Despite high risk of secondary fracture, osteoporosis treatment rates following hip fracture remain low globally. In April 2022, Japan implemented a reimbursement policy for secondary fracture prevention in patients with hip fracture. We evaluated the impact of this policy on treatment patterns during acute hospitalization. We conducted an interrupted time-series analysis using the Medical Data Vision database for patients aged ≥ 50 years hospitalized with hip fractures from April 2020 to March 2024. Primary outcome was osteoporosis medication treatment rate during hospitalization. Secondary outcomes included drug class distribution and use of medications categorized as recommended or proposed in preventing fractures according to Japanese guidelines. Segmented regression models were used to evaluate level and trend changes associated with policy implementation. Among 71,632 eligible patients with hip fracture (mean age 84, 76

Community-wide Fracture Liaison Services and educational outreach to local physicians on osteoporosis can effectively reduce the fragility fracture burden at the population level in a super-aged society. Effective prevention of osteoporosis and fractures requires not only implementing a Fracture Liaison Service (FLS) but also enhancing osteoporosis awareness among local physicians, residents, and the municipality. We examined the impact of multidisciplinary, municipality-supported FLS and osteoporosis awareness activities on the incidence of clinical vertebral and hip fractures in a rapidly ageing urban Japanese population. We conducted a population-based pre-post observational study of residents aged ≥ 65 years in Kure, Japan, following the introduction of community-wide FLS and osteoporosis awareness activities. Residents were enrolled in the National Health Insurance or Senior Elderly Care System between 2015 and 2021. Fracture events were identified using insurance claims data and ICD/treatment codes. Overall, the incidence of clinical vertebral fractures tended to increase until 2017 and then tended to decrease thereafter; the incidence of hip fractures tended to decrease after 2017 in females but not in males. Compared with the incidence in 2017, the age–sex-adjusted incidence ratio was 0.76 (95

In this meta-analysis of international cohorts, current smoking is confirmed as a significant BMD-independent predictor of future fracture with a stronger relationship in men than in women. A causative and reversible effect of smoking on fracture risk is suggested by past smoking having a significantly lower risk than current smoking. In this meta-analysis of international cohorts, the aim was to examine the relationship of current and past smoking with fracture risk to provide an update for future iterations of the FRAX tool. The risk of fracture associated with current and past smoking was estimated using an extended Poisson model applied separately to each of 58 prospective international cohort studies. Covariates included current time since start of follow up, current age, and in an additional model, BMD at the femoral neck. The results of the different studies were merged by using inverse-variance weighted β-coefficients. This analysis included a total of 1,691,024 participants (61.2

Osteoporosis is a major public health concern, particularly in the aging population, where fragility fractures significantly impact quality of life and mortality. Despite the importance of early detection, screening rates for osteoporosis in Japan remain low. The Osteoporosis Self-Assessment Tool for Asians (OSTA) and Fracture Risk Assessment Tool (FRAX) are noninvasive screening tools. This study aimed to develop an efficient method for screening osteopenia using these tools. We analyzed data from 1060 Japanese women aged 40–74 years from the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study. The OSTA and FRAX scores, as well as individual FRAX risk factors, were assessed for their ability to detect osteopenia. As FRAX score calculations are not publicly available, we evaluated the discriminative ability of the seven risk factors individually. Prior fragility fractures were deemed the most critical, and all 64 possible combinations of the remaining six risk factors were analyzed. OSTA had the highest discriminative ability (AUC = 0.81), followed by FRAX-Hip (AUC = 0.79) and FRAX-Major (AUC = 0.77). The sensitivity and specificity of OSTA ≤ –1 were 83.7

The Osteoporosis Self-Assessment Tool for Asians (OSTA) is a tool that can assess osteoporosis risk based on age and weight. Bone quality, including bone microstructure, as well as bone mineral density (BMD), is important for bone strength. The purpose of this study was to investigate the associations between the OSTA and bone strength indices other than BMD. A total of 111 postmenopausal women with osteoporosis who had undergone high-resolution peripheral quantitative computed tomography in our outpatient clinic were included. The OSTA was calculated using the age and weight, and other techniques were used to evaluate the participants' bones. To investigate the relationship between the OSTA and bone microstructure, comparisons of two groups based on OSTA and multiple regression analysis was performed. Women with OSTA below -4 had poor values for many parameters, including bone microstructural parameters. Multiple regression analysis showed that tibial microstructural parameters were associated with OSTA score independently of femoral neck BMD. OSTA was developed as a screening tool for osteoporosis, however it was found to be related to the microstructure parameters of the tibia when evaluated in postmenopausal women with osteoporosis. Among patients with osteoporosis, those with low OSTA may have deteriorated bone quality in the lower limbs.

The relationship between bone mineral density (BMD) at the femoral neck and fracture risk was determined in a meta-analysis of primary data of 307205 men and women from 53 cohort studies. Low BMD was an important predictor of fracture risk, particularly for hip fracture. This study aimed to quantify the relationship between DXA-measured femoral neck BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value on fracture risk, with a view to updating FRAX®. We studied 307,205 men and women from within 53 predominately population-based cohorts followed up for an average of 8.7 years and a total of 2,683,185 person-years. The association of BMD and fracture risk was examined using a Poisson model in each cohort separately by sex. Results were expressed as a gradient of risk (GR, hazard ratio/standard deviation decrease in BMD). The different studies were then merged using weighted coefficients. Most hip fractures arose in men and women with low bone mass or osteoporosis at baseline (73 = 0.12 for women and p = 0.89 for men). A significant decrease in GR for hip fracture was observed with increasing duration of follow-up, but the magnitude of the effect was modest compared with the effect of age. For other fracture outcomes, including non-hip major osteoporotic fracture, the gradient of risk was lower than for hip fracture. Femoral neck BMD is a risk factor for fracture of substantial importance, particularly for future hip fracture. The lower magnitude of association at older age is consistent with other non-skeletal factors contributing to hip fracture risk with advancing age. Its validation on an international basis supports its use in case finding strategies. Its use should, however, take account of the variations in predictive value of BMD with age, sex, length of follow-up, and BMD.

BACKGROUND:As the population ages, the incidence of fragility fractures increases; however, large-scale data on real-world osteoporosis management in late-stage older adults (aged ≥75 years)-a group at extremely high risk of fractures-are limited in Japan. In this study, we aimed to clarify the status of osteoporosis management in this high-risk population, using a large-scale administrative claims database. METHODS:This retrospective cohort study used data from the DeSC database. We identified 405,416 patients aged ≥75 years with an initial fragility fracture at a major osteoporotic site (the hip, vertebrae, humerus, radius, pelvis, ribs, etc.) between 2014 and 2022. We assessed osteoporosis medication prescription and diagnostic testing (bone mineral density and bone turnover markers) rates in the pre-fracture (day -180 to -1), early post-fracture (day 0-90), and late post-fracture (day 91-365) periods. RESULTS:The mean age of the cohort was 84.3 years, and 73.0% were women. The medication prescription rate was 25.0% in the pre-fracture period, increasing only slightly to 27.5% during the early post-fracture period and 28.5% during the late post-fracture period, leaving over 70% without a prescription. Annual data from 2016 to 2021 showed that post-fracture prescription rates remained consistently low, with little change over time. A marked disparity in prescription rates by fracture site was observed, with late post-fracture prescription rates of 36.7% for vertebral fractures and 20.4% for hip fractures. Even when stratified by age group, prescription rates remained consistently low among patients with hip fractures. CONCLUSIONS:This large-scale, real-world study showed that many patients aged ≥75 years remained untreated after an initial fragility fracture. Prescription rates were particularly low among patients with hip fractures, despite their expected high risk of subsequent fractures. These findings highlight the need for strategies to improve diagnosis and treatment in this vulnerable population.

In the largest meta-analysis of international cohorts to date, a family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. Parental and sibling histories of fracture carry the same significance for future fracture, including the impact of family hip fracture on future hip fracture risk. PURPOSE:We have undertaken a meta-analysis of international prospective cohorts to quantify the relationship between a family history of fracture and future fracture incidence. METHODS:The analysis dataset comprised 350,542 men and women from 42 cohorts in 29 countries followed for 2.8 million person-years. We investigated the relationship between family history of hip fracture or any fracture and the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture (MOF), and hip fracture alone using an extended Poisson model in each cohort. Models were adjusted for current age, sex, BMD, and follow-up time. RESULTS:As no difference in influence of family history of fracture was seen between genders, results are presented for men and women combined. A parental history of hip fracture was associated with a higher risk of incident fracture across all fracture outcome categories, with a stronger relationship with future hip fracture (hazard ratios (HR, 95% CI) for hip and MOF 1.37, 1.23-1.52 and 1.19, 1.12-1.27, respectively). Associations were slightly reduced but remained significant when additionally adjusted for BMD and did not vary by baseline offspring age, follow-up time, or parent affected. In a more limited analysis, parental history of any fracture or a sibling history of hip or any fracture showed similar associations to those observed with parental history of hip fracture. CONCLUSIONS:A family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. While parental hip fracture appears the strongest factor for future hip fracture, a family history of other fractures might be appropriate for inclusion in future iterations of the FRAX tool.

Objectives Osteoporosis is often undiagnosed due to the shortcomings of conventional screening, resulting in missed chances for early treatment. Advances in artificial intelligence (AI), particularly deep learning applied to chest X-rays, offer a new opportunity for opportunistic screening. This study assesses the cost-effectiveness of this approach in Japanese women aged ≥ 50 years. Methods An economic model estimated the cost per quality-adjusted life year (QALY) gained (in 2024 Japanese Yen, ¥) for a strategy involving AI-assisted chest X-ray screening followed by treatment, compared to no screening. Patient trajectories were modeled using the AI system's diagnostic performance and aligned with the Japanese osteoporosis guidelines. Analyses were conducted for Japan overall, in Kure City (a high-fracture-incidence area), and in a lower-incidence scenario. Real-world medication persistence, the probabilities of dual-energy X-ray absorptiometry examination after screening detection, and treatment initiation rates were incorporated. Results Nationwide in Japan, the cost per QALY gained from opportunistic osteoporosis screening was estimated at ¥189,713 for women aged ≥ 50, substantially lower than the accepted cost-effectiveness threshold of ¥5 million. In Kure City, opportunistic screening was dominant (lower total costs for more QALYs). In the lower-incidence scenario, 25% below the national average, the cost per QALY was ¥1,055,095, remaining below the threshold. Results were robust across all age-specific populations and in sensitivity analyses. Conclusions Leveraging AI-assisted chest X-rays for incidental osteoporosis detection demonstrates strong economic viability for older Japanese women. This approach also proves to be a dominant strategy in areas with elevated fracture rates.

The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®. RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX. The resource comprised 1,909,896 men and women, aged 20–116 years, from 29 prospective cohorts in which the prevalence of RA was 3

Initiating osteoporosis medication within 3 months after fracture reduces secondary fractures, particularly hip fractures, in individuals aged ≥ 75 years. This finding highlights the importance of early and sustained treatment in older populations. To evaluate the efficacy of initiating osteoporosis medication within 3 months after a fracture and continuing it for at least 6 months in preventing secondary fractures among individuals aged ≥ 75 years. This study used a targeted trial design, emulating a randomized controlled trial with Japanese administrative claims data from 2014–2022. Among 203,534 individuals with recent osteoporotic fractures, 40,063 initiated osteoporosis medication within 3 months (exposed), while 163,471 did not (controls). High-dimensional propensity score matching identified 53,436 individuals (26,718 exposed and 26,718 controls) for analysis. Cox regression was used to estimate hazard ratios (HRs) and 95

The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and relationship of this risk with age, sex, follow-up time, and BMD. A total of 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 had FN BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight: <18.5 kg/m2; Normal: 18.5-24.9 kg/m2; Overweight: 25.0-29.9 kg/m2; Obese I: 30.0-34.9 kg/m2; Obese II: ≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95% CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). Hip fracture risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26)]. Further adjustment for FN BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes, the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, while overweight/obesity appeared protective in base models, they became risk factors after additional adjustment for FN BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX®.

Background Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged period, has not been adequately examined; nor has stability during sample storage or intra-individual variation been assessed. Methods We assessed (1) analytical reliability in short- and long-term repeated measurements; (2) stability and analytical reliability during long-term sample storage, and (3) variability within individuals over seasons, of four cytokines—osteopontin (OPN), osteoprotegerin (OPG), vascular endothelial growth factor-A (VEGF-A), and interleukin-17A (IL-17A). Measurements in plasma or serum samples were made with commercial kits according to standard procedures. Estimation was performed by fitting a random or mixed effects linear model on the log scale. Results In repeated assays over a short period, OPN, OPG, and VEGF-A had acceptable reliability, with intra- and inter-assay coefficients of variation (CV) less than 0.11. Reliability of IL-17A was poor, with inter- and intra-assay CV 0.85 and 0.43, respectively. During long-term storage, OPG significantly decayed (− 33% per year; 95% confidence interval [− 54, − 3.7]), but not OPN or VEGF-A (− 0.3% or − 6.3% per year, respectively). Intra- and inter-assay CV over a long period were comparable to that in a short period except for a slight increase in inter-assay CV of VEGF-A. Within-individual variation was small for OPN and VEGF-A, with intra-class correlations (ICC) 0.68 and 0.83, respectively, but large for OPG (ICC 0.11). Conclusions We conclude that OPN and VEGF-A can be reliably measured in a large population, that IL-17A is suitable only for small experiments, and that OPG should be assessed with caution due to degradation during storage and intra-individual variation. The overall results of our study illustrate the need for validation under relevant conditions when measuring circulating cytokines in population studies.

Context In recent studies of childhood cancer survivors, diabetes has been considered a late effect associated with high therapeutic doses of radiation therapy. Our recent study of atomic bomb (A-bomb) survivors also suggested an association between radiation dose and diabetes incidence, with exposure city and age at exposure as radiation dose effect modifiers. Insulin resistance mediated by systemic inflammation and abnormal body composition has been suggested as a possible primary mechanism for the incidence of diabetes after total body irradiation; however, no studies have examined low to moderate radiation exposure (<4 Gy) and insulin resistance in A-bomb survivors. Objective To examine the association between radiation dose and markers of inflammation and insulin resistance. Methods This study investigated 3152 survivors who underwent a health examination between 2008 and 2012 and who were younger than 15 years at exposure. Multivariate linear regression analyses were used to evaluate the radiation effects on levels of markers of inflammation and insulin resistance. Results Radiation dose was significantly and positively associated with levels of C-reactive protein, triglycerides, homeostasis model assessment of beta-cell function (HOMA-beta), and HOMA of insulin resistance (HOMA-IR) after adjustment for relevant covariates including sex, city, and age at exposure. Adiponectin and high-density lipoprotein cholesterol levels were also associated significantly and negatively with radiation dose. However, city was not a dose modifier of the radiation response on these markers of inflammation and insulin resistance. Conclusion Insulin resistance might be a possible factor in radiation-related diabetes incidence in A-bomb survivors.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). The resource comprised 906,359 women and men (66.9

The 2004 edition of guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research had been developed based on the results of a longitudinal study by subcommittee members and the results of an analysis of patients collected by the Subcommittee to Study Diagnostic Criteria for Corticosteroid-Induced Osteoporosis, together with evidence obtained overseas and in Japan at 2004. This guideline is now going to be revised. In this review, I want to introduce the history of guidelines on the management and treatment of glucocorticoid-induced osteoporosis and American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis.

This study aims to understand how osteoporosis medication acceptance varies across countries with differing guidance on treatment threshold and influence of clinical and demographic factors. A total of 79.2