Journal of Bone and Mineral Research最新文献

{"title":"Immune Checkpoint Inhibitors and Fracture Risk: A Systematic Literature Review and Pooled and Meta-Analysis of Randomized Controlled Trials.","authors":"Manar Elsayed, Brianna Greenwood, Xiaoming Wang, Liz Dennett, Carrie Ye","doi":"10.1093/jbmr/zjag074","DOIUrl":"https://doi.org/10.1093/jbmr/zjag074","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) are indicated for numerous malignancies, but may have off-target effects called immune-related adverse events (irAEs). Fractures are not considered irAEs, but ICIs may promote osteoclast activation, leading to fractures. This study aimed to evaluate fracture risk associated with ICI therapy using data from randomized controlled trials (RCTs). We conducted a systematic literature review of phase II and III ICI RCTs in individuals with solid malignancies that reported fractures in PubMed and Embase from inception to September 25, 2024. Supplementary materials were reviewed for all eligible studies to ascertain fracture outcomes. Fractures were categorized as any fracture, osteoporotic, and pathologic. Pooled analysis, random-effects meta-analysis, and multivariate meta-regression were conducted to determine the overall risk of fracture in ICI users compared to non-ICI users. Two subgroup analyses were performed: (1) studies without an active comparator, and (2) studies without an active comparator and ≥ 6 months of ICI treatment. A total of 35 RCTs met the inclusion criteria (n = 23,404 patients). There were 91 fractures in ICI groups (66 osteoporotic and 5 pathologic), compared with 70 fractures in the controls (49 osteoporotic and 5 pathologic). Pooled analysis showed no significant association between ICI therapy and risk of any fracture (OR: 1.10, 95% CI: 0.80-1.50, p = 0.54), osteoporotic fracture (1.14, 95% CI: 0.78-1.64, p = 0.48), or pathologic fracture (OR: 0.84, 95% CI: 0.26-2.73, p = 0.79). Meta-analysis similarly showed no statistically significant differences. Meta-regression did not identify any variables associated with increased fracture risk. Statistical heterogeneity was non-significant (I2 = 0.0%). There was no statistically significant difference in reported fractures between ICI and non-ICI treatment groups. However, few studies reported fracture outcomes and observation periods for these studies were short. Longer-term comprehensive fracture-adverse-event reporting in ICI RCTs is needed to evaluate fracture risk in ICI users.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision and age-related changes of 3D-DXA reconstructions and FEA of the proximal femur in comparison to DXA.","authors":"Yvan Gugler, Daniela A Frauchiger, Kurt Lippuner, Serge Ferrari, Emmanuel Biver, Philippe Zysset","doi":"10.1093/jbmr/zjag073","DOIUrl":"https://doi.org/10.1093/jbmr/zjag073","url":null,"abstract":"<p><p>The growing interest in 3D-DXA reconstructions for possible uses in fracture risk prediction or patient follow-up, e.g., in conjunction with finite element analyses, asks for precision data to increase the interpretability of results making use of the 3D-DXA technique. Using two datasets and a total of 2427 DXA scans of the proximal femur we evaluated the short- and long-term precision of standard DXA measurements. All the available scans were reconstructed using 3D-Shaper software and processed through a nonlinear finite element pipeline for femoral strength estimation. Short- and long-term precision were computed for thirty 3D-DXA-based parameters as well as femoral strength in fall and stance configurations. Precision errors were related to change rates of the respective parameters by calculating the trend assessment interval (TAI). Simultaneously, spatially resolved precision errors were computed for cortical parameters and error progression from DXA to 3D-DXA and FEA was considered. Precision errors were amplified through the different processing steps. Long-term precision errors were 1.6%, 2.0% and 7.5% for total hip aBMD, total hip integral vBMD and strength in fall, respectively. Errors between processing steps were only weakly correlated. Higher change rates for vBMD and strength compensated the larger precision errors, resulting in similar TAIs for total hip aBMD (5.5 years), total hip integral vBMD (4.6) and strength (5.8), respectively. Relative local precision errors of cortical parameters were largest in the superior and anterior neck region and above the lesser trochanter. 3D-DXA and thereon based FEA may offer interesting insights into the densitometric and mechanical quality of the proximal femur. The here reported results should offer a help for the interpretation of sequential measurements where these are required.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Suppression of Bone Resorption by miR-141 in Aged Rhesus Monkeys.","authors":"","doi":"10.1093/jbmr/zjag061","DOIUrl":"https://doi.org/10.1093/jbmr/zjag061","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asian ethnicity is associated with shorter anti-resorptive exposure prior to atypical femur fracture (AFF): a Transcontinental Atypical Femoral Fracture Consortium (TrAFFiC) cohort study.","authors":"Lucy Collins, Cat Shore-Lorenti, Colin Chen, Frances Milat, Shoshana Sztal-Mazer, Vivian Grill, Christopher Yates, Cherie Chiang, Christian M Girgis, Aasis Unnanuntana, Richard Dell, Roderick Clifton-Bligh, Peter R Ebeling, Hanh H Nguyen","doi":"10.1093/jbmr/zjag070","DOIUrl":"https://doi.org/10.1093/jbmr/zjag070","url":null,"abstract":"<p><p>Osteoporosis prevalence is expected to increase with global ageing. Bisphosphonates and denosumab are effective treatments, but anxiety regarding safety concerns, medication-related osteonecrosis of the jaw and atypical femur fractures (AFFs), have contributed to a decline in bisphosphonate use in recent years. The Transcontinental Atypical Femoral Fracture Consortium (TrAFFiC) was established to identify potential higher risk clinical factors contributing to AFF development. Within TrAFFiC, an AFF registry was established. One hundred and sixty-six patients with AFFs were included. Seventy-seven (46%) patients sustained bilateral AFFs, totalling 243 AFFs (138 complete, 105 incomplete). Sixty-two (37%) individuals were of Asian ethnicity, with 40 (24%) specifically of Southeast Asian ethnicity. Comparisons within this AFF cohort revealed that Asian individuals were shorter and lower weight (152.0 cm vs. 154.6cm, p < 0.038; 57.5kg vs. 66.8 kg, p < 0.001) than non-Asian peers and were less likely to have a history of minimal trauma fractures prior to AFF (53% vs 84%, p < 0.001). Asian ethnicity [OR 2.10 (95% CI 1.06, 4.02), p = 0.034] and Southeast Asian ethnicity [OR 3.25 (95% CI 1.55, 6.8), p = 0.002] were associated with an increased likelihood of \"earlier onset\" AFF development, that is an AFF sustained following ≤ 5 years of anti-resorptive treatment. Lastly, teriparatide use following incomplete AFF (n=34) did not affect time to healing or pain resolution. In conclusion, Asian individuals sustained AFFs following a shorter duration of anti-resorptive treatment compared with non-Asian AFF peers. In addition, Asian individuals were less likely to sustain additional minimal trauma fractures. Whilst assessment for a drug holiday may be appropriate for patients at lower risk of AFF after five years of oral anti-resorptive treatment, in those with risk factors for \"earlier onset\" AFF, further research is required to guide whether a lower dose or shorter duration of treatment or prioritisation of bone anabolic treatments should be considered.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex clinical encounter series: Glucagon-like peptide-1 receptor agonists-induced weight loss: are we paying attention to bone health?","authors":"Elena Ambrogini","doi":"10.1093/jbmr/zjag069","DOIUrl":"https://doi.org/10.1093/jbmr/zjag069","url":null,"abstract":"<p><p>A sixty-five-year-old white woman with obesity class II, hypertension, hyperlipidemia, obstructive sleep apnea, osteoarthritis, and pre-diabetes was started on subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), for weight loss. Her DXA BMD 3 months prior to the initiation of semaglutide showed osteopenia. She did not have personal or family history of fractures. She had gone into menopause at the age of 52 with no other risk factors for osteoporosis. She maintains an adequate intake of calcium and cholecalciferol and she is active but does not exercise regularly. After 1 year on semaglutide, she lost ~15 % of her weight with improvement of blood pressure, lipid profile, and sleeping pattern. She reports two recent falls. The initial recommendation was to repeat DXA in two-three years. However, recent evidence suggests that in elderly patients experiencing ~ 9% weight loss with semaglutide, monitoring bone remodeling markers and BMD after 1 year of treatment is justified. Counseling on adequate protein intake and strengthening exercise to preserve muscle mass should also be provided.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weekend Warrior Physical Activity Pattern, Metabolomic Profiles, and Risk of Osteoporosis and Fracture.","authors":"Huan Huang, Jiong Liu, Peixuan Li, Zhilin Huang, Chunxue Yang, Lu Qi, Tao Zhou","doi":"10.1093/jbmr/zjag067","DOIUrl":"https://doi.org/10.1093/jbmr/zjag067","url":null,"abstract":"<p><strong>Background & aims: </strong>The weekend warrior pattern, characterized by infrequent but sufficient bouts of moderate-to-vigorous physical activity (MVPA), has become increasingly common. Its association with the risk of osteoporosis and fracture remains unclear. We aimed to examine the association between the weekend warrior pattern and bone outcomes, identify related metabolites, and assess the modifying role of genetic susceptibility.</p><p><strong>Methods: </strong>We included 14,069 UK Biobank (UKB) participants with accelerometer and metabolomic data. Metabolomic signatures corresponding to weekend warrior and regular physical activity patterns were identified using elastic net regression. Cox proportional hazards models were used to examine the associations of physical activity patterns and metabolomic profiles with osteoporosis and fracture risk. Stratified analyses by polygenic risk scores (PRS) for osteoporosis and fracture were conducted to evaluate the potential effect modification by genetic susceptibility.</p><p><strong>Results: </strong>During a median follow-up of 7.8 years, 267 cases of osteoporosis and 554 fracture events were documented. In comparison with the inactive group, the weekend warrior pattern was significantly associated with reduced risks of osteoporosis (HR: 0.59; 95% CI: 0.44-0.79) and fracture (HR: 0.77; 95% CI: 0.63-0.95). Using elastic net regression, we identified 51 metabolites characterizing the weekend warrior pattern and 62 metabolites representing regular physical activity. Each standard deviation (SD) increase in the weekend warrior-related metabolomic signature corresponded to a 27% lower risk of osteoporosis (HR: 0.73; 95% CI: 0.62-0.85) and a 12% lower risk of fracture (HR: 0.88; 95% CI: 0.79-0.99). These associations were not significantly modified by genetic susceptibility to osteoporosis (P = 0.429) or fracture (P = 0.221).</p><p><strong>Conclusions: </strong>The weekend warrior pattern was associated with lower risks of osteoporosis and fracture. We further identified distinct metabolomic signature characterizing this pattern, providing potential mechanistic insights into its protective effects.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-savings from fracture prevention with zoledronate in randomised controlled trials.","authors":"Mark J Bolland, Andrew Grey, Ian R Reid","doi":"10.1093/jbmr/zjag066","DOIUrl":"https://doi.org/10.1093/jbmr/zjag066","url":null,"abstract":"<p><p>Zoledronate prevented fractures in four large trials in cohorts that varied from low to high risk of fracture. Cost-effectiveness analyses are important tools used in funding and regulatory decisions about pharmaceutical agents, and zoledronate generally has appeared to be cost-effective. We used a simple approach to compare zoledronate costs with the savings from fractures prevented to complement previous cost-effectiveness analyses. 18-month costs of major osteoporotic fractures were obtained from published data from 7 US sites in the ICUROS study, costs of zoledronate medication from Medicare, and infusion costs estimated empirically. We applied these costs to data on major osteoporotic fracture from the four trials. We repeated these analyses using 12-month costs from 11 international ICUROS sites. In the trials with high-risk and intermediate-high risk cohorts, the cost-savings from major osteoporotic fractures prevented were approximately US $500,000/1000 patients/3y. In the low-intermediate-risk trial, they were $660,000/1000/6y, and in the low-risk trial, $240,000/1000/10y. When the international fracture cost data were used, these savings approximately doubled. In all four trials, the total costs of zoledronate were substantially less than the savings from fractures prevented, with annual savings ranging from $11-$88/patient/year in low-risk to high-risk patients. The cost-neutral zoledronate cost (maximum infusion cost plus medication cost) ranged from $160-$175 using the US fracture cost data, and was about $350 using international cost data. In summary, in four trials with cohorts at various risk of fracture ranging from low to high risk, zoledronate produced substantial nett savings because the costs of fractures prevented out-weighed total zoledronate costs.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monte Carlo Resampling Validates Use of Bone Mineral Density Change as Surrogate to Replace Fracture in Future Randomized Trials of Osteoporosis Treatments: Results From SABER.","authors":"Suzanne M Dufault, Austin R Thompson, Li-Yung Lui, Susan K Ewing, Mary L Bouxsein, Richard Eastell, Dennis M Black","doi":"10.1093/jbmr/zjag059","DOIUrl":"https://doi.org/10.1093/jbmr/zjag059","url":null,"abstract":"<p><p>We have proposed 24-mo between-treatment difference (active-placebo) in mean percent change in total hip bone mineral density (%THBMD) be used to evaluate whether a drug will likely reduce fracture risk, such that a mean %THBMD change greater than the surrogate threshold effect (STE) would indicate fracture benefit. However, this approach does not consider trial size. Here, we investigate using the lower limit of the 95% confidence interval (LCL) of %THBMD as an alternative to the mean to account for the impact that trial size has on estimator uncertainty. We compared the performance of these two measures (mean and LCL of %THBMD) in indicating fracture risk reduction relative to the STE by simulating trials of various sizes (100, 250, 500, 750, and 1000) based on data re-sampling from existing large trials with THBMD at 24 mo; this included 11 studies with radiographic vertebral fracture, three studies with hip fracture, and five studies with all clinical fractures. We re-sampled the THBMD data from each study 1000 times with equal numbers in treatment groups to estimate the reliability of these measures in being consistent with the observed fracture risk reduction due to treatment. Concordance between the %THBMD-STE comparisons and observed fracture risk reduction generally converged at a sample size of 500 (250 per treatment group). For vertebral fracture using mean %THBMD, 9 of the 11 studies had ≥90% of trials consistent with the observed fracture risk reduction if the sample size exceeded 500, which decreased to 7 of the 11 studies using the LCL. For both hip and all clinical fracture, all included studies had ≥90% of trials consistent with the observed fracture risk reduction if the sample size exceeded 500, regardless of using mean or LCL. Overall, the %THBMD-STE comparisons were generally consistent with the original studies' fracture risk reduction observed.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147661973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jump power testing as a screening tool to assess fracture risk: a giant leap or a hop in the right direction?","authors":"Cassandra Smith, Namki Hong","doi":"10.1093/jbmr/zjag064","DOIUrl":"https://doi.org/10.1093/jbmr/zjag064","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147661953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validating the FRAC-Stroke score: targeting those at highest risk of fracture.","authors":"Gabrielle Stokes, Anne Trinh, Nadine E Andrew, Dominique A Cadilhac, Peter R Ebeling, Karen Borschmann, Monique F Kilkenny, Joosup Kim, Lachlan L Dalli, Frances Milat","doi":"10.1093/jbmr/zjag065","DOIUrl":"https://doi.org/10.1093/jbmr/zjag065","url":null,"abstract":"<p><strong>Background: </strong>Fracture risk is increased after stroke, but there is a lack of specific, effective tools to screen and prevent minimal trauma fractures (MTF) post-stroke. While the FRAC-Stroke score, developed to predict fracture risk post-stroke, shows promising performance, it has not yet been widely adopted or validated in large cohorts outside of Canada.</p><p><strong>Aims: </strong>We aimed to: 1) evaluate the reliability and validity of the FRAC-Stroke score in predicting MTF; and 2) determine the optimal score to classify patients at highest fracture risk following ischaemic stroke.</p><p><strong>Methods: </strong>A retrospective cohort study was undertaken using data from the PRECISE study, which included person-level linked administrative data from the Australian Stroke Clinical Registry (AuSCR, 2014-2016). The FRAC-Stroke score at hospital discharge was determined for survivors of ischemic stroke, aged >50 years, using coded comorbidities derived in the prior 5-year period and modified Rankin Scale. Fine-Gray models were built to evaluate associations of the FRAC-Stroke score with MTF within 12 months post-discharge, accounting for death as the competing risk.</p><p><strong>Results: </strong>Among 4545 adults, the median FRAC-Stroke score was 8 (interquartile range 5-11) and 118 patients (2.6%) sustained a MTF within 12 months post-discharge. The optimal FRAC-Stroke score cut-point to stratify MTF risk was 11.5, with a c-statistic of 0.70. Participants with a FRAC-Stroke score >12 (vs <12) had a 5.5-fold increased risk of MTF (confidence interval 3.8-7.9, p<0.01). When stratified by quintiles of FRAC-Stroke score, those in quintile 5 (FRAC-Stroke score >14) had a 15.2-fold increased risk of MTF than those in quintile 1 (FRAC-Stroke score <3; confidence interval 6.6-35.2, p<0.01).</p><p><strong>Conclusion: </strong>The FRAC-Stroke score reliably identifies increased fracture risk in the Australian ischemic stroke population, with a score of 12+ able to discriminate those at high risk of fracture.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147661940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}