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1.
  • Gyllenberg, A, et al. (författare)
  • Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
  • 2012
  • Ingår i: Genes and Immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 76:2, s. 202-203
  • Tidskriftsartikel (refereegranskat)abstract
    • The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
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2.
  • Rydell, Emil, et al. (författare)
  • Predictors of radiographic erosion and joint space narrowing progression in patients with early rheumatoid arthritis: a cohort study
  • 2021
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Radiographic damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Different mechanisms may underlie their development. The objective of this study was to evaluate predictors of these entities separately. Methods Consecutive early RA patients (symptom duration <= 12 months) from a defined area (Malmo, Sweden) recruited during 1995-2005 were investigated. Radiographs of hands and feet were scored by a trained reader according to the modified Sharp-van der Heijde score. Fat mass and lean mass distribution were measured at baseline using dual energy x-ray absorptiometry. Potential predictors of erosion and JSN progression from inclusion to the 5-year follow-up were evaluated. Results Two hundred and thirty-three patients were included. Radiographs at baseline and 5 years were available for 162 patients. The median (interquartile) progression of erosion and JSN scores were 4 (0-8) and 8 (1-16), respectively. Rheumatoid factor (RF) was a robust significant predictor of both erosion and JSN score progression. In adjusted analyses, anti-CCP antibodies predicted erosions while the erythrocyte sedimentation rate was predictive of both outcomes. Smoking and high baseline disease activity (DAS28 > 5.1) predicted progression of erosions. Baseline erosion score was associated with progression of both erosion and JSN progression, while baseline JSN score was predictive only of the progression of JSN. Overweight/obesity (BMI >= 25 kg/m(2)) was a significant negative predictor of JSN score progression (beta = - 0.14, p = 0.018, adjusted for RF, age, baseline JSN score) also when additionally adjusting for ever smoking (p = 0.041). Among female patients, this effect was observed in those of estimated post-menopausal age (> 51 years), but not in younger women. The truncal to peripheral fat ratio was associated with less JSN score progression in women, but not in men. Conclusions Overweight RA patients had less JSN progression, independent of smoking status. This effect was seen in particular among older women (mainly post-menopausal), but not younger. Truncal fat was associated with less JSN progression in female patients. Smoking predicted erosion progression, and erosions may precede JSN. BMI and fat distribution may influence cartilage damage in early RA and might be related to hormonal factors.
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3.
  • Amkreutz, J. A. M. P., et al. (författare)
  • Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis
  • 2021
  • Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 73:6, s. 921-930
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Autoantibodies, such as anti–citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. Methods: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. Results: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm2 (95% confidence interval [95% CI] 0.91–0.93) versus 0.95 g/cm2 (95% CI 0.93–0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08–0.29] versus 0.48 [95% CI 0.33–0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti–carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. Conclusion: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed. © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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5.
  • Banefelt, Jonas, et al. (författare)
  • Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting
  • 2022
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 37:1, s. 52-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9–6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5–9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score −1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (−3.0 to –0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD–fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis.
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6.
  • Berggren, Lars, et al. (författare)
  • Studiemedel för studiero
  • 2014
  • Ingår i: Helsingborgs Dagblad. - 1103-9388.
  • Tidskriftsartikel (populärvet., debatt m.m.)
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7.
  • Berglundh, Sofia, et al. (författare)
  • C-reactive protein, bone loss, fracture, and mortality in elderly women: a longitudinal study in the OPRA cohort.
  • 2015
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 26:2, s. 727-735
  • Tidskriftsartikel (refereegranskat)abstract
    • This longitudinal study investigates the association between C-reactive protein (CRP), osteoporosis, fractures, and mortality in 1044 elderly women. CRP was not an indicator for low bone mineral density (BMD), bone loss, or fracture in elderly women; however, women with elevated CRP levels over a prolonged period lost more bone over the 10-year follow-up, although fracture risk was not increased.
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8.
  • Bobjer, Johannes, et al. (författare)
  • High Prevalence of Hypogonadism and Associated Impaired Metabolic and Bone Mineral Status in Subfertile Men.
  • 2016
  • Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 85:2, s. 189-195
  • Tidskriftsartikel (refereegranskat)abstract
    • It is yet unknown to which degree young subfertile men present with signs of hypogonadism and whether low testosterone concentration, like in older men, is associated with risk of osteoporosis and metabolic derangements in those subjects. The objective was, therefore, to investigate the prevalence of hypogonadism and its association with metabolic and bone parameters in young subfertile men.
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9.
  • Book, Christina, et al. (författare)
  • Changes in body composition after 2 years with rheumatoid arthritis
  • 2011
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 40:2, s. 95-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Rheumatoid arthritis (RA) is associated with cardiovascular disease (CVD). Possible predictors for CVD are early changes in body composition. We therefore evaluated changes in lean body mass (LBM), lean mass of arms and legs (LMAL), total body fat mass (BFM), and truncal fat distribution (FD) after 2 years with RA and possible predictors. Methods: We registered 63 (45 women) RA patients with disease duration of <= 12 months at baseline and after 2 years. Disease Activity Score using 28 joint counts (DAS28), Health Assessment Questionnaire (HAQ) score, body mass index (BMI), comorbidities, smoking, and medications were recorded. Total and regional lean mass and fat mass were measured with dual energy X-ray absorptiometry (DXA). The data were compared with 63 age- and gender-matched controls. Results: LBM and LMAL at baseline in RA patients were significantly lower in men (p = 0.020 and 0.002, respectively) compared to matched controls. Truncal FD was non-significantly increased in RA patients (women p = 0.133, men p = 0.119). The age-related deterioration with decreased LBM after 2 years (p = 0.002 in women and men) and increased BFM (p < 0.001) and truncal FD (p = 0.020) in women were all significantly less pronounced in RA patients than in matched controls. Conclusions: In patients with early RA and after initiation of therapy, the age-related deterioration with decreasing LBM and increasing truncal FD was lower than in control subjects in this observational study. These potentially harmful alterations seem to be modifiable factors in patients with early RA.
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10.
  • Book, Christina, et al. (författare)
  • Disease activity and disability but probably not glucocorticoid treatment predicts loss in bone mineral density in women with early rheumatoid arthritis
  • 2008
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 37:4, s. 248-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Osteoporosis is a known complication of rheumatoid arthritis (RA). This prospective study aimed to evaluate whether disease activity, disability, and glucocorticoid (GC) treatment in early RA were risk factors for loss of bone mineral density (BMD). Methods: We followed 97 women (mean age 58 years), for 24 months, with a history of RA of less than 12 months. At baseline, 77 women were receiving standard treatment with disease-modifying antirheumatic drugs (DMARDs) and 20 were receiving no treatment. Risk factors for osteoporosis were recorded. Disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, and medications were registered at baseline and every 6 months and calculated as areas under the curve (AUCs). Femoral neck and lumbar spine BMD were measured at baseline and after 2 years and compared to BMD in age- and gender-matched controls. Risk factors were analysed by linear regression models. Results: BMD loss was comparable to that of age-matched women in both the lumbar spine and the femoral neck, although neither was significantly different from baseline. In multivariate analyses the AUC for DAS28 was an independent predictor of changes in lumbar spine BMD (p=0.003) and that for HAQ of changes in femoral neck BMD (p=0.018). GC use was not an overall predictor of BMD loss. Conclusion: BMD loss was predicted by high disease activity and disability but not by GC treatment. With the DMARD, GC, hormone replacement therapy (HRT), and bisphosphonate treatment strategies used during the study period, the general outcome seems favourable concerning loss of BMD in patients with early RA.
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11.
  • Book, Christina, et al. (författare)
  • Early rheumatoid arthritis and body composition.
  • 2009
  • Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 48, s. 1128-1132
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. RA is associated with joint destruction and cardiovascular diseases (CVDs). Possible predictors for CVD are early changes in body composition. We therefore evaluated whether lean mass of arms and legs (LMAL), total body fat mass (BFM) or truncal fat distribution (TFD) are altered early in RA, and if so, which factors are associated. Methods. We included 132 RA patients (95 women) with disease duration of
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12.
  • Boonen, S., et al. (författare)
  • Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures
  • 2011
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 22:12, s. 2915-2934
  • Forskningsöversikt (refereegranskat)abstract
    • Vertebral compression fractures (VCFs) are the most prevalent fractures in osteoporotic patients. The classical conservative management of these fractures is through rest, pain medication, bracing and muscle relaxants. The aim of this paper is to review prospective controlled studies comparing the efficacy and safety of minimally invasive techniques for vertebral augmentation, vertebroplasty (VP) and balloon kyphoplasty (BKP), versus non-surgical management (NSM). The Fracture Working Group of the International Osteoporosis Foundation conducted a literature search and developed a review paper on VP and BKP. The results presented for the direct management of osteoporotic VCFs focused on clinical outcomes of these three different procedures, including reduction in pain, improvement of function and mobility, vertebral height restoration and decrease in spinal curvature (kyphosis). Overall, VP and BKP are generally safe procedures that provide quicker pain relief, mobility recovery and in some cases vertebral height restoration than conventional conservative medical treatment, at least in the short term. However, the long-term benefits and safety in terms of risk of subsequent vertebral fractures have not been clearly demonstrated and further prospective randomized studies are needed with standards for reporting. Referral physicians should be aware of VP/BKP and their potential to reduce the health impairment of patients with VCFs. However, VP and BKP are not substitutes for appropriate evaluation and treatment of osteoporosis to reduce the risk of future fractures.
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13.
  • Borgstrom, F., et al. (författare)
  • Health economic aspects of vertebral augmentation procedures
  • 2015
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 26:4, s. 1239-1249
  • Forskningsöversikt (refereegranskat)abstract
    • We reviewed all peer-reviewed papers analysing the cost-effectiveness of vertebroplasty and balloon kyphoplasty for osteoporotic vertebral compression fractures. In general, the procedures appear to be cost effective but are very dependent upon model input details. Better data, rather than new models, are needed to answer outstanding questions. Vertebral augmentation procedures (VAPs), including vertebroplasty (VP) and balloon kyphoplasty (BKP), seek to stabilise fractured vertebral bodies and reduce pain. The aim of this paper is to review current literature on the cost-effectiveness of VAPs as well as to discuss the challenges for economic evaluation in this research area. A systematic literature search was conducted to identify existing published studies on the cost-effectiveness of VAPs in patients with osteoporosis. Only peer-reviewed published articles that fulfilled the criteria of being regarded as full economic evaluations including both morbidity and mortality in the outcome measure in the form of quality-adjusted life years (QALYs) were included. The search identified 949 studies, of which four (0.4 %) were identified as relevant with one study added later. The reviewed studies differed widely in terms of study design, modelling framework and data used, yielding different results and conclusions regarding the cost-effectiveness of VAPs. Three out of five studies indicated in the base case results that VAPs were cost effective compared to non-surgical management (NSM). The five main factors that drove the variations in the cost-effectiveness between the studies were time horizon, quality of life effect of treatment, offset time of the treatment effect, reduced number of bed days associated with VAPs and mortality benefit with treatment. The cost-effectiveness of VAPs is uncertain. In answering the remaining questions, new cost-effectiveness analysis will yield limited benefit. Rather, studies that can reduce the uncertainty in the underlying data, especially regarding the long-term clinical outcomes of VAPs, should be conducted.
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14.
  • Briggs, Andrew M., et al. (författare)
  • Global health policy in the 21st century : Challenges and opportunities to arrest the global disability burden from musculoskeletal health conditions
  • 2020
  • Ingår i: Best Practice and Research: Clinical Rheumatology. - : Elsevier BV. - 1521-6942. ; 34:5
  • Forskningsöversikt (refereegranskat)abstract
    • The profound burden of disease associated with musculoskeletal health conditions is well established. Despite the unequivocal disability burden and personal and societal consequences, relative to other non-communicable diseases (NCDs), system-level responses for musculoskeletal conditions that are commensurate with their burden have been lacking nationally and globally. Health policy priorities and responses in the 21st century have evolved significantly from the 20th century, with health systems now challenged by an increasing prevalence and impact of NCDs and an unprecedented rate of global population ageing. Further, health policy priorities are now strongly aligned to the 2030 Sustainable Development Goals. With this background, what are the challenges and opportunities available to influence global health policy to support high-value care for musculoskeletal health conditions and persistent pain? This paper explores these issues by considering the current global health policy landscape, the role of global health networks, and progress and opportunities since the 2000–2010 Bone and Joint Decade for health policy to support improved musculoskeletal health and high-value musculoskeletal health care.
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17.
  • Bruyere, O., et al. (författare)
  • Post-fracture management of patients with hip fracture: a perspective
  • 2008
  • Ingår i: CURRENT MEDICAL RESEARCH AND OPINION. - : Informa Healthcare. - 0300-7995 .- 1473-4877. ; 24:10, s. 2841-2851
  • Konferensbidrag (refereegranskat)abstract
    • Background: Hip fracture creates a worldwide morbidity, mortality and economic burden. After surgery, many patients experience long-term disability or die as a consequence of the fracture. A fracture is a major risk factor for a subsequent fracture, which may occur within a short interval. Methods: A literature search on post-fracture management of patients with hip fracture was performed on the Medline database. Key experts convened to develop a consensus document. Findings: Management of hip-fracture patients to optimize outcome after hospital discharge requires several stages of care co-ordinated by a multidisciplinary team from before admission through to discharge. Further studies that specifically assess prevention and post-fracture management of hip fracture are needed, as only one study to date has assessed an osteoporosis medication in patients with a recent hip fracture. Proper nutrition is vital to assist bone repair and prevent further falls, particularly in malnourished patients. Vitamin D, calcium and protein supplementation is associated with an increase in hip BMD and reduction in falls. Rehabilitation is essential to improve functional disabilities and survival rates. Fall prevention and functional recovery strategies should include patient education and training to improve balance and increase muscle strength and mobility. Appropriate management can prevent further fractures and it is critical that high-risk patients are identified and treated. To foster this process, clinical pathways have been established to support orthopaedic surgeons. Conclusion: Although hip fracture is generally associated with poor outcomes, appropriate management can ensure optimal recovery and survival, and should be prioritized after a hip fracture to avoid deterioration of health and prevent subsequent fracture.
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18.
  • Brändström, Helena, et al. (författare)
  • Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women
  • 2004
  • Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:1, s. 18-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50-0.64, C1217T P = 0.51-1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61-0.66, C1217T P = 0.14-0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.
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19.
  • Buchebner, David, et al. (författare)
  • Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality
  • 2017
  • Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 1:6, s. 615-624
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear.Objective: To describe normal PTH profiles over time and the association with mortality.Design and Participants: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years).Main Outcome Measures: PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality.Results: At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082).Conclusions: Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.
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21.
  • Callréus, Mattias, et al. (författare)
  • Adverse Effects of Smoking on Peak Bone Mass May Be Attenuated by Higher Body Mass Index in Young Female Smokers.
  • 2013
  • Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 93:6, s. 517-525
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking is associated with postmenopausal bone loss and fracture, but the effect of smoking on bone in younger women is unclear. Peak bone mass is an important determinant for fracture risk; therefore, our aim was to evaluate the association between smoking and bone mass in 25-year-old women, specifically the influence of daily cigarette consumption and total exposure, duration, age at starting smoking, and time since smoking cessation on bone density and fracture risk. Smoking and bone mineral density (BMD) data were available for 1,054 women from the PEAK-25 cohort. Analyses comparing current smokers with women who never smoked were performed using number of cigarettes per day, pack-years, smoking duration, age smoking started, and, for former smokers, age at quitting. BMD did not differ between never, former, and current smokers; and the relative fracture risk in smokers was not significant (relative risk [RR] = 1.2, 95 % confidence interval 0.8-1.9). Among current smokers, BMD decreased with a dose response as cigarette consumption increased (femoral neck p = 0.037). BMD was not significantly lower in young women who had smoked for long duration or started smoking early (p = 0.07-0.64); long duration and early start were associated with higher body mass index (BMI; p = 0.038). Lower BMD persisted up to 24 months after smoking cessation (p = 0.027-0.050), becoming comparable to never-smokers after 24 months. Hip BMD was negatively associated with smoking and dose-dependent on cigarette consumption. Smoking duration was not associated with BMD, although young women with a long smoking history had higher BMI, which might attenuate the adverse effects from smoking.
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22.
  • Callréus, Mattias, et al. (författare)
  • Birth weight is more important for peak bone mineral content than for bone density: the PEAK-25 study of 1,061 young adult women.
  • 2013
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 24:4, s. 1347-1355
  • Tidskriftsartikel (refereegranskat)abstract
    • Lower birth weight has a negative association with adult BMC and body composition in young adult Swedish women. INTRODUCTION: The aim of this study was to evaluate the influence of birth weight on peak bone mass and body composition in a cohort of 25-year-old women. METHODS: One thousand sixty-one women participated in this cross-sectional population-based study using dual energy X-ray absorptiometry (DXA) to assess bone mineral content (BMC), bone mineral density (BMD), and body composition (total body (TB), femoral neck (FN), total hip (TH), lumbar spine L1-L4 (LS), and lean and fat mass). Birth weight data was available for 1,047 women and was categorized into tertiles of low (≤3,180 g), intermediate (3,181-3,620 g), and high (≥3,621 g) birth weight. RESULTS: Significant correlations were observed between birth weight and TB-BMC (r = 0.159, p < 0.001), FN-BMC (r = 0.096, p < 0.001), TH-BMC (r = 0.102, p = 0.001), LS-BMC (r = 0.095, p = 0.002), and lean mass (r = 0.215, p < 0.001). No correlation was observed between birth weight and BMD. The estimated magnitude of effect was equivalent to a 0.3-0.5 SD difference in BMC for every 1 kg difference in birth weight (151 g (TB); 0.22 g (FN); 1.5 g (TH), 2.5 kg TB lean mass). The strongest correlations between birth weight and BMC occurred in women with lowest birth weights, although excluding women who weighed <2,500 g at birth, and the correlation remained significant although slightly weaker. CONCLUSIONS: Women with lower birth weight have lower BMC and less lean and fat mass at the age of 25, independent of current body weight. Lower birth weight has a greater negative influence on bone mass than the positive influence of higher birth weight.
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23.
  • Callréus, Mattias, et al. (författare)
  • Country-Specific Young Adult Dual-Energy X-Ray Absorptiometry Reference Data Are Warranted for T-Score Calculations in Women: Data From the Peak-25 Cohort.
  • 2014
  • Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 17:1, s. 129-135
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims of this study were to provide normative data for dual-energy X-ray absorptiometry (DXA) in 25-yr-old women and evaluate whether young adult Swedish women have bone mineral density (BMD) comparable with DXA manufacturer reference values and other equivalent populations. BMD at all sites was measured in the population-based Peak-25 cohort (n = 1061 women; age, 25.5 ± 0.2yr). BMD values were standardized (sBMD) and compared against the Third National Health and Nutrition Examination Survey (NHANES III) and other cohorts. Based on the DXA manufacturer-supplied reference values, Z-scores were 0.54 ± 0.98 (femoral neck [FN]), 0.47 ± 0.96 (total hip [TH]), and 0.32 ± 1.03 (lumbar spine [LS]). In comparison with other studies, sBMD was higher in the Peak-25 cohort (FN, 1.5%-8.3%; TH, 3.9%-9.2%; and LS, 2.4%-6.5%) with the exception of trochanter-sBMD which was 2.5% lower compared with NHANES III. The concordance in identifying those in the lowest or highest quartile of BMD was highest between hip measurements (low, 71%-78% and high, 70%-84%), corresponding discordance of 0%-1%. At this age, the correlation between DXA sites was strong (r = 0.62-0.94). BMD in Swedish young adult women is generally higher than has been reported in other equivalently aged European and North American cohorts and suggests that the high fracture incidence in Sweden is not explained by lower peak bone mass. The use of nonregional-specific DXA reference data could contribute to misdiagnosed osteoporosis in elderly women.
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24.
  • Callréus, Mattias, et al. (författare)
  • Self-reported recreational exercise combining regularity and impact is necessary to maximize bone mineral density in young adult women : A population-based study of 1,061 women 25 years of age.
  • 2012
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 23:10, s. 2517-2526
  • Tidskriftsartikel (refereegranskat)abstract
    • Recreational physical activity in 25-year-old women in Sweden increases bone mineral density (BMD) in the trochanter by 5.5% when combining regularity and impact. Jogging and spinning were especially beneficial for hip BMD (6.4-8.5%). Women who enjoyed physical education in school maintained their higher activity level at age 25. INTRODUCTION: The aims of this study were to evaluate the effects of recreational exercise on BMD and describe how exercise patterns change with time in a normal population of young adult women. METHODS: In a population-based study of 1,061 women, age 25 (±0.2), BMD was measured at total body (TB-BMD), femoral neck (FN-BMD), trochanter (TR-BMD), and spine (LS-BMD). Self-reported physical activity status was assessed by questionnaire. Regularity of exercise was expressed as recreational activity level (RAL) and impact load as peak strain score (PSS). A permutation (COMB-RP) was used to evaluate combined endurance and impacts on bone mass. RESULTS: More than half of the women reported exercising on a regular basis and the most common activities were running, strength training, aerobics, and spinning. Seventy percent participated in at least one activity during the year. Women with high RAL or PSS had higher BMD in the hip (2.6-3.5%) and spine (1.5-2.1%), with the greatest differences resulting from PSS (p < 0.001-0.02). Combined regularity and impact (high-COMB-RP) conferred the greatest gains in BMD (FN 4.7%, TR 5.5%, LS 3.1%; p < 0.001) despite concomitant lower body weight. Jogging and spinning were particularly beneficial for hip BMD (+6.4-8.5%). Women with high-COMB-RP scores enjoyed physical education in school more and maintained higher activity levels throughout compared to those with low scores. CONCLUSION: Self-reported recreational levels of physical activity positively influence BMD in young adult women but to maximize BMD gains, regular, high-impact exercise is required. Enjoyment of exercise contributes to regularity of exercising which has short- and long-term implications for bone health.
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25.
  • Carry, Patrick M., et al. (författare)
  • Severity of idiopathic scoliosis is associated with differential methylation : An epigenome‐wide association study of monozygotic twins with idiopathic scoliosis
  • 2021
  • Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 12:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigenetic mechanisms may contribute to idiopathic scoliosis (IS). We identified 8 monozygotic twin pairs with IS, 6 discordant (Cobb angle difference >10°) and 2 concordant (Cobb angle difference ≤2°). Genome‐wide methylation in blood was measured with the Infinium HumanMethylation EPIC Beadchip. We tested for differences in methylation and methylation variability between discordant twins and tested the association between methylation and curve severity in all twins. Differentially methylated region (DMR) analyses identified gene promoter regions. Methylation at cg12959265 (chr. 7 DPY19L1) was less variable in cases (false discovery rate (FDR) = 0.0791). We identified four probes (false discovery rate, FDR < 0.10); cg02477677 (chr. 17, RARA gene), cg12922161 (chr. 2 LOC150622 gene), cg08826461 (chr. 2), and cg16382077 (chr. 7) associated with curve severity. We identified 57 DMRs where hyper‐ or hypo‐methylation was consistent across the region and 28 DMRs with a consistent association with curve severity. Among DMRs, 21 were correlated with bone methylation. Prioritization of regions based on methylation concordance in bone identified promoter regions for WNT10A (WNT signaling), NPY (regulator of bone and energy homeostasis), and others predicted to be relevant for bone formation/remodeling. These regions may aid in understanding the complex interplay between genetics, environment, and IS.
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26.
  • Chandran, Manju, et al. (författare)
  • Secondary Fracture Prevention: Plucking The Low Hanging Fruit
  • 2013
  • Ingår i: Annals of the Academy of Medicine, Singapore. - 0304-4602. ; 42:10, s. 541-544
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • It is well known that one fragility fracture begets another. Fracture Liaison Services have been shown to narrow the care gap that exists in the care of patients with fragility fractures. A secondary fracture prevention programme "OPTIMAL" (Osteoporosis Patient Targeted and Integrated Management for Active Living) has been in existence in the public restructured hospitals and polyclinics of Singapore since 2008 and this is beginning to show significant beneficial results in terms of identification and management of fragility fractures. However, significant obstacles in the path of appropriate management of the patient with a fragility fracture still exist. A concerted, multipronged and interdisciplinary approach is needed to overcome these barriers.
  •  
27.
  • Conley, R. B., et al. (författare)
  • Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition
  • 2020
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:1, s. 36-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
  •  
28.
  • Conley, Robert B., et al. (författare)
  • Secondary Fracture Prevention : Consensus Clinical Recommendations from a Multistakeholder Coalition
  • 2020
  • Ingår i: Journal of Orthopaedic Trauma. - 0890-5339. ; 34:4, s. 125-141
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).
  •  
29.
  • Conley, Robert B., et al. (författare)
  • Secondary Fracture Prevention : Consensus Clinical Recommendations from a Multistakeholder Coalition
  • 2020
  • Ingår i: Orthopaedic Nursing. - 0744-6020. ; 39:3, s. 145-161
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk offuture fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the riskfor second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring foradverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
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30.
  • Ebeling, P, et al. (författare)
  • Role of biochemical markers in the management of osteoporosis
  • 2001
  • Ingår i: Best Practice & Research: Clinical Rheumatology. - : Elsevier BV. - 1532-1770 .- 1521-6942. ; 15:3, s. 385-400
  • Tidskriftsartikel (refereegranskat)abstract
    • Several serum and urine biochemical markers of bone resorption and formation have been developed. Biochemical bone markers have been used as intermediate end-points in all major studies of anti-osteoporotic therapies. Bone resorption markers, in particular, may add an independent, predictive value to the assessment of bone loss and fracture risk. There are also potential advantages in monitoring anti-osteoporotic treatment in the short-term in addition to bone densitometry, to rapidly identify non-responders to therapy, or non-compliance. Despite these recent advances, until now bone markers have simply been very useful research tools, with their clinical utility being limited by intra-individual and diurnal variability. However, the probability of the true bone mineral density response to hormone replacement therapy for the individual patient may be predicted using algorithms based on a spectrum of cut-off bone marker levels with varying false positive and negative rates. Thus, the transition of biochemical bone markers into everyday clinical practice may be rapidly approaching.
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31.
  • Egund, Lisa, et al. (författare)
  • Disability and Pain are the Best Predictors of Sick Leave After a Distal Radius Fracture in Men
  • 2020
  • Ingår i: Journal of Occupational Rehabilitation. - : Springer Science and Business Media LLC. - 1053-0487 .- 1573-3688. ; 30:4, s. 656-664
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Distal radius fracture often compromises working ability, but clinical implications are less studied in men due to its lower incidence. This study therefore describes sick leave in men with distal radius fracture, specifically exploring the impact of patient- and fracture-related factors. Methods Professionally active men aged 20–65 with distal radius fracture were followed prospectively for 1-year (n = 88). Data included treatment method, radiographic parameters pre/post treatment, complications, health, lifestyle and occupational demand. Patient outcomes were self-reported sick leave; Disability of the Arm, Shoulder and Hand (DASH) score; pain (5 likert scale); SF-36: Physical Component Scale (PCS) and Mental Component Scale (MCS). Results Median sick leave was 4 weeks (IQR 0; 8); almost a third reported taking no sick leave. Categorizing sick leave into 3 groups (0–6, 7–12 and > 12 weeks), men with the longest sick leave had 22 points higher DASH score (p = 0.001) and 5 points lower PCS (p = 0.02) at 1 week and the difference remained over time; they were also older and more often treated surgically. The strongest predictors of length of sick leave were one-week post-fracture DASH score (rs = 0.4, p < 0.001), pain intensity (rs = 0.4, p < 0.001) and PCS (rs = − 0.4, p = 0.002). The correlation between sick leave and pain was even stronger analyzing treatment groups separately (closed reduction and cast rs = 0.56, p = 0.007, surgery rs = 0.42, p = 0.04). Conclusions Self-reported disability, pain and global health measurements as early as 1 week post-fracture are the strongest predictors of length of sick leave regardless of treatment; an important finding easily transferrable to clinical management of distal radius fractures.
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32.
  • Egund, Lisa, et al. (författare)
  • High Luteinizing Hormone and Lower Levels of Sex Hormones in Younger Men With Distal Radius Fracture
  • 2020
  • Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 4:11
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates the sex steroid hormone profile in younger men with distal radius fracture (DRF) to elucidate if this could explain the low bone density and osteoporosis previously observed. In a case–control study, 73 men with DRF (mean age 38 ± 9 years; range, 20–51) was compared with 194 age-matched, population controls. Performed assays: total testosterone (TT), calculated free testosterone (cFT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and total estradiol (E2). BMD hip and spine were measured. Fracture cases had lower cFT (298 versus 329 pmol/L; p = 0.008), but not TT, compared with controls. FSH and SHBG were not statistically different. LH was almost 30% higher (5.7 versus 4.5 IU/L; p < 0.001) and a lower E2 was observed (80.0 versus 87.1; p = 0.098). Men with DRF had a lower E2/SHBG ratio compared with controls (2.3 versus 2.9; p = 0.013). A higher proportion of the fracture group had low TT (<10.5 nmol/L; 21% versus 11%; p = 0.052), low cFT (<220 pmol/L; 18% versus 8%; p = 0.017), and low E2 (<73 pmol/L; 48% versus 35%; p = 0.044). Odds ratio (OR) for fracture when having low cFT was 2.3 (95% CI, 1.02–5.49; p = 0.044); with low E2, the OR was 1.7 (95% CI, 0.96–2.96). In this study in young men with DRF exploring sex hormone levels, we find that sex hormone profiles may be disturbed with a lower E2/SHBG ratio, lower cFT, and higher LH. Estrogen is also a strong determinant of bone mass in men; hence, low levels of E2 may be contributing to the observed lower BMD and these differences may be relevant to fracture risk.
  •  
33.
  • Egund, Lisa, et al. (författare)
  • Patient-related outcome, fracture displacement and bone mineral density following distal radius fracture in young and older men
  • 2020
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Distal radius fractures can adversely affect wrist function; for men with this fracture, the role played by fracture severity, age and osteoporosis on fracture outcome has not been sufficiently studied. Objective: To describe patient-reported outcome and the association with bone integrity, fracture severity and future fracture risk among young and older men with distal radius fracture. Methods: This prospective study includes 133 men with acute distal radius fracture, mean age 54 (range 21–88), who were followed for 12 months. They were categorized as younger (< 65) and older (65+). Main outcome was DASH (Disability of the Arm, Shoulder and Hand) at 12 months; DASH > 15 was defined as poor outcome. Fractures were classified and radiographic displacement identified at initial presentation and follow-up. BMD was measured and FRAX 10-year probability of fracture calculated. Results: Disability was higher in older men (DASHmedian 10 vs 2; p = 0.002); a clinically meaningful difference (ΔDASH = 10, p = 0.017) remained after adjustment for displacement, fracture classification and treatment method. Almost 50% of older men vs 14% in younger had poor outcome, p < 0.001. Bone mineral density did not independently predict outcome. Older men with a displaced fracture at initial presentation had greater disability (DASHmedian, IQR 45, 14;73) and risk of fracture (FRAXmajor osteoporotic 14, 8;21). Conclusion: Men over the age of 65 with a distal radius fracture are more likely to have post-fracture disability regardless of radiographic appearance. Fracture displacement, indicating impaired bone strength, is also more common and associated with an increased risk of fracture within 10-years. Secondary fracture prevention should therefore be considered in men presenting with distal radius fracture.
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34.
  • Einarsdottir, E., et al. (författare)
  • CELSR2 is a candidate susceptibility gene in idiopathic scoliosis
  • 2017
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c. G6859A change in exon 21 (NM_001408), leading to a predicted p. V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.
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35.
  • Garg, Gaurav, et al. (författare)
  • Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women.
  • 2014
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis is characterized by reduced bone mineral density (BMD) and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs) with body composition, BMD, Ultrasound (QUS), fracture and biomarkers (Homocysteine (Hcy), folate, Vitamin D and Vitamin B12) for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R); rs7566605 (insulin induced gene 2 (INSIG2); rs9939609 and rs1121980 (fat mass and obesity associated (FTO) were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n = 1061) and OPRA (age 75, n = 1044). Body mass index (BMI), total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r(2) = 0.2-0.6). MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs.
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36.
  • Gerdhem, Paul, et al. (författare)
  • Accelerometer-measured daily physical activity among octogenerians: results and associations to other indices of physical performance and bone density
  • 2008
  • Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 102:2, s. 173-180
  • Tidskriftsartikel (refereegranskat)abstract
    • Information on objectively assessed physical activity in elderly people is scarce. The aim of this study was to investigate accelerometer measures in elderly women, and its relation to other indices of physical activity and bone density. A subset of 57 women, all 80 years old, (range 80.0-80.7) of the Malmo OPRA study was equipped with an MTI accelerometer for a period of 5-7 days. A 7-day activity log was used. At baseline a self-assessment questionnaire was used and isometric muscle strength (knee), gait speed, balance and bone density measurements [dual-energy X-ray absorptiometry (total body, hip, and spine), and quantitative ultrasound of the calcaneus] were measured. About 14% (8 out of 57) had a moderate to vigorous physical activity (MVPA) (>1,952 counts per min [CPM]) exceeding 30 min/day. The median CPM was 18. When compared to questionnaire data, the correlation between MVPA and physical activity was 0.50 (P < 0.001). The corresponding result for CPM was 0.48, P < 0.001. When compared to the activity log, the correlation between MVPA and physical activity away from home was 0.49 (P < 0.001). The corresponding result for CPM was 0.55, P < 0.001. The correlation between MVPA and gait speed was 0.41 (P = 0.002). The corresponding result for CPM was 0.40, P = 0.002. There were no correlations to the measurements of muscle strength, balance or bone density (all P >/= 0.07). Accelerometers can be used for measuring of physical activity also of the elderly. Questions on daily physical activity correlated modestly with accelerometer results in elderly women. Accelerometer results were not correlated to measures of balance, muscle strength and bone density.
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37.
  • Gerdhem, Paul, et al. (författare)
  • Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women.
  • 2005
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 16:Mar 3, s. 1425-1431
  • Tidskriftsartikel (refereegranskat)abstract
    • Vitamin D supplements have been used to prevent fractures. The effect may be mediated through increased bone mass, but also through reduced falling propensity. The aim of this study was to evaluate the association between 25-hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of functional performance), and fracture in ambulatory women. At baseline 25OHD was measured in 986 women. Fall-associated variables were investigated at baseline. Fractures were recorded during a 3-year follow-up. Four percent of the women had 25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml (75 nmol/l). 25OHD correlated with gait speed (r =0.17, P <0.001), the Romberg balance test (r =0.14, P <0.001), self-estimated activity level (r =0.15, P <0.001), and thigh muscle strength (r =0.08, P =0.02). During the 3-year follow-up, 119 out of the 986 women sustained at least one fracture. The Cox proportional hazard ratio (HR) (95% confidence interval) for sustaining a fracture during the follow-up was 2.04 (1.04-4.04) for the group of women with 25OHD below 20 ng/ml, in which 9 out of 43 women sustained a fracture. Thirty-two of the 256 women with 25OHD levels below 30 ng/ml sustained a fracture during the follow-up, with a non-significant HR of 1.07 (1.07-1.61). This cohort of elderly, ambulatory women had a high mean 25OHD. A low 25OHD was associated with inferior physical activity level, gait speed and balance. A 25OHD level below 30 ng/ml was not associated with an increased risk of fractures in this study. However, a subgroup of women with 25OHD levels below 20 ng/ml had a tendency to an increased risk of fractures, which may be associated with an inferior physical activity and postural stability.
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38.
  • Gerdhem, Paul, et al. (författare)
  • Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women
  • 2004
  • Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:3, s. 264-269
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.
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39.
  • Gerdhem, Paul, et al. (författare)
  • Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women
  • 2007
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:1, s. 127-134
  • Tidskriftsartikel (refereegranskat)abstract
    • Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.
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40.
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41.
  • Gerdhem, Paul, et al. (författare)
  • Bone mass cannot be predicted by estimations of frailty in elderly ambulatory women.
  • 2003
  • Ingår i: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 49:3, s. 168-172
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background/Methods:</i> High biological age, or frailty, a possible risk factor for fragility fracture, and its relation to known risk factors for fracture (low bone mineral density (BMD), low muscle strength, poor gait performance and poor balance, previous falls, previous fractures and future risk of falls) were investigated in 993 randomly selected 75-year-old women. Frailty, which has no accepted definition, was here defined as a subjective immediate impression of an individual’s general health appearance and was transferred into an arbitrary scale. 993 individuals were scored by at least one of four observers. <i>Results:</i> The frailty score and BMD were not correlated. A high frailty score was significantly correlated to poor gait (r = 0.53–0.59, p < 0.0001), poor balance (r = –0.49, p < 0.0001), low muscle strength (r = –0.25 to –0.41, p < 0.0001), low activity level (r = –0.43, p < 0.0001) and a high risk of falling (r = 0.24, p < 0.0001). The group of women who had experienced at least one fall the previous year had a higher frailty score (p < 0.0001) compared to those who had not. Women who had sustained a hip or femoral fracture after the age of 70 had a higher frailty score than women with no earlier fracture at all. <i>Conclusions:</i> Bone mass cannot be predicted by our subjective frailty score in elderly, ambulant women. Since a high frailty score correlates with factors that affect or are likely to affect fall propensity, this could indicate that a high frailty score is a risk factor for fracture, independent of bone mass. Frailty may be regarded as a complex risk factor, including several assessments that can be objectively measured. Whether estimation of frailty is a method to improve the assessment of the patient at risk for a fragility fracture is yet to be proven and can only be shown in a prospective study of fracture occurrence.
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  • Gerdhem, Paul, et al. (författare)
  • Just one look, and fractures and death can be predicted in elderly ambulatory women.
  • 2004
  • Ingår i: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 50:5, s. 309-314
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> The chronological age is clearly the strongest risk factor for fractures or death. Age as a concept can be described exactly as chronological age. Age in relative terms can be described as biological age. <i>Objective:</i> We postulated that, even without taking into account known or unknown comorbidity, an immediate and totally subjective evaluation of an individual’s biological age is predictive of forthcoming fractures and death. <i>Methods:</i> At baseline the biological age was estimated in 1,004 randomly recruited ambulatory 75-year-old women. All women were of the same ethnic background. Two independent observers estimated the biological age within 15 s of first sight of each woman. Based on this estimation of the biological age, the women were divided into tertiles. The women were then followed prospectively for a mean of 4.6 (range 3.0–6.5) years. All retrospective fractures and prospective fractures and deaths were registered. <i>Results:</i> When the tertile of the biologically oldest women was compared with all other women, their odds ratio for sustaining any type of prospective fracture was 1.71 (95% confidence interval 1.22–2.39), for hip fractures 2.69 (1.42–5.11), for clinical vertebral fractures 2.83 (1.57–5.11), and for multiple fractures 3.17 (1.64–6.10). Also, when retrospectively sustained fractures were included, the predictive ability for biological age remained. The death rate amongst the tertile of biologically oldest women was increased when compared with the rest of the women (odds ratio 4.33, CI 3.62–5.17). <i>Conclusions:</i> In ambulatory elderly women, without specific consideration of comorbidity, a subjective estimate of the biological age is predictive of future fractures and death. Subjective estimation of the biological age, in relation to the chronological age, is a valuable indicator of health, conveying additional information that merits its use in clinical practice.
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  • Gerdhem, Paul, et al. (författare)
  • Rates of fracture in participants and non-participants in the Osteoporosis Prospective Risk Assessment Study
  • 2007
  • Ingår i: Journal of Bone and Joint Surgery: British Volume. - 2044-5377. ; 89B89:12, s. 1627-1631
  • Tidskriftsartikel (refereegranskat)abstract
    • We invited 1604 randomly selected women, all 75 years of age, to participate in a study on the risk factors for fracture. The women were divided into three groups consisting of 1044 (65%) who attended the complete study, 308 (19%) respondents to the study questionnaire only and 252 (16%) who did not respond. The occurrence of the life-time fracture was ascertained from radiological records in all groups and by questionnaires from the attendees and respondents. According to the radiological records, fewer of the questionnaire respondents (88 of 308, 28.6%) and non-respondents (68 of 252, 27%) had sustained at least one fracture when compared with the attendees (435 of 1044, 41.7%; chi-squared test, p < 0.001). According to the questionnaire, fewer of the respondents (96 of 308, 31.1%) had sustained at least one previous fracture when compared with the attendees (457 of 1044, 43.7%; chi-squared test, p < 0.001). Any study concerning the risk of fracture may attract those with experience of a fracture which explains the higher previous life-time incidence among the attendees. This factor may cause bias in epidemiological studies.
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