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ContextFRAX® estimates 10-year fracture probability from osteoporosis-specific risk factors. Medical comorbidity indicators are associated with fracture risk but whether these are independent from those in FRAX is uncertain.ObjectiveWe hypothesized Johns Hopkins Aggregated Diagnosis Groups (ADG®) score or recent hospitalization number may be independently associated with increased risk for fractures.MethodsThis retrospective cohort study included women and men age ≥ 40 in the Manitoba BMD Registry (1996-2016) with at least 3 years prior health care data and used linked administrative databases to construct ADG scores along with number of hospitalizations for each individual. Incident Major Osteoporotic Fracture and Hip Fracture was ascertained during average follow-up of 9 years; Cox regression analysis determined the association between increasing ADG score or number of hospitalizations and fractures.ResultsSeparately, hospitalizations and ADG score independently increased the hazard ratio for fracture at all levels of comorbidity (hazard range 1.2-1.8, all P < 0.05), irrespective of adjustment for FRAX, BMD, and competing mortality. Taken together, there was still a higher than predicted rate of fracture at all levels of increased comorbidity, independent of FRAX and BMD but attenuated by competing mortality. Using an intervention threshold of major fracture risk >20%, application of the comorbidity hazard ratio multiplier to the patient population FRAX scores would increase the number of treatment candidates from 8.6% to 14.4%.ConclusionBoth complex and simple measures of medical comorbidity may be used to modify FRAX-based risk estimates to capture the increased fracture risk associated with multiple comorbid conditions in older patients.

Summary: In a combined analysis of 25,389 postmenopausal women aged 50–79 years, enrolled in the two Women’s Health Initiative hormone therapy trials, menopausal hormone therapy vs. placebo reduced the risk of fracture regardless of baseline FRAX fracture probability and falls history. Introduction: The aim of this study was to determine if the anti-fracture efficacy of menopausal hormone therapy (MHT) differed by baseline falls history or fracture risk probability as estimated by FRAX, in a combined analysis of the two Women’s Health Initiative (WHI) hormone therapy trials. Methods: A total of 25,389 postmenopausal women aged 50–79 years were randomized to receive MHT (n = 12,739) or matching placebo (n = 12,650). At baseline, questionnaires were used to collect information on falls history, within the last 12 months, and clinical risk factors. FRAX 10-year probability of major osteoporotic fracture (MOF) was calculated without BMD. Incident clinical fractures were verified using medical records. An extension of Poisson regression was used to investigate the relationship between treatment and fractures in (1) the whole cohort; (2) those with prior falls; and (3) those without prior falls. The effect of baseline FRAX probability on efficacy was investigated in the whole cohort. Results: Over 4.3 ± 2.1 years (mean ± SD), MHT (vs. placebo) significantly reduced the risk of any clinical fracture (hazard ratio [HR] 0.72 [95% CI, 0.65–0.78]), MOF (HR 0.60 [95% CI, 0.53–0.69]), and hip fracture (0.66 [95% CI, 0.45–0.96]). Treatment was effective in reducing the risk of any clinical fracture, MOF, and hip fracture in women regardless of baseline FRAX MOF probability, with no evidence of an interaction between MHT and FRAX (p > 0.30). Similarly, there was no interaction (p > 0.30) between MHT and prior falls. Conclusion: In the combined WHI trials, compared to placebo, MHT reduces fracture risk regardless of FRAX probability and falls history in postmenopausal women.

Fractures of the proximal femur (FPF) are one of the most serious complications of osteoporosis, which has important medical, social and economic consequences. It is well known that their incidence gradually increases with age and depends on the sex, but such epidemiological studies in Ukraine are limited. This article presents the results of the first Ukrainian multicenter epidemiological study STOP (System of Registration of Osteoporotic fractures in Ukrainian Population) in terms of the incidence of FPF in persons aged 40 years and older. It was established that the FPF incidence in Ukrainian population increases with age. The study demonstrated higher rates of FPF incidence in men younger than 55 years with subsequent prevalence rates in women. The index of the overall FPF incidence was similar to that of neighboring countries (Poland and Romania). As FPF is a serious health problem in Ukraine and all over the world, the regional epidemiological data on their incidence is an important basis for the development of a national system for the prevention and treatment of osteoporosis and its complications.

The Fracture Risk Assessment Tool (FRAX®) was created to predict major osteoporotic fractures (MOF) and hip fractures in the general population. Whether FRAX accurately predicts fractures in men with prostate cancer is unknown. Our objective was to assess the performance of FRAX for predicting incident fractures in men with prostate cancer. Men from the Manitoba Bone Mineral Density (BMD) Registry (1996-2018) with prostate cancer diagnoses in the 3 years prior to dual-energy X-ray absorptiometry (DXA) were identified. FRAX scores with and without BMD were calculated. From population-based healthcare data we identified incident MOF, hip fracture, any osteoporotic fracture and death from the date of BMD testing to March 31, 2018. Cox regression was performed to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) per standard deviation increase in FRAX score. Observed 10-year probability (estimated with competing risk of mortality) was compared with 10-year FRAX-predicted fracture probability to assess calibration. The study population included 684 men with prostate cancer (mean age 74.6 years) and 8608 men without prostate cancer (mean age 65.5 years). FRAX stratified risk for MOF (HR 1.91, 95% CI 1.48-2.45 with BMD; HR 1.96, 95% CI 1.43-2.69 without BMD) and hip fracture (HR 3.37, 95% CI 1.90-6.01 with BMD; HR 4.58, 95% CI 2.17-9.67 without BMD) in men with prostate cancer. There was no effect modification observed with prostate cancer status or current androgen deprivation therapy. Observed 10-year fracture probability in men with prostate cancer showed good agreement with FRAX with and without BMD included in the calculation (observed/predicted calibration ratios MOF 0.97, hip 1.00 with BMD; MOF 0.92, hip 0.93 with BMD). In conclusion, FRAX reliably predicts incident fractures in men with prostate cancer. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

FRAX® — метод (алгоритм) оцінки 10-річного ризику переломів стегнової кістки та інших основних остеопоротичних переломів, до яких відносять переломи стегнової, променевої, плечової кісток й клінічно значущі переломи тіл хребців, в осіб віком 40 років і більше. Алгоритм розроблений на підставі використання показників віку, індексу маси тіла й різних клінічних факторів ризику переломів із врахуванням показника мінеральної щільності кісткової тканини шийки стегнової кістки або без нього. На сьогодні алгоритм FRAX включений у більшість європейських та американських рекомендацій щодо профілактики й лікування остеопорозу. Стаття присвячена результатам розробки й адаптації української моделі FRAX. У червні 2016 року завдяки співробітникам Українського науково-медичного центру проблем остеопорозу та ДУ «Інститут геронтології імені Д.Ф. Чеботарьова НАМН України» з’явилась можливість заповнювати опитувальник українською мовою, а в жовтні завдяки авторам статті на офіційному інтернет-ресурсі FRAX з’явилася нова українська модель. Її створення базується на результатах епідеміологічних досліджень, проведених останніми роками членами Української асоціації остеопорозу, співробітниками Українського науково-медичного центру проблем остеопорозу за підтримки Української асоціації травматологів-ортопедів (зокрема у м. Вінниці (1997–2002) та м. Ужгороді і Вінницькому районі (дослідження СТОП, 2011–2012)). Українська модель FRAX є першою вітчизняною моделлю прогнозування ризику основних остеопоротичних переломів й переломів стегнової кістки. Вона створена на основі оригінальної методики FRAX, яка була розроблена співробітниками Центру метаболічних захворювань кісток при ВООЗ. Усе вищезазначене робить українську модель FRAX® унікальною методикою для оцінки ризику остеопоротичних переломів та обґрунтовує необхідність широкого її впровадження в клінічну практику.

Background. Nowadays, FRAX® algorithm is an informative method for evaluation of the risk of osteoporotic fractures, implemented in European and American guidelines for osteoporosis management. However, there are differences in “intervention thresholds” for antiosteoporotic treatment, which depend on the country, the model of health care system and the reimbursement for treatment. Ukrainian version of FRAX appeared in Ukraine in 2016, but the thresholds for intervention have not yet been developed. The purpose of the study was to determine the “thresholds” for the pharmacological treatment of osteoporosis and for additional diagnostic examination of Ukrainian population using national FRAX model. Materials and methods. 3790 outpatients aged 40–90 years (mean age 61.9 ± 10.0 years) were examined. The development of the “thresholds” for intervention and additional assessment of the bone using dual-energy X-ray densitometry (DXA) based on the methodology adopted by the Natio­nal Osteoporosis Guideline Group in UK, which is further used in European guidelines. Results. There was an increase of the “thre­shold” for pharmacological intervention (“upper threshold”) with age from 6.6 % at the age of 40 to 13 % at the age of 75–85 years. The “lower threshold” (threshold for additional examination) increased significantly from 2.4 % at the age of 40 to 6.9 % in wo­men aged 85 years. The evaluation strategy begins with an analysis of the history of low-traumatic fracture. In its presence, a decision to start antiosteoporotic treatment without DXA should be made. In patients without history of fracture, calculation of fracture risk according to FRAX is required. When the risk exceeds the limit of the “upper threshold” antiosteoporotic treatment without DXA is recommended, when its values below the limit of “lower thre­shold” — additional examination or treatment is not required. In case of intermediate risk of fracture a DXA should be conducted with a reassessment of fracture risk and management tactics. Conclusions. The effectiveness of FRAX principles which uses in European guideline, but with particularities of the epidemiology of osteoporotic fractures in Ukraine, has been proved. Although this approach is cost-effective in other countries, its use in Ukraine may differ and may need to be further explored with an economic assessment of costs and benefits.

Assessment and treatment pathways using FRAX-based intervention thresholds in Chile can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk.The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Chile based on major osteoporotic fracture (MOF) probabilities derived from FRAX®.Intervention and assessment thresholds were derived using methods adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Chile. Age-dependent and hybrid assessment and intervention thresholds were applied to 1998 women and 1122 men age 50 years or more drawn from participants in the National Health Survey 2016-2017.Approximately 12% of men and women had a prior fragility fracture and would be eligible for treatment for this reason. Using age-dependent thresholds, an additional 2.6% of women (0.3% of men) were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended in 5% of men and 38% of women. With hybrid thresholds, an additional 13% of women (3.6% of men) were eligible for treatment and BMD recommended in 11% of men and 42% of women.The application of hybrid intervention thresholds ameliorates the disparity in fracture probabilities seen with age-dependent thresholds. Probability-based assessment of fracture risk, including the use of the hybrid intervention thresholds for Chile, is expected to help guide decisions about treatment.

The Fracture Risk Assessment Tool (FRAX®) combines clinical risk factors and optionally femoral neck bone density to estimate major osteoporotic fracture (MOF) and hip fracture probability. Hip dual-energy X-ray absorptiometry (DXA) simultaneously measures the trochanter and total hip, but these regions are not considered by FRAX. Our aim was to determine whether discordance in trochanter and total hip bone density (defined as ≥1 T-score difference from the femoral neck) affects fracture risk adjusted for fracture probability. Using the Manitoba bone density registry, we identified 84,773 women and men age 40 years or older undergoing baseline hip DXA. The outcomes were incident MOF and hip fracture. Cox regression hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for baseline fracture probability were used to test the association between hip T-score discordance and incident fractures. Hip T-score discordance affected more than one in five subjects (trochanter lower in 3.9%, higher in 14.2%; total hip lower in 0.3%, higher in 14.9%). After mean 8.8 years there were 8444 incident MOF including 2664 hip fractures. Discordantly lower trochanter and lower total hip T-score (≥1 below femoral neck) was associated with increased risk for MOF (adjusted HRs 1.47 and 1.60) and hip fracture (HRs 1.85 and 2.12), while discordantly higher trochanter and total hip T-score (≥1 above femoral neck) was associated with lower risk for MOF (HRs 0.83 and 0.71) and hip fracture (HRs 0.79 and 0.68). In models that examined the trochanter and total hip simultaneously, discordantly lower trochanter T-score was associated with increased incident MOF and hip fracture risk (HRs 1.43 and 1.79) whereas discordantly higher total hip T-score was associated with lower risk (HRs 0.73 and 0.75). In conclusion, trochanter and total hip regions frequently show T-scores that are discordant with the femoral neck. This information strongly affects incident fracture risk independent of fracture probability scores computed with femoral neck bone density. © 2022 American Society for Bone and Mineral Research (ASBMR).

This position paper of the International Osteoporosis Foundation (IOF) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) addresses the rationale for separate diagnostic and intervention thresholds in osteoporosis. We conclude that the current BMD-based diagnostic criteria for osteoporosis be retained whilst clarity is brought to bear on the distinction between diagnostic and intervention thresholds.

Summary: The Danish Fracture Risk Evaluation Model (FREM) was found to predict fracture risk independent of 10-year fracture probability derived with the FRAX® tool including bone mineral density from DXA. Introduction: FREM was developed from Danish public health registers without DXA information to identify high imminent risk of major osteoporotic fracture (MOF) and hip fracture (HF), while FRAX® estimates 10-year fracture probability from clinical risk factors and femoral neck bone mineral density (BMD) from DXA. The FREM algorithm showed significant 1- and 2-year fracture risk stratification when applied to a clinical population from Manitoba, Canada. We examined whether FREM predicts 10-year fracture risk independent of 10-year FRAX probability computed with BMD. Methods: Using the Manitoba BMD Program registry, we identified women and men aged ≥ 45 years undergoing baseline BMD assessment. We calculated FREM and FRAX scores, and identified incident fractures over 10 years. Hazard ratios (HRs) for incident fracture were estimated according to FREM quintile, adjusted for FRAX probability. We compared predicted with observed 10-year cumulative fracture probability estimated with competing mortality. Results: The study population comprised 74,446 women, mean age 65.2 years; 7945 men, mean age 67.5 years. There were 7957 and 646 incident MOF and 2554 and 294 incident HF in women and men, respectively. Higher FREM scores were associated with increased risk for MOF (highest vs middle quintile HRs 1.49 women, 2.06 men) and HF (highest vs middle quintile HRs 2.15 women, 2.20 men) even when adjusted for FRAX. Greater mortality with higher FREM scores attenuated its effect on 10-year fracture probability. In the highest FREM quintile, observed slightly exceeded predicted 10-year probability for MOF (ratios 1.05 in women, 1.49 in men) and HF (ratios 1.29 in women, 1.34 in men). Conclusions: Higher FREM scores identified women and men at increased fracture risk even when adjusted for FRAX probability that included BMD; hence, FREM provides additional predictive information to FRAX. FRAX slightly underestimated 10-year fracture probability in those falling within the highest FREM quintile.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well-documented, randomized, placebo-controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p

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.

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX® ) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height2 ) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height2 (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height2 was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83-0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98-1.14). There were no associations between ALM/height2 and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height2 , depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height2 and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

While many clinical guidelines recommend screening for osteoporosis for early detection and treatment, there is great diversity in the case-finding strategies globally. We sought to compare case-finding strategies, focusing on the approaches used in European and Asian countries. This article provides an overview of the current case-finding strategies in the UK, Germany (including Austria and German-speaking regions of Switzerland), China, Japan, and Korea. We conducted a review of current treatment guidelines in each country and included expert opinions from key opinion leaders. Most countries define osteoporosis among patients with a radiographically identified fracture of the hip or the vertebrae. However, for other types of fractures, or in the absence of a fracture, varying combinations of risk-factor assessment and areal bone mineral density (aBMD) assessed by dual X-ray absorptiometry are used to define osteoporosis cases. A T-score ≤ - 2.5 is accepted to identify osteoporosis in the absence of a fracture; however, not all countries accept DXA alone as the sole criteria. Additionally, the critera for requiring clinical risk factors in addition to aBMD differ across countries. In most Asian countries, aBMD scanning is only provided beyond a particular age threshold. However, all guidelines recommend fracture risk assessment in younger ages if risk factors are present. Our review identified that strategies for case-finding differ regionally, particularly among patients without a fracture. More homogenized ways of identifying osteoporosis cases are needed, in both the Eastern and the Western countries, to improve osteoporosis case-finding before a fracture occurs.Case-finding in osteoporosis is essential to initiate treatment and minimize fracture risk. We identified differences in case-finding strategies between Eastern and Western countries. In the absence of a diagnosed fracture, varying combinations of risk factors and bone density measurements are used. Standardized case-finding strategies may help improve treatment rates., Osteoporosis International, 32 (5), ISSN:0937-941X, ISSN:1433-2965, ISSN:0936-6555

The incidence of hip and major osteoporotic fracture was increased in patients with primary hyperparathyroidism even in patients not referred for parathyroidectomy. The risk of death was also increased which attenuated an effect on fracture probabilities. The findings argue for widening the indications for parathyroidectomy in mild primary hyperparathyroidism.Primary hyperparathyroidism (PHPT) is associated with an increase in the risk of fracture. In FRAX, the increase in risk is assumed to be mediated by low bone mineral density (BMD). However, the risk of death is also increased and its effect on fracture probability is not known.The aim of this study was to determine whether PHPT affects hip fracture and major osteoporotic fracture risk independently of bone mineral density (BMD) and whether this and any increase in mortality affects the assessment of fracture probability.A register-based survey of patients with PHPT and matched controls in Denmark were identified from hospital registers. The incidence of death, hip fracture, and major osteoporotic fracture were determined for computing fracture probabilities excluding time after parathyroidectomy. The gradient of risk for fracture for differences in BMD was determined in a subset of patients and in BMD controls. The severity of disease was based on serum calcium and parathyroid hormone levels.We identified 6884 patients with biochemically confirmed PHPT and 68,665 matched population controls. On follow-up, excluding time after parathyroidectomy in those undergoing surgery, patients with PHPT had a higher risk of death (+52%), hip fracture (+48%), and major osteoporotic fracture (+36%) than population controls. At any given age, average 10-year probabilities of fracture were higher in patients with PHPT than population controls. The gradient of fracture risk with differences in BMD was similar in cases and controls. Results were similar when confined to patients not undergoing parathyroidectomy. Fracture probability decreased with the severity of disease due to an increase in mortality rather than fracture risk.The risk of hip and other major osteoporotic fracture is increased in PHPT irrespective of the disease severity. Fracture probability was attenuated due to the competing effect of mortality. The increased fracture risk in patients treated conservatively argues for widening the indications for parathyroidectomy in mild PHPT.

Aims To develop and validate patient-centred algorithms that estimate individual risk of death over the first year after elective joint arthroplasty surgery for osteoarthritis. Methods A total of 763,213 hip and knee joint arthroplasty episodes recorded in the National Joint Registry for England and Wales (NJR) and 105,407 episodes from the Norwegian Arthroplasty Register were used to model individual mortality risk over the first year after surgery using flexible parametric survival regression. Results The one-year mortality rates in the NJR were 10.8 and 8.9 per 1,000 patient-years after hip and knee arthroplasty, respectively. The Norwegian mortality rates were 9.1 and 6.0 per 1,000 patient-years, respectively. The strongest predictors of death in the final models were age, sex, body mass index, and American Society of Anesthesiologists grade. Exposure variables related to the intervention, with the exception of knee arthroplasty type, did not add discrimination over patient factors alone. Discrimination was good in both cohorts, with c-indices above 0.76 for the hip and above 0.70 for the knee. Time-dependent Brier scores indicated appropriate estimation of the mortality rate (≤ 0.01, all models). Conclusion Simple demographic and clinical information may be used to calculate an individualized estimation for one-year mortality risk after hip or knee arthroplasty ( https://jointcalc.shef.ac.uk ). These models may be used to provide patients with an estimate of the risk of mortality after joint arthroplasty. Cite this article: Bone Joint Res 2020;9(11):808–820.

Glucocorticoids are widely used to suppress inflammation or the immune system. High doses and long-term use of glucocorticoids lead to an important and common iatrogenic complication, glucocorticoid-induced osteoporosis, in a substantial proportion of patients. Glucocorticoids mainly increase bone resorption during the initial phase (the first year of treatment) by enhancing the differentiation and maturation of osteoclasts. Glucocorticoids also inhibit osteoblastogenesis and promote apoptosis of osteoblasts and osteocytes, resulting in decreased bone formation during long-term use. Several indirect effects of glucocorticoids on bone metabolism, such as suppression of production of insulin-like growth factor 1 or growth hormone, are involved in the pathogenesis of glucocorticoid-induced osteoporosis. Fracture risk assessment for all patients with long-term use of oral glucocorticoids is required. Non-pharmacological interventions to manage the risk of fracture should be prescribed to all patients, while pharmacological management is reserved for patients who have increased fracture risk. Various treatment options can be used, ranging from bisphosphonates to denosumab, as well as teriparatide. Finally, appropriate monitoring during treatment is also important.

Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo-controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non-fracture-related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo-controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo-controlled period of each trial. A time-to-event analysis of first fall and exposure-adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan-Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66-0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.. ispartof: JOURNAL OF BONE AND MINERAL RESEARCH vol:35 issue:6 pages:1014-1021 ispartof: location:United States status: published

FRAX estimates 10-year fracture major osteoporotic fracture (MOF) and hip fracture probability from multiple risk factors. FRAX does not consider prior fracture site or time since fracture. Fracture risk is greater in the initial 2-year post-fracture period (imminent risk), implying that FRAX may underestimate risk in this setting. We used the population-based Manitoba Bone Mineral Density (BMD) Program registry to examine the effect of fracture recency and site on incident fracture risk predictions using FRAX. We identified women aged 40 years or older with baseline BMD and FRAX scores. Observed fracture outcomes to 10 years were compared with predicted 10-year fracture probability stratified by prior fracture status: none, recent (2 years [median 0.3 years]), and remote (≥2 years [median 10.6 years]). For women with recent fractures, we also examined proposed multipliers to adjust FRAX for the effect of fracture recency and site. The cohort comprised 33,465 women aged 40 to 64 years (1897 recent fracture, 2120 remote fracture) and 33,806 women aged ≥65 years (2365 fracture, 4135 remote fracture). Observed fracture probability was consistent with predicted probability in most analyses. In women aged 40 to 64 years, there was a significant effect of recent vertebral and humerus fracture on MOF (observed to predicted 1.61 and 1.48, respectively), but these effects were still lower than the proposed multipliers (2.32 and 1.67, respectively). No significant effect of fracture recency was found after hip or forearm fracture in either age group. Our findings contribute to accumulating evidence of the importance of recent fracture. The effect of fracture recency was not consistent across fracture sites and with a lower magnitude than previously reported. Further quantification of effect size and specificity in additional independent cohorts is warranted to validate and refine recent-fracture multipliers in fracture risk assessment. © 2022 American Society for Bone and Mineral Research (ASBMR).

Summary The adoption of the management pathway proposed by the National Osteoporosis Guideline Group (NOGG), UK applied using the Austrian FRAX® tool in a referral population of Austrian women categorises 22–29% of women age 40 years or more eligible for treatment of whom 28–34% are classified at very high risk. Purpose The aim of this study is to provide a reference document for the further development of existing guidelines for the management of osteoporosis in Austria, considering FRAX-based intervention thresholds for high and very high fracture risk. Methods The model development was based on two Austrian hospital referral cohorts. Baseline information was collected to compute the 10-year probability (using the Austrian FRAX model) of a major osteoporotic fracture (MOF) and hip fracture both with and without the inclusion of femoral neck bone mineral density (BMD). Assessment thresholds for BMD testing were defined, as well as intervention thresholds. In addition, thresholds that characterise men and women at high and very high fracture risk were established. The management pathway followed that currently recommended by the UK National Osteoporosis Guideline Group (NOGG). Results The two cohorts comprised a total of 1306 women and men with a mean age of 66.7 years. Slightly more than 50% were eligible for treatment by virtue of a prior fragility fracture. In those women without a prior fracture, 22% (n = 120) were eligible for treatment based on MOF probabilities. Of these, 28% (n = 33) were found to be at very high risk. When both MOF and hip fracture probabilities were used to characterise risk, 164 women without a prior fracture were eligible for treatment (29%). Of these, 34% (n = 56) were found to be at very high risk. Fewer men without prior fracture were eligible for treatment compared with women. Conclusion The management pathway as currently outlined is expected to reduce inequalities in patient management. The characterisation of very high risk may aid in the identification of patients suitable for treatment with osteoanabolic agents.

Summary In women of ages 75–80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. Introduction Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. Methods The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75–80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. Results During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49–6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34–1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26–2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (

SummaryThe Fracture Risk Evaluation Model (FREM) identifies individuals at high imminent risk of major osteoporotic fractures. We validated FREM on 74,828 individuals from Manitoba, Canada, and found significant fracture risk stratification for all FREM scores. FREM performed better than age alone but not as well as FRAX® with BMD.IntroductionThe FREM is a tool developed from Danish public health registers (hospital diagnoses) to identify individuals over age 45 years at high imminent risk of major osteoporotic fractures (MOF) and hip fracture (HF). In this study, our aim was to examine the ability of FREM to identify individuals at high imminent fracture risk in women and men from Manitoba, Canada.MethodsWe used the population-based Manitoba Bone Mineral Density (BMD) Program registry, and identified women and men aged 45 years or older undergoing baseline BMD assessment with 2 years of follow-up data. From linked population-based data sources, we constructed FREM scores using up to 10 years of prior healthcare information.ResultsThe study population comprised 74,828 subjects, and during the 2 years of observation, 1612 incident MOF and 299 incident HF occurred. We found significant fracture risk stratification for all FREM scores, with AUC estimates of 0.63–0.66 for MOF for both sexes and 0.84 for women and 0.65–0.67 for men for HF. FREM performed better than age alone but not as well as FRAX® with BMD. The inclusion of physician claims data gave slightly better performance than hospitalization data alone. Overall calibration for 1-year MOF prediction was reasonable, but HF prediction was overestimated.ConclusionIn conclusion, the FREM algorithm shows significant fracture risk stratification when applied to an independent clinical population from Manitoba, Canada. Overall calibration for MOF prediction was good, but hip fracture risk was systematically overestimated indicating the need for recalibration.

Summary: Assessment and treatment pathways based on age-specific intervention thresholds in Saudi Arabi can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk. Purpose: Intervention thresholds for the treatment of osteoporosis have historically been based on the measurement of bone mineral density. The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Saudi Arabia based on fracture probabilities derived from FRAX®. Methods: The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Saudi Arabia. The methodology was applied to women age 40 years or more drawn from a tertiary referral population for skeletal assessment. Missing data for the calculation of FRAX was simulated using data from the referral and FRAX derivation cohorts. Results: Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.0% at the age of 50 years increasing to 7.6% at the age of 70 years. A total of 163 of 1365 women (11.9%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 5 women were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended for 593 women (43.4%) so that FRAX could be recalculated with the inclusion of femoral neck BMD. Of these, 220 individuals would be eligible for treatment after a BMD test and 373 women categorised at low risk after a BMD test. Conclusion: Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Saudi Arabia to help guide decisions about treatment.

The Danish Fracture Risk Evaluation Model (FREM) was found to predict fracture risk independent of 10-year fracture probability derived with the FRAX® tool including bone mineral density from DXA.FREM was developed from Danish public health registers without DXA information to identify high imminent risk of major osteoporotic fracture (MOF) and hip fracture (HF), while FRAX® estimates 10-year fracture probability from clinical risk factors and femoral neck bone mineral density (BMD) from DXA. The FREM algorithm showed significant 1- and 2-year fracture risk stratification when applied to a clinical population from Manitoba, Canada. We examined whether FREM predicts 10-year fracture risk independent of 10-year FRAX probability computed with BMD.Using the Manitoba BMD Program registry, we identified women and men aged ≥ 45 years undergoing baseline BMD assessment. We calculated FREM and FRAX scores, and identified incident fractures over 10 years. Hazard ratios (HRs) for incident fracture were estimated according to FREM quintile, adjusted for FRAX probability. We compared predicted with observed 10-year cumulative fracture probability estimated with competing mortality.The study population comprised 74,446 women, mean age 65.2 years; 7945 men, mean age 67.5 years. There were 7957 and 646 incident MOF and 2554 and 294 incident HF in women and men, respectively. Higher FREM scores were associated with increased risk for MOF (highest vs middle quintile HRs 1.49 women, 2.06 men) and HF (highest vs middle quintile HRs 2.15 women, 2.20 men) even when adjusted for FRAX. Greater mortality with higher FREM scores attenuated its effect on 10-year fracture probability. In the highest FREM quintile, observed slightly exceeded predicted 10-year probability for MOF (ratios 1.05 in women, 1.49 in men) and HF (ratios 1.29 in women, 1.34 in men).Higher FREM scores identified women and men at increased fracture risk even when adjusted for FRAX probability that included BMD; hence, FREM provides additional predictive information to FRAX. FRAX slightly underestimated 10-year fracture probability in those falling within the highest FREM quintile.

Satellite cell‐dependent skeletal muscle regeneration declines during aging. Disruptions within the satellite cells and their niche, together with alterations in the myofibrillar environment, contribute to age‐related dysfunction and defective muscle regeneration. In this study, we demonstrated an age‐related decline in satellite cell viability and myogenic potential and an increase in ROS and cellular senescence. We detected a transient upregulation of miR‐24 in regenerating muscle from adult mice and downregulation of miR‐24 during muscle regeneration in old mice. FACS‐sorted satellite cells were characterized by decreased levels of miR‐24 and a concomitant increase in expression of its target: Prdx6. Using GFP reporter constructs, we demonstrated that miR‐24 directly binds to its predicted site within Prdx6 mRNA. Subtle changes in Prdx6 levels following changes in miR‐24 expression indicate miR‐24 plays a role in fine‐tuning Prdx6 expression. Changes in miR‐24 and Prdx6 levels were associated with altered mitochondrial ROS generation, increase in the DNA damage marker: phosphorylated‐H2Ax and changes in viability, senescence, and myogenic potential of myogenic progenitors from mice and humans. The effects of miR‐24 were more pronounced in myogenic progenitors from old mice, suggesting a context‐dependent role of miR‐24 in these cells, with miR‐24 downregulation likely a part of a compensatory response to declining satellite cell function during aging. We propose that downregulation of miR‐24 and subsequent upregulation of Prdx6 in muscle of old mice following injury are an adaptive response to aging, to maintain satellite cell viability and myogenic potential through regulation of mitochondrial ROS and DNA damage pathways., Age‐related changes in miR‐24 and its target gene Prdx6 contribute to defective function of myogenic progenitors and muscle regeneration during aging. miR‐24 upregulation and downregulation of its target Prdx6 is associated with an increase in mitochondrial ROS, increase in pH2Ax, decreased cell viability, myogenic potential and increased senescence. During aging, downregulation of miR‐24 in satellite cells and after muscle injury may represent a compensatory mechanism acting to preserve cell viability and myogenic potential

Introduction Intervention thresholds for the treatment of osteoporosis have been based historically on the measurement of bone mineral density. The development of FRAX® has permitted more accurate assessment of fracture risk. The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Ecuador based on FRAX. Methods A total of 2367 women aged 60–94 years were selected from the National Health, Welfare and Aging Survey (SABE) conducted in Ecuador. Probabilities of major osteoporotic and hip fracture were computed using the Ecuadorian FRAX model. The proportion of women eligible for treatment and bone mineral density assessment was determined based on age-specific intervention thresholds and a hybrid threshold was fixed from age 75 years. Results A total of 87 women (3.7%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 49 women were eligible for treatment in that MOF probabilities lay above the upper assessment threshold using age-specific thresholds. An BMD test would be recommended in 1131 women (48%) so that FRAX could be recalculated with the inclusion of femoral neck BMD. With the hybrid threshold, an additional 170 women were eligible for treatment and an BMD test recommended in 1218 women. Conclusion The hybrid threshold identifies more women eligible for treatment than age-specific thresholds. Although age-specific thresholds identify women at higher risk of fracture, the lower number of women identified results in fewer identified fracture cases.

Osteoporosis is a disease characterized by impaired bone microarchitecture and reduced bone mineral density (BMD) resulting in bone fragility and increased risk of fracture. In western societies, one in three women and one in five men will sustain an osteoporotic fracture in their remaining lifetime from the age of 50 years. Fragility fractures, especially of the spine and hip, commonly give rise to increased morbidity and mortality. In the five largest European countries and Sweden, fragility fractures were the cause of 2.6 million disability-adjusted life years in 2016 and the fracture-related costs increased from €29.6 billion in 2010 to €37.5 billion in 2017. In the European Union and the USA, only a small proportion of women eligible for pharmacological treatment are being prescribed osteoporosis medication. Secondary fracture prevention, using Fracture Liaison Services, can be used to increase the rates of fracture risk assessment, BMD testing and use of osteoporosis medication in order to reduce fracture numbers. Additionally, established primary prevention strategies, based on case-finding methods utilizing fracture prediction tools, such as FRAX, to identify women without fracture but with elevated risk, are recommended in order to further reduce fracture numbers.

Assessment and treatment pathways based on age-specific intervention thresholds in Saudi Arabi can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk.Intervention thresholds for the treatment of osteoporosis have historically been based on the measurement of bone mineral density. The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Saudi Arabia based on fracture probabilities derived from FRAX®.The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Saudi Arabia. The methodology was applied to women age 40 years or more drawn from a tertiary referral population for skeletal assessment. Missing data for the calculation of FRAX was simulated using data from the referral and FRAX derivation cohorts.Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.0% at the age of 50 years increasing to 7.6% at the age of 70 years. A total of 163 of 1365 women (11.9%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 5 women were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended for 593 women (43.4%) so that FRAX could be recalculated with the inclusion of femoral neck BMD. Of these, 220 individuals would be eligible for treatment after a BMD test and 373 women categorised at low risk after a BMD test.Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Saudi Arabia to help guide decisions about treatment.

Introduction Hip fracture rates in Botswana were used to create a FRAX® model for fracture risk assessment. Objective This paper describes the development and characteristics of a country-specific FRAX model for Botswana. Methods Age-specific and sex-specific incidence of hip fracture and national mortality rates was incorporated into a FRAX model for Botswana. Ten-year fracture probabilities were compared with those from African countries having a FRAX model and African Americans from the USA. Results The probabilities of hip fracture and major osteoporotic fracture were low compared with those from South Africa (Black and Coloured) and US Blacks. Probabilities were marginally higher than for Tunisia. Conclusion The creation of a FRAX model is expected to help guide decisions about the prevention and treatment of fragility fractures in Botswana.

Diffusion MRI (dMRI) is a growing imaging technique with the potential to provide biomarkers of tissue variation, such as cellular density, tissue anisotropy, and microvascular perfusion. However, the role of dMRI in characterizing different aspects of bone quality, especially in aging and osteoporosis, has not yet been fully established, particularly in clinical applications. The reason lies in the complications accompanied with implementation of dMRI in assessment of human bone structure, in terms of acquisition and quantification. Bone is a composite tissue comprising different elements, each contributing to the overall quality and functional competence of bone. As diffusion is a critical biophysical process in biological tissues, early changes of tissue microstructure and function can affect diffusive properties of the tissue. While there are multiple MRI methods to detect variations of individual properties of bone quality due to aging and osteoporosis, dMRI has potential to serve as a superior method for characterizing different aspects of bone quality within the same framework but with higher sensitivity to early alterations. This is mainly because several properties of the tissue including directionality and anisotropy of trabecular bone and cell density can be collected using only dMRI. In this review article, we first describe components of human bone that can be potentially detected by their diffusivity properties and contribute to variations in bone quality during aging and osteoporosis. Then we discuss considerations and challenges of dMRI in bone imaging, current status, and suggestions for development of dMRI in research studies and clinics to segregate different contributing components of bone quality in an integrated acquisition. Level of Evidence: 5 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:975-992. ispartof: JOURNAL OF MAGNETIC RESONANCE IMAGING vol:51 issue:4 pages:975-992 ispartof: location:United States status: published

Summary A simple question construct regarding number of falls in the previous year, ascertained by a single question, was strongly associated with incident fractures in routine clinical practice using a population-based dual-energy X-ray absorptiometry (DXA) registry. Introduction There is conflicting evidence from research cohorts that falls independently increase fracture risk. We examined the independent effects of falls on subsequent fractures in a large clinical registry of bone mineral density (BMD) results for the Province of Manitoba, Canada that has been systematically collecting self-reported falls information since September 1, 2012. Methods The study population consisted of 24,943 women and men aged 40 years and older (mean age 65.5 ± 10.2 years) with fracture probability assessment (FRAX), self-reported falls for the previous year (categorized as none, 1, 2, or > 3) and fracture outcomes. Adjusted hazard ratios (HR) with 95 confidence intervals (CI) for time to fracture were estimated using Cox proportional hazards models. Results During mean observation time of 2.7 ± 1.0 years, 863 (3.5%) sustained one or more major osteoporotic fractures (MOF), 212 (0.8%) sustained a hip fracture, and 1210 (4.9%) sustained any incident fracture. Compared with no falls in the previous year (referent), there was a gradient of increasing risk for fracture with increasing number of falls (all P

SummaryWe compared the utility of the current Iranian guidelines that recommend treatment in women with a T-score ≤ − 2.5 SD with a FRAX-based intervention threshold equivalent to women of average BMI with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive, and the associated fracture risk decreased markedly with age.IntroductionThe fracture risk assessment algorithm FRAX® has been recently calibrated for Iran, but guidance is needed on how to apply fracture probabilities to clinical practice.MethodsThe age-specific ten-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of − 2.5 SD, in line with current guidelines in Iran. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without BMD. The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing.ResultsWhen a BMD T-score ≤ − 2.5 SD was used as an intervention threshold, FRAX probabilities in women aged 50 years was approximately two-fold higher than in women of the same age but with an average BMD and no risk factors. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of − 2.5 SD was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture rose with age from 4.9% at the age of 50 years to 17%, at the age of 80 years, and identified women at increased risk at all ages.ConclusionIntervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a “fracture threshold” target women at high fracture risk.

Background Aromatase inhibitors (AIs) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. Materials and Methods Using a population-based BMD registry, we identified women aged at least 40 years initiating AIs for breast cancer with at least 12 months of AI exposure (n = 1,775), women with breast cancer not receiving AIs (n = 1,016), and women from the general population (n = 34,205). Fracture outcomes were assessed to March 31, 2017 (mean, 6.2 years for AI users). Results At baseline, AI users had higher body mass index (BMI), higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all p < .001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.93–1.42), hip fracture (HR, 0.90; 95% CI, 0.56–1.43), or any fracture (HR, 1.06; 95% CI, 0.88–1.28) compared with the general population. Conclusion Higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, our findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fractures. Implications for Practice In a population-based observational registry that included 1,775 patients initiating long-term aromatase inhibitor therapy, risk for major osteoporotic fracture, hip fracture, or any fracture was similar to the general population. Higher baseline body mass index, bone mineral density, and lower prevalence of prior fracture at baseline may offset the adverse effects of aromatase inhibitor exposure.