Journal of Bone and Mineral Research最新文献

{"title":"Twenty-four-hour movement composition is associated with HR-pQCT bone strength in older adults: The Study of Muscle, Mobility and Aging (SOMMA).","authors":"Lauren S Roe, Nina Z Heilmann, Reagan E Garcia, Nicole M Sekel, Kristen J Koltun, Julie M Hughes, Katelyn Guerriere Aaron, Kerri S Freeland, Yan Ma, Tong Yu, Peggy M Cawthon, Kelley Pettee Gabriel, Paolo Caserotti, Bradley C Nindl, Nancy W Glynn, Elsa S Strotmeyer, Jane A Cauley","doi":"10.1093/jbmr/zjag117","DOIUrl":"https://doi.org/10.1093/jbmr/zjag117","url":null,"abstract":"<p><p>Time in moderate-to-vigorous intensity activity (MVPA), light intensity activity (LPA), and sleep are critical for bone health in older adults but are often considered separately despite being inherently co-dependent. We examined cross-sectional associations between compositions of accelerometry-derived MVPA, LPA, inactivity, and sleep with bone microarchitecture and strength (High-Resolution Peripheral Quantitative Computed Tomography; HR-pQCT) in community-dwelling older men (n=119) and women (n=177), mean age 76.3±4.6 yrs. Participants wore an ActiGraph GT9X on their non-dominant wrist for 7 consecutive 24hr periods during the Study of Muscle, Mobility and Aging (SOMMA) baseline visit. The primary outcomes were distal radius (DR) and tibia (DT) estimated failure load, and secondarily, total volumetric bone mineral density (vBMD), and cortical (Ct) and trabecular (Tb) vBMD, area (Ar), and thickness (Th) from HR-pQCT. Compositional data analysis methods evaluated proportions of time in one behavior relative to the remaining behaviors. Sex-stratified multiple linear regression estimated associations between 24hr composition with sex-specific standardized HR-pQCT parameters. Compositional isotemporal substitution methods estimated hypothetical changes in continuous HR-pQCT measures if 10-60 min in one behavior was displaced by another. On average, women spent 90.2 min/day (6.3%) in MVPA, 346.1 min/day (24.0%) in LPA, 556.4 min/day (38.6%) in inactivity, and 447.4 min/day (31.1%) in sleep; men spent 93.6 min/day (6.5%) in MVPA, 309.5 min/day (21.5%) in LPA, 596.7 min/day (41.4%) in inactivity, and 440.2 min/day (30.6%) in sleep. Compared to the average sex-specific 24hr composition, higher proportions of MVPA were associated with higher DR and DT failure load in women; higher DR Tb.vBMD and Tb.Th in men; and higher DR Tt.vBMD, Ct.Ar, and Ct.Th, and DT Ct.vBMD, Ct.Ar, and Ct.Th in women. Hypothetically displacing 10-60 min in inactivity for MVPA resulted in more favorable HR-pQCT parameters. These data support the importance of MVPA for a healthy skeleton in older men and women.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596964","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":"Infigratinib is a weak inhibitor of the FGFR3-N540K mutant associated with hypochondroplasia.","authors":"Vlad-Constantin Ursachi, Zuzana Feketova, Aleksandra Anna Czyrek, Klara Sestakova, Katerina Svozilova, Gustavo Rico-Llanos, Pavel Krejci","doi":"10.1093/jbmr/zjag017","DOIUrl":"10.1093/jbmr/zjag017","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"903-905"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049786","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":"IRE1 signaling in osteoprogenitors augments β-catenin activity and physiologic bone accrual.","authors":"Lakshmi D Kolora, Christian Melendez-Suchi, Veronica Butler, Li Han, Maria Almeida, Kartik Shankar, Douglas J Adams, Srividhya Iyer","doi":"10.1093/jbmr/zjag001","DOIUrl":"10.1093/jbmr/zjag001","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) orchestrates the folding of the large amounts of membrane and secretory proteins that are synthesized during the process of osteogenesis. The unfolded protein response (UPR) resulting from accumulation of misfolded proteins in the ER lumen either promotes or inhibits osteoblast differentiation in vitro depending on magnitude and duration. All three transducers of the UPR, namely, IRE, PERK, and ATF6 proteins, have been implicated in skeletal biology, yet their specific contribution to osteoblast differentiation and function in vivo has not been investigated systematically. Here, the skeletal consequences of deleting each of them (ie, Ire1α, Perk, or Atf6) in the osteoblast lineage using the Osx1-Cre transgene were determined. Mice with deletion of Ire1α in Osx1+ osteoblast precursors exhibited a marked reduction in osteoblast number, bone mass, and strength. Primary bone marrow cultures of osteoprogenitors lacking Ire1α had significantly reduced proliferation, alkaline phosphatase activity, and survival. Analyses of bulk RNA-seq data revealed suppression of osteogenic signature by Ire1α deletion in Osx1+ cells and predicted suppression of β-catenin activity. Mechanistically, Ire1α augments nuclear translocation and transcriptional activity of β-catenin in Osx1+ cells. In contrast, deletion of Perk or Atf6 genes in the osteoblast lineage using the Osx1-Cre transgene did not alter bone mass or strength. Collectively, these studies demonstrate that IRE1, but not other UPR transducers, promote physiological bone accrual in part by boosting β-catenin activity in osteoprogenitors.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"890-902"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909588","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":"Rural-urban differences in osteoporosis and sarcopenia prevalence among Gambian older adults: a pilot study.","authors":"Mícheál Ó Breasail, Ayse Zengin, Camille Pearse, Isatou Drammeh, Ramatoulie Janha, Landing Jarjou, Peter R Ebeling, Ann Prentice, Kate A Ward","doi":"10.1093/jbmr/zjaf130","DOIUrl":"10.1093/jbmr/zjaf130","url":null,"abstract":"<p><p>Rural-urban BMD differences are well described in high-income countries, typically with higher BMD in rural areas. However, despite rapid urbanization and longevity across Africa, such data remain scarce. This study compares bone and muscle health in older adults living in rural and urban Gambia. Participants aged ≥55 yr from rural (n = 209) and urban (n = 101) communities were measured with DXA (TH, FN, and LS) and peripheral QCT (pQCT; diaphyseal and epiphyseal radius and tibia). Outcomes were DXA areal BMD (aBMD), BMC, bone area (BA); pQCT total volumetric BMD (vBMD), trabecular vBMD, bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Osteoporosis (NHANES III, T-score < -2.5) and sarcopenia (revised European Working Group on Sarcopenia in Older People [EWGSOP2] appendicular lean mass [ALM] and handgrip strength [HGS]) prevalence were computed. Linear regression was used to describe rural-urban differences in DXA and pQCT outcomes (1) age-adjusted and (2) adjusted for age and fat mass index (FMI). Osteoporosis at either the FN or TH was more prevalent in urban men (20% vs rural 10%) and rural women (45% vs urban 31%). LS T-scores < -2.5 were more common in rural participants (men: 27% vs 14%; women: 61% vs 35%). Sarcopenia was also higher in rural participants (men: 30% vs. 18%; women: 18% vs 15%). Adjusted for age and FMI urban Gambians had lower BMC but greater BA at the FN and TH, while aBMD differed little. Urban men had lower adjusted tibial cortical vBMD but greater tibial diaphyseal and radial epiphyseal CSA. After adjustment, urban women had greater radial CSA and estimated strength. Our findings highlight that osteoporosis and sarcopenia are highly prevalent in older Gambian adults, with differences in rural-urban prevalence influenced by sex. Given ongoing nutrition transition and urbanization across Africa, larger population-based studies are urgently required to better inform targeted prevention strategies and interventions.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"804-814"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111633","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":"Age- and sex-specific incidence rates and future projections for hip fractures in The Gambia, West Africa, and comparison across four countries in Africa.","authors":"Hannah Wilson, Kebba Marenah, Anya Burton, Momodou Jallow, Lucy Gates, Awa Touray, Samuel Hawley, Simon M Graham, James Masters, Matthew Costa, Bintou Trawally, Kate A Ward, Celia L Gregson","doi":"10.1093/jbmr/zjaf126","DOIUrl":"10.1093/jbmr/zjaf126","url":null,"abstract":"<p><p>Longevity in African populations is increasing, where deprivation and malnutrition are common; hence, fragility fracture incidence is expected to increase. Healthcare systems must adapt to provide for these aging populations; however, currently fragility fracture incidence has yet to be determined in any West African setting. This study aimed to determine age- and sex-specific hip fracture incidence rates in adults in The Gambia, compare these with rates from other African countries, and estimate future national hip fracture projections. All hip fracture cases in adults aged ≥40 yr, presenting to a hospital or traditional bone setter (TBS) in the study area over 2-yr, were identified. Age- and sex-specific hip fracture incidence per 100 000 person-years were estimated using the 2024 Gambian Population census. Incidence rate estimates were compared between The Gambia, Zimbabwe, South Africa, and Botswana. In The Gambia, future hip fracture numbers were estimated through to 2054 using United Nations population projections. Over 2-yr, 226 hip fracture patients, mean (SD) age 71.2 (12.5) yr, 64.6% female, presented to hospital (184 [81.4%]) or TBS (42 [18.6%]). Most presented with a fragility fracture (205 [90.7%]). High-impact trauma (eg, traffic accidents) was more common in younger men. Delays in presentation were common (68 [30.1%]). Incidence rates for adults ≥40 yr in The Gambia were 28.1 and 51.7 per 100 000 person years for men and women, respectively, increasing with age. In those age ≥80 yr, incidence rates plateaued in men. The number of hip fractures is estimated to increase from 166 in 2024 to 621 by 2054. Age-specific hip fracture incidence rates were broadly comparable between The Gambia, Zimbabwe, Botswana, and Black South Africans. In summary, fragility fractures in Gambian adults were common, indicative of age-associated osteoporosis. Hip fracture cases will almost quadruple over coming decades; therefore, health service capacity must expand to manage this rising demand.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"815-822"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090708","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":"Functional impact of pathogenic mutations in the runt homology domain of mouse Runx2 on skeletal and dental phenotypes in cleidocranial dysplasia.","authors":"Saki Ogawa, Shinnosuke Higuchi, Yuki Yoshimoto, Mari Hoshino, Shigenori Miura, Atsuko Hamada, Hitomi Watanabe, Tetsushi Sakuma, Kadi Hu, Shun Ogata, Kenta Uchibe, Katsumi Fujimoto, Takashi Yamamoto, Tetsuji Okamoto, Ryo Kunimatsu, Yusuke Sotomaru, Kotaro Tanimoto, Gen Kondoh, Toshihisa Komori, Denitsa Docheva, Chisa Shukunami","doi":"10.1093/jbmr/zjaf201","DOIUrl":"10.1093/jbmr/zjaf201","url":null,"abstract":"<p><p>Runt-related transcription factor 2 (RUNX2) is essential for skeletogenesis, and mutations in its gene cause cleidocranial dysplasia (CCD), an autosomal dominant skeletal disorder. The evolutionarily conserved 128-amino acid Runt homology domain (RHD) of human RUNX2 is essential for DNA binding and heterodimerization, and serves as a mutation hotspot associated with severe CCD phenotypes. To elucidate the functional impact of pathogenic RHD mutations in vivo, we generated 2 novel mouse lines: one carrying a missense mutation, c.695G>A, p.Arg232Gln (p.R232Q), corresponding to the human RUNX2 c.674G>A, p.Arg225Gln (p.R225Q), and the other harboring a frameshift mutation, c.697_698delGA, p.Glu233Thrfs*9 (p.E233Tfs*9), causing a premature stop codon. Homozygous Runx2R232Q/R232Q and Runx2E233Tfs*9/E233Tfs*9 mice lacked membranous ossification, whereas heterozygous Runx2R232Q/+ and Runx2E233Tfs*9/+ mice displayed typical CCD-like skeletal features, including an open anterior fontanelle and clavicle hypoplasia. Unexpectedly, heterozygotes carrying pathogenic RHD mutations developed small root-like protrusions, mostly 1 but rarely 2, at the pulp chamber floor of 3-rooted maxillary first molars during furcation, revealing a previously unrecognized dental phenotype. Dual luciferase assays showed that p.R232Q almost completely lost transactivation of the osteocalcin enhancer/promoter. Immunostaining showed that wild-type Runx2 was robustly expressed in osteoblasts and hypertrophic chondrocytes during bone formation, while the p.R232Q mutant Runx2 in Runx2R232Q/R232Q mice exhibited reduced expression in hypertrophic chondrocytes and partially impaired nuclear localization. These abnormalities led to defective osteoblast differentiation and chondrocyte maturation. Thus, our mutant mouse model provides a valuable in vivo platform to study CCD pathogenesis, mechanisms of tooth root furcation, and therapeutic interventions targeting dysfunctional RHD.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"874-889"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846203","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 to letter to the editor for \"Infigratinib low dose therapy is an effective strategy to treat hypochondroplasia\".","authors":"Laurence Legeai-Mallet, Bhavik P Shah","doi":"10.1093/jbmr/zjag018","DOIUrl":"10.1093/jbmr/zjag018","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"906-907"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058218","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":"Bone health across the lifespan in African populations affected by HIV.","authors":"Ryan D Ross, Michael T Yin","doi":"10.1093/jbmr/zjag072","DOIUrl":"10.1093/jbmr/zjag072","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"791-792"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13288437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148012777","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":"Autosomal dominant hypocalcemia type 1: status quo of tailored management and future perspectives.","authors":"Daisuke Harada, Noriyuki Namba","doi":"10.1093/jbmr/zjag034","DOIUrl":"10.1093/jbmr/zjag034","url":null,"abstract":"<p><p>A 28-day-old female infant presented with clonic seizures secondary to hypocalcemia (calcium [Ca], 5.7 mg/dL) and hypoparathyroidism (intact PTH, 7 pg/mL). Despite the initiation of oral alfacalcidol therapy, she experienced recurrent episodes of generalized convulsions or focal tetany, despite calcium lactate administration during febrile episodes. Her younger sister exhibited frequent irritability until day 38 of life due to hypocalcemia (Ca, 7.7 mg/dL) and hypoparathyroidism (intact PTH, 5 pg/mL). She experienced 3 febrile generalized seizures during infancy despite oral alfacalcidol treatment. Both sisters developed nephrocalcinosis despite oral hydrochlorothiazide treatment to reduce hypercalciuria. Genetic testing identified a pathogenic variant, c.2504C>A (p.Ala835Asp), in the calcium-sensing receptor (CASR) gene in both sisters. Their father carried the same variant but remained asymptomatic. This finding led to a diagnosis of autosomal dominant hypocalcemia type 1 (ADH1). Optimal active vitamin D treatment in ADH1 remains challenging because of difficulty maintaining stable serum Ca levels amid fluctuating physiological demands, as well as persistent hypercalciuria resulting from combined PTH deficiency and CaSR activation. Emerging therapies, including calcilytics, may help to address these limitations.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"793-798"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275343","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":"Chronic non-bacterial osteitis presenting with upper limb deep vein thrombosis: diagnostic clues and therapeutic considerations.","authors":"Nina Thomson, Jack Leese, James Bott, Elizabeth M Winter, Barbara Hauser","doi":"10.1093/jbmr/zjag056","DOIUrl":"10.1093/jbmr/zjag056","url":null,"abstract":"<p><p>A 40-yr-old Scandinavian man with a 10-yr history of palmoplantar pustulosis presented with left upper limb swelling and was diagnosed with a deep vein thrombosis. Imaging revealed subclavian vein compression due to marked clavicular hyperostosis. The patient reported longstanding sternoclavicular pain, inflammatory back pain, and electronic health records review showed persistently elevated inflammatory markers. CT demonstrated extensive cortical overgrowth of the clavicle consistent with chronic non-bacterial osteitis (CNO), alongside thoracic syndesmophytes suggestive of axial spondyloarthritis-like involvement. Long-term anticoagulation was initiated, and rheumatology assessment confirmed CNO. TNF inhibition therapy was started to control the inflammatory symptoms. This case highlights a rare but serious complication of CNO: thoracic outlet obstruction with secondary thrombosis from progressive bone overgrowth. Earlier recognition might have prevented irreversible structural and vascular sequelae. It also underscores current uncertainties in CNO management, including whether treatment can prevent hyperostosis, how to identify high-risk patients, and the optimal duration of treatment.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"799-803"},"PeriodicalIF":6.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508283","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}