Journal of Bone and Mineral Research最新文献

{"title":"Mortality following atypical femoral fractures in men.","authors":"Colton Hoffer, William Obremskey, Binni Makkar, Brinda Basida, Nitya Shah, Jared D Huling, Zhiping Huo, Emily Budde, Reside Jacob, John T Schousboe, Howard A Fink, Robert A Adler, Joan C Lo, Ryan Avidano, Joshua I Barzilay, Frances Weaver, Susan M Ott, KinhTu Lien, Laura D Carbone","doi":"10.1093/jbmr/zjag036","DOIUrl":"10.1093/jbmr/zjag036","url":null,"abstract":"<p><p>Atypical femoral fractures (AFFs) are an uncommon complication of bisphosphonate (BP) treatment for osteoporosis. The purpose of this report was to determine differences in mortality among men treated with BPs who experienced AFFs, hip fractures, or typical subtrochanteric/femoral shaft (ST/FS) fractures. We included men from the Veterans Affairs Corporate Data Warehouse who filled at least one BP prescription over a nearly 20-yr span (October 1, 1999, to December 31, 2022). Typical ST/FS and hip fractures after a first filled prescription for a BP were identified using ICD codes. Radiographic review was conducted for ST/FS fractures to determine which were AFFs using the American Society of Bone and Mineral Research 2014 criterion. Demographic and clinical characteristics and cumulative duration of BP exposure prior to the incident fracture were determined. There were 23 men with an AFF, 4591 with a hip fracture, and 225 with a (non-AFF) ST/FS fracture. At 12-mo post-fracture, 4% of men with an AFF had died, compared with 25% of men with a hip fracture and 15% of men with an ST/FS fracture. Over 5 yrs. of follow-up, mortality following fracture differed among the 3 different fracture groups (χ2 = 6.21, d.f. = 2, p = .045) with death occurring in 7 of 23 (30%) men with an AFF, 2380 of 4591 (52%) men with a hip fracture and 109 of 225 (48%) men with a ST/FS fracture. In Cox proportional hazard models, over 5 yrs, with and without adjustment for covariates, there were no significant differences in mortality following an AFF compared with a hip fracture or an AFF compared with a ST/FS fracture (p > .10 for all). It is possible that mortality is lower following AFF compared with a hip or ST/FS fracture; however, limited sample size among those with AFF may have precluded ascertainment of such a difference.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1087-1095"},"PeriodicalIF":6.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiscale assessment of glucocorticoid-induced alterations across bone marrow and mineralized bone in human iliac crest biopsies.","authors":"Praveer Sihota, Xenia Junimann, Johannes Krug, Jan Frischmuth, Lukas Harms, Timur A Yorgan, Imke A K Fiedler, Annegreet Vlug, Björn Jobke, Michael Amling, Mathias Werner, Katharina Jähn-Rickert, Björn Busse","doi":"10.1093/jbmr/zjag140","DOIUrl":"https://doi.org/10.1093/jbmr/zjag140","url":null,"abstract":"<p><strong>Background: </strong>Glucocorticoid-induced osteoporosis (GIOP) is associated with a fracture risk that exceeds what would be expected based on bone mineral density (BMD) alone, suggesting impaired bone quality. In contemporary clinical practice, patients receiving glucocorticoids are typically treated concomitantly with anti-osteoporotic medication, limiting the ability to define glucocorticoid-specific effects on human bone tissue.</p><p><strong>Methods: </strong>We performed a retrospective case-control study of archived iliac crest biopsies from patients with established GIOP (n=21) who had received glucocorticoid therapy without concomitant anti-osteoporotic treatment, identified through a dedicated bone biopsy registry. Age-matched non-GIOP controls (n=13) were included for comparison. A comprehensive multiscale approach combining micro-computed tomography, static histomorphometry, quantitative mineral analysis, Raman spectroscopy, and nanoindentation was used to assess trabecular microarchitecture, cellular remodeling, matrix composition, and tissue-level mechanical properties.</p><p><strong>Results: </strong>Glucocorticoid exposure was associated with significantly reduced trabecular bone volume fraction driven by trabecular thinning. Bone formation was suppressed, as reflected by decreased osteoblast surface and osteoid thickness, while erosion depth was increased. Viable osteocyte density was reduced and marrow adiposity elevated. At the material level, bone exhibited increased mean calcium content and greater mineral homogeneity, accompanied by reduced pyridinoline and glycosaminoglycan content and diminished mineral crystallinity. These compositional alterations were associated with a significantly lower elastic modulus.</p><p><strong>Conclusion: </strong>Analysis of this unique registry-based biopsy collection demonstrates coordinated alterations in bone remodeling cells, trabecular architecture, mineral distribution, collagen matrix composition, and mechanical competence in glucocorticoid-treated bone. To our knowledge, this integrated cellular-to-material characterization has not previously been performed in human biopsies exposed exclusively to glucocorticoids and provides mechanistic insight into the pathophysiology underlying glucocorticoid-associated skeletal fragility.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023422","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":"Hepatocyte ferroportin drives liver cirrhosis-induced skeletal deterioration via systemic iron overload.","authors":"Liangliang Xiang, Kaili Deng, Zixiang Gao, Qingjiang Pang, Alan Wang, Justin Fernandez, Li Chen, Yaodong Gu","doi":"10.1093/jbmr/zjag138","DOIUrl":"https://doi.org/10.1093/jbmr/zjag138","url":null,"abstract":"<p><p>Chronic liver disease frequently leads to debilitating bone fractures, yet the mechanistic link between liver injury and skeletal fragility remains elusive. This study aimed to investigate a liver-bone axis where dysregulated iron flux, mediated by hepatocyte ferroportin (FPN), drives osteoporosis during the progression of cirrhosis. We utilized a mouse model of progressive liver disease and generated hepatocyte-specific FPN deletion mice to examine systemic iron homeostasis. Bone quality and microarchitecture were evaluated via micro-computed tomography and histological analysis. To assess fracture risk and mechanical integrity, we employed engineering-based finite element simulations and physical mechanical testing. Our data reveal a critical window during liver fibrosis where compensatory mechanisms counteract iron toxicity. However, upon progression to cirrhosis, this homeostatic balance collapses, leading to massive toxic iron accumulation in the skeleton. This creates a pro-inflammatory environment that suppresses bone formation and accelerates resorption. Biomechanical simulations and testing demonstrate that combined deficits in bone material properties and architecture create distinct stress concentration zones, markedly reducing load-bearing capacity. Strikingly, hepatocyte-specific deletion of FPN attenuated liver fibrosis and restored systemic iron balance, thereby preserving bone microarchitecture and mechanical performance. Hepatocyte FPN-regulated iron homeostasis is a central mediator of the liver-bone axis. Cirrhosis-induced iron overload is a major contributor to skeletal mechanical failure, identifying FPN as a key regulator of bone health in chronic liver disease.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023287","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":"Real-World Effectiveness of Burosumab Versus Oral Phosphate and Active Vitamin D in Adults with X-Linked Hypophosphatemia (XLH): A 3-Year Follow-Up of the XLH Disease Monitoring Program.","authors":"Steven W Ing, Sasigarn A Bowden, Kathryn M Dahir, Pablo Florenzano, Ingrid A Holm, Sarah Khan, Michael A Levine, Carolina A Moreira, Laila Tabatabai, Thomas J Weber, Shubham Tewari, Ben Johnson, Marc Vincent, Jaimin Patel, Lak Nilusha Kotinkaduwa, Zhiyi Li, Leanne M Ward, Erik A Imel","doi":"10.1093/jbmr/zjag136","DOIUrl":"https://doi.org/10.1093/jbmr/zjag136","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is a progressive disease in which excess FGF23 causes renal phosphate wasting, leading to hypophosphatemia. Consequences in adults include osteomalacia, fractures, pseudofractures, joint dysfunction, pain, and impaired mobility. Treatments for XLH are the anti-FGF23 antibody burosumab and active forms of vitamin D alone or in combination with oral phosphate (Pi/D). Randomized studies comparing burosumab with Pi/D in adults with XLH are lacking. We present a 3-yr follow-up analysis evaluating real-world effectiveness of burosumab versus Pi/D based on biochemistry and standardized symptom assessments (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) using data from the XLH Disease Monitoring Program (DMP; NCT03651505), a prospective, Americas-based study. Adults with XLH initiated burosumab between baseline and the year 1 visit (N = 54) or reported being on Pi/D therapy at enrollment (N = 55) were included. After adjusting for baseline differences using inverse probability of treatment weighting, the data showed a significantly higher mean (SD) change from baseline in serum phosphate with burosumab versus Pi/D (year 1: 0.8 [0.8] vs 0.1 [0.7] mg/dL; year 3: 0.6 [0.8] vs 0.1 [0.7] mg/dL, both p < .001). A higher proportion of burosumab versus Pi/D participants achieved serum phosphate levels above the lower limit of normal (2.5 mg/dL; year 1: 70.5% vs 18.8%; year 3: 60.8% vs 25.0%, both p < .001). At year 1, changes from baseline in WOMAC pain (-6.3 [27.7] vs 2.1 [22.4], p = .055), physical function (-6.4 [19.1] vs 0.1 [29.0], p = .122), and stiffness (-11.1 [32.1] vs -2.3 [33.7], p = .073) were not statistically significant between cohorts, but were significant at year 3 (pain: -9.8 [22.6] vs 3.3 [24.1], p < .001; physical function: -10.0 [25.7] vs 3.3 [24.7], p = .001; stiffness: -15.2 [29.5] vs -3.7 [31.4], p = .016). In this real-world analysis of adults with XLH over a 3-yr follow-up, burosumab treatment was associated with improved serum phosphate and patient-reported outcomes versus Pi/D.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029474","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":"Medical treatment of adult patients with X-linked hypophosphatemia.","authors":"Seiji Fukumoto","doi":"10.1093/jbmr/zjag137","DOIUrl":"https://doi.org/10.1093/jbmr/zjag137","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975279","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":"Letter to the Editor re: Wu Q and Jung J. Uncovering Racial and Genetic Disparities in FRAX Performance for Fracture Risk Assessment in Postmenopausal Women. JBMR 2025.","authors":"Sara J Cromer, Annette L Adams, Elaine W Yu","doi":"10.1093/jbmr/zjag133","DOIUrl":"10.1093/jbmr/zjag133","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962781","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":"Skull Sutures and Craniofacial Disorders: Mind the Gap.","authors":"Shawn A Hallett, Renny T Franceschi","doi":"10.1093/jbmr/zjag135","DOIUrl":"https://doi.org/10.1093/jbmr/zjag135","url":null,"abstract":"<p><p>The human skull, whose 22 separate bones make up the cranial vault, facial bones and jaw, is arguably the most complex skeletal structure in the body. In addition to protecting the brain, it provides structures necessary for mastication and audition and serves as the underlying scaffold for the face to define our unique identities. Proper development and growth of the skull requires initial incorporation of positional information to cranial neural crest cells (CNCC) and paraxial mesoderm to define the location of each bone followed by the coordination of postnatal cranial growth with the underlying expansion of the brain, a process that is mediated by two specific growth centers, cranial sutures and cranial base synchondroses. This Perspective will provide an overview of general principles governing craniofacial development, growth, and regeneration with emphasis on the unique functions of neural crest cells, cranial sutures, cranial base synchondroses and associated stem cells. In addition, examples will be included of how defects in skull development can explain specific craniofacial disorders as well as future directions for cranial bone regeneration and correction of craniofacial anomalies that are informed by recent discoveries in this field.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954576","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":"Response Regarding FRAX Performance Across Race/Ethnicity and Genetic Risk in the Women's Health Initiative.","authors":"Qing Wu, Jongyun Jung","doi":"10.1093/jbmr/zjag134","DOIUrl":"10.1093/jbmr/zjag134","url":null,"abstract":"<p><p>The Fracture Risk Assessment Tool estimates 10-year fracture probability, but its performance may vary across populations. We respond to correspondence concerning our Women's Health Initiative analysis by clarifying prior findings and addressing questions about age structure, differential follow-up, construction of clinical inputs, polygenic-score portability, comparator choice, and model performance. Observed fracture probability was estimated using cumulative incidence with death as a competing event. Additional age-stratified analyses showed a similar qualitative pattern of overestimation in Black and Hispanic/Latina women. Using the medium polygenic-score group as the reference, associations with major osteoporotic fracture remained directionally consistent; inverse probability of censoring-weighted estimates were similar for major osteoporotic fracture but less stable for hip fracture. Adding the polygenic score produced only modest gains in time-dependent discrimination. We acknowledge that informative censoring that differs across racial and ethnic groups, sparse subgroup events, multiple comparisons, and limited cross-ancestry portability remain important limitations. These considerations support cautious interpretation and further validation of fracture-risk tools in diverse populations.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954548","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":"Circadian regulators PER1 and PER2 control osteoclastogenesis in male mice through coordinated regulation of opposing innate immunity genes.","authors":"Nobuko Katoku-Kikyo, Elizabeth K Vu, Samuel Mitchell, Ismael Y Karkache, Emily Patterson, Elizabeth W Bradley, Nobuaki Kikyo","doi":"10.1093/jbmr/zjag131","DOIUrl":"10.1093/jbmr/zjag131","url":null,"abstract":"<p><p>Bone remodeling is regulated by circadian rhythm, yet the molecular mechanisms linking circadian clock components to osteoclast function remain largely undefined. We previously showed that osteoclast-specific deletion of Per1, a core circadian regulator, increased osteoclastogenesis and reduced bone mass in male mice, whereas deletion of Per2 had little effect. Here, we investigated Per1;Per2 conditional double-knockout (dKO) mice and unexpectedly found the opposite phenotype. In contrast to Per1 deficiency, dKO suppressed osteoclastogenesis and increased bone mass specifically in male mice, revealing previously unrecognized functional interactions between PER1 and PER2 in osteoclasts. Transcriptomic analyses showed that dKO osteoclasts preferentially downregulated innate immunity genes, including both positive and negative regulators of osteoclastogenesis. Chromatin immunoprecipitation and reporter assays further identified innate immunity genes as downstream targets of PER-dependent circadian regulation. These findings indicate that PER1 and PER2 regulate osteoclastogenesis through coordinated control of a network of immune genes with opposing effects on osteoclast differentiation, rather than acting as simple promoters or inhibitors of bone resorption. More broadly, this study establishes innate immunity as a mechanistic interface between the circadian clock and osteoclast function, providing a framework for understanding how circadian disruption influences bone remodeling and inflammatory bone diseases.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890449","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: Bone microarchitecture declines in older men with impaired renal function-the prospective STRAMBO study.","authors":"","doi":"10.1093/jbmr/zjag125","DOIUrl":"https://doi.org/10.1093/jbmr/zjag125","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885902","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}