Journal of Bone and Mineral Research最新文献

{"title":"Sequential osteoanabolic therapy for osteoporosis.","authors":"Michael R McClung","doi":"10.1093/jbmr/zjaf033","DOIUrl":"10.1093/jbmr/zjaf033","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"710"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565711","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 of JBMR: sequential osteoanabolic therapy for osteoporosis.","authors":"Tomonori Kobayakawa, Yukio Nakamura","doi":"10.1093/jbmr/zjaf034","DOIUrl":"10.1093/jbmr/zjaf034","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"711"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565710","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":"Osteoporosis after kidney transplantation-no place for active vitamin D in the prevention of bone loss.","authors":"Hanne Skou Jørgensen, Pieter Evenepoel","doi":"10.1093/jbmr/zjaf049","DOIUrl":"10.1093/jbmr/zjaf049","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"567-568"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741888","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":"Calcitriol supplementation after kidney transplantation: results of a double-blinded, randomized, placebo-controlled trial.","authors":"Pascale Khairallah, Natalia E Cortez, Donald J McMahon, Stephen Sammons, Sanchita Agarwal, R John Crew, David J Cohen, Geoffrey K Dube, Sumit Mohan, Jae-Hyung Chang, Heather K Morris, Hilda E Fernandez, Maria Alejandra Aponte, Aderemi O Adebayo, Andrea Aghi, Martina Zaninotto, Mario Plebani, Giovanni Tripepi, Maurizio Gallieni, Chiara Cosma, Maria Fusaro, Thomas L Nickolas","doi":"10.1093/jbmr/zjaf044","DOIUrl":"10.1093/jbmr/zjaf044","url":null,"abstract":"<p><p>A significant number of kidney transplant recipients have low BMD. We hypothesized that calcitriol administration over the first year posttransplantation would protect the cortical skeleton in recipients managed without corticosteroids by suppressing PTH and bone remodeling. In this double-blind, placebo-controlled trial, 67 participants aged ≥18 yr on corticosteroid-sparing immunosuppressive regimen were randomized to daily calcitriol 0.5 μg or placebo for 12 mo after transplantation. The primary endpoint was the percent change in cortical density at the radius and tibia from pre- to postcalcitriol treatment compared to placebo as measured by HR-pQCT. Areal BMD was measured by DXA. Cortical and trabecular volumetric BMD and microarchitecture and total estimated bone strength were measured by HR-pQCT. Blood samples for bone metabolic markers were obtained at baseline, 1- and 12 mo. All primary analyses were intent to treat. Safety was assessed for hypercalcemia and progression of vascular calcifications. Thirty-two participants received calcitriol and 29 received placebo; 27 and 27 participants completed the study, respectively. Most participants were male and Caucasian. Baseline Z-scores at all sites were within 0.5 SD of the general population. At 12 mo posttransplantation, there were no between-group differences in areal BMD, volumetric BMD, microarchitecture or bone strength, or serum levels of bone markers. Participants with versus without bone loss had a blunted anabolic response over 12 mo measured by serum bone markers. Hypercalcemia was higher in the calcitriol group compared to placebo (p < .001). No changes in arterial calcification scores were observed. In this randomized placebo-controlled study of calcitriol administration in kidney transplant recipients on corticosteroid-sparing immunosuppression, calcitriol did not improve bone quality and strength but was associated with higher rates of hypercalcemia.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"603-616"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639389","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":"Depletion of marrow adipo-CAR cells in mice enhances bone formation by activating bone morphogenetic protein receptor (BMPR) in pre-osteoblasts.","authors":"Wei Zou, Nidhi Rohatgi, Hua Pan, Nitin Kumar Pokhrel, Matthew J Silva, Steven L Teitelbaum","doi":"10.1093/jbmr/zjaf051","DOIUrl":"10.1093/jbmr/zjaf051","url":null,"abstract":"<p><p>Diphtheria toxin (DT)-mediated deletion of marrow cells expressing its receptor (DTR), exclusively in adiponectin (Adipoq)-positive cells, results in profound osteosclerosis, a process driven by activation of bone morphogenetic protein receptor (BMPR) signaling. This enhancement of bone mass is associated with removal of Grem1 and Chrdl1, but the cellular source of these BMPR inhibitors, and whether they mediate this unique skeletal event, has not been established. In this study, we found that replacing the depleted BMPR inhibitors, using nanoparticles bearing their mRNAs, attenuates the osteogenic effect of Adipoq-positive cell depletion, confirming the essential role of Grem1 and Chrdl1 in the osteosclerotic process. Depletion of these BMPR inhibitors is accompanied by elimination of Cxcl12 and Lepr, suggesting that the Adipoq-positive subset of Cxcl12-abundant reticular (adipo-CAR) cells are the exclusive producers of Grem1 and Chrdl1 in marrow. While ablation of adipo-CAR cells does not increase osteo-CARs in the marrow, it activates BMPR in Col1*3.6-positive pre-osteoblasts, leading to their proliferation. Deletion of proliferating Col1*3.6-positive cells completely arrests bone formation induced by adipo-CAR cell ablation, suggesting that committed pre-osteoblasts, rather than earlier osteo-CARs, serve as the osteoprogenitors responsible for the new bone formation. The skeletal effects of eliminating marrow cells expressing leptin receptor (Lepr), also a marker of CAR cells, mirrors that induced by depleting those expressing adiponectin, including its initiation by BMPR activation in both male and female mice. Thus, marrow-residing Adipoq/Lepr-positive CAR cells limit excessive skeletal mass by producing BMPR inhibitors, while their depletion leads to significant osteosclerosis through BMPR activation and pre-osteoblast proliferation.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"688-698"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741758","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":"Heme metabolism mediates RANKL-induced osteoclastogenesis via mitochondrial oxidative phosphorylation.","authors":"Heng Qiu, Haiming Jin, Jiansen Miao, Hui Li, Junchun Chen, Xiaohong Yang, Xiaojun Chen, Benjamin H Mullin, Kai Chen, Ronghe Gu, An Qin, Scott G Wilson, Jiake Xu","doi":"10.1093/jbmr/zjaf040","DOIUrl":"10.1093/jbmr/zjaf040","url":null,"abstract":"<p><p>Bone undergoes life-long remodeling, in which disorders of bone remodeling could occur in many pathological conditions including osteoporosis. Understanding the cellular metabolism of osteoclasts (OCs) is key to developing new treatments for osteoporosis, a disease that affects over 200 million women worldwide per annum. We found that human OC differentiation from peripheral blood mononuclear cells derived from 8 female patients is featured with a distinct gene expression profile of mitochondrial biogenesis. Elevated mitochondrial membrane potential (MMP, Δψm) was also observed in receptor activator of NF-κB ligand (RANKL)-induced OCs. Interestingly, the gene pathways of heme synthesis and metabolism were activated upon RANKL stimulation, featured by transcriptomic profiling in murine cells at a single-cell resolution, which revealed a stepwise expression pattern of heme-related genes. The real-world human data also divulges potential links between heme-related genes and bone mineral density. Heme is known to have a role in the formation of functional mitochondrial complexes that regulate MMP. Disruption of heme biosynthesis via genetically silencing Ferrochelatase or a selective inhibitor, N-methyl Protoporphyrin IX (NMPP), demonstrated potent inhibition of OC differentiation, with a dose-dependent effect observed in NMPP treatment and a substantial efficacy even at a single dose. In vivo study further showed the protective effect of NMPP on ovariectomy-induced bone loss in female mice. Collectively, we found that RANKL-mediated signaling regulated mitochondrial formation and heme metabolism to synergistically support osteoclastogenesis. Inhibition of heme synthesis impaired OC formation and reversed excessive bone loss, representing a new therapeutic target for metabolic skeletal disorders.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"639-655"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613046","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":"cGAS-STING aggravates cartilage degradation by promoting glycolysis in temporomandibular joint osteoarthritis.","authors":"Yanhua Dong, Xueman Zhou, Zhenzhen Zhang, Jiaqi Liu, Xiayanran Wu, Jie Xiang, Yingcheng Zheng, Xin Xiong, Yating Yi, Jin Liu, Jun Wang","doi":"10.1093/jbmr/zjaf029","DOIUrl":"10.1093/jbmr/zjaf029","url":null,"abstract":"<p><p>The abnormal mechanical stress has been considered as a major contributor of temporomandibular joint osteoarthritis (TMJOA), but the mechanism by which it leads to the degeneration of condylar cartilage remains elusive. The DNA sensor cyclic GMP-AMP synthase (cGAS) plays a vital role in many sterile inflammatory responses by activating the stimulator of interferon genes (STING). In the present study, we found that mechanical stress exerted on condyle chondrocytes induced dsDNA leakage from mitochondria to cytoplasm to activate STING. Upon activation, STING exacerbated cartilage degradation by suppressing the anabolism of cartilage extracellular matrix (ECM) and accelerating the catabolic activity. Furthermore, the promoted glycolysis in chondrocytes was identified as a central mechanism in the onset of TMJOA, with critical rate-limiting enzymes downstream of STING. Our study not only establishes an important link between the intrinsic TMJOA suppressor activity of STING and chondrocyte metabolism, but also has critical implications for the development of STING-targeted therapeutic modalities of TMJOA.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"699-709"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482036","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":"Deep learning-based identification of vertebral fracture and osteoporosis in lateral spine radiographs and DXA vertebral fracture assessment to predict incident fracture.","authors":"Namki Hong, Sang Wouk Cho, Young Han Lee, Chang Oh Kim, Hyeon Chang Kim, Yumie Rhee, William D Leslie, Steven R Cummings, Kyoung Min Kim","doi":"10.1093/jbmr/zjaf050","DOIUrl":"10.1093/jbmr/zjaf050","url":null,"abstract":"<p><p>Deep learning (DL) identification of vertebral fractures and osteoporosis in lateral spine radiographs and DXA vertebral fracture assessment (VFA) images may improve fracture risk assessment in older adults. In 26 299 lateral spine radiographs from 9276 individuals attending a tertiary-level institution (60% train set; 20% validation set; 20% test set; VERTE-X cohort), DL models were developed to detect prevalent vertebral fracture (pVF) and osteoporosis. The pre-trained DL models from lateral spine radiographs were then fine-tuned in 30% of a DXA VFA dataset (KURE cohort), with performance evaluated in the remaining 70% test set. The area under the receiver operating characteristics curve (AUROC) for DL models to detect pVF and osteoporosis was 0.926 (95% CI 0.908-0.955) and 0.848 (95% CI 0.827-0.869) from VERTE-X spine radiographs, respectively, and 0.924 (95% CI 0.905-0.942) and 0.867 (95% CI 0.853-0.881) from KURE DXA VFA images, respectively. A total of 13.3% and 13.6% of individuals sustained an incident fracture during a median follow-up of 5.4 years and 6.4 years in the VERTE-X test set (n = 1852) and KURE test set (n = 2456), respectively. Incident fracture risk was significantly greater among individuals with DL-detected vertebral fracture (hazard ratios [HRs] 3.23 [95% CI 2.51-5.17] and 2.11 [95% CI 1.62-2.74] for the VERTE-X and KURE test sets) or DL-detected osteoporosis (HR 2.62 [95% CI 1.90-3.63] and 2.14 [95% CI 1.72-2.66]), which remained significant after adjustment for clinical risk factors and femoral neck bone mineral density. DL scores improved incident fracture discrimination and net benefit when combined with clinical risk factors. In summary, DL-detected pVF and osteoporosis in lateral spine radiographs and DXA VFA images enhanced fracture risk prediction in older adults.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"628-638"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750036","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":"Control of alveolar bone development, homeostasis, and socket healing by salt-inducible kinases.","authors":"Nicha Tokavanich, Byron Chan, Katelyn Strauss, Christian D Castro Andrade, Yuki Arai, Mizuki Nagata, Marc Foretz, Daniel J Brooks, Noriaki Ono, Wanida Ono, Marc N Wein","doi":"10.1093/jbmr/zjaf038","DOIUrl":"10.1093/jbmr/zjaf038","url":null,"abstract":"<p><p>Alveolar bone supports and anchors teeth. The parathyroid hormone-related protein (PTHrP) pathway plays a key role in alveolar bone biology. Salt-inducible kinases (SIKs) are important downstream regulators of PTH/PTHrP signaling in the appendicular skeleton, where SIK inhibition increases bone formation and trabecular bone mass. However, the function of these kinases in alveolar bone remains unknown. Here, we report a critical role for SIK2/SIK3 in alveolar bone development, homeostasis, and socket healing after tooth extraction. Inducible SIK2/SIK3 (Ubq-creERt;Sik2f/f;Sik3f/f) deletion led to dramatic alveolar bone defects without changes in tooth eruption. Ablating these kinases impairs alveolar bone formation due to disrupted osteoblast maturation, a finding associated with ectopic periostin expression by fibrous cells in regions of absent alveolar bone at steady state and following molar extraction. Notably, this phenotype is the opposite of the increased trabecular bone mass observed in long bones following SIK2/SIK3 deletion. Distinct phenotypic consequences of SIK2/SIK3 deletion in appendicular versus craniofacial bones prompted us to identify a specific transcriptomic signature in alveolar versus long bone osteoblasts. Thus, SIK2/SIK3 deletion illuminates a key role for these kinases in alveolar bone biology and highlights the emerging concept that different osteoblast subsets utilize unique genetic programs.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"656-670"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583898","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":"Tumor-induced rickets/osteomalacia (TIO): diagnostic pitfalls and therapeutic options.","authors":"Nobuaki Ito, Seiji Fukumoto","doi":"10.1093/jbmr/zjaf047","DOIUrl":"10.1093/jbmr/zjaf047","url":null,"abstract":"<p><p>A 10-year-old girl developed bilateral gonalgia and waddling gait. Biochemical and imaging studies showed hypophosphatemia with impaired proximal tubular phosphate reabsorption and high intact fibroblast growth factor 23 (FGF23) level, indicating FGF23-related hypophosphatemic rickets/osteomalacia. However, genetic analyses for hereditary FGF23-related hypophosphatemic rickets were negative. 111In-pentetreotide scintigraphy and 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) which were available at that time, failed to find a tumor associated with tumor-induced rickets/osteomalacia. She was first treated with active vitamin D and phosphate salt, followed by burosumab which alleviated her symptoms. She was then referred to our hospital to find the cause of her disease, and the previous imaging results were reevaluated. There was an asymmetrical uptake in the distal portion of her right femur by PET/CT. The following magnetic resonance imaging confirmed the presence of a tumor in the lateral portion of the right femur. Wide excision of the lesion corrected hypophosphatemia. The differential diagnoses and treatment of hypophosphatemic rickets/osteomalacia are discussed.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"572-576"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741900","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}