uu.seUppsala universitets publikationer
Ändra sökning
Avgränsa sökresultatet
12 1 - 50 av 51
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Benetou, Vassiliki
    et al.
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece.
    Orfanos, Philippos
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece.
    Feskanich, Diane
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Harvard Med Sch, Boston, MA USA.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Pettersson-Kymmer, Ulrika
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.; Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Eriksson, Sture
    Umea Univ, Dept Community Med, Umea, Sweden.
    Grodstein, Francine
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Harvard Med Sch, Boston, MA USA.
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Bellavia, Andrea
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Ahmed, Luai A
    UiT, Fac Hlth Sci, Dept Hlth & Care Sci, Tromso, Norway.; United Arab Emirates Univ, Coll Med & Hlth Sci, Inst Publ Hlth, Al Ain, U Arab Emirates.
    Boffeta, Paolo
    Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.; Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
    Trichopoulou, Antonia
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece .
    Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project2016Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, nr 9, s. 1743-1752Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of older adults from Europe and the United States. A total of 142,018 individuals (116,509 women) aged ≥60 years, from five cohorts, were followed up prospectively for 1,911,482 person-years, accumulating 5552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires (FFQ). Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HRs) derived by Cox proportional hazards regression were estimated for each cohort and subsequently pooled using random effects meta-analysis. Intake of ≤1 serving/day of fruit and vegetables combined was associated with 39% higher hip fracture risk (pooled adjusted HR, 1.39; 95% confidence interval [CI], 1.20 to 1.58) in comparison with moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity  = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison with the same reference. Associations were more evident among women. We concluded that a daily intake of 1 or <1 servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk.

  • 2.
    Bokrantz, Tove
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Geriatr Med, Gothenburg.
    Karlsson, Magnus
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg.
    Ljunggren, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Manhem, Karin
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg.
    Mellstrom, Dan
    Univ Gothenburg, Dept Geriatr, Inst Med, Sahlgrenska Acad, CBAR, Gothenburg.
    Peripheral Arterial Disease Predicts Hip Fracture in Men. Results from the MrOS Sweden Study2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr S1, s. S95-S95, artikel-id Meeting Abstract: FR0229Artikel i tidskrift (Övrigt vetenskapligt)
  • 3.
    Byberg, Liisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bellavia, Andrea
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Larsson, Susanna C
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Orsini, Nicola
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Wolk, Alicja
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mediterranean Diet and Hip Fracture in Swedish Men and Women.2016Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, nr 12, s. 2098-2105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A Mediterranean diet, known to have beneficial effects on cardiovascular health, may also influence the risk of hip fracture although previous studies present discrepant results. We therefore aimed to determine whether the rate of hip fracture was associated with degree of adherence to a Mediterranean diet. We combined two Swedish cohort studies consisting of 37,903 men and 33,403 women (total n = 71,333, mean age 60 years) free of previous cardiovascular disease and cancer who answered a medical and a food-frequency questionnaire in 1997. A modified Mediterranean diet score (mMED; range, 0 to 8 points) was created based on high consumption of fruits and vegetables, legumes and nuts, whole grains, fermented dairy products, fish, and olive/rapeseed oil, moderate intake of alcohol, and low intake of red and processed meat. Incident hip fractures between January 1, 1998, and December 31, 2012, were retrieved from the National Patient Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders were calculated using Cox proportional hazards regression. Differences in age at hip fracture were calculated using multivariable Laplace regression. During follow-up, 3175 hip fractures occurred at a median age of 73.3 years. One unit increase in the mMED was associated with 6% lower hip fracture rate (adjusted HR = 0.94; 95% CI, 0.92 to 0.96) and with a 3-month higher median age at hip fracture (50th percentile difference = 2.8 months; 95% CI, 1.4 to 4.2). Comparing the highest quintile of adherence to the mMED (6 to 8 points) with the lowest (0 to 2 points) conferred an adjusted HR of hip fracture of 0.78 (95% CI, 0.69 to 0.89) and a 12-month higher median age of hip fracture (50th percentile difference = 11.6 months; 95% CI, 4.2 to 19.0). Results were similar in men and women. We conclude that higher adherence to a Mediterranean-like diet is associated with lower risk of future hip fracture.

  • 4.
    Byberg, Liisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bellavia, Andrea
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Orsini, Nicola
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Wolk, Alicja
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Fruit and vegetable intake and risk of hip fracture: A cohort study of Swedish men and women2015Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 30, nr 6, s. 976-984Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dietary guidelines recommend a daily intake of five servings of fruit and vegetables. Whether such intakes are associated with a lower risk of hip fracture is at present unclear. The aim of the present study was to investigate the dose-response association between habitual fruit and vegetable intake and hip fracture in a cohort study based on 40,644 men from the Cohort of Swedish Men (COSM) and 34,947 women from the Swedish Mammography Cohort (SMC) (total n=75,591), free from cardiovascular disease and cancer, who answered lifestyle questionnaires in 1997 (age 45-83 years). Intake of fruit and vegetables (servings/day) was assessed by food frequency questionnaire and incident hip fractures were retrieved from the Swedish Patient Register (1998-2010). The mean follow-up time was 14.2 years. One third of the participants reported an intake of fruit and vegetables of >5 servings/day, one third >3 to ≤5 servings/day, 28% >1 to ≤3 servings/day, and 6% reported ≤1 serving/day. During 1,037,645 person-years we observed 3,644 hip fractures (2,266, 62%, in women). The doseresponse association was found to be strongly non-linear (P<0.001). Men and women with zero consumption had 88% higher rate of hip fracture compared with those consuming 5 servings/day; adjusted hazard ratio (HR), 1.88 (95% CI, 1.53-2.32). The rate was gradually lower with higher intakes; adjusted HR for 1 vs 5 servings/day, 1.35 (95% CI, 1.21-1.58). However, more than 5 servings/day did not confer additionally lower HRs (adjusted HR for 8 vs. 5 servings/day, 0.96 (95% CI, 0.90-1.03). Similar results were observed when men and women were analyzed separately. We conclude that there is a dose-response association between fruit and vegetable intake and hip fracture such that an intake below the recommended 5 servings/day confers higher rates of hip fracture. Intakes above this recommendation do not seem to further lower the risk.

  • 5.
    Byberg, Liisa
    et al.
    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.
    Cars, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    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.
    Prediction of fracture risk in men: A cohort study2012Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 27, nr 4, s. 797-807Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R(2) ) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526). During the total follow-up period from age 50, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 and 25.9/1000 person-years at risk from age 82. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25-45% of all fractures and 80-92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7-17% for all fractures and 41-60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40 and 53% for any fracture and between 40 and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, 1/3 of the men will have a fracture within 10 years after age 71 years and 2/3 after age 82 years. We conclude that the addition of comorbidity, medication and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. 

  • 6.
    Byberg, Liisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Goodman, Anna
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Koupil, Ilona
    Birth Weight is not Associated With Risk of Fracture: Results from Two Swedish Cohort Studies2014Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, nr 10, s. 2152-2160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Development and growth in utero has been suggested to influence bone health. However, the relationship with risk of fracture in old age is largely unknown. Using Cox proportional hazards regression, we studied the association between birth weight and fractures at ages 50-94 among 10,893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915-29) and 1334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920-24). Measured birth weight was collected from hospital or midwives' records and fractures from the Swedish National Patient Register. We observed 2796 fractures (717 of these were hip fractures) in UBCoS and 335 fractures (102 hip fractures) in ULSAM. In UBCoS, the hazard ratio (HR) per 1 kg increase in birth weight, adjusted for sex and socioeconomic status at birth, was 1.01 [95% confidence interval (CI), 0.94-1.09] for any fracture and 1.06 (95% CI, 0.91-1.23) for hip fracture. Estimates in ULSAM were similar. We did not observe a differential association of birth weight with fractures occurring before age 70 or after age 70 years. Neither birth weight standardized for gestational age nor gestational duration was associated with fracture rate. In linear regression, birth weight was not associated with bone mineral density among 303 men who were 82-years-old in ULSAM but showed positive associations with total body bone mineral content (β per kg increase in birth weight, adjusted for social class and age, 133; 95% CI, 30-227). This association was attenuated after further adjustment for body mass index and height (β, 41; 95% CI, -43-126). We conclude that birth weight is associated with bone mineral content but this association does not translate into an association with risk of fracture in men and women aged 50-94 years.

  • 7. Engström, Annette
    et al.
    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).
    Suwazono, Yasushi
    Wolk, Alicja
    Vahter, Marie
    Åkesson, Agneta
    Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women2011Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 26, nr 3, s. 486-495Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:: All people are exposed to cadmium (Cd) via food, smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. METHODS:: Within the population-based Swedish Mammography Cohort, we assessed urinary Cd (U-Cd, mug/g creatinine, cr) as a marker of life-time exposure and bone mineral density (BMD) by DXA among 2,688 women. Register-based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. RESULTS:: In linear regression U-Cd was inversely associated with BMD at the total body (p<0.001), femoral neck (p=0.025), total hip (p=0.004), lumbar spine (p=0.088), and volumetric femoral neck (p=0.013). In comparison to women with U-Cd <0.50 mug/g cr, those with U-Cd >/=0.75 mug/g cr had OR 2.45 (95% CI, 1.51-3.97) and 1.97 (95% CI, 1.24-3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never-smokers, the corresponding ORs were 3.45 (95% CI, 1.46-8.23) and 3.26 (95% CI, 1.44-7.38). For any first fracture (n=395) OR was 1.16 (95% CI, 0.89-1.50) comparing U-Cd >/=0.5 mug/g cr with lower levels. Among never-smokers, the ORs (95% CIs) were 2.03 (1.33-3.09) for any first fracture, 2.06 (1.28-3.32) for first osteoporotic fracture, 2.18 (1.20-3.94) for first distal forearm fracture and 1.89 (1.25-2.85) for multiple incident fractures. CONCLUSIONS:: U-Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures especially in never smokers indicating a larger concern than previously known.

  • 8. Eriksson, Anna L.
    et al.
    Movérare-Skrtic, Sofia
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Karlsson, Magnus
    Mellström, Dan
    Ohlsson, Claes
    High-Sensitivity CRP Is an Independent Risk Factor for All Fractures and Vertebral Fractures in Elderly Men: The MrOS Sweden Study2014Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, nr 2, s. 418-423Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological studies have shown low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) to be associated with fracture risk in women. However, it is still unclear whether hs-CRP is also associated with fracture risk in men. We therefore measured serum levels of hs-CRP in 2910 men, mean age 75 years, included in the prospective population-based MrOS Sweden cohort. Study participants were divided into tertile groups based on hs-CRP level. Fractures occurring after the baseline visit were validated (average follow-up 5.4 years). The incidence for having at least one fracture after baseline was 23.9 per 1000 person-years. In Cox proportional hazard regression analyses adjusted for age, hs-CRP was related to fracture risk. The hazard ratio (HR) of fracture for the highest tertile of hs-CRP, compared with the lowest and the medium tertiles combined, was 1.48 (95% CI, 1.20-1.82). Multivariate adjustment for other risk factors for fractures had no major effect on the associations between hs-CRP and fracture. Results were essentially unchanged after exclusion of subjects with hs-CRP levels greater than 7.5mg/L, as well as after exclusion of subjects with a first fracture within 3 years of follow-up, supporting that the associations between hs-CRP and fracture risk were not merely a reflection of a poor health status at the time of serum sampling. Femoral neck bone mineral density (BMD) was not associated with hs-CRP, and the predictive role of hs-CRP for fracture risk was essentially unchanged when femoral neck BMD was added to the model (HR, 1.37; 95% CI, 1.09-1.72). Exploratory subanalyses of fracture type demonstrated that hs-CRP was clearly associated with clinical vertebral fractures (HR, 1.61; 95% CI, 1.12-2.29). We demonstrate, using a large prospective population-based study, that elderly men with high hs-CRP have increased risk of fractures, and that these fractures are mainly vertebral. The association between hs-CRP and fractures was independent of BMD. (c) 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  • 9.
    Grundberg, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lau, Edith M. C.
    Pastinen, Tomi
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nilsson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Mellström, Dan
    Orwoll, Eric
    Redlund-Johnell, Inga
    Holmberg, Anna
    Gurd, Scott
    Leung, Ping Chung
    Kwok, Timothy
    Ohlsson, Claes
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Brändström, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vitamin D receptor 3' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong2007Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 22, nr 6, s. 832-840Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. Introduction: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. Materials and Methods: Here, we reconstructed common haplotypes in the VDR 3′ untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3′ UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. Results: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3′ UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. Conclusions: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.

  • 10.
    Harvey, Nicholas C.
    et al.
    Univ Southampton, Lifecourse Epidemiol Unit, MRC, Southampton, Hants, England;Univ Southampton, Southampton Biomed Res Ctr, NIHR, Southampton, Hants, England;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England.
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
    Karlsson, Magnus K.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Rosengren, Bjorn E.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Ribom, Eva L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cooper, Cyrus
    Univ Southampton, Lifecourse Epidemiol Unit, MRC, Southampton, Hants, England;Univ Southampton, Southampton Biomed Res Ctr, NIHR, Southampton, Hants, England;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England;Univ Oxford, Biomed Res Ctr, NIHR, Oxford, England.
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
    Kanis, John A.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Johansson, Helena
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia.
    McCloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England;Univ Sheffield, Ctr Integrated Res Musculoskeletal Ageing CIMA, Mellanby Ctr Bone Res, Sheffield, S Yorkshire, England.
    Measures of Physical Performance and Muscle Strength as Predictors of Fracture Risk Independent of FRAX, Falls, and aBMD: A Meta-Analysis Of The Osteoporotic Fractures In Men (MrOS) Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 12, s. 2150-2157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measures of muscle mass, strength, and function predict risk of incident fractures, but it is not known whether this risk information is additive to that from FRAX (fracture risk assessment tool) probability. In the Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, Hong Kong, United States), we investigated whether measures of physical performance/appendicular lean mass (ALM) by DXA predicted incident fractures in older men, independently of FRAX probability. Baseline information included falls history, clinical risk factors for falls and fractures, femoral neck aBMD, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the relationship between time for five chair stands, walking speed over a 6 m distance, grip strength, ALM adjusted for body size (ALM/height(2)), FRAX probability (major osteoporotic fracture [MOF]) with or without femoral neck aBMD, available in a subset of n = 7531), and incident MOF (hip, clinical vertebral, wrist, or proximal humerus). Associations were adjusted for age and time since baseline, and are reported as hazard ratios (HRs) for first incident fracture per SD increment in predictor using meta-analysis. 5660 men in the United States (mean age 73.5 years), 2764 men in Sweden (75.4 years), and 1987 men in Hong Kong (72.4 years) were studied. Mean follow-up time was 8.7 to 10.9 years. Greater time for five chair stands was associated with greater risk of MOF (HR 1.26; 95% CI, 1.19 to 1.34), whereas greater walking speed (HR 0.85; 95% CI, 0.79 to 0.90), grip strength (HR 0.77; 95% CI, 0.72 to 0.82), and ALM/height(2) (HR 0.85; 95% CI, 0.80 to 0.90) were associated with lower risk of incident MOF. Associations remained largely similar after adjustment for FRAX, but associations between ALM/height(2) and MOF were weakened (HR 0.92; 95% CI, 0.85 to 0.99). Inclusion of femoral neck aBMD markedly attenuated the association between ALM/height(2) and MOF (HR 1.02; 95% CI, 0.96 to 1.10). Measures of physical performance predicted incident fractures independently of FRAX probability. Whilst the predictive value of ALM/height(2) was substantially reduced by inclusion of aBMD requires further study, these findings support the consideration of physical performance in fracture risk assessment.

  • 11.
    Harvey, Nicholas C.
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England..
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA..
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China..
    Karlsson, Magnus K.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Rosengren, Björn E.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England.;Univ Oxford, NIHR Oxford Biomed Res Ctr, Oxford, England..
    McCloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Univ Sheffield, Ctr Integrated Res Musculoskeletal Ageing CIMA, Mellanby Ctr Bone Res, Sheffield, S Yorkshire, England..
    Kanis, John A.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Mellström, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Johansson, Helena
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia..
    Falls Predict Fractures Independently of FRAX Probability: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 3, s. 510-516Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although prior falls are a well-established predictor of future fracture, there is currently limited evidence regarding the specific value of falls history in fracture risk assessment relative to that of other clinical risk factors and bone mineral density (BMD) measurement. We therefore investigated, across the three Osteoporotic Fractures in Men (MrOS) Study cohorts, whether past falls predicted future fracture independently of FRAX and whether these associations varied with age and follow-up time. Elderly men were recruited from MrOS Sweden, Hong Kong, and USA. Baseline data included falls history (over the preceding 12 months), clinical risk factors, BMD at femoral neck, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the associations between falls, FRAX probability, and incident fracture, adjusting for age, time since baseline, and cohort in base models; further models were used to investigate interactions with age and follow-up time. Random-effects meta-analysis was used to synthesize the individual country associations. Information on falls and FRAX probability was available for 4365 men in USA (mean age 73.5 years; mean follow-up 10.8 years), 1823 men in Sweden (mean age 75.4 years; mean follow-up 8.7 years), and 1669 men in Hong Kong (mean age 72.4 years; mean follow-up 9.8 years). Rates of past falls were similar at 20%, 16%, and 15%, respectively. Across all cohorts, past falls predicted incident fracture at any site (hazard ratio [HR]=1.69; 95% confidence interval [CI] 1.49, 1.90), major osteoporotic fracture (MOF) (HR=1.56; 95% CI 1.33, 1.83), and hip fracture (HR=1.61; 95% CI 1.27, 2.05). Relationships between past falls and incident fracture remained robust after adjustment for FRAX probability: adjusted HR (95% CI) any fracture: 1.63 (1.45, 1.83); MOF: 1.51 (1.32, 1.73); and hip: 1.54 (1.21, 1.95). In conclusion, past falls predicted incident fracture independently of FRAX probability, confirming the potential value of falls history in fracture risk assessment.

  • 12.
    Harvey, Nicholas
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Rosengren, Bjorn
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Ribom, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cawthon, Peggy
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Ensrud, Kristine
    Univ Minnesota, Med & Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.
    Kanis, John
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Johansson, Helena
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Mccloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.
    Definitions of sarcopenia as predictors of fracture risk independent of FRAX, falls and BMD: A meta-analysis of the Osteoporotic Fractures in Men (MrOS) Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, s. 13-14Artikel i tidskrift (Övrigt vetenskapligt)
  • 13.
    Harvey, Nicholas
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants.
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland.
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland.
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong.; Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Lund.; Skåne Univ Hosp, Dept Orthoped, Lund.
    Rosengren, Bjorn
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Lund.; Skåne Univ Hosp, Dept Orthoped, Lund.
    Ljunggren, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants.
    Cawthon, Peggy
    Univ Calif, Dept Epidemiol & Biostat, Oakland.
    Kanis, John
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Johansson, Helena
    Catholic Univ Australia, Inst Hlth & Aging, Sydney, NSW.
    McCloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire.
    Measures of physical performance or function, but not appendicular lean mass, predict new fractures independently of FRAX probability: Findings from MrOS2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr S1, s. S30-S30, artikel-id Meeting Abstract: 1085Artikel i tidskrift (Övrigt vetenskapligt)
  • 14. Hesse, Bernhard
    et al.
    Varga, Peter
    Langer, Max
    Pacureanu, Alexandra
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Schrof, Susanne
    Maennicke, Nils
    Suhonen, Heikki
    Maurer, Peter
    Cloetens, Peter
    Peyrin, Francoise
    Raum, Kay
    Canalicular Network Morphology is the Major Determinant of the Spatial Distribution of Mass Density in Human Bone Tissue: Evidence by Means of Synchrotron Radiation Phase-Contrast nano-CT2015Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 30, nr 2, s. 346-356Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In bone remodeling, maturation of the newly formed osteonal tissue is associated with a rapid primary increase followed by a slower secondary increase of mineralization. This requires supply and precipitation of mineral into the bone matrix. Mineral delivery can occur only from the extracellular fluid via interfaces such as the Haversian system and the osteocyte pore network. We hypothesized that in mineralization, mineral exchange is achieved by the diffusion of mineral from the lacunar-canalicular network (LCN) to the bone matrix, resulting in a gradual change in tissue mineralization with respect to the distance from the pore-matrix interface. We expected to observe alterations in the mass density distribution with tissue age. We further hypothesized that mineral exchange occurs not only at the lacunar but also at the canalicular boundaries. The aim of this study was, therefore, to investigate the spatial distribution of mass density in the perilacunar and pericanalicular bone matrix and to explore how these densities are influenced by tissue aging. This is achieved by analyzing human jawbone specimens originating from four healthy donors and four treated with high-dosage bisphosphonate using synchrotron radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the first experimental evidence that mass density in the direct vicinity of both lacunae (p<0.001) and canaliculi (p<0.001) is different from the mean matrix mass density, resulting in gradients with respect to the distance from both pore-matrix interfaces, which diminish with increasing tissue age. Though limited by the sample size, these findings support our hypotheses. Moreover, the density gradients are more pronounced around the lacunae than around the canaliculi, which are explained by geometrical considerations in the LCN morphology. In addition, we speculate that mineral exchange occurs at all interfaces of the LCN, not only in mineralization but also in mineral homeostasis.

  • 15. Holmer, Helene
    et al.
    Svensson, Johan
    Rylander, Lars
    Johannsson, Gudmundur
    Rosén, Thord
    Bengtsson, Bengt-Åke
    Thorén, Marja
    Höybye, Charlotte
    Degerblad, Marie
    Bramnert, Margareta
    Hägg, Erik
    Edén Engström, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ekman, Bertil
    Thorngren, Karl-Göran
    Hagmar, Lars
    Erfurth, Eva-Marie
    Fracture incidence in GH-deficient patients on complete hormone replacement including GH2007Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 22, nr 12, s. 1842-1850Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients wilh confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR. 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.

  • 16.
    Hughes, Derralynn
    et al.
    Royal Free London NHS Fdn Trust, London, England;UCL, London, England.
    Mikosch, Peter
    Landesklinikum Mistelbach, Dept Internal Med 2, Mistelbach, Austria;Med Univ Vienna, Externe Lehre, Vienna, Austria.
    Belmatoug, Nadia
    Univ Hosp Paris Nord Val de Seine, Assistance Publ Hop Paris, Dept Internal Med, Referral Ctr Lysosomal Dis, Clichy, France.
    Carubbi, Francesca
    Univ Modena & Reggio Emilia, NOCSAE Hosp, AOU Modena, Dept Biomed Metab & Neural Sci, Modena, Italy.
    Cox, Timothy M.
    Univ Cambridge, Dept Med, Cambridge, England.
    Goker-Alpan, Ozlem
    Lysosomal Disorders Res & Treatment Unit, Fairfax, VA USA.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Mistry, PramodK
    Yale Univ, Sch Med, Dept Internal Med Digest Dis, New Haven, CT USA.
    Poll, Ludger
    Heinrich Heine Univ Dusseldorf, Practice Radiol & Nucl Med Duisburg Moers, Duisburg, Germany.
    Weinreb, Neal
    Univ Miami, Miller Sch Med, Dept Human Genet, Coral Gables, FL 33124 USA;Univ Miami, Miller Sch Med, Dept Med Hematol, Coral Gables, FL 33124 USA.
    Deegan, Patrick
    Addenbrookes Hosp, Lysosomal Disorders Unit, Box 135,Hills Rd, Cambridge CB2 0QQ, England.
    Gaucher Disease in Bone: From Pathophysiology To Practice2019Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 34, nr 6, s. 996-1013Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Gaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the most prevalent aspects of GD and a major cause of pain, disability, and reduced quality of life. Uniform recommendations for contemporary evaluation and management are needed. To develop practical clinical recommendations, an international group of experienced physicians conducted a comprehensive review of 20 years' of the literature, defining terms according to pathophysiological understanding and pointing out best practice and unmet needs related to the skeletal features of this disorder. Abnormalities of bone modeling, reduced bone density, bone infarction, and plasma cell dyscrasias accompany the displacement of healthy adipocytes in adult marrow. Exposure to excess bioactive glycosphingolipids appears to affect hematopoiesis and the balance of osteoblast and osteoclast numbers and activity. Imbalance between bone formation and breakdown induces disordered trabecular and cortical bone modeling, cortical bone thinning, fragility fractures, and osteolytic lesions. Regular assessment of bone mineral density, marrow infiltration, the axial skeleton and searching for potential malignancy are recommended. MRI is valuable for monitoring skeletal involvement: It provides semiquantitative assessment of marrow infiltration and the degree of bone infarction. When MRI is not available, monitoring of painful acute bone crises and osteonecrosis by plain X-ray has limited value. In adult patients, we recommend DXA of the lumbar spine and left and right hips, with careful protocols designed to exclude focal disease; serial follow-up should be done using the same standardized instrument. Skeletal health may be improved by common measures, including adequate calcium and vitamin D and management of pain and orthopedic complications. Prompt initiation of specific therapy for GD is crucial to optimizing outcomes and preventing irreversible skeletal complications. Investing in safe, clinically useful, and better predictive methods for determining bone integrity and fracture risk remains a need.

  • 17. Jamal, Sophie A.
    et al.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Stehman-Breen, Catherine
    Cummings, Steven Ron
    McClung, Michael R.
    Goemaere, Stefan
    Ebeling, Peter R.
    Franek, Edward
    Yang, Yu-ching
    Egbuna, Ogo I.
    Boonen, Steven
    Miller, Paul D.
    Effects of Denosumab on Fracture and Bone Mineral Density by Level of Kidney Function2011Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 26, nr 8, s. 1829-1835Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The incidences of osteoporosis and chronic kidney disease (CKD) both increase with increasing age, yet there is a paucity of data on treatments for osteoporosis in the setting of impaired kidney function. We examined the efficacy and safety of denosumab (DMAb) among subjects participating in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6Months (FREEDOM) Study. We estimated creatinine clearance (eGFR) using Cockcroft-Gault and classified levels of kidney function using the modified National Kidney Foundation classification of CKD. We examined incident fracture rates; changes in bone mineral density (BMD), serum calcium, and creatinine; and the incidence of adverse events after 36 months of follow-up in subjects receiving DMAb or placebo, stratified by level of kidney function. We used a subgroup interaction term to determine if there were differences in treatment effect by eGFR. Most (93%) women were white, and the mean age was 72.3 +/- 5.2 years; 73 women had an eGFR of 15 to 29mL/min; 2817, between 30 to 59mL/min; 4069, between 60 to 89mL/min, and 842 had an eGFR of 90mL/min or greater. None had stage 5 CKD. Fracture risk reduction and changes in BMD at all sites were in favor of DMAb. The test for treatment by subgroup interaction was not statistically significant, indicating that treatment efficacy did not differ by kidney function. Changes in creatinine and calcium and the incidence of adverse events were similar between groups and did not differ by level of kidney function. It is concluded that DMAb is effective at reducing fracture risk and is not associated with an increase in adverse events among patients with impaired kidney function.

  • 18. Johansson, Helena
    et al.
    Oden, Anders
    Lerner, Ulf H.
    Jutberger, Hans
    Lorentzon, Mattias
    Barrett-Connor, Elizabeth
    Karlsson, Magnus K.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Smith, Ulf
    McCloskey, Eugene
    Kanis, John A.
    Ohlsson, Claes
    Mellstrom, Dan
    High serum adiponectin predicts incident fractures in elderly men: Osteoporotic fractures in men (MrOS) Sweden2012Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 27, nr 6, s. 1390-1396Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time-to-event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4 mu g/mL (interquartile range, 7.714.3). During follow-up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.231.72) and persisted after multivariate-adjusted analysis (HR/SD, 1.30; 95% CI, 1.091.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men.

  • 19. Jutberger, Hans
    et al.
    Lorentzon, Mattias
    Barrett-Connor, Elizabeth
    Johansson, Helena
    Kanis, John A.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Magnus K.
    Rosengren, Björn E.
    Redlund-Johnell, Inga
    Orwoll, Eric
    Ohlsson, Claes
    Mellström, Dan
    Smoking Predicts Incident Fractures in Elderly Men: Mr OS Sweden2010Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 25, nr 5, s. 1010-1016Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the present study was to investigate the association between smoking and BMD, radiographically verified prevalent vertebral fractures and incident fractures in elderly men. At baseline 3003 men, aged 69 - 80 years old from the Swedish Mr Os study, completed a standard questionnaire concerning smoking habits and had BMD of the hip and spine measured using DXA; 1412 men had an X-ray of the thoracic-/lumbar spine. Radiological registers were used to confirm reported new fractures after the baseline visit. At baseline 8.4 % were current smokers. Current smokers had 6.2 % lower BMD at the total hip and 5.4 % at the lumbar spine (p<0.001). Current smoking remained independently, inversely associated with BMD at the hip and lumbar spine after adjusting for age, height, weight, calcium intake, physical activity and centres as co-variates. Prevalent vertebral fractures among current smokers were increased in unadjusted analyses (OR 1.90; 95% CI: 1.26-2.87) and after adjustment for lumbar BMD (OR 1.67; 1.09-2.55). Smokers had a high risk for two or more prevalent vertebral fractures (OR 3.18; 1.88-5.36). During the average follow-up of 3.3 years, 209 men sustained an X-ray verified fracture. Incident fracture risk among smokers was calculated with Cox proportional hazard models. Current smokers had increased risk of all new fractures (HR 1.76; 1.19-2.61), non-vertebral osteoporotic fractures defined as humerus, radius, pelvis and hip fractures (HR 2.14; 1.18-3.88), clinical and X-ray verified vertebral fractures (HR 2.53; 1.37-4.65) as well as of hip fracture (HR 3.16; 1.44-6.95). After adjustment for BMD, including other co-variates, no significant association between smoking and incident fractures was found. Current tobacco smoking in elderly men is associated with low BMD, prevalent vertebral fractures and incident fractures, especially vertebral and hip fractures.

  • 20.
    Kharazmi, Mohammad
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hallberg, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Schilcher, Jörg
    Linkoping Univ, Fac Hlth Sci, Sect Orthoped, Dept Clin & Expt Med, Linkoping, Sweden.
    Aspenberg, Per
    Linkoping Univ, Fac Hlth Sci, Sect Orthoped, Dept Clin & Expt Med, Linkoping, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mortality After Atypical Femoral Fractures: A Cohort Study2016Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, nr 3, s. 491-497Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although osteoporotic fracture rates can be reduced by bisphosphonates, prolonged therapy is associated with higher risk of atypical femoral fractures. Ordinary fragility fractures are linked to high mortality rates. We aimed to determine whether atypical femoral fractures also confer excess mortality. Radiographs were reviewed for all patients ≥55 years of age who had experienced a subtrochanteric or femoral shaft fracture in Sweden in 2008-2010. The fractures were classified as either atypical or ordinary. Data on medication use, coexisting conditions, and date of death were obtained from national registers. We estimated multivariable-adjusted relative risks of death after atypical femoral fractures compared with ordinary subtrochanteric or femoral shaft fractures and calculated age- and sex-standardized mortality ratios (SMRs) for atypical and ordinary fractures compared with the population average. During a mean of 4 years of follow-up, 39 of 172 (23%) patients with an atypical fracture had died compared with 588 of 952 (62%) with an ordinary fracture, corresponding to a relative risk of 0.51 (95% CI 0.38-0.68). The lower risk was evident in both users and non-users of bisphosphonates. No patient with atypical fracture died in the first year after fracture. Individuals with an ordinary fracture had a higher mortality risk than the general population (SMR 1.82; 95% CI 1.69-1.99) but no excess risk was found in patients with atypical fracture (SMR 0.92; 95% CI 0.65-1.26). We conclude that in contrast to ordinary subtrochanteric and femoral shaft fractures, atypical femoral fractures are not associated with excess mortality.

  • 21. Kindblom, Jenny M.
    et al.
    Ohlsson, Claes
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Magnus K.
    Tivesten, Åsa
    Smith, Ulf
    Mellström, Dan
    Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men2009Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 24, nr 5, s. 785-791Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The osteoblast-derived protein osteocalcin has recently been shown to affect adiposity and glucose homeostasis in mice, suggesting that the skeleton influences energy metabolism through an endocrine mechanism. The aim of this study was to investigate the relationship between plasma osteocalcin and parameters reflecting fat mass and glucose homeostasis in humans. Fasting levels of plasma osteocalcin, plasma glucose, serum insulin, and lipids were analyzed in elderly men (75.3 +/- 3.2 yr of age) in the Gothenburg part (all subjects, n = 1010; nondiabetic, n = 857; diabetic, n = 153) of the MrOS Sweden study. Fat mass and lean mass were analyzed using DXA. Diabetic subjects had lower plasma osteocalcin (-21.7%, p < 0.001) than nondiabetic subjects. For both all subjects and nondiabetic subjects, plasma osteocalcin was clearly inversely related to body mass index (BMI), fat mass, and plasma glucose (p < 0.001), whereas it was not associated with height or lean mass. Plasma osteocalcin explained a substantial part (6.3%) of the variance in plasma glucose, whereas it associated moderately with serum insulin. Multiple linear regression models adjusting for serum insulin and fat mass showed that plasma osteocalcin was an independent negative predictor of plasma glucose (p < 0.001). We herein, for the first time in humans, show that plasma osteocalcin is inversely related to fat mass and plasma glucose. Although one should be cautious with mechanistic interpretations of cross-sectional association studies, our human data support recently published experimental studies, showing endocrine functions of osteoblast-derived osteocalcin on glucose and fat homeostasis.

  • 22.
    Kristjansdottir, Hallgerdur Lind
    et al.
    Univ Gothenburg, Sect Hematol & Coagulat, Dept Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg.
    Ljunggren, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci & Orthopaed, Lund.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Geriatr Med, Gothenburg.
    Lerner, Ulf
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Lewerin, Catharina
    Univ Gothenburg, Sect Hematol & Coagulat, Dept Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg.
    Mellström, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Geriatr Med, Gothenburg.
    High serum Erythropoetin Predicts Incident Fractures in Men. MrOS Sweden.2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, s. S371-S371Artikel i tidskrift (Övrigt vetenskapligt)
  • 23. Lang, Dean H.
    et al.
    Conroy, E
    Lionikas, Arimantas
    Mack, A
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Vogler, P
    Vandenbergh, J
    Blizard, A
    McClearn, E
    Sharkey, Neil A.
    Bone, Muscle, and Physical Activity: Structural Equation Modeling of Relationships and Genetic Influence With Age2009Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 24, nr 9, s. 1608-1617Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Correlations among bone strength, muscle mass, and physical activity suggest that these traits may be modulated by each other and/or by common genetic and/or environmental mechanisms. This study used structural equation modeling (SEM) to explore the extent to which select genetic loci manifest their pleiotropic effects through functional adaptations commonly referred to as Wolff's law. Quantitative trait locus (QTL) analysis was used to identify regions of chromosomes that simultaneously influenced skeletal mechanics, muscle mass, and/or activity-related behaviors in young and aged B6xD2 second-generation (F-2) mice of both sexes. SEM was used to further study relationships among select QTLs, bone mechanics, muscle mass, and measures of activity. The SEM approach provided the means to numerically decouple the musculoskeletal effects of mechanical loading from the effects of other physiological processes involved in locomotion and physical activity. It was found that muscle mass was a better predictor of bone mechanics in young females, whereas mechanical loading was a better predictor of bone mechanics in older females. An activity-induced loading factor positively predicted the mechanical behavior of hindlimb bones in older males; contrarily, load-free locomotion (i.e., the remaining effects after removing the effects of loading) negatively predicted bone performance. QTLs on chromosomes 4, 7, and 9 seem to exert some of their influence on bone through actions consistent with Wolff's Law. Further exploration of these and other mechanisms through which genes function will aid in development of individualized interventions able to exploit the numerous complex pathways contributing to skeletal health. J Bone Miner Res 2009;24:1608-1617. Published online on April 27, 2009; doi: 10.1359/JBMR.090418

  • 24.
    Larsson, Susanna C
    et al.
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Stockholm, Sweden.
    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.
    Circulating Serum 25-Hydroxyvitamin D Levels and Bone Mineral Density: Mendelian Randomization Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 5, s. 840-844Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is considerable discussion of the importance for increased serum 25‐hydroxyvitamin D (S‐25OHD) concentration associated with adequacy for bone health. Accordingly, whether long‐term high S‐25OHD concentration in general positively affects bone mineral density (BMD) is uncertain. We used a Mendelian randomization design to determine the association between genetically increased S‐25OHD concentrations and BMD. Five single‐nucleotide polymorphisms (SNPs) in or near genes encoding enzymes and carrier proteins involved in vitamin D synthesis or metabolism were used as instrumental variables to genetically predict 1 standard deviation increase in S‐25OHD concentration. Summary statistics data for the associations of the S‐25OHD‐associated SNPs with dual‐energy X‐ray absorptiometry (DXA)‐derived femoral neck and lumbar spine BMD were obtained from the Genetic Factors for Osteoporosis (GEFOS) Consortium (32,965 individuals) and ultrasound‐derived heel estimated BMD from the UK Biobank (142,487 individuals). None of the SNPs were associated with BMD at Bonferroni‐corrected significance level, but there was a suggestive association between rs6013897 near CYP24A1 and femoral neck BMD (p = 0.01). In Mendelian randomization analysis, genetically predicted 1 standard deviation increment of S‐25OHD was not associated with higher femoral neck BMD (SD change in BMD 0.02; 95% confidence interval [CI] –0.03 to 0.07; p = 0.37), lumbar spine BMD (SD change in BMD 0.02; 95% CI –0.04 to 0.08; p = 0.49), or estimated BMD (g/cm2 change in BMD –0.03; 95% CI –0.05 to –0.01; p = 0.02). This study does not support a causal association between long‐term elevated S‐25OHD concentrations and higher BMD in generally healthy populations. These results suggest that more emphasis should be placed on the development of evidence‐based cut‐off points for vitamin D inadequacy rather than a general recommendation to increase S‐25OHD.

  • 25.
    Lundstam, Karolina
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Radiol,Inst Clin Sci, Gothenburg, Sweden..
    Heck, Ansgar
    Oslo Univ Hosp, Sect Specialized Endocrinol, Pb 4950, N-0424 Oslo, Norway.;Univ Oslo, Fac Med, Pb 4950, N-0424 Oslo, Norway..
    Godang, Kristin
    Oslo Univ Hosp, Sect Specialized Endocrinol, Pb 4950, N-0424 Oslo, Norway.;Univ Oslo, Fac Med, Pb 4950, N-0424 Oslo, Norway..
    Mollerup, Charlotte
    Copenhagen Univ Hosp, Ctr HOC, Clin Breast & Endocrine Surg, Rigshosp, Copenhagen, Denmark..
    Baranowski, Marek
    St Olavs Hosp, Trondheim, Norway..
    Pernow, Ylva
    Karolinska Univ Hosp, Karolinska Inst, Dept Endocrinol, Dept Mol Med & Surg, Stockholm, Sweden..
    Aas, Turid
    Haukeland Hosp, Dept Breast & Endocrine Surg, Bergen, Norway..
    Hessman, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Rosen, Thord
    Sahlgrens Univ Hosp, Dept Med, Sect Endocrinol Diabet & Metab, Gothenburg, Sweden..
    Nordenstrom, Jorgen
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Jansson, Svante
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Surg,Inst Clin Sci, Gothenburg, Sweden..
    Hellstrom, Mikael
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Radiol,Inst Clin Sci, Gothenburg, Sweden..
    Bollerslev, Jens
    Oslo Univ Hosp, Sect Specialized Endocrinol, Pb 4950, N-0424 Oslo, Norway.;Univ Oslo, Fac Med, Pb 4950, N-0424 Oslo, Norway..
    Effect of Surgery Versus Observation: Skeletal 5-Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study)2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr 9, s. 1907-1914Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm(2) and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p<0.001) and CTX-1 (p<0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm(2)) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p<0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p<0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm(2)) for all compartments (FN, p<0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p<0.001) with the exception of the LS, whereBMDwas stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT.

  • 26.
    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)
  • 27. McCloskey, Eugene V
    et al.
    Odén, Anders
    Harvey, Nicholas C
    Leslie, William D
    Hans, Didier
    Johansson, Helena
    Barkmann, Reinhard
    Boutroy, Stephanie
    Brown, Jacques
    Chapurlat, Roland
    Elders, Petra Jm
    Fujita, Yuki
    Glüer, Claus-C
    Goltzman, David
    Iki, Masayuki
    Karlsson, Magnus
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kotowicz, Mark
    Kurumatani, Norio
    Kwok, Timothy
    Lamy, Oliver
    Leung, Jason
    Lippuner, Kurt
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Lorentzon, Mattias
    Mellström, Dan
    Merlijn, Thomas
    Oei, Ling
    Ohlsson, Claes
    Pasco, Julie A.
    Rivadeneira, Fernando
    Rosengren, Björn
    Sornay-Rendu, Elisabeth
    Szulc, Pawel
    Tamaki, Junko
    Kanis, John A
    A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX2016Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, nr 5, s. 940-948Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

  • 28.
    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.

  • 29. Mellström, Dan
    et al.
    Johnell, Olof
    Ljunggren, Östen
    Eriksson, Anna-Lena
    Lorentzon, Mattias
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Holmberg, Anna
    Redlund-Johnell, Inga
    Orwoll, Eric
    Ohlsson, Claes
    Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden2006Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 21, nr 4, s. 529-535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men.

    INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men.

    MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD.

    RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD.

    CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.

  • 30. Mellström, Dan
    et al.
    Vandenput, Liesbeth
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Holmberg, Anna H.
    Lorentzon, Mattias
    Odén, Anders
    Johansson, Helena
    Orwoll, Eric S.
    Labrie, Fernand
    Karlsson, Magnus K.
    Ljunggren, Östen
    Ohlsson, Claes
    Older men with low serum estradiol and high serum SHBG have an increased risk of fractures2008Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 23, nr 10, s. 1552-60Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p < 0.001), but not fT, were independently associated with fracture risk. Further subanalyses of fracture type showed that fE2 was inversely associated with clinical vertebral fractures (HR per SD decrease, 1.57; 95% CI, 1.36-1.80), nonvertebral osteoporosis fractures (HR per SD decrease, 1.42; 95% CI, 1.23-1.65), and hip fractures (HR per SD decrease, 1.44; 95% CI, 1.18-1.76). The inverse relation between serum E2 and fracture risk was nonlinear with a strong relation <16 pg/ml for E2 and 0.3 pg/ml for fE2. In conclusion, older Swedish men with low serum E2 and high SHBG levels have an increased risk of fractures.

  • 31.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Holmberg, L.
    Uppsala universitet.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Uppsala universitet.
    Bergström, R.
    Uppsala universitet.
    Ljunghall, S.
    Uppsala universitet.
    The Influence of Dietary Factors on Hip Fracture Risk and Bone Mass1995Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 10, nr Suppl. 1, s. S178-S178s. S178-Artikel i tidskrift (Övrigt vetenskapligt)
  • 32.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nordström, Peter
    Nordström, Anna
    Garmo, Hans
    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.
    Pedersen, Nancy L
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Impact of hip fracture on mortality: a cohort study in hip fracture discordant identical twins2014Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, nr 2, s. 424-431Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several studies have shown a long-lasting higher mortality after hip fracture but the reasons of the excess risk is not well understood. We aimed to determine whether there exists a higher mortality after hip fracture when controlling for genetic constitution, shared environment, comorbidity and lifestyle by use of a nation-wide cohort study in hip fracture discordant monozygotic twins. All 286 identical Swedish twin pairs discordant for hip fracture (1972-2010) were identified. Comorbidity and lifestyle information was retrieved by registers and questionnaire information. We used intrapair Cox regression to compute multivariable-adjusted hazard ratios (HRs) for death. During follow-up, 143 twins with a hip fracture died (50%) compared to 101 twins (35%) without a hip fracture. Through the first year after hip fracture, the rate of death increased four-fold in women (HR 3.71; 95% confidence interval (CI) 1.32-10.40) and seven-fold in men (HR 6.67; 95% CI 1.47-30.13). The increased rate in women only persisted during the first year after hip fracture (HR after 1 year 0.99; 95% CI 0.66-1.50), whereas the corresponding HR in men was 2.58 (95% CI 1.02-6.62). The higher risk in men after the hip fracture event was successively attenuated during follow-up. After 5 years, the hazard ratio in men with a hip fracture was 1.19 (95% CI 0.29-4.90). On average, the hip fracture contributed to 0.9 years of life lost in women (95% CI 0.06-1.7) and 2.7 years in men (95% CI 1.7-3.7). The potential years of life lost associated with the hip fracture was especially pronounced in older men (>75 years), with an average loss of 47% (95% CI 31-61) of the expected remaining lifetime. We conclude that both women and men display a higher mortality after hip fracture independent of genes, comorbidity and lifestyle.

  • 33.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Warensjö, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Intake of milk or fermented milk combined with fruit and vegetable consumption in relation to hip fracture rates: A cohort study of Swedish women.2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 3, s. 449-457Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Milk products may differ in pro-oxidant properties and their effects on fracture risk could potentially be modified by the intake of foods with antioxidant activity. In the population-based Swedish Mammography Cohort study, we aimed to determine how milk and fermented milk combined with fruit and vegetable consumption are associated with hip fracture. Women born 1914-1948 (n=61 240) answered food frequency and lifestyle questionnaires in 1987-1990 and 38 071 women contributed with updated information in 1997. During a mean follow-up of 22 years, 5827 women had a hip fracture (ascertained via official register data). Compared with a low intake of milk (<1 glass/day) and a high intake of fruits and vegetables (≥5 servings/day), a high intake of milk (≥3 glasses/day) with a concomitant low intake of fruits and vegetables (<2 servings/day) resulted in a HR of 2.49 (95% CI, 2.03-3.05). This higher hip fracture rate among high consumers of milk was only modestly attenuated with a concomitant high consumption of fruit and vegetables (HR 2.14; 95% CI 1.69-2.71). The combination of fruits and vegetables with fermented milk (yogurt or soured milk) yielded a different pattern with lowest rates of hip fracture in high consumers: HR 0.81 (95% CI, 0.68-0.97) for ≥2 servings/day of fermented milk and ≥5 servings/day of fruits and vegetables compared with low consumption of both fruit and vegetables and fermented milk. We conclude that the amount and type of dairy products as well as fruit and vegetable intake are differentially associated with hip fracture rates in women.

  • 34.
    Mirza, Majd
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Magnus
    Mellström, Dan
    Orwoll, Eric
    Ohlsson, Claes
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Tobias
    Serum Fibroblast Growth Factor-23 (FGF-23) and Fracture Risk in Elderly Men2011Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 26, nr 4, s. 857-864Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A normal mineral metabolism is integral for skeletal development and preservation of bone integrity. Fibroblast growth factor-23 (FGF23) is a bone-derived, circulating factor that decreases serum concentrations of inorganic phosphorous (Pi) and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3). Increased FGF23 expression is a direct or indirect culprit in several skeletal disorders, however the relation between FGF23 and fracture risk remains undetermined.  We evaluated the prospective relation between serum intact FGF23 (measured by a two-site, monoclonal antibody ELISA) and fracture risk, employing the Swedish part of the population-based, Osteoporotic Fractures in Men Study (MrOS) (n=2868; mean age 75.4 ± 3.2; median follow-up period 3.35 years). The incidence of at least one validated fracture after baseline was 20.4 per 1000-person-years. FGF23 was directly related to the over-all fracture risk (age-adjusted hazard ratio [HR] per SD increase, 1.20; 95% CI, 1.03-1.40) and vertebral fracture risk (HR, 1.33; 95% CI, 1.02-1.75). Spline models revealed a non-linear relation between FGF23 and fracture risk with the strongest relation at FGF23 levels above 55.7 pg/mL. FGF23 levels above 55.7 pg/mL were also associated with an increased risk for hip and non-vertebral fractures (HR, 2.30; 95% CI, 1.16-4.58 and HR, 1.63; 95%CI, 1.01-2.63 respectively). These relations remained essentially unaltered after adjustment for BMI, BMD, glomerular filtration rate, 25(OH)D3, PTH and other fracture risk factors. In conclusion, FGF23 is a novel predictor of fracture risk in elderly men.

  • 35. Ohlsson, Claes
    et al.
    Mellström, Dan
    Carlzon, Daniel
    Orwoll, Eric
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Magnus K.
    Vandenput, Liesbeth
    Older Men With Low Serum IGF-1 Have an Increased Risk of Incident Fractures: The MrOS Sweden Study2011Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 26, nr 4, s. 865-872Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Insulin-like growth factor 1 (IGF-1) is a key determinant of bone mass, but the association between serum IGF-1 and incident fractures in men remains unclear. To determine the predictive value of serum IGF-1 for fracture risk in men, older men (n = 2902, mean age of 75 years) participating in the prospective, population-based Osteoporotic Fractures in Men (MrOS) Sweden study were followed for a mean of 3.3 years. Serum IGF-1 was measured at baseline by radioimmunoassay. Fractures occurring after the baseline visit were validated. In age-adjusted hazards regression analyses, serum IGF-1 associated inversely with risk of all fractures [hazard ratio (HR) per SD decrease = 1.23, 95% confidence interval (CI) 1.07-1.41], hip fractures (HR per SD decrease = 1.45, 95% CI 1.07-1.97), and clinical vertebral fractures (HR per SD decrease = 1.40, 95% CI 1.10-1-78). The predictive role of serum IGF-1 for fracture risk was unaffected by adjustment for height, weight, prevalent fractures, falls, and major prevalent diseases. Further adjustment for bone mineral density (BMD) resulted in an attenuated but still significant association between serum IGF-1 and fracture risk. Serum IGF-1 below but not above the median was inversely related to fracture incidence. The population-attributable risk proportion was 7.5% for all fractures and 22.9% for hip fractures. Taken together, older men with low serum IGF-1 have an increased fracture risk, especially for the two most important fracture types, hip and vertebral fractures. The association between serum IGF-1 and fracture risk is partly mediated via BMD.

  • 36.
    Ohlsson, Claes
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11SE, SE-41345 Gothenburg, Sweden.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11SE, SE-41345 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden.
    Karlsson, Magnus K.
    Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden;Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.
    Rosengren, Bjorn E.
    Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden;Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.
    Ribom, Eva L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11SE, SE-41345 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Geriatr Med,Inst Med, Gothenburg, Sweden.
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11SE, SE-41345 Gothenburg, Sweden.
    Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 7, s. 1227-1232Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. Many of the actions of DHEAS are considered to be mediated through metabolism into androgens and estrogens in peripheral target tissues. The predictive value of serum DHEA and DHEAS for the likelihood of falling is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEA and DHEAS levels and incident fall risk in a large cohort of older men. Serum DHEA and DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n=2516, age 69 to 81 years). Falls were ascertained every 4 months by mailed questionnaires. Associations between steroid hormones and falls were estimated by generalized estimating equations. During a mean follow-up of 2.7 years, 968 (38.5%) participants experienced a fall. High serum levels of both DHEA (odds ratio [OR] per SD increase 0.85; 95% CI, 0.78 to 0.92) and DHEAS (OR 0.88, 95% CI, 0.81 to 0.95) were associated with a lower incident fall risk in models adjusted for age, BMI, and prevalent falls. Further adjustment for serum sex steroids or age-related comorbidities only marginally attenuated the associations between DHEA or DHEAS and the likelihood of falling. Moreover, the point estimates for DHEA and DHEAS were only slightly reduced after adjustment for lean mass and/or grip strength. Also, the addition of the narrow walk test did not substantially alter the associations between serum DHEA or DHEAS and fall risk. Finally, the association with incident fall risk remained significant for DHEA but not for DHEAS after simultaneous adjustment for lean mass, grip strength, and the narrow walk test. This suggests that the associations between DHEA and DHEAS and falls are only partially mediated via muscle mass, muscle strength, and/or balance. In conclusion, older men with high DHEA or DHEAS levels have a lesser likelihood of a fall.

  • 37.
    Ohlsson, Claes
    et al.
    Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, Dept Internal Med & Clin Nutr,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Lorentzon, Mattias
    Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, Dept Internal Med & Clin Nutr,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, Gothenburg, Sweden.
    Rosengren, Bjorn E.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Karlsson, Magnus K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Mellstrom, Dan
    Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, Dept Internal Med & Clin Nutr,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, Gothenburg, Sweden.
    Vandenput, Liesbeth
    Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, Dept Internal Med & Clin Nutr,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden.
    Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr 8, s. 1607-1614Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n = 594; non-vertebral major osteoporotic, n = 255; hip, n = 175; clinical vertebral, n = 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease = 1.14, 95% confidence interval [CI] 1.05-1.24), non-vertebral major osteoporotic fractures (HR = 1.31, 95% CI 1.16-1.48), and hip fractures (HR = 1.18, 95% CI 1.02-1.37) but not clinical vertebral fractures (HR = 1.09, 95% CI 0.95-1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 mg/mL). In conclusion, low serum DHEAS levels are a risk marker of mainly non-vertebral fractures in older men, of whom those with DHEAS levels below 0.60 mg/mL are at highest risk.

  • 38.
    Olofsson, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Mohsen, Rawya
    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.
    Lithell, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Smoking and the Risk of Fracture in Older Men2005Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 20, nr 7, s. 1208-15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of smoking on fracture risk in older men was studied within a longitudinal population-based cohort study. Using time-dependent exposure information and analysis, smoking was detected to be a stronger, dose-dependent and a more long lasting risk factor for fracture than has previously been estimated. INTRODUCTION: Although several studies have indicated a negative influence of smoking on fracture risk in women, there are few studies in men. No study in either sex has considered that smoking exposure may vary during follow-up in a cohort study. There is a need for a prospective study with repeated measures to analyze smoking exposure and fracture risk in men. MATERIALS AND METHODS: A total of 2322 men, 49-51 years of age, were enrolled in a longitudinal, population-based cohort study. Smoking status and other lifestyle habits were established at baseline and additionally at 60, 70, and 77 years of age. One or more fractures were documented in 272 men during 30 years of follow-up. Cox proportional hazards regression was used to determine the rate ratio (RR) of fracture according to time-dependent smoking habits and covariates. RESULTS: The overall adjusted fracture risk was increased in current (RR, 2.71; 95% CI, 1.86-3.95) and former smokers (RR, 1.66, 95% CI; 1.18-2.34), and persistent until 30 years after cessation. Among current smokers, the adjusted risk of any fracture increased by 30% (95% CI, 6-58%) for every 5 g of tobacco smoked each day. Smoking duration did not substantially influence fracture risk in either current or former smokers. One-half (52%; 95% CI, 35-65%) of all fractures were attributable to current smoking. CONCLUSIONS: Tobacco smoking seems to be a long-lasting major risk factor for fracture in older men, and the risks depends both on recency of smoking and on the daily amount of tobacco smoked, rather than smoking duration.

  • 39.
    Orwoll, Eric S.
    et al.
    Oregon Hlth & Sci Univ, Sch Med, Bone & Mineral Unit, Div Endocrinol Diabet & Clin Nutr, 3181 SW Sam Jackson Pk Rd CR 113, Portland, OR 97201 USA..
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA..
    Wang, Patty Y.
    Oregon Hlth & Sci Univ, Sch Med, Bone & Mineral Unit, Div Endocrinol Diabet & Clin Nutr, 3181 SW Sam Jackson Pk Rd CR 113, Portland, OR 97201 USA..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Hoffman, Andrew
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Fink, Howard A.
    VA Med Ctr, Geriatr Res Educ & Clin Ctr, Minneapolis, MN USA.;Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA..
    Laughlin, Gail A.
    Univ Calif San Diego, Sch Med, Dept Family Med & Publ Hlth, Div Epidemiol, La Jolla, CA 92093 USA..
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Geriatr Med, Gothenburg, Sweden..
    Karlsson, Magnus K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden.;Malmo Univ, Dept Orthopaed, Malmo, Sweden..
    Mellström, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Geriatr Med, Gothenburg, Sweden..
    Kwok, Anthony
    Chinese Univ Hong Kong, Dept Orthopaed & Traumatol, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Jockey Club Ctr Osteoporosis Care & Control, Hong Kong, Hong Kong, Peoples R China..
    Khosla, Sundeep
    Mayo Clin, Div Endocrinol, Rochester, MN USA..
    Kwok, Timothy
    Chinese Univ Hong Kong, Jockey Club Ctr Osteoporosis Care & Control, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    The Limited Clinical Utility of Testosterone, Estradiol, and Sex Hormone Binding Globulin Measurements in the Prediction of Fracture Risk and Bone Loss in Older Men2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr 3, s. 633-640Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurement of serum testosterone (T) levels is recommended in the evaluation of osteoporosis in older men and estradiol (E2) and sex hormone binding globulin (SHBG) levels are associated with the rate of bone loss and fractures, but the clinical utility of sex steroid and SHBG measurements for the evaluation of osteoporosis in men has not been examined. To evaluate whether measurements of T, E2, and/or SHBG are useful for the prediction of fracture risk or the rate of bone loss in older men, we analyzed longitudinal data from 5487 community-based men participating in the Osteoporotic Fractures in Men (MrOS) study in the United States, Sweden, and Hong Kong. Serum T, E2, and SHBG levels were assessed at baseline; incident fractures were self-reported at 4-month intervals with radiographic verification (US), or ascertained via national health records (Sweden, Hong Kong). Rate of bone loss was assessed by serial measures of hip bone mineral density (BMD). We used receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to assess improvement in prediction. Mean age at baseline was 72 to 75 years and the prevalence of low T levels (<300 ng/dL) was 7.6% to 21.3% in the three cohorts. There were 619 incident major osteoporotic and 266 hip fractures during follow-up of approximately 10 years. Based on ROC curves, there were no improvements in fracture risk discrimination for any biochemical measure when added to models, including the Fracture Risk Assessment Tool (FRAX) with BMD. Although minor improvements in NRI were observed for the dichotomous parameters low bioavailable E2 (BioE2) (<11.4 pg/mL) and high SHBG(>59.1 nM), neither sex steroids nor SHBG provided clinically useful improvement in fracture risk discrimination. Similarly, they did not contribute to the prediction of BMD change. In conclusion, there is limited clinical utility of serum E2, T, and SHBG measures for the evaluation of osteoporosis risk in elderly men.

  • 40.
    Rubin, Carl-Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Brändström, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wright, Dominic
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Kerje, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Gunnarsson, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Schütz, Karin
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Jensen, Per
    Andersson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Ohlsson, Claes
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Larsson, Sune
    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.
    Quantitative Trait Loci for BMD and Bone Strength in an Intercross Between Domestic and Wildtype Chickens2007Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 22, nr 3, s. 375-384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    With chicken used as a model species, we used QTL analysis to examine the genetic contribution to bone traits. We report the identification of four QTLs for femoral traits: one for bone strength, one for endosteal circumference, and two affecting mineral density of noncortical bone. Introduction: BMD is a highly heritable phenotype, governed by elements at numerous loci. In studies examining the genetic contribution to bone traits, many loci have been identified in humans and in other species. The goal of this study was to identify quantitative trait loci (QTLs) controlling BMD and bone strength in an intercross between wildtype and domestic chickens. Materials and Methods: A set of 164 markers, covering 30 chromosomes (chr.), were used to genotype 337 F 2-individuals from an intercross of domesticated white Leghorn and wildtype red junglefowl chicken. DXA and pQCT were used to measure BMD and bone structure. Three-point bending tests and torsional strength tests were performed to determine the biomechanical strength of the bone. QTLs were mapped using forward selection for loci with significant marginal effects. Results: Four QTLs for femoral bone traits were identified in QTL analysis with body weight included as a covariate. A QTL on chr. 1 affected female noncortical BMD (LOD 4.6) and is syntenic to human 12q21-12q23. Also located on chr. 1, a locus with synteny to human 12q 13-1.4 affected endosteal circumference (LOD 4.6). On chr. 2, a QTL corresponding to human 5p13-p15, 7p12, 18q12, 18q21, and 9q22-9q31 affected BMD in females; noncortical (LOD 4.0) and metaphyseal (LOD 7.0) BMD by pQCT and BMD by DXA (LOD 5.9). A QTL located on chr. 20 (LOD 5.2) affected bone biomechanical strength and had sex-dependent effects. In addition to the significant QTLs, 10 further loci with suggestive linkage to bone traits were identified. Conclusions: Four QTLs were identified: two for noncortical BMD, one for endosteal circumference, and one affecting bone biomechanical strength. The future identification of genes responsible for these QTLs will increase the understanding of vertebrate skeletal biology.

  • 41.
    Stattin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hållmarker, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Mora Lasarett, Dept Internal Med, Mora, Sweden.
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Dalarna, Sweden.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Decreased Hip, Lower Leg, and Humeral Fractures but Increased Forearm Fractures in Highly Active Individuals2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 10, s. 1842-1850Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 42.
    Stattin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Larsson, Susanna C
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Stockholm, Sweden.
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, Stockholm, Sweden.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Leisure-Time Physical Activity and Risk of Fracture: A Cohort Study of 66,940 Men and Women2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr 8, s. 1599-1606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 43. Thomas, Laura D. K.
    et al.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Julin, Bettina
    Wolk, Alicja
    Akesson, Agneta
    Dietary Cadmium Exposure and Fracture Incidence Among Men: A Population-Based Prospective Cohort Study2011Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 26, nr 7, s. 1601-1608Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cadmium is an osteotoxic metal present in food. It causes multiple fractures in those highly exposed and is associated with reduced bone mineral density at considerably lower exposures. Little is known about fracture rates following low-level cadmium exposure. We assessed the associations between dietary cadmium exposure and fracture incidence. Within a population-based prospective cohort of 22,173 Swedish men, we estimated individual dietary cadmium exposure using food frequency questionnaire data and levels of cadmium in food. The average intake was 19 mu g/day. Hazard ratios (HRs) for any fracture and hip fracture were estimated using Cox's regression. During 10 years of follow-up, we ascertained 2183 cases of any fracture and 374 hip fractures by computerized linkage of the cohort to registry data. Multivariable-adjusted dietary cadmium intake was associated with a statistically significant 19% [HR= 1.19, 95% confidence interval (Cl) 1.06-1.34] higher rate of any fracture comparing highest tertile with lowest (p <= .01 for trend). Moreover, men in the highest tertile of dietary cadmium and lowest tertile of fruit and vegetable consumption had a 41% higher rate of any fracture compared with contrasting tertiles. Hip fracture rates also were,higher in the highest tertile of cadmium intake but only statistically significant among never smokers (HR = 1.70, 95% Cl 1.04-2.77). Our results indicate that dietary cadmium exposure at general population levels is associated with an increased rate of fractures among men. This association was independent of smoking and was most pronounced among men with low fruit and vegetable consumption.

  • 44. van Bezooijen, Rutger L.
    et al.
    Svensson, J. Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Eefting, Daniel
    Visser, Annemieke
    van der Horst, Geertje
    Karperien, Marcel
    Quax, Paul H. A.
    Vrieling, Harry
    Papapoulos, Socrates E.
    ten Dijke, Peter
    Löwik, Clemens W. G. M.
    Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation2007Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 22, nr 1, s. 19-28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that is required for BMP-stimulated osteoblastic differentiation. Introduction: Sclerostin is a member of the Dan family of glycoproteins of which many members have been reported to antagonize BMP activity. Sclerostin has been shown to inhibit BMP-stimulated bone formation, but its mechanism of action seems to be different from classical BMP antagonists. In this study, we investigated the mechanism by which sclerostin inhibits BMP-stimulated bone formation. Materials and Methods: DNA electroporation of calf muscle of mice using expression plasmids for BMP and sclerostin was used to study the effect of sclerostin on BMP-induced bone formation in vivo. Transcriptional profiling using microarrays of osteoblastic cells treated with BMP in the absence or presence of sclerostin was used to find specific growth factor signaling pathways affected by sclerostin. The affected pathways were further studied using growth factor-specific reporter constructs. Results: BMP-induced ectopic bone formation in calf muscle of mice was prevented by co-expression of sclerostin in vivo. Transcriptional profiling analysis of osteoblastic cultures indicated that sclerostin specifically affects BMP and Wnt signaling out of many other growth signaling pathways. Sclerostin, however, did not inhibit stimulation of direct BMP target genes. Furthermore, we did not obtain any evidence for sclerostin acting as a direct BMP antagonist using a BMP-specific reporter construct. In contrast, sclerostin shared many characteristics with the Wnt antagonist dickkopf-1 in antagonizing BMP-stimulated bone formation and BMP- and Wnt-induced Wnt reporter construct activation. Conclusions: Sclerostin inhibits BMP-stimulated bone formation but does not affect BMP signaling. Instead, it antagonizes Wnt signaling in osteoblastic cells. High bone mass in sclerosteosis and van Buchem disease may, therefore, result from increased Wnt signaling.

  • 45. Vandenput, Liesbeth
    et al.
    Labrie, Fernand
    Mellström, Dan
    Swanson, Charlotte
    Knutsson, Thomas
    Peeker, Ralph
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Orwoll, Eric
    Eriksson, Anna L
    Damber, Jan-Erik
    Ohlsson, Claes
    Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men2007Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 22, nr 2, s. 220-227Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Androgens are important regulators of bone and prostate health in elderly men. The role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in men is unclear. We show that specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men.Introduction: Androgens are important regulators of bone and prostate health in elderly men. Local synthesis and degradation of androgens are likely to be important parameters of biological action of androgens in androgen-responsive tissues. The aim of this study was to determine the role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in elderly men.Materials and Methods: A subsample of the population-based Swedish part of the MrOS study (n = 631, average age = 75.9 years) was investigated. Bone parameters were measured using DXA. Serum levels of total testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography/mass spectroscopy (GC-MS); androstane-3,17-diol-3glucuronide (3G) and androstane-3,17-diol-17glucuronide (17G) were measured by liquid chromatography/mass spectroscopy. Prostate volume (n = 159) was measured by transrectal ultrasound.Results: The general pattern is that two of the glucuronidated androgen metabolites, namely 17G and 3G, are stronger positive predictors of BMD than the bioactive androgens (T and DHT). In addition, 17G is a clear positive predictor of prostate volume, explaining 4.5% of the variance in prostate volume, whereas the bioactive androgens do not display any association with prostate volume.Conclusions: Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Future studies should determine if the glucuronidated androgen metabolites also reflect other biological correlates of androgenic activity, including prostate cancer, and if low levels might be a marker of general androgen deficiency in men.

  • 46.
    Vandenput, Liesbeth
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden..
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, Gothenburg, Sweden..
    Laughlin, Gail A.
    Univ Calif San Diego, Sch Med, Dept Family Med & Publ Hlth, Div Epidemiol, La Jolla, CA 92093 USA..
    Cawthon, Peggy M.
    Univ Calif San Francisco, Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA..
    Cauley, Jane A.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA..
    Hoffman, Andrew R.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Karlsson, Magnus K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden..
    Rosengren, Bjorn E.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden..
    Eriksson, Anna L.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden..
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, Gothenburg, Sweden..
    Leung, Jason
    Chinese Univ Hong Kong, Prince Wales Hosp, Jockey Club Ctr Osteoporosis Care & Control, Shatin, Hong Kong, Peoples R China..
    Kwok, Timothy
    Chinese Univ Hong Kong, Prince Wales Hosp, Jockey Club Ctr Osteoporosis Care & Control, Shatin, Hong Kong, Peoples R China..
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Dept Med, Bone & Mineral Unit, Portland, OR 97201 USA..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden..
    Low Testosterone, but Not Estradiol, Is Associated With Incident Falls in Older Men: The International MrOS Study2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr 6, s. 1174-1181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fracture risk is determined by bone strength and the risk of falls. The relationship between serum sex steroids and bone strength parameters in men is well known, whereas the predictive value of sex steroids for falls is less studied. The aim of this study was to assess the associations between serum testosterone (T) and estradiol (E2) and the likelihood of falls. Older men (aged > 65 years) from the United States (n = 1919), Sweden (n = 2495), and Hong Kong (n = 1469) participating in the Osteoporotic Fractures in Men Study had baseline T and E2 analyzed by mass spectrometry. Bioavailable (Bio) levels were calculated using mass action equations. Incident falls were ascertained every 4 months during a mean follow-up of 5.7 years. Associations between sex steroids and falls were estimated by generalized estimating equations. Fall rate was highest in the US and lowest in Hong Kong (US 0.50, Sweden 0.31, Hong Kong 0.12 fall reports/person/year). In the combined cohort of 5883 men, total T (odds ratio [OR] per SD increase = 0.88, 95% confidence interval [CI] 0.86-0.91) and BioT (OR = 0.86, 95% CI 0.83-0.88) were associated with incident falls in models adjusted for age and prevalent falls. These associations were only slightly attenuated after simultaneous adjustment for physical performance variables (total T: OR = 0.94, 95% CI 0.91-0.96; BioT: OR = 0.91, 95% CI 0.89-0.94). E2, BioE2, and sex hormone-binding globulin (SHBG) were not significantly associated with falls. Analyses in the individual cohorts showed that both total T and BioT were associated with falls in MrOS US and Sweden. No association was found in MrOS Hong Kong, and this may be attributable to environmental factors rather than ethnic differences because total T and BioT predicted falls in MrOS US Asians. In conclusion, low total T and BioT levels, but not E2 or SHBG, are associated with increased falls in older men.

  • 47. Vandenput, Liesbeth
    et al.
    Mellström, Dan
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Johansson, Helena
    Lorentzon, Mattias
    Leung, Jason
    Redlund-Johnell, Inga
    Rosengren, Björn E
    Karlsson, Magnus K
    Wang, Yi-Xiang
    Kwok, Timothy
    Ohlsson, Claes
    High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men.2016Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, nr 3, s. 683-689Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone-binding globulin (SHBG) associate with non-vertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the MrOS study had baseline estradiol and testosterone analyzed by GC-MS and SHBG by IRMA. Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow-up of 9.1 years. In a subsample of these men (n = 2256), spine X-rays were obtained at baseline and after an average follow-up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (HR per SD increase, 95% CI: 0.93, 0.80-1.08) nor testosterone (1.05, 0.91-1.21) predicted incident clinical vertebral fractures in age-adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12-1.37). This association remained significant after further adjustment for FRAX with or without BMD. SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; OR per SD increase, 95% CI: 1.23, 1.05-1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction.

  • 48.
    Vandenput, Liesbeth
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Inst Med,Ctr Bone & Arthrit Res, Gothenburg, Sweden.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Inst Med,Ctr Bone & Arthrit Res, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthopaed, Lund, Sweden.
    Rosengren, Bjorn
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthopaed, Lund, Sweden.
    Ribom, Eva L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Geriatr Med, Gothenburg, Sweden.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Inst Med,Ctr Bone & Arthrit Res, Gothenburg, Sweden.
    Serum DHEA and its Sulfate Are Associated with Incident Fall Risk in Older Men - the MrOS Sweden Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, s. 310-310Artikel i tidskrift (Övrigt vetenskapligt)
  • 49. Wilson, Scott G.
    et al.
    Jones, Michelle R.
    Mullin, Ben H.
    Dick, Ian M.
    Richards, J. Brent
    Pastinen, Tomi M.
    Grundberg, Elin
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Surdulescu, Gabriela L.
    Dudbridge, Frank
    Elliott, Katherine S.
    Cervino, Alessandra C. L.
    Spector, Timothy D.
    Prince, Richard L.
    Common sequence variation in FLNB regulates bone structure in women in the general population and FLNB mRNA expression in osteoblasts in vitro2009Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 24, nr 12, s. 1989-1997Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous data from our group indicate that BMD is linked to chromosome 3p14-p21. Because the filamin B (FLNB gene resides in this region, is the cause of skeletal dysplasias, and was identified among the top genes in our bioinformatics analysis, we hypothesized a role for FLNB in the regulation of bone structure in the general population. Using a tag single nucleotide polymorphism (SNP) approach, a family study of 767 female sibs in which the 3p14-p21 linkage with BMD was previously shown was examined. FLNB variants showing a BMD association were tested in two additional data sets, a study of 1085 UK female twins and a population study (CAIFOS) of 1315 Australian women. Genotype-expression studies were performed in 96 human osteoblast lines to examine the variants in vitro. rs7637505, rs9822918, rs2177153, and rs2001972 showed association with femoral neck (p = 0.0002-0.02) in the family-based study. The twin study provided further support for an association between rs7637505 and femoral neck and spine BMD (p = 0.02-0.03). The CAIFOS study further suggested an association between rs2177153 and rs9822918 and femoral neck BMD (p = 0.004-0.03). Prevalent fractures were increased in carriers of the A allele of rs2177153 (p = 0.009). In vitro studies showed association between rs11130605, itself in strong LD with rs7637505, and FLNB mRNA expression. These findings suggest common variants in FLNB have effects on bone structure in women. Although the location of variants having effects is not entirely consistent, variation at the 5' end of the gene may reflect effects on levels of FLNB transcription efficiency.

  • 50.
    Xie, Meng
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm.
    Gol'din, Pavel
    Stockholm Univ, Stockholm.
    Estsfa, Jordi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi.
    Li, Lei
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm.
    Arregui, Irene Linares
    KTH, Dept Solid Mech, Stockholm.
    Gasser, Christian
    KTH, Dept Solid Mech, Stockholm.
    Medvedeva, Ekaterina
    Sechenov Med Univ, Moscow.
    Svetlana, Kotova
    Sechenov Med Univ, Moscow.
    Timashev, Peter
    Sechenov Med Univ, Moscow.
    Adameyko, Igor
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm.
    Eriksson, Anders
    KTH, Dept Mech, Stockholm.
    Sanchez, Sophie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Chagin, Andrei
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm.
    Evolutional Separation of Epiphyseal and Articular Cartilage is a Bone Adaptation to Terrestrial Growth.2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr S1, s. S328-S328, artikel-id Meeting Abstract: MO0490Artikel i tidskrift (Övrigt vetenskapligt)
12 1 - 50 av 51
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf