Journal of Bone and Mineral Research最新文献

{"title":"Deep learning-based identification of vertebral fracture and osteoporosis in lateral spine radiographs and DXA VFA 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":"https://doi.org/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 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 prevalent vertebral fracture 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 [HR] 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 BMD. DL scores improved incident fracture discrimination and net benefit when combined with clinical risk factors. In summary, DL-detected prevalent vertebral fracture 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":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-01","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":"Depletion of marrow adipo-CAR cells in mice enhances bone formation by activating 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":"https://doi.org/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 replacing the depleted BMPR inhibitors, using nanoparticles bearing their mRNAs, attenuates the osteogenic effect of adiponectin 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 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":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/10.1093/jbmr/zjaf049","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-29","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":"Tumor-induced rickets/osteomalacia (TIO): diagnostic pitfalls and therapeutic options.","authors":"Nobuaki Ito, Seiji Fukumoto","doi":"10.1093/jbmr/zjaf047","DOIUrl":"https://doi.org/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 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":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-28","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}

{"title":"Single cell RNA sequencing shows that cells expressing Sox9 postnatally populate most skeletal lineages in mouse bone.","authors":"Neal P Smith, Christopher Janton, Ana Clara Morellato Alcantara, Majd George, Kasidet Mankongtreecheep, Guping Mao, Alexandra-Chloé Villani, Henry M Kronenberg","doi":"10.1093/jbmr/zjaf043","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf043","url":null,"abstract":"<p><p>In growing bones of mice, multiple cell types contribute to the osteoblast lineage, including growth plate chondrocytes, perichondrial cells and CXCL12-abundant reticular (CAR) marrow stromal cells. Here we use single-cell RNA sequencing and lineage tracing to show that all these osteoblast precursors, even postnatally, derive from Sox9-expressing progenitors. We also characterize a distinct group of chondrocytes located between the perichondrium and the columns of growth plate chondrocytes that contribute to the osteoblast lineage.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717814","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: Affinity targeting of therapeutic proteins to the bone surface-local delivery of sclerostin-neutralizing antibody enhances efficacy.","authors":"","doi":"10.1093/jbmr/zjaf042","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf042","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727300","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":"Structural alterations during fracture healing lead to void spaces developing in surrounding bone microarchitecture.","authors":"Danielle E Whittier, Matthias Walle, Penny R Atkins, Caitlyn J Collins, Matthias A Zumstein, Patrik Christen, Kurt Lippuner, Ralph Müller","doi":"10.1093/jbmr/zjaf046","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf046","url":null,"abstract":"<p><p>Distal radius fractures are among the most common fracture sites, with a high incidence across all age groups. High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled assessment of bone microarchitecture in vivo at the distal radius, providing new insights into the healing process. However, we have observed structural bone loss that is not captured by standard analysis. This study uses void space analysis to quantify development of localized structural bone loss during fracture healing. Twenty-six participants (21 female, 5 male, aged 18-79 years) with conservatively-treated distal radius fractures were scanned using HR-pQCT at 6 study visits post-fracture (weeks 1, 3, 5, 12, 26, and 52). Total BMD (Tt.BMD), bone volume fraction (BV/TV), and void space volume fraction (VS/TV) were measured. Grip strength relative to the non-fractured wrist and Patient Rated Wrist Evaluation (PRWE) were measured at all study visits after cast removal. The cumulative expansion of VS/TV across sequential study visits was quantified to differentiate voids that developed during healing from pre-existing void space. A five-fold increase in median VS/TV was observed during the follow-up period, from 1.0% (0.6-9.0%) to 5.5% (2.5-12.4%). Tt.BMD and BV/TV did not significantly change in this same time interval. Relative grip strength after cast removal was significantly inversely correlated with final VS/TV (⍴ = -0.63, p=.02) and cumulative expansion of new void space during healing (R = -0.67, p<.01), whereas no significant associations were found with age or PRWE. This study suggests that there are adverse changes in bone microarchitecture during fracture healing, despite the preservation of overall Tt.BMD and BV/TV in the same region. Reduced grip strength is correlated with more severe void space formation, but the mechanistic relationship requires further exploration. The formation of void spaces may have long-term implications on bone strength and could provide insight into risk of re-fracture.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672902","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":"https://doi.org/10.1093/jbmr/zjaf044","url":null,"abstract":"<p><strong>Background: </strong>A significant number of kidney transplant recipients have low BMD. We hypothesized that calcitriol administration over the first year post-transplantation would protect the cortical skeleton in recipients managed without corticosteroids by suppressing PTH and bone remodeling.</p><p><strong>Methods: </strong>In this double-blind, placebo-controlled trial, 67 participants aged ≥18 years on corticosteroid-sparing immunosuppressive regimen were randomized to daily calcitriol 0.5 mcg or placebo for 12 months after transplantation. The primary endpoint was the percent change in cortical density at the radius and tibia from pre- to post-calcitriol 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, one- and twelve-months. All primary analyses were intent to treat. Safety was assessed for hypercalcemia and progression of vascular calcifications.</p><p><strong>Results: </strong>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-months post-transplantation, 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 months 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.</p><p><strong>Conclusions: </strong>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":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated abdominal aortic calcification and major adverse cardiovascular events in people undergoing osteoporosis screening: the Manitoba Bone Mineral Density Registry.","authors":"Cassandra Smith, Marc Sim, Zaid Ilyas, Syed Zulqarnain Gilani, David Suter, Siobhan Reid, Barret A Monchka, Mohammed Jafari Jozani, Gemma Figtree, John T Schousboe, Joshua R Lewis, William D Leslie","doi":"10.1093/jbmr/zjae208","DOIUrl":"10.1093/jbmr/zjae208","url":null,"abstract":"<p><p>Vertebral fracture assessment (VFA) images from bone density machines enable the automated machine learning assessment of abdominal aortic calcification (ML-AAC), a marker of cardiovascular disease (CVD) risk. The objective of this study was to describe the risk of a major adverse cardiovascular event (MACE, from linked health records) in patients attending routine bone mineral density (BMD) testing and meeting specific criteria based on age, BMD, height loss, or glucocorticoid use have a VFA in the Manitoba BMD Registry. The cohort included 10 250 individuals (mean age 75.5 yr, 94% women without CVD) with VFA (February 2010 to March 2017). ML-AAC24 scores were categorized (low <2; moderate 2-<6; high ≥6). Over follow-up (mean 3.9 yr), 1265 people (12.3%) experienced a MACE. Among those with low, moderate, and high ML-AAC24, MACE rates per 1000 person-years were 18.4 (95% CI 16.4-20.5), 34.1 (95% CI 30.9-37.4), and 55.6 (95% CI 50.8-60.1), respectively. A similar gradient was observed after stratifying by age and sex. Incidence rate ratios (IRRs) for low vs moderate and high groups were 1.9 (95% CI 1.6-2.2) and 3.0 (95% CI 2.6-3.5), respectively. In those most likely to benefit from pharmaceutical intervention (<80 yr, not on statins), MACE rates among those with low, moderate, and high ML-AAC24 were 13.5 (95% CI 11.5-15.8), 26.0 (95% CI 22.1-30.3) and 44.1 (95% CI 37.0-52.0). Corresponding IRRs for low vs moderate 1.9 (95% CI 1.5-2.4) and high ML-AAC24 was 3.3 (95% CI 2.6-4.1]), respectively. In routine osteoporosis screening, individuals with moderate and high ML-AAC24 had substantially greater MACE rates compared to those with low ML-AAC24. Consequently, AAC detection during osteoporosis screening (especially in women) may guide intensification of preventative cardiovascular strategies.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"323-331"},"PeriodicalIF":5.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918835","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 relationship between baseline bone mineral density and fracture incidence in the placebo groups of randomized controlled trials using individual patient data from the FNIH-ASBMR-SABRE project.","authors":"Marian Schini, Li-Yung Lui, Tatiane Vilaca, Susan K Ewing, Austin Thompson, Douglas C Bauer, Mary L Bouxsein, Dennis M Black, Richard Eastell","doi":"10.1093/jbmr/zjae201","DOIUrl":"10.1093/jbmr/zjae201","url":null,"abstract":"<p><p>We have proposed to the Food and Drug Administration (FDA) that treatment-related increases in total hip BMD (TH BMD) at 2 yr could be a surrogate endpoint for fracture risk reduction in clinical trials. The qualification of a surrogate includes a strong association of the surrogate with the clinical outcome. We compiled a large database of individual patient data (IPD) through the Foundation for the National Institutes of Health-American Society for Bone and Mineral Research- A Study to Advance BMD as a Regulatory Endpoint (FNIH-ASBMR-SABRE) project, and this analysis aimed to assess the relationship between baseline BMD and fracture risk in the placebo groups. We estimated the association of baseline TH, femoral neck (FN), and lumbar spine (LS) BMD with fracture risk using IPD from the combined placebo groups, which included data from 46 666 placebo participants in 25 RCTs. We estimated the relative risk (RR) of fracture per SD decrease in baseline BMD using logistic regression models for radiographic vertebral fractures and proportional hazards models for hip, non-vertebral, \"all,\" and \"all clinical\" fractures. Total person-years in the combined placebo groups was 250 662 (mean baseline age 70.2 ± 7.2 yr, mean TH BMD T-score -1.97 ± 0.90). We observed significant relationships between baseline TH BMD and vertebral (RR = 1.55/SD), hip (RR = 2.27), non-vertebral (RR = 1.31), all (RR = 1.43), and all clinical (RR = 1.35) fracture risk. Fracture risk estimates were similar for FN BMD and after adjustment for age, race, and study. Fracture incidence increased with decreasing TH BMD quintile, confirming the strong graded association between TH BMD and fracture risk. There was a strong relationship between LS BMD and vertebral fracture risk (RR = 1.56/SD), but only a weak association with non-vertebral (RR = 1.07) and no association with hip (RR = 1.01) fracture risk. These data support the very strong relationship between hip BMD and fracture risk and provide supporting rationale for change in TH BMD as a surrogate for fracture risk reduction in future RCTs.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"307-314"},"PeriodicalIF":5.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833173","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}