What Proportion of Incident Radiographic Vertebral Fractures in Older Men Is Clinically Diagnosed and Vice Versa: A Prospective Study

To determine the proportion of incident radiographic vertebral fractures (vfx) also diagnosed as incident clinical vfx in older men and vice‐versa, we used data from 4398 community‐dwelling men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study. Incident radiographic vfx were identified by comparing baseline and follow‐up lateral thoracic and lumbar spine study films (average 4.6 years between films) using a semiquantitative (SQ) method and defined as a change in SQ reading of ≥1 at a given vertebral level from baseline to follow‐up study radiograph. Participants were contacted triannually to ascertain incident clinical vfx; community spinal imaging studies were obtained and clinical vfx were confirmed when the study radiologist determined that the community imaging study showed a new deformity of higher grade than was present in the same vertebra on the baseline study radiograph. A total of 237 incident radiographic vfx were identified in 197 men, whereas 31 men experienced 37 confirmed incident clinical vfx. Of incident radiographic vfx, 13.5% were also clinically diagnosed as incident fractures, with clinical diagnoses made for 16.3% of the radiographic vfx with SQ grade change ≥2. Of incident clinical vfx, 86.5% were identified as incident radiographic vfx, most of them with SQ grade change ≥2. In summary, less than 15% of incident radiographic vfx were also clinically diagnosed, whereas the majority of incident clinical vfx were identified as severe radiographic vfx. These results in men supplement those previously published for women and suggest a complex relationship between clinical and radiographic vfx in older adults. Published 2016.^? American Society for Bone and Mineral Research.     

Impact of Competing Risk of Mortality on Association of Weight Loss With Risk of Central Body Fractures in Older Men: A Prospective Cohort Study

To determine the association of weight loss with risk of clinical fractures at the hip, spine, and pelvis (central body fractures [CBFs]) in older men with and without accounting for the competing risk of mortality, we used data from 4523 men (mean age 77.5 years). Weight change between baseline and follow‐up (mean 4.5 years between examinations) was categorized as moderate loss (loss ≥10%), mild loss (loss 5% to <10%), stable (<5% change) or gain (gain ≥5%). Participants were contacted every 4 months after the follow‐up examination to ascertain vital status (deaths verified by death certificates) and ask about fractures (confirmed by radiographic reports). Absolute probability of CBF by weight change category was estimated using traditional Kaplan‐Meier method and cumulative incidence function accounting for competing mortality risk. Risk of CBF by weight change category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average of 8 years, 337 men (7.5%) experienced CBF and 1569 (34.7%) died before experiencing this outcome. Among men with moderate weight loss, CBF probability was 6.8% at 5 years and 16.9% at 10 years using Kaplan‐Meier versus 5.7% at 5 years and 10.2% at 10 years using a competing risk approach. Men with moderate weight loss compared with those with stable weight had a 1.6‐fold higher adjusted risk of CBF (HR 1.59; 95% CI, 1.06 to 2.38) using Cox models that was substantially attenuated in models accounting for competing mortality risk and no longer significant (subdistribution HR 1.16; 95% CI, 0.77 to 1.75). Results were similar in analyses substituting hip fracture for CBF. Older men with weight loss who survive are at increased risk of CBF, including hip fracture. However, ignoring the competing mortality risk among men with weight loss substantially overestimates their long‐term fracture probability and relative fracture risk. © 2016 American Society for Bone and Mineral Research.     

Grade 1 Vertebral Fractures Identified by Densitometric Lateral Spine Imaging Predict Incident Major Osteoporotic Fracture Independently of Clinical Risk Factors and Bone Mineral Density in Older Women

Because prevalent vertebral fracture (VF) is a strong predictor of future fractures, they are important to identify in clinical practice as osteoporosis medications are effective and can be used to reduce fracture risk in postmenopausal women with VF. Lateral spine imaging (LSI) with dual-energy X-ray absorptiometry (DXA) can be used to diagnose VFs accurately but is not widespread in clinical practice. The prognostic value of grade 1 (20% to 25% compression) VFs diagnosed by LSI with DXA has been insufficiently studied. The aim of this study was to determine if grade 1 VF is associated with incident fracture in older women. Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a population-based study of 3028 older women from Gothenburg, Sweden. Included women were 75 to 80 years of age at baseline, answered questionnaires, and were scanned with DXA (Discovery A, Hologic, Waltham, MA, USA). LSI was used to diagnose VFs, which were classified using the Genant semiquantitative method. Cox regression models were used to estimate the association between VFs at baseline and X-ray–verified incident fractures, with adjustment for confounders. Women with a grade 1 VF (n = 264) or a grade 2–3 VF (n = 349) were compared with women without any fracture (n = 1482). During 3.6 years (median, interquartile range [IQR] 1.5 years) of follow-up, 260 women had any incident fracture and 213 a major osteoporotic fracture (MOF). Women with only grade 1 VF had increased risk of any fracture (hazard ratio [HR] = 1.67; 95% confidence interval [CI] 1.18–2.36) and MOF (HR = 1.86; 95% CI 1.28–2.72). For MOF, this association remained after adjustment for clinical risk factors and femoral neck bone mineral density (BMD). In conclusion, grade 1 VFs were associated with incident MOF, also after adjustment for clinical risk factors and BMD, indicating that all VF identified by DXA should be considered in the evaluation of fracture risk in older women. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..     

Inflammatory Markers and Risk of Hip Fracture in Older White Women: The Study of Osteoporotic Fractures

Hip fractures are the most devastating consequence of osteoporosis and impact 1 in 6 white women leading to a two‐ to threefold increased mortality risk in the first year. Despite evidence of inflammatory markers in the pathogenesis of osteoporosis, few studies have examined their effect on hip fracture. To determine if high levels of inflammation increase hip fracture risk and to explore mediation pathways, a case‐cohort design nested in a cohort of 4709 white women from the Study of Osteoporotic Fractures was used. A random sample of 1171 women was selected as the subcohort (mean age 80.1 ± 4.2 years) plus the first 300 women with incident hip fracture. Inflammatory markers interleukin‐6 (IL‐6) and soluble receptors (SR) for IL‐6 (IL‐6 SR) and tumor necrosis factor (TNF SR1 and TNF SR2) were measured, and participants were followed for a median (interquartile range) of 6.3 (3.7, 6.9) years. In multivariable models, the hazard ratio (HR) of hip fracture for women in the highest inflammatory marker level (quartile 4) was 1.64 (95% confidence interval [CI], 1.09–2.48, p trend = 0.03) for IL‐6 and 2.05 (95% CI, 1.35–3.12, p trend <0.01) for TNF SR1 when compared with women in the lowest level (quartile 1). Among women with 2 and 3–4 inflammatory markers in the highest quartile, the HR of hip fracture was 1.51 (95% CI, 1.07–2.14) and 1.42 (95% CI, 0.87–2.31) compared with women with zero to one marker(s) in the highest quartile (p trend = 0.03). After individually adjusting for seven potential mediators, cystatin‐C (a biomarker of renal function) and bone mineral density (BMD) attenuated HRs among women with the highest inflammatory burden by 64% and 50%, respectively, suggesting a potential mediating role. Older white women with high inflammatory burden are at increased risk of hip fracture in part due to poor renal function and low BMD. © 2014 American Society for Bone and Mineral Research.     

Height Loss in Old Age and Fracture Risk Among Men in Late Life: A Prospective Cohort Study

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3491 community-dwelling men (mean age 79.2 years). Height loss between baseline and follow-up (mean 7.0 years between examinations) was categorized as <1 cm (referent group), ≥1 to <2 cm, ≥2 to <3 cm, and ≥3 cm. Men were contacted every 4 months after the follow-up examination to ask about fractures (confirmed by radiographic reports) and ascertain vital status (deaths verified by death certificates). Competing risk methods were used to estimate absolute probabilities of fracture outcomes by height loss category and calculate adjusted risks of fracture outcomes by height loss. During an average of 7.8 years, 158 (4.5%) men experienced a hip fracture and 1414 (40.5%) died before experiencing this event. The absolute 10-year probability of fracture events accounting for the competing risk of death increased with greater height loss. For example, the hip fracture probability was 2.7% (95% confidence interval [CI] 1.9–3.8%) among men with height loss <1 cm increasing to 11.6% (95% CI 8.0–16.0%) among men with height loss ≥3 cm. After adjustment for demographics, fall history, multimorbidity, baseline height, weight change, and femoral neck bone mineral density and considering competing mortality risk, men with height loss ≥3 cm versus <1 cm had a nearly twofold (subdistribution hazard ratio [HR] = 1.94, 95% CI 1.06–3.55) higher risk of hip fracture and a 1.4-fold (subdistribution HR = 1.42, 95% CI 1.05–1.91) increased risk of any clinical fracture. Height loss ≥3 cm in men during old age was associated with higher subsequent risk of clinical fractures, especially hip fractures, even after accounting for the competing risk of death and traditional skeletal and non-skeletal risk factors. © 2021 American Society for Bone and Mineral Research (ASBMR)     

Relationship Between Obesity and Risk of Major Osteoporotic Fracture in Postmenopausal Women: Taking Frailty Into Consideration

The role of obesity in fracture risk remains uncertain and inconclusive in postmenopausal women. Our study aimed to assess the relationship between obesity and risk of major osteoporotic fracture (MOF; ie, a clinical fracture of upper arm or shoulder, hip, spine, or wrist) in postmenopausal women, after taking frailty into consideration. We used the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 5-year Hamilton cohort for this study. Frailty was measured by a frailty index (FI) of deficit accumulation at baseline. We incorporated an interaction term (obesity × FI) in the Cox proportional hazards regression model. We included 3985 women (mean age 69.4 years) for analyses, among which 29% were obese (n = 1118). There were 200 (5.02%) MOF events documented during follow-up: 48 (4.29%) in obese women and 152 (5.65%) in the nonobese group. Significant relationships between obesity, frailty, and MOF risk were found: hazard ratio (HR) = 0.72 (95% confidence interval [CI] 0.67–0.78) for those with an FI of zero regarding MOF risk among obese women, and HR = 1.34 (95% CI 1.11–1.62) per SD increase in the FI among nonobese women. The interaction term was also significant: HR = 1.16 (95% CI 1.02–1.34) per SD increase in the FI among obese women. Increased HRs were found with higher FIs regarding the relationship between obesity and MOF risk, indicating increasing frailty attenuated the protective effect of obesity. For example, although the HR for obesity and MOF risk among those who were not frail (FI = 0) was 0.72 (95% CI 0.67–0.78), among those who were very frail (FI = 0.70), the HR was 0.91 (95% CI 0.85–0.98). To conclude, after taking frailty into consideration, obesity was significantly associated with decreased risk of MOF in postmenopausal women among those who were not frail; however, increasing frailty attenuated this protective effect of obesity. Evaluating frailty status may aid in understanding of the complex relationship between obesity and fracture risk. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Increased Cortical Porosity in Older Men With Fracture

Cortical porosity increases with age and affects bone strength, but its association with fracture in older men is unknown. The aim of this study was to investigate whether cortical porosity is associated with prevalent fractures in older men. A subsample of 456 men aged 80.2 ± 3.5 (mean ± SD) years, with available high‐resolution peripheral quantitative computed tomography measurements at the tibia from the 5‐year follow‐up exam, was drawn from the prospective MrOS Gothenburg study. Dual‐energy X‐ray absorptiometry was used to measure areal bone mineral density (aBMD). Data on physical activity, calcium intake, medications, diseases, and smoking were collected on questionnaires at the follow‐up exam. Of 87 men (19.1%) with fracture at or after age 50 years (all fracture group), 52 (11.4%) had had a self‐reported fracture before the baseline exam and 35 (7.7%) had had an X‐ray–verified fracture between baseline and follow‐up. Men in the all‐fracture group and in the X‐ray–verified group had 15.8% (13.2% ± 4.9% versus 11.4% ± 3.8%; p < 0.001) and 21.6% (14.1% ± 5.2% versus 11.6% ± 3.9%; p < 0.01) higher cortical porosity, respectively, than men in the nonfracture group. The independent associations between bone microstructure parameters and fracture were tested using multivariate logistic regression with age, height, weight, calcium intake, smoking, physical activity, medications, and diseases as covariates. Cortical porosity was independently associated with any fracture (reported or X‐ray–verified; OR per SD increase 1.49; 95% confidence interval (CI), 1.17 to 1.90) and with any X‐ray–verified fracture alone (OR 1.73; 95% CI, 1.23 to 2.42). Including aBMD (spine or hip, respectively) in the multivariate logistic regression above revealed that cortical porosity was associated with any fracture (OR 1.54; 95% CI, 1.17 to 2.01) and with X‐ray–verified fracture alone (OR 1.49; 95% CI, 1.00 to 2.22). Cortical porosity was associated with prevalence of fracture even after adjustment for aBMD. © © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Health Service Use and Quality of Life Recovery 12 Months Following Major Osteoporotic Fracture: Latent Class Analyses of the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS)

Major osteoporotic fractures (MOFs) are associated with a rapid decline in health-related quality of life (HRQoL); however, there is limited knowledge about which healthcare services positively affect HRQoL postfracture. This study aimed to identify specific combinations of health service use associated with recovery of HRQoL 12 months post-MOF. The analyses included 4126 adults aged ≥50 years with an MOF (1657 hip, 1354 distal forearm, 681 vertebrae, 434 humerus) participating in the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS), a multinational observational study (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, United Kingdom, and United States). HRQoL at prefracture and 12 months postfracture was measured using the EuroQoL questionnaire (EQ-5D-3L). Health service use data were collected via participant interviews and medical record reviews including in-hospital care; outpatient care; community services; and medication use. Data analyses involved two stages: (i) latent class analyses to identify different combinations of health service use (“classes”); and (ii) logistic regression to assess effects of classes on HRQoL recovery. Analyses were repeated excluding hip fractures (non-hip MOFs). Overall, 2057 MOF participants (49.9%) recovered to their prefracture HRQoL at 12-month follow-up; this proportion was higher for non-hip MOFs (n = 1439; 58.3%). Several distinct classes were identified across countries (range, 2–5 classes). Classes that were associated with increased odds of HRQoL recovery were characterized by a combination of hospital presentations without admission; outpatient department visits; allied health visits; vitamin D/calcium supplementation; and/or non-opioid analgesic use. Similar classes were observed for non-hip MOFs. Understanding country-specific healthcare service pathways that influence greater recovery of HRQoL, particularly services that are uncommon in some countries and routine in others, could improve postfracture care on a global scale. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Relationship of Weight,Height, and Body Mass Index With Fracture Risk at Different Sites in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women (GLOW)

Low body mass index (BMI) is a well‐established risk factor for fracture in postmenopausal women. Height and obesity have also been associated with increased fracture risk at some sites. We investigated the relationships of weight, BMI, and height with incident clinical fracture in a practice‐based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Data were collected at baseline and at 1, 2, and 3 years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle, lower leg, and upper leg fractures, we modeled the time to incident self‐reported fracture over a 3‐year period using the Cox proportional hazards model and fitted the best linear or nonlinear models containing height, weight, and BMI. Of 52,939 women, 3628 (6.9%) reported an incident clinical fracture during the 3‐year follow‐up period. Linear BMI showed a significant inverse association with hip, clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) per increase of 5 kg/m² were 0.80 (0.71–0.90), 0.83 (0.76–0.92), and 0.88 (0.83–0.94), respectively (all p < 0.001). For ankle fractures, linear weight showed a significant positive association: adjusted HR per 5‐kg increase 1.05 (1.02–1.07) (p < 0.001). For upper arm/shoulder and clavicle fractures, only linear height was significantly associated: adjusted HRs per 10‐cm increase were 0.85 (0.75–0.97) (p = 0.02) and 0.73 (0.57–0.92) (p = 0.009), respectively. For pelvic and rib fractures, the best models were for nonlinear BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low BMI/body weight and positive associations at high values. These data demonstrate that the relationships between fracture and weight, BMI, and height are site‐specific. The different associations may be mediated, at least in part, by effects on bone mineral density, bone structure and geometry, and patterns of falling. © 2014 American Society for Bone and Mineral Research.     

The Importance of Previous Fracture Site on Osteoporosis Diagnosis and Incident Fractures in Women

Previous fracture increases the risk of subsequent fractures regardless of the site of the initial fracture. Fracture risk assessment tools have been developed to guide clinical management; however, no discrimination is made as to the site of the prior fracture. Our objective was to determine which sites of previous nontraumatic fractures are most strongly associated with a diagnosis of osteoporosis, defined by a bone mineral density (BMD) T‐score of ≤ ?2.5 at the femoral neck, and an incident major osteoporotic fracture. Using administrative health databases, we conducted a retrospective historical cohort study of 39,991women age 45 years and older who had BMD testing with dual‐energy X‐ray absorptiometry (DXA). Logistic regression and Cox proportional multivariate models were used to test the association of previous fracture site with risk of osteoporosis and incident fractures. Clinical fractures at the following sites were strongly and independently associated with higher risk of an osteoporotic femoral neck T‐score after adjustment for age: hip (odds ratio [OR], 3.58; 95% confidence interval [CI], 3.04–4.21), pelvis (OR, 2.23; 95% CI, 1.66–3.0), spine (OR, 2.16; 95% CI, 1.77–2.62), and humerus (OR, 1.74; 95% CI, 1.49–2.02). Cox proportional hazards models, with adjustment for age and femoral neck BMD, showed the greatest increase in risk for a major osteoporotic fracture for women who had sustained previous fractures of the spine (hazard ratio [HR], 2.08; 95% CI, 1.72–2.53), humerus (HR, 1.70; 95% CI, 1.44–2.01), patella (HR, 1.54; 95% CI, 1.10–2.18), and pelvis (HR, 1.45; 95% CI, 1.04–2.02). In summary, our results confirm that nontraumatic fractures in women are associated with osteoporosis at the femoral neck and that the site of previous fracture impacts on future osteoporotic fracture risk, independent of BMD. © 2014 American Society for Bone and Mineral Research.     

Low Vitamin D Status Is Associated With Impaired Bone Quality and Increased Risk of Fracture-Related Hospitalization in Older Australian Women

The vitamin D debate relates in part to ideal public health population levels of circulating 25-hydroxyvitamin D (25OHD) to maintain bone structure and reduce fracture. In a secondary analysis of 1348 women aged 70 to 85 years at baseline (1998) from the Perth Longitudinal Study of Aging in Women (a 5-year calcium supplementation trial followed by two 5-year extensions), we examined the dose-response relations of baseline plasma 25OHD with hip DXA BMD at year 1, lumbar spine BMD, and trabecular bone score (TBS) at year 5, and fracture-related hospitalizations over 14.5 years obtained by health record linkage. Mean baseline plasma 25OHD was 66.9 ± 28.2 nmol/L and 28.5%, 36.4%, and 35.1% of women had levels <50, 50 to 74.9, and ≥75 nmol/L, respectively. Generalized additive models showed that total hip and femoral neck BMD and TBS, but not spine BMD, were higher with increasing plasma 25OHD up to 100 nmol/L. Compared with those with 25OHD <50 nmol/L, women with 25OHD ≥75 nmol/L had significantly higher total hip and femoral neck BMD at year 1 (3.3% to 3.9%) and TBS at year 5 (2.0%), all P < 0.05. During the follow-up, 27.6% of women experienced any fracture-related hospitalization and 10.6% hip fracture-related hospitalization. Penalized spline regression models showed a decrease in risk with increased 25OHD levels up to 65 nmol/L and 75 nmol/L for hip fracture and any fracture-related hospitalization, respectively. Cox regression grouped analyses showed that compared with women with 25OHD <50 nmol/L, those with 25OHD levels 50 to 74.9 and ≥75 nmol/L had significantly lower risk for hip fracture [HR 0.60 (95% CI, 0.40 to 0.91) and 0.61 (95% CI, 0.40 to 0.92), respectively], and any fracture-related hospitalization [HR 0.77 (95% CI, 0.59 to 0.99) and 0.70 (95% CI, 0.54 to 0.91), respectively]. In older white women, 25OHD levels >50 nmol/L are a minimum public health target and 25OHD levels beyond 75 nmol/L may not have additional benefit to reduce fracture risk. © 2019 American Society for Bone and Mineral Research.     

Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS)

Almost 30% of hip fractures occur in men; the mortality, morbidity, and loss of independence after hip fractures are greater in men than in women. To comprehensively evaluate risk factors for hip fracture in older men, we performed a prospective study of 5994 men, primarily white, age 65+ years recruited at six US clinical centers. During a mean of 8.6 years of 97% complete follow‐up, 178 men experienced incident hip fractures. Information on risk factors including femoral neck bone mineral density (FNBMD) was obtained at the baseline visit. Cox proportional hazards models were used to calculate the hazard ratio (HR) with 95% confidence intervals; Fine and Gray models adjusted for competing mortality risk. Older age (≥75 years), low FNBMD, currently smoking, greater height and height loss since age 25 years, history of fracture, use of tricyclic antidepressants, history of myocardial infarction or angina, hyperthyroidism or Parkinson's disease, lower protein intake, and lower executive function were all associated with an increased hip fracture risk. Further adjustment for competing mortality attenuated HR for smoking, hyperthyroidism, and Parkinson's disease. The incidence rate of hip fracture per 1000 person‐years (PY) was greatest in men with FNBMD T‐scores <–2.5 (white women reference database) who also had 4+ risk factors, 33.4. Men age ≥80 years with 3+ major comorbidities experienced hip fracture at rates of 14.52 versus 0.88 per 1000 PY in men age <70 years with zero comorbidities. Older men with low FNBMD, multiple risk factors, and multimorbidity have a high risk of hip fracture. Many of these assessments can easily be incorporated into routine clinical practice and may lead to improved risk stratification. © 2016 American Society for Bone and Mineral Research.     

Diminished Bone Strength Is Observed in Adult Women and Men Who Sustained a Mild Trauma Distal Forearm Fracture During Childhood

Children and adolescents who sustain a distal forearm fracture (DFF) owing to mild, but not moderate, trauma have reduced bone strength and cortical thinning at the distal radius and tibia. Whether these skeletal deficits track into adulthood is unknown. Therefore, we studied 75 women and 75 men (age range, 20 to 40 years) with a childhood (age <18 years) DFF and 150 sex‐matched controls with no history of fracture using high‐resolution peripheral quantitative computed tomography (HRpQCT) to examine bone strength (ie, failure load) by micro–finite element (µFE) analysis, as well as cortical and trabecular bone parameters at the distal radius and tibia. Level of trauma (mild versus moderate) was assigned using a validated classification scheme, blind to imaging results. When compared to sex‐matched, nonfracture controls, women and men with a mild trauma childhood DFF (eg, fall from standing height) had significant reductions in failure load (p < 0.05) of the distal radius, whereas women and men with a moderate trauma childhood DFF (eg, fall while riding a bicycle) had values similar to controls. Consistent findings were observed at the distal tibia. Furthermore, women and men with a mild trauma childhood DFF had significant deficits in distal radius cortical area (p < 0.05), and significantly lower dual‐energy X‐ray absorptiometry (DXA)‐derived bone density at the radius, hip, and total body regions compared to controls (all p < 0.05). By contrast, women and men with a moderate trauma childhood DFF had bone density, structure, and strength that did not differ significantly from controls. These findings in young adults are consistent with our observations in children/adolescents with DFF, and they suggest that a mild trauma childhood DFF may presage suboptimal peak bone density, structure, and strength in young adulthood. Children and adolescents who suffer mild trauma DFFs may need to be targeted for lifestyle interventions to help achieve improved skeletal health. © 2014 American Society for Bone and Mineral Research.     

Effects of a Targeted Multimodal Exercise Program Incorporating High‐Speed Power Training on Falls and Fracture Risk Factors in Older Adults: A Community‐Based Randomized Controlled Trial

Multimodal exercise programs incorporating traditional progressive resistance training (PRT), weight‐bearing impact training and/or balance training are recommended to reduce risk factors for falls and fracture. However, muscle power, or the ability to produce force rapidly, has emerged as a more crucial variable to functional decline than muscle strength or mass. The aim of this 12‐month community‐based randomized controlled trial, termed Osteo‐cise: Strong Bones for Life, was to evaluate the effectiveness and feasibility of a multimodal exercise program incorporating high‐velocity (HV)‐PRT, combined with an osteoporosis education and behavioral change program, on bone mineral density (BMD), body composition, muscle strength and functional muscle performance in older adults. Falls incidence was evaluated as a secondary outcome. A total of 162 older adults (mean ± SD; 67 ± 6 years) with risk factors for falls and/or low BMD were randomized to the Osteo‐cise program (n = 81) or a control group (n = 81). Exercise consisted of fitness center‐based HV‐PRT, weight‐bearing impact and challenging balance/mobility activities performed three times weekly. After 12 months, the Osteo‐cise program led to modest but significant net gains in femoral neck and lumbar spine BMD (1.0% to 1.1%, p < 0.05), muscle strength (10% to 13%, p < 0.05), functional muscle power (Timed Stair Climb, 5%, p < 0.05) and dynamic balance (Four Square Step Test 6%, p < 0.01; Sit‐to‐Stand, 16%, p < 0.001) relative to controls. There was no effect on total body lean mass or mobility (timed‐up‐and‐go), and no difference in falls rate (incidence rate ratio [IRR], 1.22; 95% confidence interval [CI], 0.72–2.04). In conclusion, this study demonstrates that the Osteo‐cise: Strong Bones for Life community‐based, multimodal exercise program represents an effective approach to improve multiple musculoskeletal and functional performance measures in older adults with risk factors for falls and/or low BMD. Although this did not translate into a reduction in the rate of falls, further large‐scale trials are needed to evaluate the efficacy of this multimodal approach on reducing falls and fracture. © 2014 American Society for Bone and Mineral Research.     

Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study

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.     

Gastric Bypass But Not Sleeve Gastrectomy Increases Risk of Major Osteoporotic Fracture: French Population-Based Cohort Study

The objective of this work was to investigate the risk of major osteoporotic fracture (MOF; hip, proximal humerus, wrist and distal forearm, and clinical spine) in bariatric surgery patients versus matched controls. Bariatric surgery is associated with an increase in fracture risk. However, it remains unclear whether the same degree of fracture risk is associated with sleeve gastrectomy, which has recently surpassed gastric bypass. Records from the French National Inpatient database were used from 2008 to 2018. Bariatric surgery patients, aged 40 to 65 years, with BMI ≥40 kg/m², hospitalized between January 1, 2010 and December 31, 2014, were matched to one control (1:1) by age, sex, Charlson comorbidity index, year of inclusion, and class of obesity (40 to 49.9 kg/m² versus ≥50 kg/m²). We performed a Cox regression analysis to assess the association between the risk of any MOF and, respectively, (i) bariatric surgery (yes/no) and (ii) type of surgical procedure (gastric bypass, gastric banding, vertical banded gastroplasty, and sleeve gastrectomy) versus no surgery. A total of 81,984 patients were included in the study (40,992 in the bariatric surgery group, and 40,992 matched controls). There were 585 MOFs in the surgical group (2.30 cases per 1000 patient-year [PY]) and 416 MOFs in the matched controls (1.93 cases per 1000 PY). The risk of MOF was significantly higher in the surgical group (hazard ratio [HR] 1.22; 95% CI, 1.08–1.39). We observed an increase in risk of MOF for gastric bypass only (HR 1.70; 95% CI, 1.46–1.98) compared with the matched controls. In patients aged 40 to 65 years, gastric bypass but not sleeve gastrectomy or the other procedures increased risk of major osteoporotic fractures. © 2020 American Society for Bone and Mineral Research.     

Fracture Risk in Trans Women and Trans Men Using Long-Term Gender-Affirming Hormonal Treatment: A Nationwide Cohort Study

Concerns about bone health in transgender people using gender-affirming hormonal treatment (HT) exist, but the fracture risk is not known. In this nationwide cohort study, we aimed to compare the fracture incidence in transgender people using long-term HT with an age-matched reference population. All adult transgender people who started HT before 2016 at our gender-identity clinic were included and were linked to a random population-based sample of 5 age-matched reference men and 5 age-matched reference women per person. Fracture incidence was determined using diagnoses from visits to hospital emergency rooms nationwide between 2013 and 2015. A total of 1089 trans women aged <50 years (mean 38 ± 9 years) and 934 trans women aged ≥50 years (mean 60 ± 8 years) using HT for median 8 (interquartile range [IQR] 3–16) and 19 (IQR 11–29) years, respectively, were included. A total of 2.4% of the trans women aged <50 years had a fracture, whereas 3.0% of the age-matched reference men (odds ratio [OR] = 0.78, 95% confidence interval [CI] 0.51–1.19) and 1.6% of the age-matched reference women (OR = 1.49, 95% CI 0.96–2.32) experienced a fracture. In trans women aged ≥50 years, 4.4% experienced a fracture compared with 2.4% of the age-matched reference men (OR = 1.90, 95% CI 1.32–2.74) and 4.2% of the age-matched reference women (OR = 1.05, 95% CI 0.75–1.49). A total of 1036 trans men (40 ± 14 years) using HT for median 9 (IQR 2–22) years were included. Fractures occurred in 1.7% of the trans men, 3.0% of the age-matched reference men (OR = 0.57, 95% CI 0.35–0.94), and 2.2% of the age-matched reference women (OR = 0.79, 95% CI 0.48–1.30). In conclusion, fracture risk was higher in older trans women compared with age-matched reference men. In young trans women, fracture risk tended to be increased compared with age-matched reference women. Fracture risk was not increased in young trans men. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.