Journal of Bone and Mineral Research最新文献

{"title":"Editorial on \"Evidence-based classification of genes implicated in skeletal disorders using the ClinGen curation framework\".","authors":"Eric T Rush","doi":"10.1093/jbmr/zjag035","DOIUrl":"https://doi.org/10.1093/jbmr/zjag035","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224822","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":"Performance of U.S.- FRAX TM by Race and Ethnicity for Short-term Hip and Major Osteoporotic Fracture Prediction in U.S. Women with Rheumatoid Arthritis.","authors":"Rachel E Elam, Jing Li, Angel Paul, Emma Kersey, Gabriela Schmajuk, William D Leslie, Laura D Carbone","doi":"10.1093/jbmr/zjag033","DOIUrl":"https://doi.org/10.1093/jbmr/zjag033","url":null,"abstract":"<p><p>Women with rheumatoid arthritis (RA) face elevated fracture risk, yet performance of the U.S.-FRAX™ across racial and ethnic groups in RA remains understudied. In this retrospective cohort study, we examined 14,533 women aged ≥65 years with RA from the U.S. national Rheumatology Informatics System for Effectiveness registry, linked to Medicare claims (2016-2018), to assess the performance of race- and ethnicity-adapted U.S.-FRAX calculators without BMD for predicting short-term (2-year) hip and major osteoporotic fracture (MOF) risk across racial and ethnic groups. Most participants were White (86.5%), with smaller proportions of Black or African American (7.8%), Hispanic or Latina (4.7%), and Asian (1.1%) women. Overall fracture incidence was high (15.3 per 1,000 person-years for hip fracture; 55.8 for MOF), with variability by race and ethnicity. Hip fracture incidence (per 1,000 person-years) was lowest among Asian (6.5) and Black or African American (7.0) women and highest among Hispanic or Latina (16.3) and White (16.2) women. MOF incidence (per 1,000 person-years) was lowest in Black or African American (26.0) and highest in White (58.7) women. Discrimination of U.S.-FRAX for short-term fractures was modest, with overall cross-validated AUCs of 0.71 (95% confidence interval (CI): 0.69-0.73) for hip fracture and 0.66 (95% CI: 0.65-0.68) for MOF. No significant differences in AUCs were found between Black or African American, Hispanic or Latina, and White women with RA. Short observation period for fractures precluded formal calibration testing, but our data suggests U.S.-FRAX without BMD may underestimate MOF risk, particularly among Black or African and Hispanic or Latina women with RA. Performance in Asian women was not reported due to low fracture rates. The modest discrimination and insufficient calibration data in all racial and ethnic RA groups studied underscore the need for larger studies in diverse RA populations. Ultimately, RA-specific fracture risk assessment tools may be needed.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211541","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":"In Vivo Mechanical Assessment of Cortical Bone Rigidity Enhances Fracture Discrimination Beyond DXA in Postmenopausal Women.","authors":"Brian C Clark, Todd M Manini, Janet E Simon, Leatha A Clark, Charalampos Lyssikatos, Stuart J Warden","doi":"10.1093/jbmr/zjag032","DOIUrl":"10.1093/jbmr/zjag032","url":null,"abstract":"<p><p>Dual-energy x-ray absorptiometry (DXA)-derived areal bone mineral density (BMD) remains the clinical standard for assessing osteoporosis risk, yet it fails to identify over 75% of individuals who sustain fragility fractures. Direct in vivo mechanical assessment of cortical bone strength may address this diagnostic gap by capturing structural and material properties that govern whole-bone strength but are not reflected by BMD. We conducted a multicenter case-control study with cross-sectional exposure assessment to compare ulna flexural rigidity, a biomechanical property correlated with whole-bone strength (R2 ≈ 0.99), estimated using Cortical Bone Mechanics Technology (CBMT), with DXA-derived BMD for discriminating prior fragility fractures in postmenopausal women. A total of 372 women aged 50-80 years (109 with low-trauma fractures, 263 matched controls) were enrolled across four U.S. sites. Ulna flexural rigidity was assessed by dynamic vibrational analysis; BMD was measured at the spine, hip, and 1/3 radius. Women with prior fractures had significantly lower flexural rigidity than controls (absolute: 20.0 vs. 24.8 N·m2; 21% lower; weight-normalized: 0.29 vs. 0.36 N·m2/kg; 22% lower; both P < .001). CBMT demonstrated good discriminatory accuracy (AUC = 0.80 normalized; 0.76 absolute), with significantly better AUCs than DXA, which showed only fair to poor performance (AUC ≤ 0.63). In multivariable models including CBMT and DXA-derived BMD, CBMT remained independently associated with fracture status, whereas BMD did not. Subgroup analyses showed CBMT retained good performance in treatment-naïve women (AUC = 0.85) and in those with non-osteoporotic BMD (AUC = 0.80). Exploratory fracture-site analyses demonstrated that ulna EI discriminated upper and lower extremity fractures, including hip, whereas DXA-derived BMD generally showed fair to poor discrimination. Biomechanical assessment of bone rigidity provides clinically relevant information beyond areal BMD, including women not classified high risk. Direct in vivo assessment of cortical bone rigidity may enhance fracture risk stratification and enhance osteoporosis screening.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199633","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":"Waiting for Godot: Why Therapeutic Hesitancy Fails Patients with Early CKD.","authors":"Hazem El-Bilbeisi, Thomas L Nickolas","doi":"10.1093/jbmr/zjag031","DOIUrl":"https://doi.org/10.1093/jbmr/zjag031","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199650","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":"Impact of Current and Previous Smoking on Fracture Risk in Older Women: The Role of Physical Function, Bone Density and Bone Microarchitecture.","authors":"M Zoulakis, M Ambjörn, R Jaiswal, K F Axelsson, H Litsne, L Johansson, M Lorentzon","doi":"10.1093/jbmr/zjag028","DOIUrl":"https://doi.org/10.1093/jbmr/zjag028","url":null,"abstract":"<p><p>While smoking is a known risk factor for fractures, its precise mechanisms among older women, particularly involving physical function, bone density, and bone microarchitecture, remain incompletely understood. This prospective cohort study included 3,024 community-dwelling Swedish women aged 75-80 years, followed for a median of 7.3 years. Participants were categorized as current smokers (n = 157), former smokers (n = 1,343), and never smokers (n = 1,524). Radiographically verified fractures and all-cause mortality were assessed. Cox proportional hazards models, mediation analyses, and competing risk models evaluated associations between smoking status, fracture risk, and potential mediators, including walking speed and total volumetric bone mineral density (vBMD). Current smokers had significantly increased risks of any fracture (HR 1.35, 95% CI 1.04-1.75) and hip fracture (HR 2.23, 95% CI 1.43-3.49) compared to never smokers. Former smokers exhibited intermediate risks. Women who had ceased smoking for 5-10 years had substantially lower fracture risk than current smokers. Each year since cessation conferred an ~1% relative reduction in fracture and mortality risk. Mediation analyses revealed significant indirect effects via slower walking speed (18-28%) and lower total vBMD, suggesting these factors are key contributors to fracture risk. Importantly, competing risk models confirmed elevated fracture risk in smokers even after accounting for increased mortality. These findings demonstrate that smoking is associated with increased fracture risk in older women, partly through impairments in physical function and vBMD. Smoking cessation appears to confer meaningful skeletal benefits, indicating a need for integrated strategies targeting both behaviour change and physical function to reduce fracture burden in aging populations.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148581","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":"Phenotypic Diversity in Autosomal Recessive Hypophosphatemic Rickets Type 2.","authors":"Maimoona Al Qanoobi, Maryam Al Badi, Aisha Al Sinani, M Zulf Mughal","doi":"10.1093/jbmr/zjag029","DOIUrl":"https://doi.org/10.1093/jbmr/zjag029","url":null,"abstract":"<p><p>Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) caused by biallelic ENPP1 mutations is a rare disorder with a broad phenotypic spectrum. We describe three affected siblings from a consanguineous family who presented with markedly heterogeneous clinical features. The proband exhibited classical signs of rickets with progressive lower-limb deformities, short stature, and elevated alkaline phosphatase. Her older sister demonstrated limited elbow extension, conductive hearing loss, and vascular stenoses, while the youngest sibling developed early biochemical abnormalities before overt skeletal manifestations of rickets emerged. All affected children had hypophosphatemia, reduced TmP/GFR, and elevated or inappropriately normal FGF23 concentrations, consistent with FGF23-mediated phosphate wasting. Notably, plasma inorganic pyrophosphate (PPi) levels were markedly reduced in the affected children and mildly reduced in the carriers of monoallelic mutation. Genetic testing identified a homozygous ENPP1 variant, c.2559_2561del p.(Leu854del), which was essential for establishing the diagnosis and distinguishing ARHR2 from other hereditary forms of hypophosphatemic rickets. The father had low lumbar spine bone mineral density. These cases highlight the clinical heterogeneity of ENPP1 deficiency and reinforce the essential role of genetic testing in establishing the correct diagnosis.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148499","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 regulator PER1 inhibits osteoclastogenesis by activating inflammatory genes.","authors":"Nobuko Katoku-Kikyo, Elizabeth K Vu, Samuel Mitchell, Ismael Y Karkache, Elizabeth W Bradley, Nobuaki Kikyo","doi":"10.1093/jbmr/zjag025","DOIUrl":"10.1093/jbmr/zjag025","url":null,"abstract":"<p><p>Disruption of circadian rhythms predisposes shift workers to many chronic conditions, including osteoporosis. However, the effects of disrupted circadian rhythms on bone remodeling remain largely unknown. Here, we show that one of the core circadian regulators PER1 inhibits osteoclastogenesis by upregulating genes involved in inflammation. The conditional knockout of Per1 in osteoclasts and related cells resulted in decreased bone mass in the femurs of mice, along with increased osteoclasts and decreased osteoblasts. Osteoclastogenesis was also promoted by Per1 depletion in vitro with 16 downregulated inflammatory genes. Seven of these genes were known to promote or inhibit osteoclastogenesis depending on the stage of osteoclastogenesis and the presence or absence of infection. Knockdown of Nlrp3, Tlr8, or Tlr9 in the group of genes promoted osteoclastogenesis, mirroring the effects of Per1 knockout and offering a mechanistic explanation for the Per1-mediated inhibition of osteoclastogenesis. These results were not observed following the knockout of a paralog Per2. Per1 knockout mice maintain general circadian rhythms, unlike arrhythmic Per1;Per2 double knockout mice. This gives credence to Per1 as a selective target for therapeutic interventions without disrupting the circadian rhythms. This study uncovered a molecular link between a circadian regulator and osteoclastogenesis in the broader context of inflammatory reactions. Our findings may be mechanistically relevant to inflammatory bone diseases influenced by circadian rhythms, such as rheumatoid arthritis and osteoarthritis, as well as other bone diseases predisposed by chronic circadian disruption.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123093","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":"Palopegteriparatide for Adults with Chronic Hypoparathyroidism: Skeletal Dynamics Through 3 yr of the Phase 2 paTH Forward Trial.","authors":"Mishaela R Rubin, Bart L Clarke, Lorenz C Hofbauer, Aliya Khan, Peter Schwarz, Tamara Vokes, Intekhab Ahmed, Andrea Palermo, Filomena Cetani, Uberto Pagotto, Carol Zhao, Michael S Ominsky, Bryant Lai, Jenny Ukena, Aimee D Shu, Lars Rejnmark","doi":"10.1093/jbmr/zjag013","DOIUrl":"https://doi.org/10.1093/jbmr/zjag013","url":null,"abstract":"<p><p>Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH), which acts directly on bone and kidney and indirectly on the intestine to regulate calcium and phosphate balance. In clinical trials, palopegteriparatide (TransCon PTH) treatment enabled independence from conventional therapy (no active vitamin D, ≤500 mg/d calcium) and maintained serum biochemistries within normal ranges. The current analyses describe patterns of change in bone mineral density (BMD), serum bone turnover markers, and serum and urine calcium in adults with chronic hypoparathyroidism treated with palopegteriparatide through 3 yr of the PaTH Forward trial. Baseline BMD Z-scores for the lumbar spine, total hip, femoral neck, and 1/3 distal radius were above zero, indicating bone mass exceeding age-adjusted normative values. BMD decreased from these elevated baseline levels with palopegteriparatide treatment, with larger reductions during the first 26 wk and modest declines thereafter. Mean BMD Z-scores at week 162 remained above zero for all 4 sites. Participants with lower baseline BMD (Z-scores below -1 and T-scores below -2.5) generally exhibited lesser declines in BMD versus those with higher baseline BMD. Palopegteriparatide treatment was associated with early increases in bone resorption (serum C-terminal telopeptide of type I collagen, CTx) and bone formation (serum procollagen type 1 N-terminal propeptide, P1NP) that peaked at weeks 12 and 26, respectively, followed by declines to levels moderately higher than baseline at week 162. Mean CTx and P1NP in the overall population and the subgroup of postmenopausal women were below their upper limits of normal from weeks 58-162. At week 162, mean serum and median urine calcium remained within normal ranges and 91% of participants were independent from conventional therapy. These results suggest that long-term palopegteriparatide therapy in adults with chronic hypoparathyroidism gradually returns the skeleton toward its natural state thereby enhancing the skeleton's contribution to calcium homeostasis.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117190","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":"Leg Power and Velocity Predict the Risk of Major Osteoporotic Fractures (MOF): the Osteoporotic Fractures in Men (MrOS) Study.","authors":"Tong Yu, Elsa S Strotmeyer, Nina Z Heilmann, Deborah M Kado, Kristine Ensrud, Mary Winger Knueven, Paolo Caserotti, Peggy Cawthon, Jane A Cauley","doi":"10.1093/jbmr/zjag014","DOIUrl":"10.1093/jbmr/zjag014","url":null,"abstract":"<p><p>Lower extremity muscle function has been associated with risk of falls and fractures; however, most studies have examined strength (force), but not power (force*velocity). A jump test on a force plate measures weight-bearing power and allows the dissection of peak power into its components, force and velocity. We investigated the association between jump test power measures and MOF risk in 1841 older men (median age 84 yr). Peak jump power (Watt/kg body weight), force (Newton/kg body weight) at peak power, and velocity (m/s) at peak power were measured by jump tests on a force plate. Fractures were identified by triannual questionnaires, with all self-reported fractures confirmed by medical record. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) by continuous (per one SD increment) and across quartiles of jump test measurements. Participants that were excluded from the jump tests were classified into the \"lowest\" group (referent; N = 599). A total of 136 incident MOF occurred over 5 yr of follow-up. In the multiply adjusted models, one SD increment of peak power/kg body weight was associated with a lower risk of MOF (HR 0.71, 95% CI 0.54-0.92), with a similar risk reduction observed with velocity at peak power (HR 0.76, 95%CI:0.59-0.98). Further adjustment for femoral neck (FN) bone mineral density (BMD) did not attenuate the association. There was significant trend of decreasing MOF with increasing power and velocity. For force, only the highest quartile was significantly associated with lower risk of MOF, but this was not significant after adjusting for FN BMD. In older men, peak leg power and velocity, but not force, predicted MOF risk independent of FN BMD. Power, which incorporates velocity, may play a more important role than force in reducing the risk of a fracture.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12875646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117122","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":"Gsα, Albright's hereditary osteodystrophy, and craniosynostosis.","authors":"Murat Bastepe","doi":"10.1093/jbmr/zjag002","DOIUrl":"10.1093/jbmr/zjag002","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"102-103"},"PeriodicalIF":5.9,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909623","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}