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It is important to identify the patients at highest risk of fractures. A recent large-scale meta-analysis identified 63 autosomal single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD), of which 16 were also associated with fracture risk. Based on these findings, two genetic risk scores (GRS63 and GRS16) were developed. Our aim was to determine the clinical usefulness of these GRSs for the prediction of BMD, BMD change, and fracture risk in elderly subjects. We studied two male (Osteoporotic Fractures in Men Study [MrOS] US, MrOS Sweden) and one female (Study of Osteoporotic Fractures [SOF]) large prospective cohorts of older subjects, looking at BMD, BMD change, and radiographically and/or medically confirmed incident fractures (8067 subjects, 2185 incident nonvertebral or vertebral fractures). GRS63 was associated with BMD (≅3% of the variation explained) but not with BMD change. Both GRS63 and GRS16 were associated with fractures. After BMD adjustment, the effect sizes for these associations were substantially reduced. Similar results were found using an unweighted GRS63 and an unweighted GRS16 compared with those found using the corresponding weighted risk scores. Only minor improvements in C-statistics (AUC) for fractures were found when the GRSs were added to a base model (age, weight, and height), and no significant improvements in C-statistics were found when they were added to a model further adjusted for BMD. Net reclassification improvements with the addition of the GRSs to a base model were modest and substantially attenuated in BMD-adjusted models. GRS63 is associated with BMD, but not BMD change, suggesting that the genetic determinants of BMD differ from those of BMD change. When BMD is known, the clinical utility of the two GRSs for fracture prediction is limited in elderly subjects., (© 2014 American Society for Bone and Mineral Research.)

Osteoporosis and fractures are a common consequence of glucocorticoid therapy for inflammatory disorders. Men fracture approximately 10 yr later in life than women and receive less attention as regards osteoporosis risk, including in glucocorticoid-induced osteoporosis (GIOP). In addition, while men are less likely to have certain rheumatologic disorders often treated with glucocorticoids, men are more likely to have chronic obstructive pulmonary disease, inflammatory bowel disease, and organ transplantation as reasons for use of oral glucocorticoids. Attempts to improve recognition of GIOP in general have not been successful, and since men are considered less at risk for osteoporosis in general, attention to men with GIOP is even less. Evaluation of GIOP is similar in men and women, and most modern treatment studies of GIOP have included men. Thus, alendronate, risedronate, and zoledronic acid are Food and Drug Administration (FDA)-approved bisphosphonates for GIOP in men. Teriparatide is also FDA-approved for GIOP. In one 36-month trial of teriparatide vs alendronate for GIOP in men and women, the anabolic agent led to a greater increase in bone density and was associated with a lower incidence of morphologic vertebral fractures. Thus, while good management is available for GIOP, recognition of men at risk is the most important step in improving outcomes.

Background: In general there is a lack of data on osteoporosis and fracture in men; this also includes low-energy distal radius fractures. The objectives of this study were to examine BMD and identify factors associated with distal radius fractures in male patients compared with controls recruited from the background population., Methods: In a 2-year period, 44 men 50 years or older were diagnosed with low-energy distal radius fractures, all recruited from one hospital. The 31 men who attended for osteoporosis assessment were age-matched with 35 controls. Demographic and clinical data were collected and BMD at femoral neck, total hip and spine L2-4 was assessed by dual energy X-ray absorptiometry., Results: Apart from weight and living alone, no significant differences were found between patient and controls for demographic variables (e.g. height, smoking) and clinical variables (e.g. co-morbidity, use of glucocorticoids, osteoporosis treatment, falls and previous history of fracture). However, BMD expressed as T-score was significant lower in patients than in controls at all measurement sites (femoral neck: -2.24 vs. -1.15, p < 0.001; Total hip: -1.65 vs. -0.64, p < 0.001; Spine L2-4: -1.26 vs. 0.25, p = 0.002). Among the potential risk factors for fracture evaluated, only reduced BMD was found to be significantly associated with increased risk for low-energy distal radius fractures in men., Conclusion: The results from our study indicate that reduced BMD is an important risk factor for low-energy distal radius fracture in men. This suggests that improvement of BMD by both pharmacological and non-pharmacological initiatives may be a strategy to reduce fracture risk in men.

Objective: Radiographic hip osteoarthritis (RHOA) is associated with increased hip areal bone mineral density (aBMD). This study was undertaken to examine whether femoral geometry is associated with RHOA independent of aBMD., Methods: Participants in the Study of Osteoporotic Fractures in whom pelvic radiographs had been obtained at visits 1 and 5 (mean 8.3 years apart) and hip dual x-ray absorptiometry (DXA) had been performed (2 years after baseline) were included. Prevalent and incident RHOA phenotypes were defined as composite (osteophytes and joint space narrowing [JSN]), atrophic (JSN without osteophytes), or osteophytic (femoral osteophytes without JSN). Analogous definitions of progression were based on minimum joint space and total osteophyte score. Hip DXA scans were assessed using the Hip Structural Analysis program to derive geometric measures, including femoral neck length, width, and centroid position. Relative risks and 95% confidence intervals for prevalent, incident, and progressive RHOA per SD increase in geometric measure were estimated in a hip-based analysis using multinomial logistic regression with adjustment for age, body mass index, knee height, and total hip aBMD., Results: In 5,245 women (mean age 72.6 years), a wider femoral neck with a more medial centroid position was associated with prevalent and incident osteophytic and composite RHOA phenotypes (P < 0.05). Increased neck width and centroid position were associated with osteophyte progression (both P < 0.05). No significant geometric associations with atrophic RHOA were found., Conclusion: Differences in proximal femoral bone geometry and spatial distribution of bone mass occur early in hip OA and predict prevalent, incident, and progressive osteophytic and composite phenotypes, but not the atrophic phenotype. These bone differences may reflect responses to loading occurring early in the natural history of RHOA.

Summary: While nitrogen-containing bisphosphonates have been shown to reduce fracture risk in postmenopausal women and men, their safety in the period after a fracture is unclear. In fully adjusted multivariable regression models, bisphosphonate use in the post-fracture period was associated with an increased probability of non-union [odds ratio (OR) 2.37, 95% confidence interval (CI) 1.13-4.96]. Clinicians might consider waiting for several months before introduction of a bisphosphonate after a fracture., Introduction: While nitrogen-containing bisphosphonates have been shown to reduce fracture risk in postmenopausal women and men, their safety in the period after a fracture is unclear. We examined the risk of non-union associated with post-fracture bisphosphonate use among a group of older adults who had experienced a humerus fracture., Methods: We conducted a nested case-control study among subjects who had experienced a humerus fracture. From this cohort, cases of non-union were defined as those with an orthopedic procedure related to non-union 91-365 days after the initial humerus fracture. Bisphosphonate exposure was assessed during the 365 days prior to the non-union among cases or the matched date for controls. Multivariable logistic regression models were examined to calculate the OR and 95% CI for the association of post-fracture bisphosphonate use with non-union., Results: From the cohort of 19,731 patients with humerus fractures, 81 (0.4%) experienced a non-union. Among the 81 cases, 13 (16.0%) were exposed to bisphosphonates post-fracture, while 69 of the 810 controls (8.5%) were exposed in the post-fracture interval. In fully adjusted multivariable regression models, bisphosphonate use in the post-fracture period was associated with an increased odds of non-union (OR 2.37, 95% CI 1.13-4.96). Albeit limited by small sample sizes, the increased risk associated with bisphosphonate use persisted in the subgroup of patients without a history of osteoporosis or prior fractures (OR 1.91, 95% CI 0.75-4.83)., Conclusions: In this study of older adults, non-union after a humerus fracture was rare. Bisphosphonate use after the fracture was associated with an approximate doubling of the risk of non-union.

Objectives: To determine whether positive affect is associated with a lower incidence of frailty over 2 years in elderly community-dwelling women and to test the stress-buffering hypothesis by evaluating whether these associations differed in caregivers and noncaregivers., Design: Prospective cohort study with three annual interviews conducted in four U.S. communities between 1999 and 2004., Setting: Home-based interviews., Participants: Three hundred thirty-seven caregiver and 617 noncaregiver participants from the Caregiver-Study of Osteoporotic Fractures (Caregiver-SOF) who were not frail at the baseline Caregiver-SOF interview., Measurements: High and low positive affect and depressive symptoms were derived from the baseline 20-item Center for Epidemiologic Studies Depression Scale. Frailty was the development of three or more indicators (weight loss, exhaustion, slow walking speed, or weak grip strength) at the first or second follow-up interview., Results: Respondents' mean age was 81.2. Caregivers and noncaregivers had similar levels of positive affect (56.3% vs 58.3%) and frailty incidence (15.4% vs 15.9%) but differed in perceived stress (mean Perceived Stress Scale score 16.7 vs 14.8, P<.001). Frailty risk was lower in respondents with high positive affect than in those with low positive affect in the total sample (adjusted hazard ratio (HR)=0.49, 95% confidence interval (CI)=0.35-0.70), caregivers (adjusted HR=0.44, 95% CI=0.24-0.80) and noncaregivers (adjusted HR=0.50, 95% CI=0.32-0.77)., Conclusion: These findings add to the evidence that positive affect protects against health decline in older adults, although it had no additional stress-buffering effect on health in elderly caregivers.

Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This review evaluates the use of commercially available bone turnover markers as aids in diagnosis and monitoring response to treatment in patients with osteoporosis. High within-person variability complicates but does not preclude their use. Elevated bone resorption markers appear to be associated with increased fracture risk in elderly women, but there is less evidence of a relationship between bone formation markers and fracture risk. The critical question of predicting fracture efficacy with treatment has not been answered. Changes in bone markers as currently determined do not predict BMD response to either bisphosphonates or hormone replacement therapy. Single measurements of markers do not predict BMD cross-sectionally (except possibly in the very elderly), or change in BMD in individual patients, either treated or untreated. On the other hand, research applications of bone turnover markers are of value in investigating the pathogenesis and treatment of bone diseases. Markers have potential in the clinical management of osteoporosis, but their use in this regard is not established. Additional studies with fracture endpoints and information on negative and positive predictive value are needed to evaluate fully the utility of bone turnover markers in individual patients.

Objective: To examine the association between osteoarthritis (OA), as defined by radiographic evidence and self report, and osteoporotic fractures, falls, and bone loss in a cohort of elderly white women., Methods: A cohort of 5,552 elderly women from the Study of Osteoporotic Fractures was followed up prospectively for a mean of 7.4 years. Self-reported, physician-diagnosed OA was recorded at interview, and radiologic OA of the hip and hand were defined from pelvis and hand radiographs obtained at baseline by validated techniques. Prevalent and incident vertebral fractures were detected by vertebral morphometry, and data on incident fractures and falls were collected by postcard surveys; fractures were confirmed by radiography. Bone mineral density (BMD) was measured on 2 occasions at the hip, lumbar spine, and calcaneus, and rates of bone loss were calculated., Results: Women with radiographic hip OA had a reduced risk of recurrent falls in the first year (relative risk [RR] 0.7, 95% confidence interval [95% CI] 0.5-0.95). However, those with self-reported OA had an increased risk of falls (RR 1.4, 95% CI 1.2-1.5). Radiographic hip OA was associated with reduced bone loss in the femoral neck compared with controls (mean +/- SD -0.29+/-0.09%/year versus -0.51+/-0.03%/year; P = 0.018). However, radiographic hip OA showed nonsignificant trends toward increased bone loss at the calcaneus and lumbar spine. There was no significant association between self-reported OA or radiographic hand OA with bone loss. No definition of OA was associated with incident nonvertebral fracture, hip fracture, or vertebral fracture., Conclusion: Despite having increased BMD compared with controls, subjects with OA did not have a significantly reduced risk of osteoporotic fracture, although there was a trend toward a reduced risk of femoral neck fractures in subjects with severe radiographic OA. The failure of the observed increase in BMD to translate into a reduced fracture risk may be due, in part, to the number and type of falls sustained by subjects with OA. Patients with OA should not be considered to be at a lower risk of fracture than the general population. Physicians should be aware that a high BMD in patients with OA may be falsely reassuring.

Objective: To examine the relationship between axial and hip bone mineral density (BMD) and radiographic changes of knee osteoarthritis (OA)., Methods: BMD of the lumbar spine and/or right hip was measured, using dual photon absorptiometry, in 402 men and 247 women in the Baltimore Longitudinal Study of Aging who had bilateral standing knee radiographs taken between 1984 and 1991. Radiographs were read for features of OA using Kellgren-Lawrence and reliable individual feature scales. The relationship between BMD and radiographic changes of OA was examined using multiple linear regression adjusting for age, body mass index, and smoking. Additional analyses with adjustment for menopausal status and estrogen replacement therapy were performed in a subset of women., Results: Adjusted mean lumbar spine BMD was higher in subjects with knee osteophytes in both sexes: 1.23 +/- 0.02 vs 1.18 +/- 0.01 g/cm2 (p = 0.02) in men, and 1.12 +/- 0.02 vs 1.08 +/- 0.01 g/cm2 (p = 0.07) in women. There were no differences in levels of adjusted hip BMD by presence of any radiographic features of OA in either men or women., Conclusion: These results show that both men and women with radiographic changes of knee OA, specifically osteophytosis, have higher levels of adjusted spine but not hip BMD.

Arthritis and other musculoskeletal disorders are common causes of disability in the United States. Osteoporosis is the major nonarthritic musculoskeletal condition affecting postmenopausal women. An increased incidence of osteoporosis is seen in some rheumatic diseases resulting in a potential increase in risk of fracture. Patients with rheumatoid arthritis and spondyloarthropathies appear to have decreased bone mineral density whereas patients with osteoarthritis of the hip have increased bone mineral density. In this article studies of bone mass and related fractures in patients with rheumatic disorders are reviewed.

UnlabelledCalcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0% in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7%) and women supplementing pharmacologic therapy with calcium (22.5%).IntroductionCalcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort.MethodsSubject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US(TM)) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use.ResultsAt entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0% during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7% (95 % confidence interval [CI], 20.7 - 27.0) among calcium-only subjects and 22.5% (95% CI, 20.7-24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8%). Overall 54.2% of calcium-only subjects who discontinued calcium and 42.3% of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry.ConclusionsCalcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.

A number of antiresorptive agents reduce the risk of vertebral fractures, but few have shown consistent effects on hip and other non-spine fractures. Meta-analysis provides a more precise estimate than individual trials when results are consistent across pooled trials. Earlier meta-analyses summarised the results for vertebral and non-spine fractures. New data have emerged for hormone therapy (HT), alendronate (ALN), risedronate (RIS) and ibandronate (IBN). We surveyed recent reports of randomised, placebo-controlled trials with non-spine and/or hip fracture data, and used meta-analysis where appropriate to test for heterogeneity and derive pooled estimates. The magnitude of effect on hip fracture appears to be similar to that for non-spine fracture for each drug, but differs among drugs. Based on the current data, ALN reduces the risk of hip and non-spine fracture by 49–55%, HT by 25–36% and RIS by 26–27%. There is insufficient and/or inconsistent evidence of an effect on these fractures for IBN, calcitonin and raloxifene. [ABSTRACT FROM AUTHOR]

The evidence from randomised, controlled trials of the ability of antiresorptive treatments to reduce the risk of fractures in postmenopausal women with osteoporosis is reviewed and summarised. The aminobisphosphonates, alendronic acid and risedronic acid, and the selective estrogen receptor modulator raloxifene have all been shown to reduce the incidence of radiographic vertebral fractures. Only alendronic acid and risedronic acid have been shown to reduce the incidence of non-spine fractures in women with postmenopausal osteoporosis. There is evidence of antifracture efficacy for calcium plus vitamin D, primarily in a nursing home setting or in people with low intakes of these nutrients. Furthermore, since both the placebo and active treatment groups received calcium and vitamin D in most controlled trials of antiresorptive agents, it appears that the other agents provide benefits beyond those of calcium and vitamin D alone. There is insufficient published evidence from randomised controlled trials to convincingly support the antifracture efficacy of other agents, including calcitonin, estrogen and etidronic acid, at this time. Data from observational studies suggest, however, that estrogen and etidronic acid may have antifracture efficacy in this population. [ABSTRACT FROM AUTHOR]

To estimate the prevalence and impact of self-reported hip fracture in elderly women an age-stratified random sample of 3841 community-dwelling women aged 65 years and above were interviewed to determine the occurrence of 13 chronic conditions and difficulty performing 15 tasks. Associations were examined using multiple logistic regression analysis. The weighted prevalence of hip fracture was 4.7 per 100. Prevalence increased with increasing age from 2.9 per 100 in women aged 65–74 years to 12.6 per 100 in women aged 85 years and above, and was higher in white women than black women. Women with hip fracture were significantly more likely to report concomitant Parkinson's disease (age-adjusted odds ratio [aOR] = 2.8) and stroke (aOR = 1.8). After adjustment for potential confounding variables, women with hip fracture were significantly more likely to report difficulty performing 11 activities that map into domains of mobility/exercise tolerance, self-care tasks and higher functioning domains. Hip fracture is common among elderly community-dwelling women and is associated with difficulty in performing activities of daily living. [ABSTRACT FROM AUTHOR]