Journal of Bone and Mineral Research最新文献

{"title":"Programmed cell death protein 1 (PD-1) blockade regulates skeletal remodeling in a sex- and age-dependent manner.","authors":"Gwenyth J Joseph, Lawrence A Vecchi Iii, Sasidhar Uppuganti, Jeremy F Kane, Margaret Durdan, Paige Hill, Ashtyn G McAdoo, Hidenori Tanaka, David Kell, Madeline B Searcy, Wei Chen, Eben L Rosenthal, David G Harrison, Jeffry S Nyman, Megan M Weivoda, Rachelle W Johnson","doi":"10.1093/jbmr/zjaf055","DOIUrl":"10.1093/jbmr/zjaf055","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) block immunoregulatory receptor-ligand interactions and robustly increase survival of cancer patients but frequently result in immune-related adverse events (irAEs). While rheumatologic toxicities are commonly reported as irAEs, the effect of immune checkpoint blockade on the underlying mechanisms of ICI-induced fractures and bone loss is controversial, with reports of both positive and negative effects on bone mass in preclinical models. However, no previous reports have investigated the impact of ICIs on females or aged mice, or on fracture risk in either sex. We report that global deletion of programmed cell death protein 1 (PD-1) broadly results in bone loss in skeletally mature male and female PD-1-/- mice, with a sexually divergent phenotype in adolescent mice, decreased bone strength in adult males and young females, and expansion of multiple T cell subsets in the bone marrow. In a model of pharmacologic PD-1 blockade, administration of α-PD-1 reduced bone mass, expanded multiple T cell subsets in the bone marrow, and increased osteoclast activity and resorptive capacity. T cell deficient mice were resistant to osteoclast-mediated bone loss following α-PD-1 therapy, suggesting that T cells in the bone marrow are necessary for bone loss in the setting of ICI therapy. These findings may be leveraged to identify patients at greater fracture risk following ICI therapy due to enrichment of effector T cell populations in the bone marrow.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"950-964"},"PeriodicalIF":5.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952841","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":"Functions of secretory calcium-binding phosphoproteins in dental mineralization.","authors":"Yong-Hee P Chun, Brian L Foster, Tian Liang, Kazuhiko Kawasaki","doi":"10.1093/jbmr/zjaf062","DOIUrl":"10.1093/jbmr/zjaf062","url":null,"abstract":"<p><p>Biomineralization of skeletal and dental tissues has evolved via a suite of regulatory extracellular matrix proteins. The secretory calcium-binding phosphoproteins (SCPPs) are encoded by genes that arose by duplication. In the human genome, 23 SCPP genes have been identified, and 2 groups of SCPPs regulate dental mineralization: bone, dentin, and/or cementum matrix proteins and enamel proteins. In the past 2 decades, the functional roles of SCPPs in dental mineralization have been revealed by studies of human disorders and genetically edited mice. Five enamel SCPPs, amelogenin (AMEL), enamelin (ENAM), ameloblastin (AMBN), odontogenic ameloblast associated (ODAM), and amelotin (AMTN), are secreted by ameloblasts during sequentially arranged stages of amelogenesis. Sequence variants in 4 of the enamel SCPP genes (AMEL, ENAM, AMBN, and AMTN) have been associated with inherited malformations of enamel, termed amelogenesis imperfecta. Loss-of-function variants contribute to enamel of reduced thickness and/or mineral density. Two bone/dentin/cementum SCPPs, dentin matrix protein 1 and dentin sialophosphoprotein (DSPP), are critical for dentin mineralization. Functional studies in genetically edited mice imply that dentin sialoprotein (the N-terminal fragment of DSPP) promotes the propagation of mineralization, and that dentin phosphoprotein (the C-terminal fragment of DSPP) is essential for the fusion and the increase of mineral density of calcospherites. Pathogenic variants in DSPP can cause 2 distinct entities of isolated hereditary dentinogenesis imperfecta. Bone sialoprotein (BSP) and osteopontin are markers of cementum (and bone) in multiple species. Global ablation of BSP in mice resulted in acellular cementum hypoplasia, hypomineralized alveolar bone and breakdown of periodontal function. Osteopontin appears to have a more complex role in regulating mineralized tissues via several direct and indirect mechanisms. Research into SCPPs has provided new insights into the evolution of biomineralization, normal dental development, and inherited disorders, as well as translational directions for tissue repair and regeneration.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"909-930"},"PeriodicalIF":5.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958926","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":"The janus-faced effect of PD1 signaling on bone: do sex and age matter?","authors":"Sonia Vallet","doi":"10.1093/jbmr/zjaf078","DOIUrl":"10.1093/jbmr/zjaf078","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"907-908"},"PeriodicalIF":5.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493281","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":"A new publicly available database of human calcium-sensing receptor variants that disrupt calcium homeostasis.","authors":"Arthur D Conigrave, Edward F Nemeth","doi":"10.1093/jbmr/zjaf071","DOIUrl":"10.1093/jbmr/zjaf071","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"946-949"},"PeriodicalIF":5.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118471","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":"Treatment-related changes in total hip bone mineral density are applicable to trials of varied study designs and to drugs with differing mechanisms of action: meta-regression results from the FNIH-ASBMR SABRE study","authors":"Tatiane Vilaca, Li-Yung Lui, Marian Schini, Susan K Ewing, Austin Thompson, Eric Vittinghoff, Douglas C Bauer, Dennis M Black, Mary L Bouxsein, Richard Eastell","doi":"10.1093/jbmr/zjaf100","DOIUrl":"10.1093/jbmr/zjaf100","url":null,"abstract":"<p><p>Emerging anti-osteoporosis therapies might present varied mechanisms of action and demand active control groups or sequential therapies due to ethical or mechanistic reasons. We previously showed a strong association between treatment-induced changes in total hip bone mineral density(THBMD) at 12 and 24 mo and reduced fracture risk in placebo-controlled trials. We determined the surrogate threshold effect(STE): the minimum THBMD difference (active-placebo) in a trial that would predict a significant reduction in fracture risk in trials. In this analysis, we investigated whether these associations are influenced by drug mechanism of action or trial design, including treatment with an anabolic followed by an anti-resorptive compared to active control or placebo. We analyzed individual patient data from 22 randomized, placebo-controlled trials (17 anti-resorptive, 3 PTH analogues, 1 odanacatib, and 1 romosozumab placebo-controlled phase), and three trials of an anabolic followed by an anti-resorptive(1 PTH analogue and 2 romosozumab). We established treatment-related differences in THBMD changes, calculated fracture risk reductions for radiologic vertebral and all clinical fractures, and estimated study-level associations between these features via meta-regression. We found consistent associations between treatment-related THBMD changes and fracture risk reduction across different drug mechanisms and trial designs. Among placebo-controlled trials, the r2 values for vertebral fractures were 0.73(p = .0001) and 0.78(p = .0002) at 24 mo, and 0.59(p = .0003) and 0.70(p = .0007) at 12 mo for all drugs versus only anti-resorptive drugs, respectively. Similarly, for all clinical fractures, the r2 were 0.71(p < .0001) and 0.65(p = .0009) at 24 mo and 0.46(p = .0007) and 0.51(p = .002) at 12 mo for all drugs versus only anti-resorptive drugs. For trials of an anabolic followed by an anti-resorptive, the association between THBMD change and fracture risk reduction was similar to that for the placebo-controlled monotherapy trials. Our analyses indicate robust associations between treatment-induced THBMD changes and fracture risk reduction across various anti-osteoporosis therapies and trial designs, suggesting that treatment-induced changes in THBMD predict anti-fracture efficacy regardless of drug mechanism or trial design.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726247","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":"Parity and lactation cause transient bone loss but are not risk factors for osteoporosis later in life.","authors":"Christopher S Kovacs","doi":"10.1093/jbmr/zjaf095","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf095","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648090","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":"Burosumab: What can it do in children and adult patients with X-linked hypophosphatemia?","authors":"Seiji Fukumoto","doi":"10.1093/jbmr/zjaf097","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf097","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648088","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":"Invisible seams: dorsal and ventral elements of long bones are formed by distinct cells.","authors":"Federico La Manna, Matthew B Greenblatt","doi":"10.1093/jbmr/zjaf096","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf096","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648089","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":"3D-DXA reveals significant effects of burosumab on trabecular and cortical skeletal envelopes in symptomatic adults with X-linked Hypophosphatemia.","authors":"Rucha Patki, Thomas Carpenter, Keerti Murari, Stephen Parziale, Yanhong Deng, Ludovic Humbert, Mirella Lopez Picazo, Karl Insogna","doi":"10.1093/jbmr/zjaf092","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf092","url":null,"abstract":"<p><p>Fractures and pseudofractures cause considerable morbidity in adults with X-linked Hypophosphatemia (XLH). They frequently occur in cortically-enriched bones of the lower extremities. Burosumab, a neutralizing antibody to FGF23, heals fractures in adults with XLH, presumably by healing osteomalacia. Histomorphometry has documented healing of osteomalacia in trabecular bone. The effects of burosumab on cortical bone have not been reported. Therefore, 3D-DXA measurements of the proximal femur were used to examine the impact of 1 yr of burosumab therapy on cortical and trabecular bone in symptomatic adults with XLH. Twenty volunteers from the registration trial for burosumab were separately consented for this study. DXA scans of the hip were obtained before and 6, 12 and 18-24 mo (mo.) after drug therapy (1 mg/kg every 4 wk). 3D-DXA analyses were performed using 3D-Shaper software (3D-Shaper Medical). Changes in femoral neck (FN) areal BMD (aBMD), total hip (TH) aBMD, TH trabecular volumetric BMD (vBMD), FN trabecular vBMD, TH cortical surface BMD (sBMD), FN cortical sBMD, and FN cross-sectional moment of inertia (CSMI) were analyzed. Both TH and FN trabecular vBMD showed significant increases over the course of therapy (13.6% and 14.1% respectively at the end of treatment compared to baseline; p < .0001 for each). Fractures and pseudofractures often occur in the cortically-enriched FN in XLH. Burosumab induced a significant increase in FN cortical sBMD between 6 and 12 mo. (p < .05) and between 6 and 18-24 mo. of drug treatment (p < .05). The FN CSMI, an indicator of FN strength, also significantly increased at 12 and 18-24 mo. when compared to baseline; p < .05 and p < .01 respectively. These data demonstrate that burosumab increases both cortical and trabecular bone in the hip a site of frequent fracture in XLH.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615596","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":"Type 1 and 2 diabetes mellitus: comprehensive fracture risk relationships in UK Biobank.","authors":"Elizabeth M Curtis, Rebecca J Moon, Stefania D'Angelo, Zahra Raisi-Estabragh, Cyrus Cooper, Nicholas C Harvey","doi":"10.1093/jbmr/zjaf094","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf094","url":null,"abstract":"<p><p>We aimed to investigate associations between diabetes mellitus and incident fracture, stratified by diabetes type (1 or 2), disease duration and microvascular complications of diabetes. This prospective cohort analysis used data from the UK Biobank, a large population-based cohort of participants recruited 2006-2010 at age 40-69 yr. The exposure was type 1 or type 2 diabetes at baseline, with the outcome of first incident osteoporotic fracture. Poisson regression was used to calculate incidence rate ratios (IRRs) for osteoporotic fracture to investigate prospective relationships between diabetes type 1 or 2 and fracture risk independent of traditional clinical risk factors, estimated bone mineral density by heel ultrasound (eBMD), adiposity, and C-reactive protein. The role of diabetic microvascular complications and associations between diabetes duration and fracture risk were studied. There were 498 949 participants (271 882 women, mean age 56 yr; 227 067 men, 57 yr). In fully adjusted models, type 1 and 2 diabetes were associated with increased fracture risk [type 1; IRR: 2.93 (95%CI:2.37,3.62); type 2: 1.25 (1.14,1.38)], similar by sex. The magnitude of risk associated with type 2 diabetes increased with duration of disease. Increasing number of microvascular complications was associated with greater fracture risk [any vs no complications, IRR 2.03 (1.57,2.62)]. Diabetes is associated with increased risk of fracture (magnitude of effect greater in type 1 than type 2 diabetes). Associations were partly independent of traditional risk factors, adiposity, eBMD and CRP. Type 2 diabetes disease duration and the presence of microvascular complications in both types were dose-dependent risk factors for fracture.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606950","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}