JBMR Plus最新文献

{"title":"High-resolution profiling of osteocyte transcriptomes via single-nucleus RNA sequencing.","authors":"Yukiko Kitase, Jia Ji, Lynda F Bonewald, Matthew Prideaux, Hyun Cheol Roh, Gang Peng","doi":"10.1093/jbmrpl/ziag051","DOIUrl":"10.1093/jbmrpl/ziag051","url":null,"abstract":"<p><p>High-throughput transcriptomic technologies have advanced rapidly, enabling genome-wide gene expression profiling. Microarrays, introduced in 1995, laid the foundation for large-scale analysis but were later surpassed in 2008 by RNA sequencing (RNA-seq), which offers single-nucleotide resolution, detects low-abundance transcripts, and does not require prior sequence knowledge. Bulk RNA-seq provides robust insights into global transcriptomic changes but lacks single-cell resolution. Single-cell RNA-seq (scRNA-seq), introduced in 2009, addressed this limitation by revealing cellular heterogeneity and dynamic gene expression. However, its application in bone research is constrained due to difficulties in releasing bone cells called osteocytes from the mineralized matrix, often resulting in low yield and dissociation-induced artifacts. In order to address these challenges, single-nucleus RNA-seq (snRNA-seq), first introduced in 2016 to enable transcriptomic profiling from isolated nuclei, was used in this study. We developed a protocol for snRNA-seq on bone tissue, achieving high-yield recovery of osteocyte nuclei from snap-frozen, marrow-flushed long bones. This approach minimized dissociation bias and enhanced osteocyte representation. We applied this robust method to long bones from young adult male and female mice, generating a high-resolution map of osteocyte gene expression under physiological conditions. Compared to scRNA-seq datasets, where osteocytes represent only 0.18%-6.64% of cells, our snRNA-seq approach increased osteocyte capture and transcriptomic fidelity to 18.5%. We identified an osteocyte transcriptomic signature highlighting the top 30 genes, including <i>Sost</i>, which is typically undetected or lowly-expressed in scRNA-seq. Notably, 23 of these genes have not been well-characterized in osteocytes, including <i>Tg</i>, <i>Kcnq5</i>, <i>Rapgef4os1</i>, <i>Cacna1a</i>, <i>Egr3</i>, <i>Dok5</i>, and <i>Lgr6</i>, which may represent novel regulators of osteocyte biology. This study represents the first application of snRNA-seq specifically for osteocyte analysis in bone tissue, providing a valuable resource for investigating osteocyte biology and skeletal disorders.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag051"},"PeriodicalIF":3.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health-related quality of life in French adults with X-linked hypophosphatemia: real-world data from the International XLH Registry.","authors":"Karine Briot, Sandrine Lemoine, Bernard Cortet, Paulina Szafors, Nadia Mehsen, Guillaume Couture, Kerry Sandilands, Angela J Rylands, Haruka Ishii, Annabel Bowden, Jennifer E Dent, Peter Kamenicky","doi":"10.1093/jbmrpl/ziag050","DOIUrl":"10.1093/jbmrpl/ziag050","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is a rare genetic condition in which excess fibroblast growth factor 23 causes renal phosphate wasting, leading to skeletal morbidities. Patients experience musculoskeletal pain, stiffness, and fatigue, with impaired physical function and health-related quality of life (HRQL). Burosumab has been available in France for the treatment of XLH since 2021; European treatment guidelines suggest use in adults with pseudofractures or with insufficient response and/or intolerance to oral phosphate supplements and active vitamin D. The International XLH Registry is collecting long-term observational data in a real-world setting from patients with XLH. Here, we report data from French adults from their first completion of the Short-Form 36 (SF-36) version 2 health survey, a measure of health-related quality of life. The analysis used data from 123 adults who completed the survey at least once (73% women; mean age at completion 42.5 yr [SD 13.4]; mean age at diagnosis 8.8 [12.6] yr). Group mean T-scores in the current International XLH Registry sample were <47 on all SF-36 scale and summary scores, indicating impaired functioning. Physical and mental component summary scores were similar (43.0 [SD 9.1] vs 43.4 [11.3]). Worse physical component summary scores were significantly related to older age (<i>p</i> = .032), not working (excluding students) (<i>p</i> < .001), history of fracture (<i>p</i> < .001), lower-extremity fracture (<i>p</i> = .010), surgery as an adult (<i>p</i> < .001), current burosumab treatment (<i>p</i> = .006), and previous burosumab treatment (<i>p</i> = .002), possibly because treatment guidelines direct use to patients with more severe disease. Lower mental component summary scores were related to younger age (<i>p</i> = .010). Physical summary scores were better in the current analysis than in adults with other chronic musculoskeletal conditions, mental summary scores were worse. Further exploration of the relationships between modifiable influences on HRQL is warranted, including the impact of earlier intervention with burosumab on physical symptoms, notably fractures, and HRQL.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag050"},"PeriodicalIF":3.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain medication use in patients with X-linked hypophosphatemia treated with burosumab: a retrospective real-world study.","authors":"Carolyn M Macica, Zhiyi Li, Ben Johnson, Ahmed Noman, Catherine Park, Gina N Woods","doi":"10.1093/jbmrpl/ziag047","DOIUrl":"10.1093/jbmrpl/ziag047","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is a rare, progressive phosphate-wasting disorder that leads to significant skeletal morbidity and pain. The current study used real-world administrative claims data to assess the demographic and clinical characteristics of patients with XLH related to claims for prescription pain medication (PPM) during the 12 mo before starting burosumab treatment (baseline) and explores changes in PPM claims after starting burosumab treatment. Claims for XLH-related musculoskeletal and deformity-related conditions, obesity, and osteoarthritis were common among the adult cohort (<i>n</i> = 387). Claims for PPM (vs no claims) during baseline were significantly (<i>p</i> < .05) associated with: age ≥ 50 yr (odds ratio [OR] 2.54), Medicaid coverage (2.25), myalgia (2.54), scoliosis (3.19), obesity (2.07), dental complications (2.53), and physical therapy (2.94). Approximately half of the adult cohort (54%) made PPM claims during baseline, and 38% for opioids, with little change after starting burosumab. Claims for arthralgia, hip/leg deformities and rickets were common in pediatric patients (<i>n</i> = 524). Claims for PPM were significantly associated with race (OR 0.13), chronic pulmonary disease (4.34), renal disease (4.88), arthralgia (2.20), cholecalciferol claims (1.93), and physical therapy (3.48). About one-fifth of pediatric patients (25%) had claims for PPM prescriptions during baseline, with little change after 12 mo, but showed a modest decrease during the second year of follow-up; 12%-17% of pediatric patients had claims for opioids during baseline and follow-up. The number of days covered by opioid prescriptions was lower in pediatric patients than in adults. Multiple factors are associated with PPM use in patients with XLH. Understanding these factors may inform patient-centered pain management strategies. A longer study is needed to determine how burosumab treatment affects pain and the use of PPM in patients with XLH.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag047"},"PeriodicalIF":3.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the vitamin D metabolite ratio with bone turnover markers and changes in volumetric BMD.","authors":"Emma Mulligan, Terri Blackwell, Andrew N Hoofnagle, Olivia Alison Potok, Jane A Cauley, Andrew J Burghardt, Kristine Ensrud, Deborah M Kado, Joachim H Ix, Eric Orwoll, Peggy M Cawthon, Charles Ginsberg","doi":"10.1093/jbmrpl/ziag044","DOIUrl":"10.1093/jbmrpl/ziag044","url":null,"abstract":"<p><p>The vitamin D metabolite ratio (VMR), calculated as the ratio of 24,25(OH)₂D₃ to 25(OH)D, is a marker of vitamin D stores that may provide a more accurate reflection of bone health outcomes than 25(OH)D alone. In this analysis, we examined the relationship between VMR and 25(OH)D with bone turnover markers (BTM's) and changes in volumetric BMD (Tt.BMD) in older community-dwelling men participating in the Osteoporotic Fractures in Men (MrOS) study. Tt.BMD was measured at the distal radius and tibia by HR-pQCT at 2 separate visits approximately 6 yr apart. Bone turnover markers were measured at the time of the first HR-pQCT scan and included PTH, C-terminal telopeptide of type I collagen (CTX-I), and N-terminal propeptide of type I procollagen (PINP). Linear regression was used to evaluate the association of VMR and 25(OH)D with BTM's and annualized percent change in Tt.BMD. The mean (SD) age of the 254 men was 83(3) yr, with an eGFR of 71(14) mL/min/1.73 m². Mean VMR and 25(OH)D were 6.5(2.2) (ng/mL)/(ng/mL) and 39(14) ng/mL, respectively. Both the VMR and 25(OH)D were inversely associated with PTH concentrations (<i>p</i> < .02 for both). In fully adjusted models, a 2-fold higher VMR was associated with a 34% [12%; 55%] lower CTX-I and a 16% [1.3%;30%] lower PINP while 25(OH)D was not associated with these BTMs. The relationship of VMR with BTM's appeared stronger among men with CKD (eGFR <60 mL/min/1.73 m²) than in persons with normal renal function. Neither VMR nor 25(OH)D were associated with annualized change in Tt.BMD in fully adjusted models.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag044"},"PeriodicalIF":3.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the use of segmentation-based and deconvolution-based three-dimensional joint space width analysis of the hand and wrist.","authors":"Jilmen Quintiens, Tadiwa H Waungana, Michael T Kuczynski, Sarah L Manske, G Harry van Lenthe","doi":"10.1093/jbmrpl/ziag048","DOIUrl":"10.1093/jbmrpl/ziag048","url":null,"abstract":"<p><p>Three-dimensional morphometric analyses of joint space from CT scans can provide a quantitative and unbiased evaluation of radiographic damage from arthritis. This potentially offers greater sensitivity for disease assessment and monitoring than traditional ordinal scoring systems. Previously established methods for 3-dimensional joint space analysis from CT scans can be categorized into segmentation-based and grayscale deconvolution-based methods. However, segmentation-based methods have not been employed for joints other than metacarpophalangeal joints, nor have they been compared to deconvolution-based methods. This study compared the joint space width (JSW) distribution from various hand and wrist joints in photon-counting CT images, using both measurement approaches. From these distributions, the mean (JSW.Mean), standard deviation (JSW.SD), maximum (JSW.Max), minimum (JSW.Min), 95th percentile (JSW.95%), and fifth percentile (JSW.5%) values were calculated. For each morphometry parameter, agreement between the 2 methods was assessed by calculating the coefficient of determination (R²), and the mean and SD of the individual biases. General estimating equations were used to assess the relationship between morphometry and an equivalent/modified Sharp/van der Heijde (SvdH) ordinal radiographic score. In general, agreement between the 2 methods was low: R² ranged between 0.42 and 0.87; biases up to 0.18 mm [Formula: see text] 0.33 mm. For both methods, an increased degree of joint space narrowing as assessed with SvdH was associated with reduced JSW.Min and increased JSW.SD; for the deconvolution method, it was also associated with decreased JSW.Mean and increased JSW.Max. Interactions between the methods showed a weaker association to SvdH score for JSW.Min and a stronger association for JSW.SD when measured with the deconvolution method, compared to the segmentation method. We conclude that both methods lead to fundamentally different measurement outcomes, and that the deconvolution method might be more sensitive to radiographic damage.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag048"},"PeriodicalIF":3.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the cortical bone metabolome of C57BL/6J mice with adenine-induced kidney disease.","authors":"Shane Stauffer, Hope D Welhaven, Brady D Hislop, Bryce A Jones, Moshe Levi, Ronald K June, Chelsea M Heveran","doi":"10.1093/jbmrpl/ziag043","DOIUrl":"10.1093/jbmrpl/ziag043","url":null,"abstract":"<p><p>The loss of bone fracture resistance in CKD results from both a loss of bone mass and decreased bone material properties, which together result from changes to the health and activities of bone cells. Determining changes to bone tissue metabolism with CKD may reveal insights important to monitoring and mitigating the decrease in bone fracture resistance with this disease. In this study, untargeted metabolomics was conducted on marrow-flushed cortical tibiae from female and male C57BL/6J mice fed either control or 0.2% w/w adenine diets for 3.5 or 7 wk. Liquid chromatography mass spectrometry assessed metabolites from tibia extracts. Group comparisons (adenine vs control, 7 wk vs 3.5 wk, female vs male) were conducted using principal components analysis and partial least squares discriminant analysis. Clusters of metabolites were also assessed using ensemble clustering with cluster optimization analysis. Volcano plots and variable importance in projections (VIP) scores identified metabolites that differed between groups, and pathway analyses were conducted using these features. Adenine-induced CKD produced few differences in cortical bone tissue metabolism, based on the comparison of pooled adenine vs control groups. However, pantothenate and Coenzyme-A biosynthesis, along with essential and nonessential amino acid pathways, registered notably high VIP scores for adenine vs control comparisons. There were many significant differences between 3.5- and 7-wk treatment groups (adenine and control). The pathways different between diet lengths for control mice reveal potential effects of skeletal aging. However, there were significant changes in the pentose phosphate pathway and cysteine metabolism between 3.5- and 7-wk adenine diets, indicating an effect of CKD severity. While sex differences in this study were modest, there was greater separation between female adenine vs control groups compared to male adenine vs control groups, indicating potential sex differences in the impacts of CKD on bone tissue metabolism.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag043"},"PeriodicalIF":3.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of cocoa extract supplementation on physical performance measures: results from the randomized controlled COcoa Supplement and Multivitamin Outcomes study.","authors":"Sharon H Chou, Nancy Cook, Eunjung Kim, Gregory Kotler, David A Ganz, Peggy M Cawthon, Allison Clar, Aladdin H Shadyab, JoAnn E Manson, Howard D Sesso, Carolyn J Crandall, Meryl LeBoff","doi":"10.1093/jbmrpl/ziag041","DOIUrl":"10.1093/jbmrpl/ziag041","url":null,"abstract":"<p><p>Poor physical performance is associated with a higher risk of falls, fractures, and premature death among older adults. We determined whether supplementation with cocoa extract vs placebo or multivitamin/multimineral (MVM) vs placebo for 2 yr benefited physical performance measures. The COcoa Supplement and Multivitamin Outcomes Study was a double-blinded, placebo-controlled randomized trial of supplemental cocoa extract and/or MVM vs placebo for the primary prevention of cardiovascular disease and cancer in 21 442 US adults. This ancillary study was completed in a New England sub-cohort that underwent physical performance measurements, including grip strength, walking speed, standing balance, repeated chair stands, and timed-up and go (TUG) test, at baseline and 2-yr follow-up. In the clinic sub-cohort (<i>n</i> = 603) with a mean (±SD) age of 69.7 ± 5.5 yr and 49.3% women, supplemental cocoa extract, compared to cocoa-extract placebo, did not affect 2-yr changes in our primary pre-specified, co-equal outcomes of grip strength, walking speed, and the Short Physical Performance Battery (composite of walking speed, standing balance, and chair stands) or in secondary outcomes of standing balance, chair stands, or TUG tests. No effect modification by baseline characteristics of age, sex, body mass index, or randomization to MVM supplementation was observed. In parallel analyses, MVM, compared to MVM placebo, also did not affect physical performance measures. Supplementation with cocoa extract did not prevent age-related declines in physical performance measures in older ambulatory US men and women.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag041"},"PeriodicalIF":3.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Romosozumab for the treatment of thalassemia-associated osteoporosis in two female patients.","authors":"Maria P Yavropoulou, Maria-Evangelia Koloutsou, Polyxeni Delaporta, Polyzois Makras, Athanasios D Anastasilakis, Eva Kassi, Antonis Kattamis, Paraskevi Xekouki","doi":"10.1093/jbmrpl/ziag020","DOIUrl":"10.1093/jbmrpl/ziag020","url":null,"abstract":"<p><p>Osteoporosis is a major complication of thalassemia bone disease, leading to increased fracture risk and impaired quality of life. Anti-resorptive agents, such as bisphosphonates and denosumab, have shown efficacy in randomized trials, but data are scarce, regarding the role of anabolic agents in severe cases with fragility fractures. We report 2 cases with severe osteoporosis associated to thalassemia with multiple vertebral and non-vertebral fractures, despite long term-treatment with anti-resorptive agents. Both patients were initiated on subcutaneous romosozumab (210 mg once monthly) for 12 mo. At 12 mo, BMD showed marked improvement at the LS by 6.8%-15.4%, TH by 14.6%, and FN by 8.7%-24.6%. Bone turnover markers changed in line with clinical trials of postmenopausal osteoporosis. No adverse events occurred during the treatment period. Following completion of romosozumab therapy, each patient received a single infusion of zoledronate to consolidate the bone mass gained. Over 24 mo follow-up, no new fragility fractures were observed. Romosozumab can be an effective and safe anabolic option for patients with thalassemia and high fracture risk. While anti-resorptive therapy remains the standard of care, romosozumab may provide additional benefit in thalassemia patients with severe osteoporosis and increased fracture risk.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag020"},"PeriodicalIF":3.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vertebral remodeling with denosumab after infection control in <i>Escherichia coli</i> spondylodiscitis: case report.","authors":"Bing-Hao Lu, Tung-Ying Lin, Kuo-Yuan Huang","doi":"10.1093/jbmrpl/ziag040","DOIUrl":"10.1093/jbmrpl/ziag040","url":null,"abstract":"<p><p>Infectious spondylodiscitis can cause progressive vertebral destruction and instability even after infection control, and some patients decline or are unsuitable for surgery. We report a 67-yr-old man with poorly controlled type 2 diabetes mellitus and hypertension who developed <i>Escherichia coli</i> bacteremia and subsequent infectious spondylodiscitis. Four months after treatment of a traumatic open tibial wound with debridement and split-thickness skin grafting, he presented with progressive low back pain, intermittent fever, and systemic illness with acute kidney injury and hepatic dysfunction. A distal common bile duct stone was treated endoscopically, but fever persisted. A gallium-67 scan raised suspicion for L2-L3 involvement, and LS MRI demonstrated L2-L3 infectious spondylodiscitis with extensive paraspinal and epidural inflammatory changes and bilateral psoas abscesses. CT-guided aspiration and bone biopsy were culture-negative. He improved clinically after approximately 5 wk of antimicrobial therapy and declined operative debridement or stabilization. One week after completing antibiotics, denosumab (60 mg, s.c.) was administered. Given that denosumab is not a guideline-supported therapy for infectious spondylodiscitis, it was used off-label as a speculative adjunct to suppress inflammation-associated bone resorption; a second dose was given 6 mo later. Back pain and function improved with bracing, and serial radiographs showed new bone formation along the superior endplate of L3 with progressive remodeling. At 6-yr follow-up, the patient remained free of adverse effects and demonstrated spontaneous fusion of L2 and L3 with sustained symptom relief. This report is descriptive and hypothesis-generating. The observed remodeling may also reflect expected post-infectious healing under conservative management. Nevertheless, the course raises a testable hypothesis that carefully timed antiresorptive therapy after confirmed infection control may support structural recovery in selected nonoperative patients with marked infection-related vertebral osteolysis.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag040"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A metabolomics-driven machine learning model for osteoporosis risk prediction.","authors":"Chuan Qiu, Boluwatife L Afolabi, Jeffrey Deng, Kuanjui Su, Lindong Jiang, Martha Gonzalez-Ramirez, Shashank S Mungasavalli Gnanesh, Zhe Luo, Qing Tian, Hui Shen, Hong-Wen Deng","doi":"10.1093/jbmrpl/ziag042","DOIUrl":"10.1093/jbmrpl/ziag042","url":null,"abstract":"<p><p>Osteoporosis, marked by decreased bone mineral density (BMD), poses a major public health concern by increasing fracture risk, lowering quality of life, and raising healthcare costs in aging populations. Accurate risk prediction is essential for early diagnosis and targeted intervention. While machine learning (ML) models have been used to predict osteoporosis risk based on clinical factors, their accuracy and generalizability are limited. Multi-omics studies, especially in genomics and proteomics, have shown promise in predicting osteoporosis-related traits, such as BMD and fracture risk. However, the integration of metabolomics, critical for bone metabolism, remodeling, and mineralization remains underexplored in this context. This study aimed to identify novel metabolites associated with osteoporosis risk and assess their predictive utility. Using hip BMD measurements, clinical data, and metabolomic profiles from 2041 participants aged 40 and older, we developed a predictive model integrating metabolomics with clinical risk factors. Model performance was evaluated using the area under the receiver operating curve (AUC). We identified 44 metabolites significantly associated with osteoporosis risk (<i>p</i> < .05), many enriched in small molecule transport and metabolic pathways. Notably, 25 had prior links to bone metabolism. Incorporating these metabolites into our metabolomics-driven ML model improved predictive performance compared to a clinical-only model (AUC_{clinical + metabolomics} = 0.763 vs AUC_clinical = 0.741, <i>p</i> = .017). Feature importance analysis identified 5 key clinical predictors (weight, grip strength, height, age, and sex) and 5 top metabolites (N-acetylcarnosine, hypotaurine, homoarginine, epiandrosterone sulfate, and dehydroepiandrosterone sulfate). Mendelian randomization confirmed causal effects of these top metabolites on BMD variation. We identified a metabolomic signature for osteoporosis risk and demonstrated that integrating metabolomics with clinical data significantly enhances ML-based prediction. These findings point to the promise of metabolomics in advancing strategies for early detection and personalized care in aging populations at risk for osteoporosis.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag042"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}