruce
    Univ Tasmania, Menzies Inst Med Res, Locked Bag 23, Hobart, Tas 7000, Australia..
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, S-43180 Molndal, Sweden.;Sahlgrens Univ Hosp, Geriatr Med, S-43180 Molndal, Sweden..
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, S-22241 Malmo, Sweden.;Skane Univ Hosp, Dept Orthopaed, S-22241 Malmo, Sweden..
    Jaddoe, Vincent V. W.
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Tiemeier, Henning
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Child & Adolescent Psychiat Psychol, NL-3015 GE Rotterdam, Netherlands..
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Utterlinden, Andre G.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Broer, Linda
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands..
    Ham, Annelies C.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, NL-3015 GE Rotterdam, Netherlands..
    Karasik, David
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands..
    Rosendaal, Frits R.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands..
    den Heijer, Martin
    Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, NL-1081 HV Amsterdam, Netherlands..
    Wang, Thomas J.
    Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN 37232 USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2333 ZA Leiden, Netherlands..
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kestenbaum, Bryan
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden..
    Mellström, Dan K
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, S-43180 Molndal, Sweden..
    de Groot, Lisette C. P. G. M.
    Wageningen Univ, Div Human Nutr, NL-6708 WE Wageningen, Netherlands..
    Grant, Struan F. A.
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA..
    Kiel, Douglas P.
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02142 USA.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Sawcer, Stephen
    Univ Cambridge, Dept Clin Neurosci, Box 165,Cambridge Biomed Campus,Hills Rd, Cambridge CB2 0QQ, England..
    Timpson, Nicholas J.
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Richards, J. Brent
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.;McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada..
    Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis2017Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 101, nr 2, s. 227-238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 x 10(-88)). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 3 10 x(-12)). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 3 10 x(-5)) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.

  • 162.
    Melhus, Håkan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Serum retinol levels and fracture risk: Authors reply2003Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 348, nr 19, s. 1928-Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 163. Melhus, Håkan
    et al.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Tillskott av D-vitamin kan göra mer skada än nytta: Evidensbaserade tröskelvärden för D-vitaminstatus saknas ännu2015Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, nr 23-24Artikel i tidskrift (Refereegranskat)
  • 164.
    Melhus, Håkan
    et al.
    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.
    Vitamin D och hälsa: Evidensbristen är det stora problemet2012Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 12, s. 604-605Artikel i tidskrift (Refereegranskat)
  • 165.
    Melhus, Håkan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wolk, Alicja
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Smoking, Antioxidant Vitamins, and the Risk of Hip Fracture1999Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 14, nr 1, s. 129-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Smoking increases the concentrations of free radicals, which have been suggested to be involved in bone resorption. We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking. We prospectively studied 66,651 women who were 40-76 years of age. Forty-four of the cohort members who sustained a first hip fracture within 2-64 months of follow-up (n = 247) and 93 out of 873 age-matched controls were current smokers. Information on diet was obtained by a validated food-frequency questionnaire. The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories (low/high), where median intakes among the controls were used as cut-off points. After adjustment for major osteoporosis risk factors, the odds ratio (OR) for hip fracture among current smokers with a low intake of vitamin E was 3.0 (95% confidence interval 1.6-5.4) and of vitamin C 3.0 (1.6-5.6). In contrast, the OR decreased to 1.1 (0.5-2.4) and 1.4 (0.7-3.0) with high intakes of vitamin E and C, respectively. This effect was not seen for beta-carotene, selenium, calcium, or vitamin B6. In current smokers with a low intake of both vitamins E and C, the OR increased to 4.9 (2.2-11.0). The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers. Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking, and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers, whereas a more adequate intake seems to be protective.

  • 166.
    Melhus, Håkan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Dietary vitamin A intake and risk for hip fracture: Response1999Ingår i: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 131, nr 5, s. 392-392Artikel i tidskrift (Refereegranskat)
  • 167.
    Melhus, Håkan
    et al.
    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.
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, SE-17177 Stockholm, Sweden.
    Serum Parathyroid Hormone and Risk of Coronary Artery Disease: Exploring Causality Using Mendelian Randomization2019Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, nr 11, s. 5595-5600Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Elevated circulating parathyroid hormone concentrations have been associated with increased risk of cardiovascular disease in observational studies, but whether the association is causal is unknown.

    Objective: We used the Mendelian randomization design to test whether genetically increased serum parathyroid hormone (S-PTH) concentrations are associated with coronary artery disease (CAD).

    Design, Setting, and Participants: Five single-nucleotide polymorphisms robustly associated with S-PTH concentrations were used as instrumental variables to estimate the association of genetically higher S-PTH concentrations with CAD. Summary statistics data for CAD were obtained from a genetic consortium with data from 184,305 individuals (60,801 CAD cases and 123,504 noncases).

    Main Outcome Measure: OR of CAD per genetically predicted one SD increase of S-PTH concentrations.

    Results: Genetically higher S-PTH concentration was not associated with CAD as a whole or myocardial infarction specifically (similar to 70% of total cases). The ORs per genetically predicted one SD increase in S-PTH concentration were 1.01 (95% CI: 0.93 to 1.09; P = 0.88) for CAD and 1.02 (95% CI: 0.94 to 1.10; P = 0.64) for myocardial infarction. The lack of association remained in various sensitivity analyses.

    Conclusion: Genetic predisposition to higher S-PTH concentrations does not appear to be an independent risk factor for CAD.

  • 168.
    Melhus, Håkan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Risérus, Ulf
    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, Klinisk nutrition och metabolism.
    Wernroth, Mona-Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Jensevik, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Michaëlsson, Karl
    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).
    A high activity index of stearoyl-CoA desaturase is associated with increased risk of fracture in men2008Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 19, nr 7, s. 929-934Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The activity index of stearoyl-CoA desaturase (SCD), a key enzyme in lipogenesis, was associated with increased risk of fracture in a longitudinal population-based cohort of men. This indicates that elevated levels of endogenous lipogenesis increase the risk of fracture and suggest a role for saturated fat in the pathogenesis of osteoporosis. INTRODUCTION: Osteoblasts and marrow adipocytes are derived from a common mesenchymal progenitor, and experimental studies have indicated that increased adipogenesis can occur at the expense of osteoblasts, leading to bone loss. Stearoyl-CoA desaturase (SCD) converts saturated to monounsaturated fatty acids and is a key enzyme in lipogenesis. METHODS: Analysis was performed in a population-based, longitudinal cohort study of men (n = 2009). A product-to-precursor index (palmitoleic acid/palmitic acid) was used to estimate SCD activity in fasting serum analyzed in samples obtained at enrollment at age 50 years. Fractures were documented in 422 men during 35 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to SCD activity index. RESULTS: The risk of fracture was highest among men with the highest levels of SCD activity index. Multivariable analysis of the risk of fracture in the highest quintile as compared to the lowest one showed that the rate ratio was 1.71 (95% CI 1.26-2.33) for any fracture, with an estimated population attributable risk of 15%. The risk was further increased within the highest quintile. CONCLUSIONS: Our results indicate that elevated levels of endogenous lipogenesis increase the risk of fracture and suggest a role for saturated fat in the pathogenesis of osteoporosis.

  • 169.
    Melhus, Håkan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Snellman, Greta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    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 kliniskt forskningscentrum (UCR).
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Blomhoff, Rune
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden2010Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, nr 6, s. 2637-2645Artikel i tidskrift (Refereegranskat)
    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.

  • 170.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Calcium supplements do not prevent fractures2015Ingår i: The BMJ, ISSN 1756-1833, Vol. 351, artikel-id h4825Artikel i tidskrift (Refereegranskat)
  • 171.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cardiovascular Disease, Hypertension, and Risk of Hip Fracture: Reply2010Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 303, nr 8, s. 731-732Artikel i tidskrift (Refereegranskat)
  • 172.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Does cardiovascular disease increase the risk of hip fracture?2010Ingår i: Aging Health, ISSN 1745-509X, E-ISSN 1745-5103, Vol. 6, nr 2, s. 203-205Artikel i tidskrift (Övrigt vetenskapligt)
  • 173.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Does cardiovascular disease increase therisk of hip fracture?2010Ingår i: Aging Health, ISSN 1745-509X, E-ISSN 1745-5103, Vol. 6, nr 2, s. 203-205Artikel i tidskrift (Övrigt vetenskapligt)
  • 174.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Reply RE: The positive effect of dietary vitamin D intake on bone mineral density in men is modulated by the polyadenosine repeat polymorphism of the vitamin D2007Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 40, nr 6, s. 1670-1670Artikel i tidskrift (Refereegranskat)
  • 175.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Surgeon volume and early complications after primary total hip arthroplasty: Surgeons who do at least 35 procedures a year seem safer than surgeons who do fewer2014Ingår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 348, artikel-id g3433Artikel i tidskrift (Refereegranskat)
  • 176.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The calcium quandary2009Ingår i: Nutrition (Burbank, Los Angeles County, Calif.), ISSN 0899-9007, E-ISSN 1873-1244, Vol. 25, nr 6, s. 655-6Artikel i tidskrift (Refereegranskat)
  • 177.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The complicated research field of nutrients and osteoporosis2000Ingår i: Nutrition reviews, ISSN 0029-6643, E-ISSN 1753-4887, Vol. 58, nr 8, s. 249-50Artikel i tidskrift (Refereegranskat)
  • 178.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The puzzling world of vitamin D insufficiency2014Ingår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 2, nr 4, s. 269-270Artikel i tidskrift (Refereegranskat)
  • 179.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Aspenberg, Per
    Linkoping Univ, Linkoping, Sweden..
    Postmenopausal Osteoporosis2016Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 374, nr 21, s. 2095-2095Artikel i tidskrift (Refereegranskat)
  • 180.
    Michaëlsson, 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.
    Baron, J.A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Farahmand, Bahman Y.
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Use of low potency estrogens does not reduce the risk of hip fracture2002Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 30, nr 4, s. 613-618Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High endogenous sexual hormone levels and use of medium potency estrogens are associated with a reduced risk of hip fracture in postmenopausal women. However, it is not clear if low potency estrogens confer the same benefits as the more widely used forms of menopausal hormone replacement. We examined the association between postmenopausal use of low potency estrogens, mainly estriol, and hip fracture risk in a population-based, case-control study. Using data from mailed questionnaires and telephone interviews, we analyzed the association between low potency estrogen use and hip fracture risk among 1327 cases, 50-81 years of age, and 3262 randomly selected age-matched controls. Ever use of low potency estrogens was reported by 19% of the cases and 23% of controls. Compared to with never users of any hormone replacement therapy, ever users of low potency estrogens had a multivariate odds ratio (OR) for hip fracture of 0.96 (95% confidence interval [CI] 0.67-1.39). Current use was also not associated with a reduction in risk: OR 0.94 (95% CI 0.58-1.53), and longer duration of use was also not associated with a risk reduction. Even current use of the highest dose of oral estriol (2 mg/day) conferred no risk reduction (OR 1.01, 95% CI 0.61-1.67) compared with never use of hormone replacement therapy. After exclusion of ever users of medium potency estrogens from the analyses, we found a risk reduction of fracture among current vaginal low potency estrogen users (multivariate OR 0.67, 95% CI 0.49-0.92). In contrast to medium potency estrogens, low potency estrogens did not confer a substantial overall reduction in hip fracture risk.

  • 181.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Baron, J.A.
    Johnell, O.
    Persson, I.
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Variation in the Efficacy of Hormone Replacement Therapy in the Prevention of Hip Fracture1998Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 8, nr 6, s. 540-546Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Use of postmenopausal hormone replacement therapy (HRT) has been associated with a reduced risk of osteoporotic fractures. However, it is uncertain whether this risk reduction is modified by other risk factors for hip fracture. In a population-based case-control study in Sweden, we investigated the association between HRT and hip fracture risk within categories of age, body measures and lifestyle factors in postmenopausal women, 50-81 years of age. Mailed questionnaires and telephone interviews were used to collect data. Of those eligible, 1328 incident cases with hip fracture (82.5%) and 3312 randomly selected controls (81.6%) answered the questionnaire. Ever use of HRT in women less than 75 years old was associated with an odds ratio (OR) of 0.66 (95% confidence interval: 95% CI 0.50-0.87) for hip fracture compared with OR 0.40 (95% CI 0.21-0.77) in women 75 years or older. We found a significant interaction between HRT and both weight and physical activity (p < 0.05). The protective effect of HRT was particularly pronounced in lean women: compared with never HRT users, ever users weighing under 60 kg had an OR of 0.44 (95% CI 0.30-0.66) whereas women weighing more than 70 kg had an OR of 0.91 (95% CI 0.53-1.56). Women with low recent leisure physical activity (less than 1 h/week) similarly benefited more from HRT for hip fracture prevention than women with a higher degree of recreational physical activity. The observed interactions with weight and physical activity suggest that HRT has the best protective effect against hip fracture among high-risk women.

  • 182.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Baron, John A.
    Farahmand, Bahman Y.
    Johnell, Olof
    Magnusson, Cecilia
    Persson, Per-Gunnar
    Persson, Ingemar
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hormone replacement therapy and hip fracture risk: population based case-control study1998Ingår i: BMJ - British Medical Journal, ISSN 1756-1833, Vol. 316, nr 7148, s. 1858-63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. Setting: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.

  • 183.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Baron, John A.
    Farahmand, Bahman Y.
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Influence of parity and lactation on hip fracture risk2001Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 153, nr 12, s. 1166-1172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several studies indicate that parity and lactation are associated with modest, short-term bone loss, but the long-term effect on osteoporotic fracture risk is uncertain. The authors therefore analyzed data from a population-based case-control study among Swedish postmenopausal women aged 50-81 years between October 1993 and February 1995. Mailed questionnaires and telephone interviews were used to collect data on 1,328 incident cases with hip fracture and 3,312 randomly selected controls. In age-adjusted analyses, the risk of hip fracture among all women was reduced by 10% per child (95% confidence interval (CI): 5, 14). After multivariate adjustment including body mass index as a covariate, the risk reduction was 5% per child (95% CI: 0, 10). Oral contraceptive use modified the association of parity with hip fracture risk. Among never users of oral contraceptives, the risk of hip fracture was reduced by 8% per child (95% CI: 2, 13), whereas among ever users of oral contraceptives, the risk was in the opposite direction, with an increase in risk by 19% per child (95% CI: 0, 41). After parity was considered, there was no association of duration of lactation period with fracture risk. The authors conclude that parity is modestly associated with a reduced hip fracture risk among women who had not used oral contraceptives previously.

  • 184.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Baron, John A.
    Farahmand, Bahman Y.
    Persson, Ingemar
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Oral contraceptive use and hip fracture risk: a case-control study1999Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 353, nr 9175, s. 1481-1484Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain. METHOD: We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded. FINDINGS: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30. INTERPRETATION: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.

  • 185.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Baron, John A
    Snellman, Greta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    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).
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sundström, Johan
    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.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Blomhoff, Rune
    Wolk, Alicja
    Garmo, Hans
    Regional Oncologic Center, Uppsala University, Uppsala.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Melhus, Håkan
    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, Klinisk farmakologi.
    Plasma vitamin D and mortality in older men: a community-based prospective cohort study2010Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, nr 4, s. 841-848Artikel i tidskrift (Refereegranskat)
    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.

  • 186.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bergström, R.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wolk, Alicja
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Screening for osteopenia and osteoporosis: selection by body composition1996Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 6, nr 2, s. 120-126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a great need for simple means of identifying persons at low risk of developing osteoporosis, in order to exclude them from screening with bone mineral measurements, since this procedure is too expensive and time-consuming for general use in the unselected population. We have determined the relationships between body measure (weight, height, body mass index, lean tissue mass, fat mass, waist-to-hip ratio) and bone mineral density (BMD) in 175 women of ages 28-74 years in a cross-sectional study in a county in central Sweden. Dual-energy X-ray absorptiometry was performed at three sites: total body, L2-4 region of lumbar spine, and neck region of the proximal femur. Using multiple linear regression models, the relationship between the dependent variable, BMD, and each of the body measures was determined, with adjustment for confounding factors. Weight alone, in a multivariate model, explained 28%, 21% and 15% of the variance in BMD of total body, at the lumbar spine and at the femoral neck according to these models. The WHO definition of osteopenia was used to dichotomize BMD, which made it possible, in multivariate logistic regression models, to estimate the risk of osteopenia with different body measures categorized into tertiles. Weight of over 71 kg was associated with a very low risk of being osteopenic compared with women weighing less than 64 kg, with odds ratios (OR) of 0.01 (95% confidence interval (CI) 0.00-0.09), 0.06 (CI 0.02-0.22) and 0.13 (CI 0.04-0.42) for osteopenia of total body, lumbar spine and femoral neck, respectively. Furthermore a sensitivity/specificity analysis revealed that, in this population, a woman weighing over 70 kg is not likely to have osteoporosis. Test specifics of a weight under 70 kg for osteoporosis (BMD less than 2.5 SD compared with normal young women) of femoral neck among the postmenopausal women showed a sensitivity of 0.94, a specificity of 0.36, positive predictive value (PPV) of 0.21, and negative predictive value (NPV) of 0.97. Thus, exclusion of the 33% of women with the highest weight meant only that 3% of osteoporotic cases were missed. The corresponding figures for lumbar spine were sensitivity 0.89, specificity 0.38, PPV 0.33, and NPV 0.91. All women who were defined as being osteoporotic of total body weighed under 62 kg. When the intention was to identify those with osteopenia of total body among the postmenopausal women we attained a sensitivity of 0.92 and a NPV of 0.91 for a weight under 70 kg, whereas we found that weight could not be used as an exclusion criterion for osteopenia of femoral neck and lumbar spine. Our data thus indicate that weight could be used to exclude women from a screening program for postmenopausal osteoporosis.

  • 187.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Bergström, Reinhold
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wolk, Alicja
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Calcium intake among women aged 40-76 in Sweden: Study Group MRS SWEA. Multiple Risk Survey on Swedish Women for Eating Assessment1996Ingår i: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 50, nr 5, s. 577-578Artikel i tidskrift (Refereegranskat)
  • 188.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bruce, Åke
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    What´s hip in diet and osteoporosis?1997Ingår i: Scandinavian Journal of Nutrition/Næringsforskning, ISSN 1102-6480, E-ISSN 1651-2359, Vol. 41, nr 1, s. 2-8Artikel i tidskrift (Refereegranskat)
  • 189.
    Michaëlsson, Karl
    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.
    Interpretation of milk research results2018Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, nr 3, s. 773-775Artikel i tidskrift (Övrigt vetenskapligt)
  • 190.
    Michaëlsson, Karl
    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.
    MILK AND MORTALITY Authors' reply to Labos and Brophy, Kerr, Hill, Hettinga, Sundar, and Bonneux2014Ingår i: BMJ-BRIT MED J, ISSN 1756-1833, Vol. 349, s. g7023-Artikel i tidskrift (Refereegranskat)
  • 191.
    Michaëlsson, Karl
    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.
    Ahlbom, Anders
    Melhus, Håkan
    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, Klinisk farmakologi.
    Farahmand, Bahman Y.
    Risk of Severe Knee and Hip Osteoarthritis in Relation to Level of Physical Exercise: A Prospective Cohort Study of Long-Distance Skiers in Sweden2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 3, s. e18339-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To complete long-distance ski races, regular physical exercise is required. This includes not only cross-country skiing but also endurance exercise during the snow-free seasons. The aim of this study was to determine whether the level of physical exercise is associated with future risk of severe osteoarthritis independent of previous diseases and injuries. Methodology/Principal Findings: We used a cohort that consisted of 48 574 men and 5 409 women who participated in the 90 km ski race Vasaloppet at least once between 1989 and 1998. Number of performed races and finishing time were used as estimates of exercise level. By matching to the National Patient Register we identified participants with severe osteoarthritis, defined as arthroplasty of knee or hip due to osteoarthritis. With an average follow-up of 10 years, we identified 528 men and 42 women with incident osteoarthritis. The crude rate was 1.1/1000 person-years for men and 0.8/1000 person-years for women. Compared with racing once, participation in >= 5 races was associated with a 70% higher rate of osteoarthritis (multivariable-adjusted hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.33 to 2.22). The association was dose-dependent with an adjusted HR of 1.09, 95% CI 1.05 to 1.13 for each completed race. A faster finishing time, in comparison with a slow finishing time, was also associated with an increased rate (adjusted HR 1.51, 95% CI 1.14 to 2.01). Contrasting those with 5 or more ski races and a fast finish time to those who only participated once with a slow finish time, the adjusted HR of osteoarthritis was 2.73, 95% CI 1.78 to 4.18. Conclusions/Significance: Participants with multiple and fast races have an increased risk of subsequent arthroplasty of knee and hip due to osteoarthritis, suggesting that intensive exercise may increase the risk.

  • 192.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Elmståhl, Sölve
    Kostfaktorers betydelse för osteoporos2001Ingår i: Socialmedicinsk Tidskrift, ISSN 0037-833X, nr 4, s. 333-Artikel i tidskrift (Övrigt vetenskapligt)
  • 193.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Persson, Per-Gunnar
    Wolk, Alicja
    Effect of prefracture versus postfracture dietary assessment on hip fracture risk estimates1996Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 25, nr 2, s. 403-10Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND. Dietary factors are presumed to have influence on bone mass and hence fracture susceptibility. Most information in this respect is based on retrospective assessment of previous dietary habits. In a population-based case-control study nested within a cohort, we collected dietary information both before and after a first hip fracture. Thus it was possible to study reported changes in dietary habits, intentional as well as unintentional, among hip fracture patients after a first hip fracture and to compare postfracture with prefracture dietary information. METHODS. More than 65 000 women born 1914-1948 in two counties in central Sweden completed a food frequency questionnaire regarding their usual current dietary habits, before attending a mammographic screening between the years 1987 and 1990. Subsequently 123 of them sustained a first hip fracture and were defined as cases in the present study. For every case, one control, individually matched by age and county of residence, was selected from the cohort. A second identical food frequency questionnaire was mailed to both cases and controls on average 2 years after the hip fracture event. In total 98 case/control pairs could be included in the analysis. The association between diet and hip fracture was evaluated and the results from the two dietary assessments were contrasted. Women who themselves claimed that they had not changed their diet in recent years were analysed separately. RESULTS. The hip fracture cases, compared with the controls, had reduced their reported dietary intake of dairy products after the fracture. Apparently this was not intentional since this effect was more pronounced among those cases who claimed that their diet was unchanged. The changes were most apparent among the younger cases with a more recent hip fracture and with a body mass index above the median. Half of the cases, more than twice the frequency in controls, who were initially classified as having high intake of dairy products were classified as having low intake (<800 mg calcium/day) after the hip fracture. This also lowered, in fact reversed, the relative risk estimates of hip fracture both for intake of dairy products and calcium. Crude odds ratios of highest quartile of intake versus lowest, changed from 3.0 to 0.6 for dairy products and from 2.6 to 0.9 for calcium. No other foods or nutrients displayed such notable differences between the two surveys. CONCLUSION. We conclude that the use of current and retrospective dietary information after a hip fracture can lead to a differential misclassification in dietary studies and to biased estimates of hip fracture risk as compared with prospectively collected dietary information.

  • 194.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wolk, Alicja
    Bergström, R.
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Diet, bone mass, and osteocalcin: A cross-sectional study1995Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 57, nr 2, s. 86-93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To determine the relationships among nutrients intake, bone mass, and bone turnover in women we have investigated these issues in a population-based, cross-sectional, observational study in one county in central Sweden. A total of 175 women aged 28-74 at entry to the study were included. Dietary assessment was made by both a semiquantitative food frequency questionnaire and by four 1-week dietary records. Dual energy X-ray absorptiometry was performed at five sites: total body, L2-L4 region of the lumbar spine, and three regions of the proximal femur. Serum concentrations of osteocalcin (an osteoblast-specific protein reflecting bone turnover) were measured by a radioimmunoassay. Linear regression models, with adjustment for possible confounding factors were used for statistical analyses. A weak positive association was found between dietary calcium intake as calculated from the semiquantitative food frequency questionnaire and total body bone mineral density (BMD) among premenopausal women. No association emerged between dietary calcium intake and site-specific bone mass, i.e., lumbar spine and femoral neck, nor was an association found between dietary calcium intake and serum osteocalcin. BMD at some of the measured sites was positively associated with protein and carbohydrates and negatively associated with dietary fat. In no previous studies of diet and bone mass have dietary habits been ascertained so carefully and the results adjusted for possible confounding factors. Neither of the two methods of dietary assessment used in this study revealed any effect of calcium intake on BMD at fracture-relevant sites among these healthy, mostly middle-aged women. A weak positive association was found between calcium intake estimates based on the food frequency questionnaire and total body BMD. In this study population the preventive effect of high dietary calcium on osteoporosis is probably very weak. The independent significance of protein, carbohydrates, and fat is uncertain.

  • 195.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Jacobson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Wolk, Alicja
    Byberg, Liisa
    Mitchell, Adam
    Melhus, Håkan
    The Free Hormone Hypothesis: Is Free Serum 25-Hydroxyvitamin D a Better Marker for Bone Mineral Density in Older Women?2018Ingår i: JBMR plus, ISSN 2473-4039, Vol. 2, nr 6, s. 367-374Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is presently unclear whether free serum 25-hydroxyvitamin D (S-25(OH)D) better reflects bone health than total S-25(OH)D. We have previously shown that summer total S-25(OH)D values are more useful to predict bone mineral density (BMD) than winter values. Our objective was therefore to compare the relative importance of free and total S-25(OH)D for BMD by season. BMD was measured by dual-energy X-ray absorptiometry (DXA) in 5002 Swedish women (mean age 68 years) randomly selected from a large population-based longitudinal cohort study. Free S-25(OH)D was analyzed by a commercial ELISA and total S-25(OH)D by HPLC-tandem mass spectrometry (MS/MS). Free and total S-25(OH)D co-varied with season, with 26% and 29% higher values in August compared with those in January-March (nadir). There were no differences in mean BMD between categories of free or total S-25(OH)D in samples collected during winter. Women with higher total S-25(OH)D measured during summer had higher BMD at the total hip. Compared with women who had total S-25(OH)D values above 80 nmol/L during summer, adjusted BMD at the total hip was 6% (95% CI, 1% to 11%) lower for S-25(OH)D concentrations between 30 and 40 mmol/L, and 11% (95% CI, 3% to 19%) lower for those with total S-25(OH)D <30 nmol/L. In contrast, free S-25(OH)D measured during summer was not associated with BMD. Compared with women who had highest free S-25(OH)D measured during summer (>8.8 pmol/L), those with intermediate (2.4-3.5 pmol/L) and lowest (<2.4 pmol/L) free S-25(OH)D during summer did not have lower total hip BMD values (3% [95% CI, -2% to 7%] and -2% [95% CI, -8% to 4%]). In addition, we found no added value for the prediction of BMD with the combined measurement of total and free S-25(OH)D during summer or winter. We conclude that vitamin D status assessed by direct measurements of free S-25(OH)D does not reflect BMD better than total S-25(OH)D. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

  • 196.
    Michaëlsson, 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.
    Frystyk, Jan
    Flyvbjerg, Allan
    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.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Söderberg, Stefan
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Serum adiponectin in elderly men does not correlate with fracture risk2008Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, nr 10, s. 4041-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Recent evidence suggests that adiponectin may play a role in bone metabolism, but studies of the correlation between serum adiponectin and bone mineral density (BMD) have given conflicting results, and the impact on fracture risk is unknown. OBJECTIVE: Our objective was to investigate the association between serum adiponectin levels and BMD and fracture risk. DESIGN, SETTING, PARTICIPANTS, MAIN OUTCOME MEASURES: We used regression analyses to estimate the relationship between adiponectin and BMD in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort of 441 men and 457 women aged 70 yr. The association was thereafter analyzed in the Uppsala Longitudinal Study of Adult Men (ULSAM), in which adiponectin was analyzed at age 70 yr and BMD at 82 yr in 507 men. Fractures in the ULSAM were documented in 314 men during 15 yr follow-up. Cox regression analysis was used to determine the risk of fracture according to serum adiponectin levels. RESULTS: In multivariable analysis a negative association between adiponectin and BMD was found in both cohorts. When individuals in the highest quintile of adiponectin were compared with those in the lowest quintile, adjusted BMD was 9.7% lower at the lumbar spine, 7.1% lower at the proximal femur, and 5.2% lower for total body in the Prospective Investigation of the Vasculature in Uppsala Seniors (P < 0.001 for all three), and 8.1, 5.1, and 4.1% (P < 0.003 for all three), respectively, in the ULSAM. However, the hazard ratio for fracture per 1 sd of serum adiponectin was 0.99 (95% confidence interval 0.89-1.11). CONCLUSION: Although adiponectin was a negative determinant of BMD in two independent cohorts, it was not associated with fracture risk in men.

  • 197.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lithell, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Serum retinol levels and the risk of fracture2003Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 348, nr 4, s. 287-94Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Although studies in animals and epidemiologic studies have indicated that a high vitamin A intake is associated with increased bone fragility, no biologic marker of vitamin A status has thus far been used to assess the risk of fractures in humans. METHODS: We enrolled 2322 men, 49 to 51 years of age, in a population-based, longitudinal cohort study. Serum retinol and beta carotene were analyzed in samples obtained at enrollment. Fractures were documented in 266 men during 30 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to the serum retinol level. RESULTS: The risk of fracture was highest among men with the highest levels of serum retinol. Multivariate analysis of the risk of fracture in the highest quintile for serum retinol (>75.62 microg per deciliter [2.64 micromol per liter]) as compared with the middle quintile (62.16 to 67.60 microg per deciliter [2.17 to 2.36 micromol per liter]) showed that the rate ratio was 1.64 (95 percent confidence interval, 1.12 to 2.41) for any fracture and 2.47 (95 percent confidence interval, 1.15 to 5.28) for hip fracture. The risk of fracture was further increased within the highest quintile for serum retinol. Men with retinol levels in the 99th percentile (>103.12 microg per deciliter [3.60 micromol per liter]) had an overall risk of fracture that exceeded the risk among men with lower levels by a factor of seven (P<0.001). The level of serum beta carotene was not associated with the risk of fracture. CONCLUSIONS: Our findings, which are consistent with the results of studies in animals, as well as in vitro and epidemiologic dietary studies, suggest that current levels of vitamin A supplementation and food fortification in many Western countries may need to be reassessed.

  • 198.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lohmander, L S
    Turkiewicz, A
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nilsson, P
    Englund, M
    Association between statin use and consultation or surgery for osteoarthritis of the hip or knee: a pooled analysis of four cohort studies.2017Ingår i: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, nr 11, s. 1804-1813, artikel-id S1063-4584(17)31102-0Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Experimental findings and previous observational data have suggested lower risk of osteoarthritis (OA) with statin use but results are inconsistent. Large-scale studies with a clinically important outcome are needed. Thus, we aimed to determine whether statin use is associated with a reduced risk of developing clinically-defined hip or knee OA.

    DESIGN: Pooled analysis based on time-to-event analysis of four population-based large cohorts, encompassing in total 132,607 persons aged 57-91 years resident in southern and central Sweden. We studied the association between statin use and time to consultation or surgery for OA of the hip or knee by time-dependent exposure analysis and Cox regression.

    RESULTS: During 7.5 years of follow-up, we identified 7468 out- or inpatient treated cases of hip or knee OA. Compared with never use, current use of statins conferred no overall reduction in the risk of OA with an adjusted pooled hazard ratio (HR) of 1.04 (95% confidence intervals [95% CI] 0.99-1.10). We found no dose-response relation between duration of current statin use and the risk of OA, with similar HRs among patients with less than 1 year of use (HR 1.09; 95% CI 0.92-1.32) as in patients with use for 3 years or more (HR 1.05; 0.93-1.16). Results were comparable in those with low, medium and high dose of current statin use, without indications of heterogeneity of study results.

    CONCLUSION: Statin use is not associated with reduced risk of consultation or surgery for OA of the hip or knee.

  • 199.
    Michaëlsson, Karl
    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, Klinisk farmakogenomik och osteoporos.
    Response to 'Letter to the Editor' regarding the article 'The seasonal importance of serum 25-hydroxyvitamin D for bone mineral density in older women'2017Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, nr 3, s. 274-275Artikel i tidskrift (Övrigt vetenskapligt)
  • 200.
    Michaëlsson, Karl
    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.
    Bellocco, Rino
    Wolk, Alicja
    Dietary calcium and vitamin D intake in relation to osteoporotic fracture risk2003Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 32, nr 6, s. 694-703Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The etiologic role of dietary calcium and vitamin D intake in primary prevention of osteoporotic fractures is uncertain, despite considerable research efforts. With the aim to examine these associations with an improved precision, we used data from a large population-based prospective cohort study in central Sweden. We estimated nutrient intake from a self-administered food-frequency questionnaire filled in by 60,689 women, aged 40-74 years at baseline during 1987-1990. During follow-up, we observed 3986 women with a fracture at any site and 1535 with a hip fracture. Rate ratio of fractures (RR) and 95% CI were estimated using Cox proportional hazards models. We found no dose-response association between dietary calcium intake and fracture risk. The age-adjusted RR of hip fracture was 1.01 (95% CI 0.96-1.06) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 (95% CI 0.96-1.03). Furthermore, women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes: RR 1.07 (95% CI 0.92-1.24) and RR 1.00 (95% CI 0.79-1.27), respectively. Vitamin D intake was not associated with fracture risk. Furthermore, women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures (95% CI 0.88-1.17). Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women.

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