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We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Dual‐energy X‐ray absorptiometry (DXA)‐derived appendicular lean mass/height2 (ALM/ht2) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX‐MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T‐score. Results were synthesized by meta‐analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T‐score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures.

ObjectiveStatistical shape modelling (SSM) of hip dual-energy X-ray absorptiometry (DXA) scans has identified relationships between hip shape and radiographic hip OA (rHOA). We aimed to further elucidate shape characteristics related to rHOA by focusing on subregions identified from whole-hip shape models.MethodSSM was applied to hip DXAs obtained in the Osteoporotic Fractures in Men Study. Whole-hip shape modes (HSMs) associated with rHOA were combined to form a composite at-risk-shape. Subsequently, subregional HSMs (cam-type and lesser trochanter modes) were built, and associations with rHOA were examined by logistic regression. Subregional HSMs were further characterised, by examining associations with 3D-HSMs derived from concurrent hip CT scans.Results4,098 participants were identified with hip DXAs and radiographs. Composite shapes from whole-hip HSMs revealed that lesser trochanter size and cam-type femoral head are related to rHOA. From sub-regional models, lesser trochanter mode (LTM)1 [OR 0.74; 95%CI 0.63.0.87] and cam-type mode (CTM)3 [OR 1.27; 1.13.1.42] were associated with rHOA, associations being similar to those for whole hip HSMs. 515 MrOS participants had hip DXAs and 3D-HSMs derived from hip CT scans. LTM1 was associated with 3D-HSMs that also represented a larger lesser trochanter [3D-HSM7 (beta (β)-0.23;-0.33,-0.14) and 3D-HSM9 (β0.36; 0.27.0.45)], and CTM3 with 3D-HSMs describing cam morphology [3D-HSM3 (β-0.16;-0.25,-0.07) and 3D-HSM6 (β0.19; 0.10.0.28)].ConclusionSubregional SSM of hip DXA scans suggested larger lesser trochanter and cam morphology underlie associations between overall hip shape and rHOA. 3D hip modelling suggests our subregional SSMs represent true anatomical variations in hip shape, warranting further investigation.

Accelerated bone loss (ABL) shown on routine dual-energy X-ray absorptiometry (DXA) may be accompanied by microarchitectural changes, increased cortical porosity, and lower bone strength. To test this hypothesis, we performed a cross-sectional study and used high-resolution peripheral quantitative computed tomography (HR-pQCT) scans (Scanco Medical AG, Brüttisellen, Switzerland) to measure estimated bone strength and microarchitecture in the distal radius and distal and diaphyseal tibia. We studied 1628 men who attended the year 14 exam of the Osteoporotic Fractures in Men (MrOS) study. We retrospectively characterized areal bone mineral density (aBMD) change from the year 7 to year 14 exam in three categories: "accelerated" loss, ≥10% loss at either the total hip or femoral neck (n = 299, 18.4%); "expected" loss,10% (n = 1061, 65.2%), and "maintained" BMD, ≥0% (n = 268, 16.5%). The ABL cut-off was a safety alert established for MrOS. We used regression models to calculate adjusted mean HR-pQCT parameters in men with ABL, expected loss, or maintained BMD. Men who experienced ABL were older and had a lower body mass index and aBMD and experienced greater weight loss compared with other men. Total volumetric BMD and trabecular and cortical volumetric BMD were lower in men with ABL compared with the expected or maintained group. Men with ABL had significantly lower trabecular bone volume fraction (BV/TV), fewer trabeculae, and greater trabecular separation at both the distal radius and tibia than men with expected loss or who maintained aBMD, all p trend0.001. Men with ABL had lower cortical thickness and lower estimated bone strength, but there was no difference in cortical porosity except at the tibia diaphyseal site. In summary, men with ABL have lower estimated bone strength, poorer trabecular microarchitecture, and thinner cortices than men without ABL but have similar cortical porosity. These impairments may lead to an increased risk of fracture. © 2018 American Society for Bone and Mineral Research.

Measures of muscle mass, strength, and function predict risk of incident fractures, but it is not known whether this risk information is additive to that from FRAX (fracture risk assessment tool) probability. In the Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, Hong Kong, United States), we investigated whether measures of physical performance/appendicular lean mass (ALM) by DXA predicted incident fractures in older men, independently of FRAX probability. Baseline information included falls history, clinical risk factors for falls and fractures, femoral neck aBMD, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the relationship between time for five chair stands, walking speed over a 6 m distance, grip strength, ALM adjusted for body size (ALM/height2), FRAX probability (major osteoporotic fracture [MOF]) with or without femoral neck aBMD, available in a subset of n = 7531), and incident MOF (hip, clinical vertebral, wrist, or proximal humerus). Associations were adjusted for age and time since baseline, and are reported as hazard ratios (HRs) for first incident fracture per SD increment in predictor using meta‐analysis. 5660 men in the United States (mean age 73.5 years), 2764 men in Sweden (75.4 years), and 1987 men in Hong Kong (72.4 years) were studied. Mean follow‐up time was 8.7 to 10.9 years. Greater time for five chair stands was associated with greater risk of MOF (HR 1.26; 95% CI, 1.19 to 1.34), whereas greater walking speed (HR 0.85; 95% CI, 0.79 to 0.90), grip strength (HR 0.77; 95% CI, 0.72 to 0.82), and ALM/height2 (HR 0.85; 95% CI, 0.80 to 0.90) were associated with lower risk of incident MOF. Associations remained largely similar after adjustment for FRAX, but associations between ALM/height2 and MOF were weakened (HR 0.92; 95% CI, 0.85 to 0.99). Inclusion of femoral neck aBMD markedly attenuated the association between ALM/height2 and MOF (HR 1.02; 95% CI, 0.96 to 1.10). Measures of physical performance predicted incident fractures independently of FRAX probability. Whilst the predictive value of ALM/height2 was substantially reduced by inclusion of aBMD requires further study, these findings support the consideration of physical performance in fracture risk assessment. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

ObjectiveStatistical shape modelling (SSM) of radiographs has been used to explore relationships between altered joint shape and hip osteoarthritis (OA). We aimed to apply SSM to Dual-energy X-ray Absorptiometry (DXA) hip scans, and examine associations between resultant hip shape modes (HSMs), radiographic hip OA (RHOA), and hip pain, in a large population based cohort.MethodSSM was performed on baseline hip DXA scans from the Osteoporotic Fractures in Men (MrOS) Study. Associations between the top ten HSMs, and prevalent RHOA from pelvic radiographs obtained 4.6 years later, were analysed in 4100 participants. RHOA was defined as Croft score ≥2. Hip pain was based on pain on walking, hip pain on examination, and Western Ontario and McMaster Universities Arthritis Index (WOMAC).ResultsThe five HSMs associated with RHOA showed features of either pincer- or cam-type deformities. HSM 1 (increased pincer-type deformity) was positively associated with RHOA [1.23 (1.09, 1.39)] [odds ratio (OR) and 95% CI]. HSM 8 (reduced pincer-type deformity) was inversely associated with RHOA [0.79 (0.70, 0.89)]. HSM 10 (increased cam-type deformity) was positively associated with RHOA [1.21 (1.07, 1.37)]. HSM 3 and HSM 4 (reduced cam-type deformity) were inversely associated with RHOA [0.73 (0.65, 0.83) and 0.82 (0.73, 0.93), respectively]. HSM 3 was inversely related to pain on examination [0.84 (0.76, 0.92)] and walking [0.88, (0.81, 0.95)], and to WOMAC score [0.87 (0.80, 0.93)].ConclusionsDXA-derived measures of hip shape are associated with RHOA, and to a lesser extent hip pain, possibly reflecting their role in the pathogenesis of hip OA.

© 2017 Osteoarthritis Research Society International Objective Statistical shape modelling (SSM) of radiographs has been used to explore relationships between altered joint shape and hip osteoarthritis (OA). We aimed to apply SSM to Dual-energy X-ray Absorptiometry (DXA) hip scans, and examine associations between resultant hip shape modes (HSMs), radiographic hip OA (RHOA), and hip pain, in a large population based cohort. Method SSM was performed on baseline hip DXA scans from the Osteoporotic Fractures in Men (MrOS) Study. Associations between the top ten HSMs, and prevalent RHOA from pelvic radiographs obtained 4.6 years later, were analysed in 4100 participants. RHOA was defined as Croft score ≥2. Hip pain was based on pain on walking, hip pain on examination, and Western Ontario and McMaster Universities Arthritis Index (WOMAC). Results The five HSMs associated with RHOA showed features of either pincer- or cam-type deformities. HSM 1 (increased pincer-type deformity) was positively associated with RHOA [1.23 (1.09, 1.39)] [odds ratio (OR) and 95% CI]. HSM 8 (reduced pincer-type deformity) was inversely associated with RHOA [0.79 (0.70, 0.89)]. HSM 10 (increased cam-type deformity) was positively associated with RHOA [1.21 (1.07, 1.37)]. HSM 3 and HSM 4 (reduced cam-type deformity) were inversely associated with RHOA [0.73 (0.65, 0.83) and 0.82 (0.73, 0.93), respectively]. HSM 3 was inversely related to pain on examination [0.84 (0.76, 0.92)] and walking [0.88, (0.81, 0.95)], and to WOMAC score [0.87 (0.80, 0.93)]. Conclusions DXA-derived measures of hip shape are associated with RHOA, and to a lesser extent hip pain, possibly reflecting their role in the pathogenesis of hip OA.

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P, Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.

We investigated the associations of 3D geometric measures and volumetric bone mineral density (vBMD) of the proximal femur assessed by quantitative computed tomography (QCT) with hip fracture risk among elderly men. This study was a prospective case-cohort design nested within the Osteoporotic Fractures in Men Study (MrOS) cohort. QCT scans of 230 men (65 with confirmed hip fractures) were evaluated with Mindways' QCTPRO-BIT software. Measures that are indicative of bone strength for the femoral neck (FN) and for the trochanteric region (TR) were defined. Bending strength measures were estimated by minimum section modulus, buckling strength by buckling ratio, and a local thinning index (LTI). Integral and trabecular vBMD measures were also derived. Areal BMD (aBMD) of the total proximal femur from dual-energy X-ray absorptiometry (DXA) is presented for comparison. Associations of skeletal measures with incident hip fracture were estimated with hazard ratios (HR) per standard deviation and their 95% confidence intervals (CI) from Cox proportional hazard regression models with adjustment for age, body mass index (BMI), site, and aBMD. Men with hip fractures were older than men without fracture (77.1 ± 6.0 years versus 73.3 ± 5.7 years, p 0.01). Age, BMI, and site-adjusted HRs were significant for all measures except TR_LTI. Total femural BMD by DXA (HR = 4.9, 95% CI 2.5-9.9) and QCT (HR = 5.5, 95% CI 2.5-11.7) showed the strongest association followed by QCT FN integral vBMD (HR = 3.6, 95% CI 1.8-6.9). In models that additionally included aBMD, FN buckling ratio (HR = 1.9, 95% CI 1.1-3.2) and trabecular vBMD of the TR (HR = 2.0, 95% CI 1.2-3.4) remained associated with hip fracture risk, independent of aBMD. QCT-derived 3D geometric indices of instability of the proximal femur were significantly associated with incident hip fractures, independent of DXA aBMD. Buckling of the FN is a relevant failure mode not entirely captured by DXA. Further research to study these relationships in women is warranted. © 2016 American Society for Bone and Mineral Research.

Study Objectives: Maintaining adequate serum levels of vitamin D may be important for sleep duration and quality; however, these associations are not well understood. We examined whether levels of serum 25(OH)D are associated with objective measures of sleep in older men. Setting and Participants: Cross-sectional study within a large cohort of community-dwelling older men, the MrOS study. Interventions: Among 3,048 men age 68 years or older, we measured total serum vitamin D. Objective estimates of nightly total sleep time, sleep efficiency, and wake time after sleep onset (WASO) were obtained using wrist actigraphy worn for an average of 5 consecutive 24-h periods. Results: 16.4% of this study population had low levels of vitamin D (< 20.3 ng/mL 25(OH)D). Lower serum vitamin D levels were associated with a higher odds of short (< 5 h) sleep duration, (odds ratio [OR] for the highest (≥ 40.06 ng/mL) versus lowest (< 20.3 ng/mL) quartile of 25(OH)D, 2.15; 95 % confidence interval (CI), 1.21-3.79; Ptrend = 0.004) as well as increased odds of actigraphy-measured sleep efficiency of less than 70% (OR, 1.45; 95% CI, 0.97-2.18; Ptrend = 0.004), after controlling for age, clinic, season, comorbidities, body mass index, and physical and cognitive function. Lower vitamin D levels were also associated with increased WASO in age-adjusted, but not multivariable adjusted models Conclusions: Among older men, low levels of total serum 25(OH)D are associated with poorer sleep including short sleep duration and lower sleep efficiency. These findings, if confirmed by others, suggest a potential role for vitamin D in maintaining healthy sleep.

ObjectiveTo assess bone-muscle (B-M) indices as risk factors for incident fractures in men.MethodsParticipants of the Osteoporotic Fractures in Men (MrOS) Study completed a peripheral quantitative computed tomography scan at 66% of their tibial length. Bone macrostructure, estimates of bone strength, and muscle area were computed. Areal bone mineral density (aBMD) and body composition were assessed with dual-energy X-ray absorptiometry. Four year incident non-spine and clinical vertebral fractures were ascertained. B-M indices were expressed as bone-to-muscle ratios for: strength, mass and area. Discriminative power and hazards ratios (HR) for fractures were reported.ResultsIn 1163 men (age: 77.2±5.2 years, body mass index (BMI): 28.0±4.0 kg/m(2), 4.1±0.9 follow-up years, 7.7% of men ⋝1 fracture), B-M indices were smaller in fractured men except for bending and areal indices. Smaller B-M indices were associated with increased fracture risk (HR: 1.30 to 1.74) independent of age and BMI. Strength and mass indices remained significant after accounting for lumbar spine but not total hip aBMD. However, aBMD correlated significantly with B-M indices.ConclusionMass and bending B-M indices are risk factors for fractures in men, but may not improve fracture risk prediction beyond that provided by total hip aBMD.

Although increasing body weight has been regarded as protective against osteoporosis and fractures, there is accumulating evidence that fat mass adversely affects skeletal health compared with lean mass. We examined skeletal health as a function of estimated total body lean and fat mass in 40,050 women and 3600 men age ≥ 50 years at the time of baseline dual-energy X-ray absorptiometry (DXA) testing from a clinical registry from Manitoba, Canada. Femoral neck bone mineral density (BMD), strength index (SI), cross-sectional area (CSA), and cross-sectional moment of inertia (CSMI) were derived from DXA. Multivariable models showed that increasing lean mass was associated with near-linear increases in femoral BMD, CSA, and CSMI in both women and men, whereas increasing fat mass showed a small initial increase in these measurements followed by a plateau. In contrast, femoral SI was relatively unaffected by increasing lean mass but was associated with a continuous linear decline with increasing fat mass, which should predict higher fracture risk. During mean 5-year follow-up, incident major osteoporosis fractures and hip fractures were observed in 2505 women and 180 men (626 and 45 hip fractures, respectively). After adjustment for fracture risk assessment tool (FRAX) scores (with or without BMD), we found no evidence that lean mass, fat mass, or femoral SI affected prediction of major osteoporosis fractures or hip fractures. Findings were similar in men and women, without significant interactions with sex or obesity. In conclusion, skeletal adaptation to increasing lean mass was positively associated with BMD but had no effect on femoral SI, whereas increasing fat mass had no effect on BMD but adversely affected femoral SI. Greater fat mass was not independently associated with a greater risk of fractures over 5-year follow-up. FRAX robustly predicts fractures and was not affected by variations in body composition.

Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause arthritis and kidney stones. Conversely, UA also appears to function as an antioxidant and may protect against the oxidative stress associated with aging and disease. We performed a prospective fracture case-cohort study to understand the relation of UA and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men aged 65 years and older attending the baseline MrOS examination, we evaluated a subgroup 1680 men in a case-cohort study design. The analytic group included 387 men with incident nonspine fractures (73 hip) and a random sample of 1383. Serum UA was measured in baseline serum samples. Modified proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score, frailty, and total. Subjects with incident nonspine fractures were older, had lower total hip bone mineral density (BMD), and higher serum phosphorus. There was an 18% decreased risk of nonspine fractures (95% confidence interval [CI] 0.71-0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI 0.49-0.89; p = 0.028) compared with nonfracture cases after multivariate adjustment. Hip fractures were not significantly associated with UA. Total hip BMD was significantly higher in the group of men with high UA levels compared with lower UA levels and increased linearly across quartiles of UA after multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels were associated with a reduction in risk of incident nonspine fractures but not hip fractures and higher hip BMD. © 2014 American Society for Bone and Mineral Research.

Normal mineral metabolism is critical for skeletal integrity, and recently serum fibroblast growth factor 23 (FGF23) levels were found to be directly related to overall fracture risk in elderly Swedish men. To confirm this association, we performed a prospective case-cohort study to understand the relation of FGF23 and fracture risk in older white men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men attending the baseline MrOS examination, we evaluated a subgroup of 387 men with incident nonvertebral fracture including 73 hip fractures and a sample of 1385 men randomly selected from the cohort with baseline mineral and calcium hormone measurements. FGF23 was measured in baseline serum samples by ELISA (Millipore, Billerica, MA, USA). Modified Cox proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of fracture in men across quartiles of FGF23. Subjects were also stratified by renal function, and RH per strata was estimated in men with the highest quartile of FGF23 compared with quartiles 3, 2, and 1. Overall, there was no difference in risk of nonspine or hip fracture by baseline FGF23. However, associations differed by strata of eGFRCrCy. Among men with eGFRCrCys60 mL/min/1.73 m2(304/1370 fractures) the RH was 0.91 (95% CI 0.66-1.25) after adjustment for age, clinic site, body mass index, race, total hip bone mineral density, vitamin D, parathyroid hormone, alcohol use, physical activity, fracture history, and serum phosphorus. Serum FGF23 levels are not associated with incident fractures in elderly men overall. However, higher levels of serum FGF23 are associated with fracture risk in those with poor renal function. © 2013 American Society for Bone and Mineral Research.

We used a microsimulation model to estimate the threshold body weights at which screening bone densitometry is cost-effective. Among women aged 55–65 years and men aged 55–75 years without a prior fracture, body weight can be used to identify those for whom bone densitometry is cost-effective.

UnlabelledRadiographs and spinal bone mineral density (BMD) were evaluated from 342 elderly men regarding possible effects of diffuse idiopathic skeletal hyperostosis (DISH) on vertebral fractures and densitometry measurements. Prevalent vertebral fractures were more frequent among men with DISH compared to men with no DISH even after fracture prevalence was adjusted for BMD. Paravertebral calcifications should be considered in patients with DISH when interpreting BMD measurements because both dual X-ray absorptiometry (DXA) and quantitative CT (QCT) densitometry may not be reliable.IntroductionThe purpose of this study is to evaluate the prevalence of DISH in older men and its association with vertebral fractures and with BMD determined by DXA and QCT.MethodsLateral radiographs of the spine were analyzed in a sample of 342 men aged ≥ 65 years participating in the MrOS Study concerning the presence and grade of DISH and vertebral fractures. Lumbar BMD was measured by both DXA (areal, grams per square centimeter) and QCT (volumetric, grams per cubic centimeter). The association between DISH, BMD, and presence of fractures was studied using χ ( 2 ) and t tests.ResultsDISH was present in 52% (178/342) of the men. Men with DISH were older (mean, 75.1 vs 73.3, p < 0.05) and more likely to have prevalent fractures (28% vs 20%, p < p = 0.09). BMD assessed with DXA (1.08 vs 1.00 g/cm(2), p ≤ 0.0001), but not with QCT (0.11 vs 0.11 g/cm3, p = 0.65), was significantly higher in men with DISH compared to men without DISH. Significantly lower BMD of men with both DISH and fractures compared to men with DISH but without fractures was only detected by QCT (-25%, 0.09 vs 0.12, p < 0.05). Both DXA BMD and QCT BMD were significantly higher in severe lumbar DISH (+22% and +31%, p < 0.0001), respectively.ConclusionDISH was associated with a higher prevalence of vertebral fractures in elderly men. Lumbar ossifications related to DISH should be considered when interpreting BMD measurements to predict their fracture risk.

Objectives To quantify incremental effects of applying different criteria to identify men who are candidates for drug treatment to prevent fracture and to examine the extent to which fracture probabilities vary across distinct categories of men defined by these criteria.Design Cross sectional and longitudinal analysis of a prospective cohort study.Setting Multicenter Osteoporotic Fractures in Men (MrOS) study in the United States.Participants 5880 untreated community dwelling men aged 65 years or over classified into four distinct groups: osteoporosis by World Health Organization criteria alone; osteoporosis by National Osteoporosis Foundation (NOF) but not WHO criteria; no osteoporosis but at high fracture risk (at or above NOF derived FRAX intervention thresholds recommended for US); and no osteoporosis and at low fracture risk (below NOF derived FRAX intervention thresholds recommended for US).Main outcome measures Proportion of men identified for drug treatment; predicted 10 year probabilities of hip and major osteoporotic fracture calculated using FRAX algorithm with femoral neck bone mineral density; observed 10 year probabilities for confirmed incident hip and major osteoporotic (hip, clinical vertebral, wrist, or humerus) fracture events calculated using cumulative incidence estimation, accounting for competing risk of mortality.Results 130 (2.2%) men were identified as having osteoporosis by using the WHO definition, and an additional 422 were identified by applying the NOF definition (total osteoporosis prevalence 9.4%). Application of NOF derived FRAX intervention thresholds led to 936 (15.9%) additional men without osteoporosis being identified as at high fracture risk, raising the total prevalence of men potentially eligible for drug treatment to 25.3%. Observed 10 year hip fracture probabilities were 20.6% for men with osteoporosis by WHO criteria alone, 6.8% for men with osteoporosis by NOF (but not WHO) criteria, 6.4% for men without osteoporosis but classified as at high fracture risk, and 1.5% for men without osteoporosis and classified as at low fracture risk. A similar pattern was noted in observed fracture probabilities for major osteoporotic fracture. Among men with osteoporosis by WHO criteria, observed fracture probabilities were greater than FRAX predicted probabilities (20.6% v 9.5% for hip fracture and 30.0% v 17.4% for major osteoporotic fracture).Conclusions and relevance Choice of definition of osteoporosis and use of NOF derived FRAX intervention thresholds have major effects on the proportion of older men identified as warranting drug treatment to prevent fracture. Among men identified with osteoporosis by WHO criteria, who comprised 2% of the study population, actual observed fracture probabilities during 10 years of follow-up were highest and exceeded FRAX predicted fracture probabilities. On the basis of findings from randomized trials in women, these men are most likely to benefit from treatment. Expanding indications for treatment beyond this small group has uncertain value owing to lower observed fracture probabilities and uncertain benefits of treatment among men not selected on the basis of WHO criteria.

Parathyroid hormone (PTH) radioimmunoassays have conventionally utilized [125I]bPTH1-84 as a radioligand, but more region-specific PTH assays are now possible with the use of recently available synthetic PTH peptides as standards and radioligands. A radioiodination procedure has been developed that utilizes hypochlorite as an oxidant and that is capable of producing PTH tracers of high specific activity (200 to 250 microCi/micrograms), prolonged stability, and excellent immunologic potency. Radioiodinated hPTH1-34 and [Tyr43]hPTH44-68 produced by hypochlorite iodination techniques can be used to develop sensitive and region-specific PTH assays of use in clinical and research situations.