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ABSTRACT In the United States, osteoporosis affects over 10 million adults, has high societal costs ($22 billion in 2008), and is currently being underdiagnosed and undertreated. Given an aging population, this burden is expected to rise. We projected the fracture burden in US women by modeling the expected demographic shift as well as potential policy changes. With the anticipated population aging and growth, annual fractures are projected to increase from 1.9 million to 3.2 million (68%), from 2018 to 2040, with related costs rising from $57 billion to over $95 billion. Policy‐driven expansion of case finding and treatment of at‐risk women could lower this burden, preventing 6.1 million fractures over the next 22 years while reducing payer costs by $29 billion and societal costs by $55 billion. Increasing use of osteoporosis‐related interventions can reduce fractures and result in substantial cost‐savings, a rare and fortunate combination given the current landscape in healthcare policy. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Study Design: A population-based cohort study.Objective: The aim of this study was to examine whether 15-year trajectories of low back pain (LBP) and sciatica are associated with cardiovascular autonomic function in a large general population sample.Summary Of Background Data: Previous studies using mainly small patient samples have suggested that LBP and sciatica are associated with abnormal cardiovascular autonomic function, namely altered heart rate variability (HRV) and baroreflex sensitivity (BRS). We examined this association in a large general population sample.Methods: The data collections of the Northern Finland Birth Cohort 1966 consisted of pain questionnaires at 31 and 46 years (history of LBP, sciatica, and other musculoskeletal pains during the previous year; yes/no for each) and measurements of HRV and BRS at 46 years (heart rate, HR; root mean square of successive differences in beat-to-beat intervals, rMSSD; low-frequency systolic blood pressure variability, SBPV; cross-spectral BRS, BRS; each while seated and standing). The data collections also comprised several confounders. Trajectories for LBP, sciatica, and both together ("no pain," "decreasing," "increasing," "long-term pain") were constructed and general linear models were used to perform comparisons between trajectories (for HR/rMSSD, n = 3398; for SBPV/BRS, n = 1667).Results: In the crude models, LBP and sciatica were associated with higher HR, lower rMSSD, higher SBPV, and lower BRS, but these associations were mostly attenuated by adjustments. Regarding both LBP and sciatica, only the "increasing" trajectory was associated with two of the eight outcomes (standing SBPV, seated BRS) after adjustments. Regarding LBP, the "increasing" trajectory was associated with three (standing SBPV, seated BRS, standing BRS), the "long-term pain" trajectory with one (standing BRS), and the "decreasing" trajectory with one outcome (seated SBPV) after adjustments. Sciatica showed no association with the outcomes after adjustments.Conclusion: We conclude that the 15-year trajectories of LBP and sciatica do not have a consistent independent association with cardiovascular autonomic function among the general population.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Epidemiologic studies have replicated positive associations between obesity and bone health, but their mechanisms are still debatable. We aimed to scrutinize an association between bone health and obesity using genetic instrumental variables (IVs) with the distinction of general versus abdominal obesity. We selected independent IVs of body mass index (BMI) and BMI‐adjusted waist circumference (aWC, a proxy of a central fat distribution) by combining novel genomewide searches from the Korean Genome Epidemiology Study (KoGES) consortium and existing reports. We evaluated the associations of obesity indices with bone health measures for weight‐bearing and non–weight‐bearing bones, applying standard Mendelian randomization analyses. The IVs for BMI and aWC selected from KoGES cohort studies (n = 14,389) explained its own trait only, negating the mutual correlation at the phenotypic level. Two‐stage least squares analyses using an independent cohort study (n = 2507, mean age = 44.4 years, men = 44.3%) showed that BMI but not aWC was positively associated with bone mineral density (BMD for weight‐bearing bones: 0.063 ± 0.016 g/cm2 per one standard deviation increase in BMI), implying the fat distribution might be neutral. The association was weaker for non–weight‐bearing bones (BMI on BMD: 0.034 ± 0.011 g/cm2), and for postmenopausal women the association was absent. Obesity increased both bone area and bone mineral content (BMC) to a lesser degree, but the increase in BMC was not evident for menopausal women. When we stratified the weight into lean body mass and fat mass, the increase in BMD was more evident for lean body mass, and fat mass showed a beneficial role only for men and premenopausal women. Our findings suggest that bone health might gain little from obesity, if any, through its added weight, and other means to prevent bone loss would be essential for postmenopausal women. © 2019 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Summary Background Maintenance of skeletal muscle in older age is critical to reducing frailty and the risk of falls and fractures. Nutrition has established importance for muscle health in general, but less research has looked at associations of dietary intake of specific micronutrients on skeletal muscle mass in older adults. Aims This study aimed to investigate the influence of dietary and circulating magnesium on skeletal muscle mass in a UK population of 14,340 middle to older-aged men and women participating in the EPIC-Norfolk cohort study. Methods Dietary nutrient intakes were estimated from 7-day food diaries and fat-free mass (FFM) by bioelectrical impedance analysis. Multivariable regression was used to investigate associations of FFM-based indices of muscle mass with quintiles of dietary magnesium intake or serum magnesium concentration groups. All analyses were stratified by sex, and regression models were adjusted for relevant covariates. Results Significant positive trends in FFM measures were evident across magnesium dietary intake quintiles for both sexes (all p < 0.001; n = 6350 men; n = 7990 women) and both <60 and ≥ 60 year olds, with all-age quintile 5 versus quintile 1 maximal differences of 4.6% in men and 6.3% in women; highly relevant compared to the estimated 1% decline per year after 40 years of age. These observations were not reflected in serum magnesium analyses, where no consistent trends were found across the skeletal muscle mass indices tested. Conclusion Further investigation will be required to improve our understanding of the relationship between serum magnesium concentration and skeletal muscle mass. However, this study has demonstrated strong associations between dietary magnesium intake and indices of skeletal muscle mass in a UK population of middle to older-aged adults, highlighting the likely importance of dietary magnesium for optimal muscle health in this population. [ABSTRACT FROM AUTHOR]

Summary: Among 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women.Introduction: Prior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12-24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management.Methods: This retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥  2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk.Results: Among 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65-74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7-14% fractured again within 1 year depending on initial fracture site; risk rose to 15-26% within 2 years and 28-42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those < 75 years with an initial tibia/fibula or ankle fracture.Conclusions: We observed a high and early risk of subsequent fracture following a broad array of initial fractures. Timely management with consideration of pharmacotherapy is warranted in older women following all fracture types evaluated. [ABSTRACT FROM AUTHOR]

Nonunion is a clinically significant complication of fracture associated with worse outcomes, including increased pain, disability, and higher healthcare costs. The risk for nonunion is likely to be complex and multifactorial, and as such, the biology underlying such risk remains poorly understood. Genetic studies represent one approach to identify implicated biology for further investigation, but to date the lack of large cohorts for study has limited such efforts. We utilized the electronic health records of two large academic medical centers in Boston to identify individuals with fracture nonunion and control individuals with fracture but no evidence of nonunion. We conducted a genomewide association study among 1760 individuals of Northern European ancestry with upper or lower extremity fracture, including 131 with nonunion, to examine whether common variants were associated with nonunion in this cohort. In all, one locus in the Calcyon (CALY) gene exceeded a genomewide threshold for statistical significance (p = 1.95e–8), with eight additional loci associated with p < 5e–7. Previously reported candidate genes were not supported by this analysis. Electronic health records should facilitate identification of common genetic variations associated with adverse orthopedic outcomes. The loci we identified in this small cohort require replication and further study to characterize mechanism of action, but represent a starting point for the investigation of genetic liability for this costly outcome. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38,971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31,213 without. An equal amount of well‐balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation 1‐year postsurgery was investigated. During a median follow‐up time of 3.1 (interquartile range [IQR], 1.7 to 4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (hazard ratio [HR] 1.26; 95% CI, 1.05 to 1.53; and HR 1.32; 95% CI, 1.18 to 1.47; respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Prognostic tools are available to identify individuals at high risk of osteoporotic fracture and to assist physicians in management decisions. Some authors have suggested improving the predictive ability of these tools by integrating characteristics of prior fractures (number, location, and time since prior fracture). The objectives of this study were: (1) to evaluate the sex‐ and age‐specific associations between characteristics of prior fractures and the occurrence of a future osteoporotic fracture; and (2) to assess whether the characteristics of prior fractures could increase the discriminative ability of fracture risk prediction tools. A retrospective cohort study was conducted using administrative data. Men and women aged ≥66 years were selected and grouped into two cohorts. In cohort #1 (N = 759,500), history of fractures was measured between fiscal years 1997–1998 and 2003–2004, and future fractures were identified between 2004–2005 and 2013–2014. In cohort #2 (N = 807,245), history of fractures was measured between 1997–1998 and 2008–2009, and future fractures were identified between 2009–2010 and 2013–2014. Time until a first hip/femur and major osteoporotic fracture were the outcomes of interest. Adjusted HRs and c‐indices were calculated. The association between history of prior fractures and future fracture was stronger in men and younger individuals. The locations of prior fractures associated with the lowest and highest risks were foot/ankle/tibia/fibula (maximal HR = 1.64) and hip/femur (maximal HR = 9.02), respectively. The association was stronger for recent fractures (maximal HR = 4.93), but was still significant for fractures occurring 10 to 12 years prior to the beginning of follow‐up (maximal HR = 1.99). Characteristics of prior fractures did not increase model discrimination. Our study confirms that the risk of future fracture increases with the number of prior fractures, varies according to prior fracture location, and decreases with time since prior fracture. However, the integration of these characteristics in current fracture risk prediction tools is not required because it does not improve predictive ability. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The diagnostic threshold for osteoporosis, a bone mineral density (BMD) T-score ≤ −2.5, signals an increased risk for fracture. However, most fragility fractures arise among the majority of women with ‘osteopenia’ or ‘normal’ BMD. We hypothesized that a BMD T-score of −2.5, even if not intended as a treatment threshold, paradoxically may create disincentive to initiating treatment of women with osteopenia or normal BMD at high risk for fracture. From a population-based BMD registry covering the Province of Manitoba, Canada, we identified 3735 untreated women aged ≥ 50 years undergoing BMD screening in 2006–2015 found to qualify for Osteoporosis Canada guidelines-based treatment. The main outcome was prescription of an approved osteoporosis medications in the year after BMD testing ascertained from a population-based pharmacy database. We estimated adjusted odds ratios (OR, 95% confidence interval [CI]) for treatment initiation based on BMD, major fracture history (non-traumatic vertebral, hip or multiple fractures), age, and calendar year (to examine the impact of treatment guidelines published in 2010). Among these women, 50% (1853) initiated treatment: 71% with osteoporosis, 21% with osteopenia, and 5% with normal BMD with similar values in those with a prior major fracture (71%, 19%, 5%, respectively). Compared to women with osteoporosis, adjusted ORs for treatment of high risk women with osteopenia or normal BMD alone were 0.10 (95% CI 0.09–0.12) and 0.02 (95% CI 0.01–0.04), respectively, and no higher in women with a prior major fracture (OR 1.00, 95% CI 0.84–1.19) or following introduction of treatment guidelines ( p  = 0.294). In summary, we found evidence that the diagnostic threshold for osteoporosis may serve as a disincentive to initiation of treatment in many women at high risk for incident fracture. [ABSTRACT FROM AUTHOR]

ABSTRACT: The association between body mass index (BMI) and hip fracture may differ by ethnic group. We examined the association between BMI and hip fracture according to sex and age and to identify BMI ranges associated with the lowest risk in Korean men and women. We followed up 288,068 Korean adults (aged 50 to 80 years), who underwent health examinations in 2002–03 to 2013; we examined national hospital discharge records. Hazard ratios (HRs) were calculated using Cox proportional hazard models after adjusting for confounders. During a mean follow‐up period of 10.5 years, 1502 men and 2432 women suffered a hip fracture. Nonlinear associations were observed between BMI and hip fracture: a U‐curve for women and a reverse J‐curve for men. Men with BMIs of 27.5 to 29.9 kg/m2 and women with BMIs of 25 to 27.4 kg/m2 showed the lowest incidence of hip fracture. The multivariate‐adjusted HRs for hip fracture per 5 kg/m2 decrease in BMI were 2.09 (95% confidence interval [CI] 1.83–2.38) and 1.34 (95% CI 1.19–1.51) in men and women with BMI <25 kg/m2. The HRs were generally highest in the age group of 50 to 59 years (HR = 3.42 in men and 2.27 in women) and thereafter decreased with age. Among participants with BMI ≥25 kg/m2, the HRs for hip fracture per 5 kg/m2 increase in BMI were 1.26 (95% CI 1.08–1.47) in women and 0.91 (95% CI 0.62–1.33) in men. In conclusion, the overweight range of BMI was associated with the lowest risk of hip fracture. Lower BMI was a risk factor for hip fracture, whereas obesity was associated with an increased risk of hip fracture, particularly in women. Overweight may be protective against hip fracture in Asian adults but not obesity. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Summary: Use of anti-osteoporotic drugs (AODs) was examined in a Norwegian population 50-85 years. Among them with Fracture Risk Assessment Tool (FRAX) score for major osteoporotic fracture ≥ 20, 25% of the women and 17% of the men received AODs. The strongest predictors for AODs were high age in women and use of glucocorticoids among men.Introduction: To examine the use of anti-osteoporotic drugs (AODs) and to identify predictors for prescriptions.Methods: Data were obtained from the Nord-Trøndelag Health Study (HUNT3) performed in 2006-2008 and the Norwegian Prescription Database, including 15,075 women and 13,386 men aged 50-85 years. Bone mineral density (BMD) in the femoral neck was measured in a subgroup of 4538 women and 2322 men. High fracture risk was defined as a FRAX score for major osteoporotic fracture (MOF) ≥ 20%; in the subgroup with BMD, high risk was in addition defined as FRAXMOF ≥ 20% or T-score ≤ − 2.5. Hazard ratios (HRs) for predictors of incident use of AODs within 2 years after HUNT3 were estimated by Cox’ proportional hazards model.Results: Among individuals with FRAX MOF ≥ 20%, 25% of the women and 17% of the men were treated with AODs. Among those with FRAX MOF < 20%, 3% and 1% were treated, respectively. In the subgroup with BMD measurement, 24% of the women and 16% of the men at high risk of fractures were treated, compared to 3 and 1% in women and men not fulfilling the criteria. In women, high age was the strongest predictor for treatment (HR 3.84: 95% confidence interval 2.81-5.24), followed by use of glucocorticoids (GCs) (2.68:1.84-3.89). In men, predictors were use of GCs (5.28: 2.70-10.35) followed by multimorbidity (3.16:1.31-7.63). In the subgroup with BMD, T-score ≤ − 2.5 was the strongest predictor (women 3.98:2.67-5.89; men 13.31:6.17-28.74).Conclusions: This study suggests an undertreatment of AODs in individuals at high risk of fracture. [ABSTRACT FROM AUTHOR]

ABSTRACT: The risk of cardiovascular events (CVEs) with alendronate use in real‐world hip fracture patients is unknown. This study aimed to investigate the risk of CVE with and without use of alendronate in patients with hip fracture. We conducted a retrospective cohort study using a population‐wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with hip fracture from 2005 through 2013 were followed until November 6, 2016. Alendronate and other antiosteoporosis medications use during the study period were examined. We matched treated and nontreated patients based on time‐dependent propensity score. The risks of cardiovascular mortality, myocardial infarction, and stroke between treatment groups were evaluated using conditional Cox regression stratified by match pairs. To examine the associations over time, outcomes were assessed at 1 year, 3 years, 5 years, and 10 years. Among 34,991 patients with newly diagnosed hip fracture, 4602 (13.2%) received antiosteoporosis treatment during follow‐up. Physical functioning or survival prospect was not significantly different between treated and nontreated patients. A total of 4594 treated patients were matched with 13,568 nontreated patients. Results of Cox regression analysis revealed that alendronate was associated with a significantly lower risk of 1‐year cardiovascular mortality (HR 0.33; 95% CI, 0.17 to 0.65) and incident myocardial infarction (HR 0.55; 95% CI, 0.34 to 0.89), whereas marginally significant reduction in risk of stroke was observed at 5 years and 10 years (HR at 5 years: 0.82; 95% CI, 0.67 to 1.00; p = 0.049; HR at 10 years: 0.83; 95% CI, 0.69 to 1.01; p = 0.065). The strength of the association declined over time but remained significant. Similar results were observed when all nitrogen‐containing bisphosphonates (N‐BPs) were analyzed together. These findings were robust in multiple sensitivity analyses. Additional studies in other population samples and randomized clinical trials may be warranted to further understand the relationship between use of various antiosteoporosis medication and risk of CVE in patients with hip fracture. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Estimated lifetime risk of an osteoporotic fracture in men over the age of 50 years is substantial and lifestyle factors such as physical activity may explain variation in bone mass and bone loss associated with aging. Men (n = 253) aged 20-66 years were followed for 7.5 years and factors that influence changes in means and rates of change in bone mass, density, and size using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) were investigated; in particular, seasons of sports participation during high school and college. Men with greater sports participation had higher total hip bone mineral content (BMC) (48.4 ± 0.9 and 48.6 ± 0.9 g for 7-12 and 13+ seasons vs. 45.6 ± 0.8 and 45.4 ± 0.7 g for 0 and 1-6 seasons, respectively p < 0.05) and areal bone mineral density (aBMD) (1.082 ± 0.015 and 1.087 ± 0.015 g/cm2 for 7-12 and 13+ seasons vs. 1.011 ± 0.015 and 1.029 ± 0.013 g/cm2 for 0 and 1-6 seasons, respectively p < 0.05) than men who participated in less sport-seasons. However, men with higher sports participation also had greater rates of bone loss in their mid-twenties at the hip (BMC - 0.8 and - 1.2% and aBMD - 0.8 and - 0.9% for 7-12 and 13+ seasons of sport participation, respectively) compared to those with 0 seasons of sport participation (BMC - 0.6% and aBMD - 0.6%) (all p < 0.05). Similar results were observed for femoral neck aBMD. Men with 7+ seasons of sport participation had higher cross-sectional area at the 20% distal radius site than those with no sports participation (all p < 0.05). These findings support significant effects of high school and/or college sports participation on bone mass and geometry in men throughout adulthood. [ABSTRACT FROM AUTHOR]

ABSTRACT: With population aging, prevalence of low bone mineral density (BMD) and associated fracture risk are increased. To determine whether low circulating thyroid stimulating hormone (TSH) levels within the normal range are causally related to BMD, we conducted a two‐sample Mendelian randomization (MR) study. Furthermore, we tested whether common genetic variants in the TSH receptor (TSHR) gene and genetic variants influencing expression of TSHR (expression quantitative trait loci [eQTLs]) are associated with BMD. For both analyses, we used summary‐level data of genomewide association studies (GWASs) investigating BMD of the femoral neck (n = 32,735) and the lumbar spine (n = 28,498) in cohorts of European ancestry from the Genetic Factors of Osteoporosis (GEFOS) Consortium. For the MR study, we selected 20 genetic variants that were previously identified for circulating TSH levels in a GWAS meta‐analysis (n = 26,420). All independent genetic instruments for TSH were combined in analyses for both femoral neck and lumbar spine BMD. In these studies, we found no evidence that a genetically determined 1–standard deviation (SD) decrease in circulating TSH concentration was associated with femoral neck BMD (0.003 SD decrease in BMD per SD decrease of TSH; 95% CI, –0.053 to 0.048; p = 0.92) or lumbar spine BMD (0.010 SD decrease in BMD per SD decrease of TSH; 95% CI, −0.069 to 0.049; p = 0.73). A total of 706 common genetic variants have been mapped to the TSHR locus and expression loci for TSHR. However, none of these genetic variants were associated with BMD at the femoral neck or lumbar spine. In conclusion, we found no evidence for a causal effect of circulating TSH on BMD, nor did we find any association between genetic variation at the TSHR locus or expression thereof and BMD. © 2018 The Authors. Journal of Bone and Mineral Research Published by WileyPeriodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT: The adrenal‐derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. Many of the actions of DHEAS are considered to be mediated through metabolism into androgens and estrogens in peripheral target tissues. The predictive value of serum DHEA and DHEAS for the likelihood of falling is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEA and DHEAS levels and incident fall risk in a large cohort of older men. Serum DHEA and DHEAS levels were analyzed with mass spectrometry in the population‐based Osteoporotic Fractures in Men study in Sweden (n = 2516, age 69 to 81 years). Falls were ascertained every 4 months by mailed questionnaires. Associations between steroid hormones and falls were estimated by generalized estimating equations. During a mean follow‐up of 2.7 years, 968 (38.5%) participants experienced a fall. High serum levels of both DHEA (odds ratio [OR] per SD increase 0.85; 95% CI, 0.78 to 0.92) and DHEAS (OR 0.88, 95% CI, 0.81 to 0.95) were associated with a lower incident fall risk in models adjusted for age, BMI, and prevalent falls. Further adjustment for serum sex steroids or age‐related comorbidities only marginally attenuated the associations between DHEA or DHEAS and the likelihood of falling. Moreover, the point estimates for DHEA and DHEAS were only slightly reduced after adjustment for lean mass and/or grip strength. Also, the addition of the narrow walk test did not substantially alter the associations between serum DHEA or DHEAS and fall risk. Finally, the association with incident fall risk remained significant for DHEA but not for DHEAS after simultaneous adjustment for lean mass, grip strength, and the narrow walk test. This suggests that the associations between DHEA and DHEAS and falls are only partially mediated via muscle mass, muscle strength, and/or balance. In conclusion, older men with high DHEA or DHEAS levels have a lesser likelihood of a fall. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

This study aimed to explore the relationships of several indicators of cigarette smoking habits (smoking status, pack-years, age at smoking initiation and smoking cessation) with quantitative computed tomographic (QCT)-derived proximal femur bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total tissue volume (cvol/ivol)) and with subsequent change in these measures over the next five years. A total of 2673 older adults (55.9% women), aged 66–92 years at baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, who had two QCT scans of the hip were studied. In multivariable linear regression models, compared to never-smokers, current smokers had lower cvol/ivol at baseline and former-smokers had poorer measures on all outcomes (lower trabecular vBMD, integral vBMD and cvol/ivol), even when adjusted for several potential confounders. Further, among former smokers, those with higher pack-years had worse bone outcomes and those with longer duration since smoking cessation had better bone health at baseline. Analyses of change in bone measures revealed that compared to never-smokers, current smokers had significantly greater loss of trabecular vBMD, integral vBMD, and cvol/ivol. The regression models included adjustment for sex, age, education, and baseline body mass index, creatinine, % weight change from age 50, 25OHD, physical activity level, high-sensitive C-Reactive protein levels, alcohol and coffee consumption, history of diabetes mellitus, arthritis, and respiratory diseases. In conclusion, both current and former smoking showed adverse associations with bone health assessed with QCT. Results suggest that current smoking in particular may aggravate the rate of bone loss at older age and highlight implications for targeting this risk factor in populations that present higher smoking prevalence and vulnerability to bone fragility. [ABSTRACT FROM AUTHOR]

ABSTRACT: Historically, osteoporosis has not been considered a public health priority for the Hispanic population. However, recent data indicate that Mexican Americans are at increased risk for this chronic condition. Although it is well established that there is heterogeneity in social, lifestyle, and health‐related factors among Hispanic subgroups, there are currently few studies on bone health among Hispanic subgroups other than Mexican Americans. The current study aimed to determine the prevalence of osteoporosis and low bone mass (LBM) among 953 Puerto Rican adults, aged 47 to 79 years and living on the US mainland, using data from one of the largest cohorts on bone health in this population: The Boston Puerto Rican Osteoporosis Study (BPROS). Participants completed an interview to assess demographic and lifestyle characteristics and bone mineral density measures. To facilitate comparisons with national data, we calculated age‐adjusted estimates for osteoporosis and LBM for Mexican American, non‐Hispanic white, and non‐Hispanic black adults, aged ≥50 years, from the National Health and Nutrition Examination Survey (NHANES). The overall prevalence of osteoporosis and LBM were 10.5% and 43.3% for participants in the BPROS, respectively. For men, the highest prevalence of osteoporosis was among those aged 50 to 59 years (11%) and lowest for men ≥70 years (3.7%). The age‐adjusted prevalence of osteoporosis for Puerto Rican men was 8.6%, compared with 2.3% for non‐Hispanic white, and 3.9% for Mexican American men. There were no statistically significant differences between age‐adjusted estimates for Puerto Rican women (10.7%), non‐Hispanic white women (10.1%), or Mexican American women (16%). There is a need to understand specific factors contributing to osteoporosis in Puerto Rican adults, particularly younger men. This will provide important information to guide the development of culturally and linguistically tailored interventions to improve bone health in this understudied and high‐risk population. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT: We recently reported impaired bone strength in girls with low‐ to moderate‐energy distal radius fractures (Fx) compared with girls with no history of forearm fractures (Non‐Fx). We aimed to determine whether bone strength deficits observed at baseline were still present after 2 years. We assessed bone strength, microarchitecture, and bone mineral density (BMD) of the non‐fractured (Fx) and non‐dominant (Non‐Fx) distal radius (7% site) at baseline, 12, and 24 months using high‐resolution pQCT (Scanco Medical, Brüttisellen, Switzerland) in 104 girls (aged 11.0 ± 1.7 years; 47 Fx, 57 Non‐Fx) and 157 boys (aged 12.7 ± 1.7 years; 86 Fx, 71 Non‐Fx). Bone outcomes included total area (Tt.Ar) and bone mineral density (Tt.BMD), trabecular bone volume ratio (BV/TV), thickness (Tb.Th), separation (Tb.Sp), and number (Tb.N), and cortical BMD (Ct.BMD), thickness (Ct.Th), and porosity (Ct.Po). We used finite element analysis to estimate bone strength (failure load [F.Load]; ultimate stress [U.Stress]; load‐to‐strength ratio). We used sex‐specific mixed‐effects models to compare bone outcomes between Fx and Non‐Fx over 2 years. In girls, those with fractures had 18% to 24% lower U.Stress and 5% to 9% lower Tt.BMD than Non‐Fx at all time points (p < 0.017). In secondary analysis by fracture degree, girls with low‐energy (LE) fractures had 19% to 21% lower F.Load, 25% to 47% lower U.Stress, 11% to 14% lower Tt.BMD, and 11% to 15% lower BV/TV than Non‐Fx at all time points (p < 0.017). In contrast, boys’ bone outcomes were similar between Fx and Non‐Fx at all time points. In secondary analysis by fracture degree, boys with LE fractures had 10% lower Tt.BMD and 10% lower Ct.Th compared with Non‐Fx at 12 months only. Deficits in distal radius bone strength and trabecular bone microarchitecture appear to track across 2 years after a forearm fracture in girls but not in boys. Longer follow‐up is needed to determine whether deficits persist into adulthood in women and how they may influence future risk of fragility fracture. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT: A majority of low‐trauma fractures occur in subjects with only moderate decrease of areal bone mineral density (aBMD), ie, osteopenia, assessed by dual‐energy X‐ray absorptiometry (DXA) or low fracture probability assessed by FRAX. We investigated whether peripheral bone microstructure and estimated strength improve the prediction of incident fractures beyond central DXA and FRAX. In this population‐based study of 740 postmenopausal women (aged 65.0 ± 1.4 years) from the Geneva Retirees Cohort (ISRCTN registry 11865958), we assessed at baseline cortical (Ct) and trabecular (Tb) volumetric bone mineral density (vBMD) and microstructure by peripheral quantitative computed tomography (HR‐pQCT); bone strength by micro‐finite element analysis; aBMD and trabecular bone score (TBS) by DXA; and FRAX fracture probability. Eighty‐five low‐trauma fractures occurred in 68 women over a follow‐up of 5.0 ± 1.8 years. Tb and Ct vBMD and microstructure predicted incident fractures, independently of each other and of femoral neck (FN) aBMD and FRAX (with BMD ± TBS). However, the associations were markedly attenuated after adjustment for ultra‐distal radius aBMD (same bone site). The best discrimination between women with and without fracture was obtained at the radius with total vBMD, the combination of a Tb with a Ct parameter, or with failure load, which improved the area under the curve (AUC) for major osteoporotic fracture when added to FN aBMD (0.760 versus 0.695, p = 0.022) or to FRAX‐BMD (0.759 versus 0.714, p = 0.015). The replacement of failure load by ultra‐distal aBMD did not significantly decrease the AUC (0.753, p = 0.747 and 0.750, p = 0.509, respectively). In conclusion, peripheral bone microstructure and strength improve the prediction of fractures beyond central DXA and FRAX but are partially captured in aBMD measured by DXA at the radius. Because HR‐pQCT is not widely available for clinical purposes, assessment of ultra‐distal radius aBMD by DXA may meanwhile improve fracture risk estimation. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT: Older adults with type 2 diabetes (T2D) tend to have normal or greater areal bone mineral density (aBMD), as measured by DXA, than those who do not have diabetes (non‐T2D). Yet risk of fracture is higher in T2D, including 40% to 50% increased hip fracture risk. We used HR‐pQCT to investigate structural mechanisms underlying skeletal fragility in T2D. We compared cortical and trabecular bone microarchitecture, density, bone area, and strength in T2D and non‐T2D. In secondary analyses we evaluated whether associations between T2D and bone measures differed according to prior fracture, sex, and obesity. Participants included 1069 members of the Framingham Study, who attended examinations in 2005 to 2008 and underwent HR‐pQCT scanning in 2012 to 2015. Mean age was 64 ± 8 years (range, 40 to 87 years), and 12% (n = 129) had T2D. After adjustment for age, sex, weight, and height, T2D had lower cortical volumetric BMD (vBMD) (p < 0.01), higher cortical porosity (p = 0.02), and smaller cross‐sectional area (p = 0.04) at the tibia, but not radius. Trabecular indices were similar or more favorable in T2D than non‐T2D. Associations between T2D and bone measures did not differ according to sex or obesity status (all interaction p > 0.05); however, associations did differ in those with a prior fracture and those with no history of fracture. Specifically, cortical vBMD at the tibia and cortical thickness at the radius were lower in T2D than non‐T2D, but only among those individuals with a prior fracture. Cortical porosity at the radius was higher in T2D than non‐T2D, but only among those who did not have a prior fracture. Findings from this large, community‐based study of older adults suggest that modest deterioration in cortical bone and reductions in bone area may characterize diabetic bone disease in older adults. Evaluation of these deficits as predictors of fracture in T2D is needed to develop prevention strategies in this rapidly increasing population of older adults. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT There are no longitudinal pQCT data of bone growth and development from sub-Saharan Africa, where rapid environmental, societal, and economic transitions are occurring, and where fracture rates are predicted to rise. The aim of this study was to compare skeletal development in black and white South African adolescents using longitudinal data from the Birth to Twenty study. The Birth to Twenty Bone Health subcohort consisted of 543 adolescents (261 [178 black] girls, 282 [201 black] boys). Annual pQCT measurements of the radial and tibial metaphysis and diaphysis were obtained between ages 12 and 22 years (distal metaphysis: cross-sectional area [CSA] and trabecular bone mineral density [BMD]; diaphysis: total and cortical CSA, cortical BMD, and polar stress-strain index [SSIp]). Age at peak height velocity (APHV) was calculated to account for differences in maturational timing between ethnic groups and sexes. Mixed-effects models were used to describe trajectories for each pQCT outcome. Likelihood-ratio tests were used to summarize the overall difference in trajectories between black and white participants within each sex. APHV (mean ± SD years) was similar in black (11.8 ± 0.8) and white (12.2 ± 1.0) girls, but delayed in black (14.2 ± 1.0) relative to white boys (13.3 ± 0.8). By 4 years post-APHV, white adolescents had significantly greater cortical CSA and SSIp than black adolescents at the radius. There were no significant differences at the radial metaphysis but there was some divergence, such that black adolescents had greater radial trabecular BMD by the end of follow-up. At the tibia, white adolescents had lower diaphyseal CSA and SSIp, and greater metaphyseal CSA. There was no ethnic difference in tibial trabecular BMD. There are ethnic differences in bone growth and development, independent of maturation, in South African adolescents. This work gives new insights into the possible etiology of childhood fractures, which occur most commonly as peripheral sites. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. [ABSTRACT FROM AUTHOR]

Objective: Ascertain whether there are differences in the prevalence of osteoporosis drugs in patients with type 2 diabetes (DM2) and non-diabetic patients. Material and methods: Retrospective cohort study with data from the Information System for the Development of Primary Care Research (SIDIAP), which contains anonymous clinical information from more than 5 million patients in Catalonia. All 50-year-old patients diagnosed with DM2, who were matched with two subjects without diabetes, were selected. Information on descriptive variables, prevalent fractures and the use of osteoporosis drugs grouped in bisphosphonates (BF), calcium and vitamin D supplements (CaD), and any osteoporosis drug (OD) were collected. Through logistic regression, the association between the presence of DM2 and the use of OD was calculated, adjusting for confounding variables. Results: A total of 166,106 patients with DM2 and 332,212 non-diabetics. The DM2 group presented a higher prevalence of fracture than did diabetics (1.3% vs 0.3%). The use of BF in patients with DM2 was 6.6%, compared to 9.3% in non-diabetics (p<0.001). Of CaD, 9.7% vs 12.3% (p<0.001) and OD, 7.6% vs 10.7% (p<0.001). After adjusting for variable confounders, the patients with DM2 presented a lower probability of being treated with BF (OR=0.67, 95% CI: 0.64-0.68), with CaD (OR=0.71, 95% CI: 0.70-0.73) or with OD (OR=0.66, 95% CI: 0.64-0.67) than non-diabetics. Conclusions: Despite having a higher prevalence of fractures in patients with DM2, they have more than 30% chance of not having received an OD than non-diabetic patients. This may be attributed to an underestimation of risk in these patients.. [ABSTRACT FROM AUTHOR]

Objective: Ascertain whether there are differences in the prevalence of osteoporosis drugs in patients with type 2 diabetes (DM2) and non-diabetic patients. Material and methods: Retrospective cohort study with data from the Information System for the Development of Primary Care Research (SIDIAP), which contains anonymous clinical information from more than 5 million patients in Catalonia. All 50-year-old patients diagnosed with DM2, who were matched with two subjects without diabetes, were selected. Information on descriptive variables, prevalent fractures and the use of osteoporosis drugs grouped in bisphosphonates (BF), calcium and vitamin D supplements (CaD), and any osteoporosis drug (OD) were collected. Through logistic regression, the association between the presence of DM2 and the use of OD was calculated, adjusting for confounding variables. Results: A total of 166,106 patients with DM2 and 332,212 non-diabetics. The DM2 group presented a higher prevalence of fracture than did diabetics (1.3% vs 0.3%). The use of BF in patients with DM2 was 6.6%, compared to 9.3% in non-diabetics (p<0.001). Of CaD, 9.7% vs 12.3% (p<0.001) and OD, 7.6% vs 10.7% (p<0.001). After adjusting for variable confounders, the patients with DM2 presented a lower probability of being treated with BF (OR=0.67, 95% CI: 0.64-0.68), with CaD (OR=0.71, 95% CI: 0.70-0.73) or with OD (OR=0.66, 95% CI: 0.64-0.67) than non-diabetics. Conclusions: Despite having a higher prevalence of fractures in patients with DM2, they have more than 30% chance of not having received an OD than non-diabetic patients. This may be attributed to an underestimation of risk in these patients. [ABSTRACT FROM AUTHOR]

Summary: Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD) for hip fracture prediction was validated in a Norwegian population 50-90 years. Fracture risk increased with higher FRAX score, and the observed number of hip fractures agreed well with the predicted number, except for the youngest and oldest men. Self-reported fall was an independent risk factor for fracture in women. Introduction: The primary aim was to validate FRAX without BMD for hip fracture prediction in a Norwegian population of men and women 50-90 years. Secondary, to study whether information of falls could improve prediction of fractures in the subgroup aged 70-90 years. Methods: Data were obtained from the third survey of the Nord-Trøndelag Health Study (HUNT3), the fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database (NorPD), including 15,432 women and 13,585 men. FRAX hip without BMD was calculated, and hip fractures were registered for a median follow-up of 5.2 years. The number of estimated and observed fractures was assessed, ROC curves with area under the curve (AUC), and Cox regression analyses. For the group aged 70-90 years, self-reported falls the last year before HUNT3 were included in the Cox regression model. Results: The risk of fracture increased with higher FRAX score. When FRAX groups were categorized in a 10-year percentage risk for hip fracture as follows, <4, 4-7.9, 8-11.9, and ≥12%, the hazard ratio (HR) for hip fracture between the lowest and the highest group was 17.80 (95% CI: 12.86-24.65) among women and 23.40 (13.93-39.30) in men. Observed number of hip fractures agreed quite well with the predicted number, except for the youngest and oldest men. AUC was 0.81 (0.78-0.83) for women and 0.79 (0.76-0.83) for men. Self-reported fall was an independent risk factor for fracture in women (HR 1.64, 1.20-2.24), and among men, this was not significant (1.09, 0.65-1.83). Conclusions: FRAX without BMD predicted hip fracture reasonably well. In the age group 70-90 years, falls seemed to imply an additional risk among women. [ABSTRACT FROM AUTHOR]

Abstract: Low bone mineral density (BMD) and microvascular diseases (MVD) share various common risk factors; however, whether MVD is an independent risk factor of vertebral fractures is incompletely understood. The aim of this study is to clarify whether MVD is an independent risk factor of vertebral fractures. In this prospective study, calcaneal BMD and retinal microvascular abnormalities were assessed at baseline from June 2011 to January 2012. A total of 2176 premenopausal women, 2633 postmenopausal women, 2998 men aged <65 years, and 737 men aged ≥65 were included. Then with/without retinal microvascular abnormalities cohorts were followed for an average of 2.93 years to find out the relationship between MVD and vertebral fractures. At the baseline, after full adjustment, retinal microvascular abnormalities were related to risk of low BMD only in men aged ≥65 years (odds ratio [OR] = 2.506; 95% confidence interval [CI] 1.454–4.321; p = 0.001). After follow‐up of 2.93 years, retinal microvascular abnormalities were related to risk of vertebral fractures in men aged ≥65 years (OR = 2.475; 95% CI 1.085–5.646; p = 0.031) when adjustment for confounding factors. However, no associations were found between MVD and vertebral fractures in men aged <65 years, premenopausal women, and postmenopausal women. When stratified by diabetes, in the without‐diabetes group, the men with retinal microvascular abnormalities had higher risk for vertebral fractures than without retinopathy (OR = 2.194; 95% CI 1.097–4.389; p = 0.026); however, the difference was not found in women. In the diabetes group, there were no significant differences of risk for vertebral fractures between those with retinal microvascular abnormalities and those without both in men and women. Stratified by hypertension, the men with retinopathy had higher risk for vertebral fractures than those without among the hypertension group (OR = 2.034; 95% CI 1.163–3.559; p = 0.013), but a difference was not found among women. In the without‐hypertension group, no relation was found between MVD and fracture both in men and women. In conclusion, MVD is an independent risk factor of vertebral fractures in old men. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Summary: Post-fracture mortality in type 2 diabetes mellitus (T2DM) patients has been poorly studied. We report an absolute and relative excess all-cause mortality following a fracture in these patients compared to non-diabetic patients. Introduction: T2DM and osteoporotic fractures are independently associated with a reduced lifespan, but it is unknown if T2DM confers an excess post-fracture mortality compared to non-diabetic fracture patients. We report post-fracture all-cause mortality according to T2DM status. Methods: This is a population-based cohort study using data from the SIDIAP database. All ≥50 years old T2DM patients registered in SIDIAP in 2006-2013 and two diabetes-free controls matched on age, gender, and primary care center were selected. Study outcome was all-cause mortality following incident fractures. Participants were followed from date of any fracture (AF), hip fracture (HF), and clinical vertebral fracture (VF) until the earliest of death or censoring. Cox regression was used to calculate mortality according to T2DM status after adjustment for age, gender, body mass index, smoking, alcohol intake, and previous ischemic heart and cerebrovascular disease. Results: We identified 166,106 T2DM patients and 332,212 non-diabetic, of which 11,066 and 21,564, respectively, sustained a fracture and were then included. Post-fracture mortality rates (1000 person-years) were (in T2DM vs non-diabetics) 62.7 vs 49.5 after AF, 130.7 vs 112.7 after HF, and 54.9 vs 46.2 after VF. Adjusted HR (95% CI) for post-AF, post-HF, and post-VF mortality was 1.30 (1.23-1.37), 1.28 (1.20-1.38), and 1.20 (1.06-1.35), respectively, for T2DM compared to non-diabetics. Conclusions: T2DM patients have a 30% increased post-fracture mortality compared to non-diabetics and a remarkable excess in absolute mortality risk. More research is needed on the causes underlying such excess risk, and on the effectiveness of measures to reduce post-fracture morbi-mortality in T2DM subjects. [ABSTRACT FROM AUTHOR]

Small vertebral size is an independent risk factor for osteoporotic vertebral fractures. Physical growth in early life is related to bone health in later life, but the relationship of early growth versus vertebral size has been inconclusively studied. Utilizing the Northern Finland Birth Cohort 1966 with a 47-year follow-up, we investigated how physical growth in early life is associated with midlife vertebral dimensions. We obtained several physical growth parameters of 1) birth (gestational age, length, weight, BMI), 2) infancy and childhood (peak height velocity (PHV), peak weight velocity (PWV), adiposity peak (AP), adiposity rebound (AR)), and 3) puberty (BMI at growth spurt take-off (TO), PHV, height change). We also studied 4) the ages at which AP, AR, pubertal TO and pubertal PHV occurred. The outcome variable, vertebral cross-sectional area (CSA), was obtained from magnetic resonance imaging scans at the mean age of 46.7 years ( n = 517). Sex-stratified linear regression analyses were used with adjustments for gestational age, smoking, and education. Birth length/weight/BMI, and adult height/weight/BMI were also used as covariates, depending on the model. According to our results, birth weight ( p ≤ 0.006) and infant PWV ( p ≤ 0.001) were positively associated with midlife vertebral CSA among both sexes. Length/height variables were associated with vertebral size only before including adult height in the models, and became non-significant thereafter. Among women, BMIs at birth, AP, AR, and pubertal TO were positively associated with midlife vertebral CSA ( p < 0.05), whereas among men, only high BMI at AR was associated with large vertebral size ( p = 0.028). Gestational age and timing of growth were not associated with future vertebral CSA. We conclude that early life weight gain is positively associated with midlife vertebral CSA, and suggest that adult height may mediate the effect of height gain on vertebral size. [ABSTRACT FROM AUTHOR]

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

ABSTRACT Longitudinal studies assessing age-related changes using high-resolution peripheral quantitative computed tomography (HR-pQCT) provide novel insight compared with cross-sectional analyses. The purpose of this cohort study was 1) to determine individuals' change in HR-pQCT parameters over 5 years relative to least significant change (LSC), and 2) to evaluate if predicted rate of change from cross-sectional data is comparable to actual change from longitudinal investigation. A cohort of 466 (162 male, 304 female) participants completed two HR-pQCT scans with 5 years between assessments. After image registration, standard and cortical morphological analyses were conducted. Rate of bone microarchitectural change was compared between cross-sectional models and actual change calculated from longitudinal analyses. At the young end of the life span, we observed gains in total bone density of +0.2% to +2.9% per year, whereas the older participants (aged >50 years) lost total bone density at a rate of -0.3% to -1.3% per year. Declines in total bone density begin at age 40 years in females and 60 years in males, and significant adaptation was found at both ends of the age spectrum with respect to the LSC. Models predicting rate of change from cross-sectional data were similar to the actual change reported in this longitudinal study for total density and cortical thickness at the radius and cortical density at the tibia, but we found that changes in comparison to our 5-year longitudinal results were often overestimated from cross-sectional data. Studies aimed at observing age-related changes in a normative cohort, especially in a follow-up period of less than 5 years, are better to focus on the tibia rather than the radius because of the increased sensitivity to change at the tibia. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Fracture risk is determined by bone strength and the risk of falls. The relationship between serum sex steroids and bone strength parameters in men is well known, whereas the predictive value of sex steroids for falls is less studied. The aim of this study was to assess the associations between serum testosterone (T) and estradiol (E2) and the likelihood of falls. Older men (aged ≥65 years) from the United States ( n = 1919), Sweden ( n = 2495), and Hong Kong ( n = 1469) participating in the Osteoporotic Fractures in Men Study had baseline T and E2 analyzed by mass spectrometry. Bioavailable (Bio) levels were calculated using mass action equations. Incident falls were ascertained every 4 months during a mean follow-up of 5.7 years. Associations between sex steroids and falls were estimated by generalized estimating equations. Fall rate was highest in the US and lowest in Hong Kong (US 0.50, Sweden 0.31, Hong Kong 0.12 fall reports/person/year). In the combined cohort of 5883 men, total T (odds ratio [OR] per SD increase = 0.88, 95% confidence interval [CI] 0.86-0.91) and BioT (OR = 0.86, 95% CI 0.83-0.88) were associated with incident falls in models adjusted for age and prevalent falls. These associations were only slightly attenuated after simultaneous adjustment for physical performance variables (total T: OR = 0.94, 95% CI 0.91-0.96; BioT: OR = 0.91, 95% CI 0.89-0.94). E2, BioE2, and sex hormone-binding globulin (SHBG) were not significantly associated with falls. Analyses in the individual cohorts showed that both total T and BioT were associated with falls in MrOS US and Sweden. No association was found in MrOS Hong Kong, and this may be attributable to environmental factors rather than ethnic differences because total T and BioT predicted falls in MrOS US Asians. In conclusion, low total T and BioT levels, but not E2 or SHBG, are associated with increased falls in older men. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Childhood growth has been linked with bone properties in adulthood, whereas less is known about the contribution of early growth to bone fracture risk. We investigated the association of body size at birth and childhood growth with hip fractures and pharmacotherapy for osteoporosis in older age. Men and women, born full term, from the Helsinki Birth Cohort Study ( n = 8345) were followed until the age of 68 to 80 years. Height and weight from birth to 11 years were obtained from health care records and diagnoses of hip fractures and osteoporosis drug purchases from national registers. Independent associations of each age period were analyzed using Cox models adjusted for age, childhood and adulthood socioeconomic status, and drugs affecting bone metabolism. In men, the risk of hip fractures was nonlinearly associated with childhood growth. Compared to intermediate increase, low and high increase in height between 2 and 7 years ( p < 0.001) were associated with all hip fractures and hip fractures sustained after the age of 50 years. Further, compared to intermediate gain, low and high gain in BMI between 7 and 11 years ( p = 0.001) were associated with greater risk of hip fractures in men. In women, growth was not associated with the risk of hip fractures but greater weight (hazard ratio [HR] = 0.85; 95% CI, 0.77 to 0.94; p = 0.001) and BMI (HR 0.86; 95% CI, 0.78 to 0.95; p = 0.003) gain between ages 2 and 7 years were associated with a decreased risk of pharmacotherapy for osteoporosis. In men, growth was not associated with the risk of pharmacotherapy for osteoporosis. In conclusion, growth during childhood may contribute to the risk of hip fractures in later life among men. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT The long-term consequences of bariatric surgery on fracture risk are unclear but are likely to vary by procedure type. In physiologic studies, Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) have differential effects on rates of bone loss. Therefore, our objective was to compare fracture risk in obese adults after RYGB and AGB procedures. Using claims data from a US commercial health plan, we analyzed rates of nonvertebral fractures within a propensity score-matched cohort ( n = 15,032) of morbidly obese adults who received either RYGB or AGB surgery between 2005 and 2013. A total of 281 nonvertebral fractures occurred during a mean follow-up time of 2.3 ± 1.9 years. RYGB patients had an increased risk of nonvertebral fracture (hazard ratio [HR] = 1.43, 95% confidence interval [CI] 1.13-1.81) compared with AGB patients. In fracture site-specific analyses, RYGB patients had increased risk of fracture at the hip (HR = 1.54, 95% CI 1.03-2.30) and wrist (HR = 1.45, 95% CI 1.01-2.07). Nonvertebral fracture risk associated with RYGB manifested >2 years after surgery and increased in subsequent years, with the highest risk in the fifth year after surgery (HR = 3.91, 95% CI 1.58-9.64). In summary, RYGB is associated with a 43% increased risk of nonvertebral fracture compared with AGB, with risk increasing >2 years after surgery. Fracture risk should be considered in risk/benefit discussions of bariatric surgery, particularly among patients with high baseline risk of osteoporosis who are deciding between RYGB and AGB procedures. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Summary: Dietary potassium may neutralize acid load and reduce calcium loss from the bone, leading to beneficial effect on bone mineral density. In this nationwide Korean population study, dietary potassium intake was associated with improved bone mineral density in older men and postmenopausal women. Introduction: Nutrition is a major modifiable factor that affects bone health. The accompanying anion in dietary potassium may act as an alkaline source by neutralizing the acid load and reducing calcium loss from the bone. We aimed to evaluate the association between dietary potassium intake and bone mineral density (BMD) in the Korean population. Methods: We analyzed a total of 3135 men aged >50 years and 4052 postmenopausal women from the Korean National Health and Nutrition Examination Survey (KNHANES). Lumbar spine, total hip, and femur neck BMD were measured using dual energy X-ray absorptiometry. The daily food intake was assessed using a food frequency questionnaire. Results: When we divided the participants into tertiles based on the intake of potassium intake, the highest potassium intake tertile group showed a significantly higher total hip and femur neck BMD as compared to lower tertile groups (0.914 ± 0.004, 0.928 ± 0.003, 0.925 ± 0.004 mg/day across the tertiles, P = .014 for total hip; 0.736 ± 0.003, 0.748 ± 0.003, 0.750 ± 0.004 mg/day, P = .012 for femur neck). Postmenopausal women in the highest potassium intake tertile group showed significantly higher lumbar, total hip, and femur neck BMD as compared to those in lower potassium intake tertile groups (0.793 ± 0.004, 0.793 ± 0.003, 0.805 ± 0.004 mg/day across the tertiles, P = .029 for lumbar spine; 0.766 ± 0.003, 0.770 ± 0.002, 0.780 ± 0.003 mg/day, P = .002 for total hip; 0.615 ± 0.003, 0.619 ± 0.002, 0.628 ± 0.003 mg/day, P = .002 for femur neck). Conclusions: Dietary potassium intake was positively associated with BMD in men aged >50 years and postmenopausal women, indicating the beneficial effects of dietary potassium intake on bone health. [ABSTRACT FROM AUTHOR]

Background and aims Lateral spine radiographs provide an inexpensive resource for characterizing abdominal aortic calcification (AAC). A widely accepted measurement of AAC is the semi-quantitative technique generated by the Framingham Heart Study (F-AAC-24). We sought to develop an analytical method to quantify ACC (Q AAC ) on lateral spine radiographs and compare the finding to conventional subjective measurements. Methods Severity of AAC was quantified by measuring pixel intensities in the user-defined region of the aorta with internal standardization to the vertebral endplates and background calibration to the density of the vertebral body. The association between bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) and AAC measured by Q AAC , F-AAC-24 and a modified Framingham score (F-AAC-12) was determined in 110 participants of the Canadian Multicenter Osteoporosis Study (CaMOS). Results The inter-observer reliability for the Q AAC was slightly higher than with the visual and semi-quantitative Framingham method and the pseudo-colored images illustrate the potential to meaningfully resolve severity of calcification. There was a significant negative association between Q AAC and BMD measures of the hip and spine. This association remained significant after adjustment for age, sex, estimated glomerular filtration rate, phosphate and hypertension. Significant predictors of F-ACC-12 and 24 included age and hypertension. Conclusions The Q AAC is a reproducible approach to measuring AAC. Whether it is capable of monitoring subtle calcific changes over time requires further study. This technique could be applied to large studies that seek to determine the impact of interventions that modify bone density as a treatment for vascular calcification and cardiovascular disease in the general population. [ABSTRACT FROM AUTHOR]

ABSTRACT Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (aged 80.8 ± 8.2 years [mean ± SD], 58% women) from the Swedish registry 'Senior Alert' and linked the data to several nationwide registers. We identified 79,159 individuals with T2DM (45% with insulin [T2DM-I], 41% with oral antidiabetics [T2DM-O], and 14% with no antidiabetic treatment [T2DM-none]) and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years, we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted hazard ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]), and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (1.22 [1.16-1.29]) and T2DM-O (1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I, but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin-treated patients, whereas the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT McCune-Albright syndrome (MAS) is a rare bone disorder characterized by fibrous dysplasia (FD), endocrinopathies, and café-au-lait patches. FD patients have been shown to respond favorably to treatment with bisphosphonates, but data are scarce in the more severe polyostotic form (PFD), including MAS, and factors determining treatment outcome are not known, particularly in the long-term. We evaluated the biochemical (bone turnover markers [BTMs]) and clinical (pain reduction) outcome of bisphosphonate therapy in 11 patients with MAS and 30 patients with PFD: median duration of treatment 6 years (range, 2 to 25 years). Prognostic factors for treatment outcome were identified in both groups. Patients with MAS were younger at diagnosis ( p = 0.001), all had precocious puberty, and four (36%) had additional growth hormone (GH) excess associated with severe craniofacial FD. Extent of skeletal disease was more severe in MAS compared to PFD. MAS patients had higher serum alkaline phosphatase (ALP) concentrations ( p = 0.005), higher skeletal burden scores ( p < 0.001), and more fractures ( p = 0.021). MAS patients had also higher levels of FGF-23 ( p = 0.008) and higher prevalence of hypophosphatemia ( p = 0.013). Twenty-four of 30 PFD patients (80%) demonstrated a complete clinical and biochemical response within a year of starting treatment ( p = 0.015), compared to only four of 11 MAS patients (36%). There were no nonresponders. In the whole group, FGF-23, total ALP, P1NP, and CTX positively correlated with skeletal burden scores (all p ≤ 0.001), which was the only significant risk factor for an incomplete response to bisphosphonate therapy ( p < 0.01). Our data suggest a beneficial and safe outcome of long-term bisphosphonate therapy in the majority of patients with PFD, although response to therapy was limited by the higher skeletal disease burden in MAS patients. In the PFD/MAS population studied, the only identified prognostic factor that influenced the outcome of bisphosphonate therapy was a high skeletal burden score. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT High-resolution peripheral quantitative computed tomography (HR-pQCT) measures bone microarchitecture and volumetric bone mineral density (vBMD), important risk factors for osteoporotic fractures. We estimated the heritability (h2) of bone microstructure indices and vBMD, measured by HR-pQCT, and genetic correlations (ρG) among them and between them and regional aBMD measured by dual-energy X-ray absorptiometry (DXA), in adult relatives from the Framingham Heart Study. Cortical (Ct) and trabecular (Tb) traits were measured at the distal radius and tibia in up to 1047 participants, and ultradistal radius (UD) aBMD was obtained by DXA. Heritability estimates, adjusted for age, sex, and estrogenic status (in women), ranged from 19.3% (trabecular number) to 82.8% ( p < 0.01, Ct.vBMD) in the radius and from 51.9% (trabecular thickness) to 98.3% (cortical cross-sectional area fraction) in the tibia. Additional adjustments for height, weight, and radial aBMD had no major effect on h2 estimates. In bivariate analyses, moderate to high genetic correlations were found between radial total vBMD and microarchitecture traits (ρG from 0.227 to 0.913), except for cortical porosity. At the tibia, a similar pattern of genetic correlations was observed (ρG from 0.274 to 0.948), except for cortical porosity. Environmental correlations between the microarchitecture traits were also substantial. There were high genetic correlations between UD aBMD and multivariable-adjusted total and trabecular vBMD at the radius (ρG = 0.811 and 0.917, respectively). In summary, in related men and women from a population-based cohort, cortical and trabecular microarchitecture and vBMD at the radius and tibia were heritable and shared some h2 with regional aBMD measured by DXA. These findings of high heritability of HR-pQCT traits, with a slight attenuation when adjusting for aBMD, supports further work to identify the specific variants underlying volumetric bone density and fine structure of long bones. Knowledge that some of these traits are genetically correlated can serve to reduce the number of traits for genetic association studies. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Obesity has been traditionally considered to protect the skeleton against osteoporosis and fracture. Recently, body fat, specifically visceral adipose tissue (VAT), has been associated with lower bone mineral density (BMD) and increased risk for some types of fractures. We studied VAT and bone microarchitecture in 710 participants (58% women, age 61.3 ± 7.7 years) from the Framingham Offspring cohort to determine whether cortical and trabecular BMD and microarchitecture differ according to the amount of VAT. VAT was measured from CT imaging of the abdomen. Cortical and trabecular BMD and microarchitecture were measured at the distal tibia and radius using high-resolution peripheral quantitative computed tomography (HR-pQCT). We focused on 10 bone parameters: cortical BMD (Ct.BMD), cortical tissue mineral density (Ct.TMD), cortical porosity (Ct.Po), cortical thickness (Ct.Th), cortical bone area fraction (Ct.A/Tt.A), trabecular density (Tb.BMD), trabecular number (Tb.N), trabecular thickness (Tb.Th), total area (Tt.Ar), and failure load (FL) from micro-finite element analysis. We assessed the association between sex-specific quartiles of VAT and BMD, microarchitecture, and strength in all participants and stratified by sex. All analyses were adjusted for age, sex, and in women, menopausal status, then repeated adjusting for body mass index (BMI) or weight. At the radius and tibia, Ct.Th, Ct.A/Tt.A, Tb.BMD, Tb.N, and FL were positively associated with VAT (all p-trend <0.05), but no other associations were statistically significant except for higher levels of cortical porosity with higher VAT in the radius. Most of these associations were only observed in women, and were no longer significant when adjusting for BMI or weight. Higher amounts of VAT are associated with greater BMD and better microstructure of the peripheral skeleton despite some suggestions of significant deleterious changes in cortical measures in the non-weight bearing radius. Associations were no longer significant after adjustment for BMI or weight, suggesting that the effects of VAT may not have a substantial effect on the skeleton independent of BMI or weight. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Amino acids are the building blocks of proteins, and sufficient protein intake is important for skeletal health. We utilized stored serum from the Cardiovascular Health Study in 1992-1993 to examine the relationship between levels of the essential amino acid tryptophan (trp) and its oxidized and nonoxidized metabolites to risk for incident hip fractures and mortality over 12 years of follow-up. We included 131 persons who sustained a hip fracture during this time period and 131 without a hip fracture over these same 12 years of follow-up; 58% female and 95% White. Weighted multivariable Cox hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of incident hip fracture associated with a one standard deviation (SD) higher trp or its metabolites exposure. Relative risk regression was used to evaluate the cross-sectional association of trp and its metabolites with frailty. Higher serum levels of trp were significantly associated with lower risk of incident hip fractures (HR = 0.75 per SD of trp (95% CI 0.57-0.99) but were not significantly associated with mortality or frailty status by Freid's frailty index. There were no statistically significant associations between any of the oxidized or nonoxidized products of trp with incident hip fractures ( p  ≥ 0.64), mortality ( p  ≥ 0.20), or cross-sectional frailty status ( p  ≥ 0.13) after multiple testing adjustment. Randomized clinical trials examining whether increasing trp intake is beneficial for osteoporosis are needed. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Low countermovement jump power is associated with prevalent fracture, osteoporosis, and sarcopenia in older adults. However, whether jump power predicts incident fracture risk remains uninvestigated. Data of 1366 older adults in a prospective community cohort were analyzed. Jump power was measured using a computerized ground force plate system. Fracture events were ascertained by follow-up interview and linkage to the national claim database (median follow-up 6.4 years). Participants were divided into normal and low jump power groups using a predetermined threshold (women <19.0 W/kg; men <23.8 W/kg; or unable to jump). Among the study participants (mean age 71.6 years, women 66.3%), low jump power was associated with a higher risk of fracture (hazard ratio [HR] = 2.16 versus normal jump power, p < 0.001), which remained robust (adjusted HR = 1.45, p = 0.035) after adjustment for fracture risk assessment tool (FRAX) major osteoporotic fracture (MOF) probability with bone mineral density (BMD) and Asian Working Group for Sarcopenia (AWGS) 2019 sarcopenia definition. In the AWGS no sarcopenia group, participants with low jump power had a significantly higher risk of fracture than those with normal jump power (12.5% versus 6.7%; HR = 1.93, p = 0.013), comparable to that of possible sarcopenia without low jump power (12.0%). Possible sarcopenia group with low jump power had a similar risk of fracture (19.3%) to sarcopenia group (20.8%). When the definition of sarcopenia was modified with jump power measurement (step-up approach: no sarcopenia to possible sarcopenia; possible sarcopenia to sarcopenia when low jump power present), jump power-modified sarcopenia improved sensitivity (18%-39.3%) to classify individuals who sustained MOF during follow-up to high risk compared with AWGS 2019 sarcopenia, while maintaining positive predictive value (22.3%-20.6%). In summary, jump power predicted fracture risk in community-dwelling older adults independently of sarcopenia and FRAX MOF probabilities, suggesting potential contribution of complex motor function measurement in fracture risk assessment. © 2023 American Society for Bone and Mineral Research (ASBMR)., (© 2023 American Society for Bone and Mineral Research (ASBMR).)

ABSTRACT Cytokines play major roles in regulating bone remodeling, but their relationship to incident fractures in older men is uncertain. We tested the hypothesis that men with higher concentrations of pro-inflammatory markers have a higher risk of fracture. We used a case-cohort design and measured inflammatory markers in a random sample of 961 men and in men with incident fractures including 120 clinical vertebral, 117 hip, and 577 non-spine fractures; average follow-up 6.13 years (7.88 years for vertebral fractures). We measured interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of non-spine, hip, and clinical vertebral fracture was compared across quartiles (Q) of inflammatory markers using Cox proportional hazard models with tests for linear trend. In multivariable-adjusted models, men with the highest (Q4) TNFa cytokine concentrations and their receptors had a 2.0-4.2-fold higher risk of hip and clinical vertebral fracture than men with the lowest (Q1). Results were similar for all non-spine fractures, but associations were smaller. There was no association between CRP and IL-6SR and fracture. Men in the highest Q of IL-10 had a 49% lower risk of vertebral fracture compared with men in Q1. Among men with ≥3 inflammatory markers in the highest Q, the hazard ratio (HR) for hip fractures was 2.03 (95% confidence interval [CI] 1.11-3.71) and for vertebral fracture 3.06 (1.66-5.63). The HRs for hip fracture were attenuated by 27%, 27%, and 15%, respectively, after adjusting for appendicular lean mass (ALM), disability, and bone density, suggesting mediating roles. ALM also attenuated the HR for vertebral fractures by 10%. There was no association between inflammation and rate of hip BMD loss. We conclude that inflammation may play an important role in the etiology of fractures in older men. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]