JBMR Plus最新文献

{"title":"Spatial transcriptomic analysis of mouse parathyroid gland cells expressing an activating variant of <i>Gcm2</i>.","authors":"Priyanka Bolel, Jeremie Oliver Piña, Fabio R Faucz, James R Iben, Wafa Abbas, Smita Jha, William F Simonds, Lee S Weinstein, Sunita K Agarwal","doi":"10.1093/jbmrpl/ziaf147","DOIUrl":"10.1093/jbmrpl/ziaf147","url":null,"abstract":"<p><p>Glial cells missing 2 (<i>GCM2</i>) is an essential transcription factor for the development of parathyroid glands. Germline <i>GCM2</i> variants that repress or enhance transcriptional activity predispose a subset of patients to hypoparathyroidism or hyperparathyroidism, respectively. A recurrent germline heterozygous activating missense variant of <i>GCM2</i>, p.Y394S has been identified in some patients with primary hyperparathyroidism. A genetically engineered knock-in mouse model of this variant corresponding to p.Y392S in the mouse <i>Gcm2</i> gene (<i>Gcm2</i> ^+/Y392S) did not show obvious parathyroid tumors. However, in GCM2-binding site mediated luciferase reporter assays in HEK293 cells, the mouse and the human variant both exhibited enhanced transcriptional activity. Therefore, we assessed the effect of this variant on gene expression in vivo in parathyroid glands from <i>Gcm2</i> ^+/Y392S and WT mice. Using the 10x Genomics Visium platform, spatially resolved transcriptomic analysis was performed on formalin-fixed and paraffin-embedded (FFPE) tracheal tissue sections of <i>Gcm2</i> ^+/Y392S and WT mice to capture RNA from parathyroid glands together with other cell types in the tissue sections. Transcriptome sequence data analysis detected 8 different clusters in the tissue sections based on similarity of gene expression profiles. Cluster-1, which contained parathyroid gland cells expressing <i>Pth</i> and <i>Gcm2</i>, was further evaluated for transcripts that were differentially expressed more than 2-fold in <i>Gcm2</i> ^+/Y392S compared to WT. Increased transcript level of <i>Lgals3</i> (galectin-3) was seen in <i>Gcm2</i> ^+/Y392S parathyroid gland cells which is among markers of parathyroid carcinoma. Galectin-3 protein was detected in available FFPE human parathyroid samples of patients with germline heterozygous activating <i>GCM2</i> variants, p.Y394S (<i>n</i> = 4/10) or p.L379Q (<i>n</i> = 2/2). These results indicate a potential for growth and malignancy of parathyroid glands expressing <i>GCM2</i> variants. The transcriptomic data of mouse parathyroid gland cells generated in this study can serve as a valuable resource for investigating genes and pathways in normal or abnormal parathyroid gland growth and physiology.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 10","pages":"ziaf147"},"PeriodicalIF":2.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191695","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":"Comparative analysis of osteoclast function in symptomatic and asymptomatic individuals with cherubism-causing SH3BP2 mutation.","authors":"Chen Abramovitch-Dahan, Svetlana Katchkovsky, Yuval Zur, Gal Gozlan, Nitsan Nimni, Eitan Bar Droma, Navot Givol, Alex Geftler, Merav Fraenkel, Anat Reiner-Benaim, Kent Søe, Noam Levaot","doi":"10.1093/jbmrpl/ziaf148","DOIUrl":"10.1093/jbmrpl/ziaf148","url":null,"abstract":"<p><p>Cherubism is a rare autosomal dominant bone disease of the maxilla and mandible with variable severity. Most patients harbor a mutation in SH3 domain-binding protein 2 (SH3BP2), yet factors influencing genetic penetrance and clinical severity remain unclear. In mice, this mutation induces tumor necrosis factor alpha (TNF-α)-mediated systemic inflammation, though its role in human cherubism is debated. Multinucleated osteoclasts (OCs), rather than macrophages, are linked to symptom severity, but whether this results from progenitor differentiation or environmental factors is unknown. To elucidate this, OC differentiation and resorption were compared in PBMCs from two symptomatic and one asymptomatic carrier of the same cherubism mutation. All carriers exhibited larger OCs than healthy controls when cultured with RANKL or TNF-α. On bone slices, OCs from carriers resorbed more bone than controls, with TNF-α exerting a weaker effect than RANKL. No significant differences were observed between symptomatic and asymptomatic carriers, suggesting that symptom severity is influenced by microenvironmental factors external to OCs. Additionally, while TNF-α promotes giant cell formation in cherubism OCs, its impact on resorption is limited. These findings may explain why TNF-α inhibition reduces giant cell numbers in cherubism lesions without improving clinical outcomes.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 10","pages":"ziaf148"},"PeriodicalIF":2.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185887","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":"Mechanisms of dexamethasone-induced bone toxicity in developing bone: a single-cell perspective.","authors":"Kelly Warmink, Philip Lijnzaad, Stephanie A Schubert, Baojie Zhang, Tristan C W Vermaat, Lisa Jansen, Marloes C C van Gend, Aleksandra Balwierz, Natalie Proost, Marieke van de Ven, Johannes H M Merks, Thanasis Margaritis, Claudia Y Janda","doi":"10.1093/jbmrpl/ziaf146","DOIUrl":"10.1093/jbmrpl/ziaf146","url":null,"abstract":"<p><p>Glucocorticoids, such as dexamethasone, are essential for treating severe childhood conditions, including cancer, organ transplantation, and inflammatory disorders. However, their long-term use can impair bone development, posing risks to pediatric bone health, which is vital for lifelong skeletal integrity. A mechanistic insight into how glucocorticoids negatively impact bone could improve decision-making in patient care, thereby improving the quality of life for pediatric cancer patients and survivors. In this study, we aimed to elucidate the molecular mechanisms underlying dexamethasone-induced bone toxicity in developing bones using single-cell transcriptomics. We treated skeletally immature C57BL/6JRj male mice with dexamethasone for 28 days, and assessed the bone architecture with micro-computed tomography, and characterized bone and bone marrow cells from the femurs using single-cell RNA sequencing. Our findings revealed a marked reduction in osteoblast and chondrocyte cell populations and impaired function of pre-osteoblasts. Additionally, dexamethasone adversely affected B cell subsets, significantly depleting early B cell progenitors while allowing some further developed immature B cells to persist. These cellular changes were accompanied by reduced longitudinal bone growth, compromised bone architecture, and increased bone fragility at the highest doses of dexamethasone. Interestingly, unlike observations in adults, dexamethasone did not enhance osteoclast activity in our model. Overall, our study suggests that the adverse effects of dexamethasone on bone development are primarily due to its impact on osteoblastic, chondroblastic, and B cell lineages. This disruption affects the critical signaling crosstalk between the cells necessary for both bone development and hematopoiesis.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 10","pages":"ziaf146"},"PeriodicalIF":2.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191760","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":"Neutralization of Receptor activator of nuclear factor-κB ligand reduces fibrosis and promotes osteoblast differentiation in a mouse model of fibrous dysplasia driven by somatic expression of <i>Gnas^R201H</i>.","authors":"Renee T Ormsby, Yongxing Zhang, Cole Hodys, Lella A Wake, Samantha Menendez Perez, Kelly Tsang, Yingzi Yang, Julia F Charles","doi":"10.1093/jbmrpl/ziaf145","DOIUrl":"10.1093/jbmrpl/ziaf145","url":null,"abstract":"<p><p>Fibrous dysplasia (FD) is a rare disorder caused by somatic activating mutations in <i>GNAS</i>, encoding the alpha subunit of the Gs protein. Activating <i>GNAS</i> mutations result in focal expansile bone lesions, which cause pain, deformity, and increased risk of fracture. Somatic mosaicism in FD leads to both <i>GNAS</i> mutant and genetically WT osteoprogenitor cells, which jointly contribute to the formation of fibrotic lesions within the bone. Additionally, these lesions contain numerous osteoclasts formed in response to robust lesional expression of RANKL. Neutralizing antibody to RANKL is effective in reducing lesion growth in patients with FD and in preclinical models. To determine the effect of RANKL neutralization specifically on mutant cells early after onset of FD, we used a murine model of C57BL/6 <i>Sox9^CreERT;Gnas^(R201H)fl/+;Rosa26^LSL-tdTomato</i> mice, which recapitulates the somatic mosaicism of FD bone lesions and in which mutant cells are lineage traced. Analysis of <i>Gnas^(R201H)fl/+</i> mice showed a diffuse accumulation of SMA⁺ early osteoblastic cells, with contribution from both tdTomato⁺ mutant and tdTomato^- WT populations. Anti-RANKL treatment of <i>Gnas^(R201H)fl/+</i> mice inhibited osteoclast formation and substantially reduced fibrosis, detected by Masson's trichrome staining within the proximal metaphysis of the femur and the femoral head. Treatment with anti-RANKL decreased the accumulation of both mutant and WT SMA⁺ cells, accompanied by an increased number of mutant cells expressing the mature osteoblast marker osteocalcin, and an increase in overall osteoblast density. To elucidate the role of RANKL expression by mutant cells in the formation of FD lesions, we generated <i>Sox9^CreERT;Gnas^(R201H)fl/+;Rosa26^LSL-tdTomato;Rankl^fl/fl</i> mice. Deletion of <i>Rankl</i> in <i>Gnas^(R201H)fl/+</i> mutant cells did not prevent fibrosis in this model. The results suggest that while anti-RANKL treatment promotes osteoprogenitor differentiation to reduce fibrosis, the loss of RANKL expression from <i>GNAS</i> mutant cells alone is not sufficient to reverse the pathology of FD bone lesions.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 10","pages":"ziaf145"},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199297","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":"Increased lifelong burden of comorbidities without increased early mortality in hereditary hypophosphatemia: a Danish register study.","authors":"Signe Sparre Beck-Nielsen, Rikke Færgemann Hansen, Ulla Ege Johansen, Angela Williams","doi":"10.1093/jbmrpl/ziaf143","DOIUrl":"10.1093/jbmrpl/ziaf143","url":null,"abstract":"<p><p>Hereditary hypophosphatemia (HH) is a rare diseases characterized by excessive renal phosphate wasting. Hereditary hypophosphatemia presents as rickets and osteomalacia in children, and osteomalacia in adults. Previous studies have suggested an increased burden of comorbidities and higher risk of early death in individuals with HH compared with controls. This study investigates the comorbidities in HH throughout life and their association with survival compared with controls. Possible HH cases were initially identified from the Danish National Patient Register (DNPR) using diagnostic codes for rickets or hypophosphatemia between 1971 and 2019, and the diagnosis was verified by the review of medical files. A total of 120 individuals with verified HH (case population) were matched by gender, birth year, and month with 50 controls per individual with HH, totaling 6000 controls randomly selected from the Danish Civil Registration System. Comorbidity data related to HH were retrieved from the DNPR. The burden of investigated comorbidities was significantly higher in individuals with HH than controls, with multiple conditions diagnosed and at an earlier age. The lifelong risk of arthrosis was significantly higher and diagnosed earlier in individuals with HH (<i>p</i> < .001). By age 50, 31.9% of individuals with HH received their first diagnosis of arthrosis, compared with 4.4% of controls. The lifelong risk of hearing loss was elevated (<i>p</i> < .001), often diagnosed by school age, with a rapid increase by age 60. Additionally, risks of hyperparathyroidism and renal failure were higher (both <i>p</i> < .001), along with increased rates of hypertensive disease (<i>p</i> < .001) and obesity (<i>p</i> = .021), with diagnoses increasing from the third decade of life. However, there was no significant increase in ischemic heart disease risk or overall mortality in HH. Further analysis revealed that comorbidities in HH were not associated with a higher risk of death compared with controls with the same conditions.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 10","pages":"ziaf143"},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185825","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 pediatric patients with X-linked hypophosphatemia: real-world data from the International XLH Registry.","authors":"Agnès Linglart, Cyril Amouroux, Iva Gueorguieva, Jerome Harambat, Jean-Pierre Salles, Diana-Alexandra Ertl, Kerry Sandilands, Angela Rylands, Angela Williams, Haruka Ishii, Annabel Bowden, James W Varni, Justine Bacchetta","doi":"10.1093/jbmrpl/ziaf142","DOIUrl":"10.1093/jbmrpl/ziaf142","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is a phosphate-wasting disorder caused by increased fibroblast growth factor 23 (FGF23); it leads to skeletal deformities, muscle weakness, and pain. In a pediatric phase 3 trial, the FGF23 inhibitor burosumab improved rickets severity and bone biochemistry. The current study characterizes health-related quality of life (HRQL) in children with XLH using real-world data collected at centers in France for the International XLH Registry from April 2017 to January 2024. Age-appropriate versions of the Pediatric Quality of Life Inventory were completed. Data from the first completion after registry entry were analyzed. Variation in scores by demographic, medical history, and treatment history variables was assessed using bivariate analysis. The data were collected from 96 children (59% female; mean age 8.1 [SD 4.4] yr); 82% were taking burosumab. Mean total, summary, and domain scores were similar in different age groups. Mean total score (74.2 [SD 14.1]), Psychosocial Health Summary (72.0 [16.8]), and Physical Health Summary (78.3 [12.3]) scores were lowest in patients aged 5-7 yr and highest in patients aged 13-17 yr (81.0 [13.3], 79.8 [14.1], and 83.1 [15.2]). The mean Psychosocial Health Summary score was lower than the Physical Health Summary score for all patients combined (77.8 [13.9] vs 81.7 [14.3]). Better total scores were associated with not currently taking phosphate/vitamin D analogs, better Psychosocial Health Summary scores with higher serum phosphate and not taking phosphate/vitamin D analogs, and better Physical Health Summary scores with lower serum PTH and currently taking burosumab. Patients with XLH who were taking burosumab at the time of PedsQL completion had better total and summary scores than children with other chronic musculoskeletal disorders. Children aged 5-7 yr had worse HRQL than a healthy Dutch sample. Overall, better HRQL was associated with higher serum phosphate levels and burosumab treatment.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 10","pages":"ziaf142"},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199449","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":"Bone texture by clinical magnetic resonance imaging is directly related to bone tissue maturity by Fourier-transform infrared spectroscopy.","authors":"Olivia Blumberg, Quinton Wright, Ryan Breighner, Alexander Dash, Asher Lal, Zaina K Mosalam, Donald McMahon, Matthew F Koff, Jeri W Nieves, Eve Donnelly, Emily M Stein","doi":"10.1093/jbmrpl/ziaf126","DOIUrl":"10.1093/jbmrpl/ziaf126","url":null,"abstract":"<p><p>Opportunistic screening for osteoporosis using images acquired for other purposes is a burgeoning area that may be of particular utility for the identification of surgical candidates with poor bone health. Texture analysis of clinical MRIs can be used to evaluate the heterogeneity of trabecular bone as a potential metric of bone quality. This cohort study investigated relationships between MRI-based vertebral trabecular bone texture and material properties by Fourier-transform infrared (FTIR) spectroscopy. We hypothesized that texture features from preoperative MRI images would reflect vertebral bone mineralization and collagen properties. In a cohort of 30 postmenopausal women (mean age 65) undergoing spine fusion surgery, T1-weighted MRI images were obtained using standard clinical sequences. A gray-level co-occurrence matrix was used to characterize the distribution and spatial organization of voxel intensities and derive texture features, including inverse difference moment, feature correlation, and contrast. Lumbar vertebral bone biopsies were obtained intraoperatively and analyzed with FTIR spectroscopy to assess composition, including metrics of mineral maturity (acid phosphate and carbonate:phosphate ratio). We found that vertebral trabecular bone texture by MRI was related to directly measured bone material properties: more heterogeneous texture was associated with less mature bone. Women with lower inverse difference moment had higher acid phosphate (<i>r</i> = -0.43, <i>p</i> < .02). Similarly, women with lower feature correlation had higher acid phosphate (<i>r</i> = -0.39, <i>p</i> < .04) and higher carbonate: phosphate (<i>r</i> = -0.47, <i>p</i> < .01). Women with higher contrast had higher acid phosphate (<i>r</i> = 0.381, <i>p</i> < .04). Our results suggest that preoperative MRI texture may predict intraoperative bone properties, specifically FTIR metrics of tissue age that may reflect local remodeling or microdamage repair processes. This finding supports the potential of MRI as a screening tool to identify individuals with abnormal bone quality.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 9","pages":"ziaf126"},"PeriodicalIF":2.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954668","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":"Burosumab treatment for fibroblast growth factor-23-associated hypophosphatemia in an adult patient with severe fibrous dysplasia in McCune-Albright syndrome: case report and review of the literature.","authors":"Maria Stelmachowska-Banaś, Karolina Cylke-Falkowska, Wojciech Zgliczyński, John P Bilezikian, Waldemar Misiorowski","doi":"10.1093/jbmrpl/ziaf125","DOIUrl":"10.1093/jbmrpl/ziaf125","url":null,"abstract":"<p><p>McCune-Albright syndrome (MAS) is a rare mosaic genetic disorder caused by a mutation in the <i>GNAS</i> gene and typically presents with a triad of symptoms: fibrous dysplasia of bones, café-au-lait macules, and precocious puberty. The <i>GNAS</i> mutation leads to overproduction of fibroblast growth factor-23 (FGF23), which may result in hypophosphatemia. Burosumab, a monoclonal antibody against FGF23, is approved for the treatment X-linked hypophosphatemia and tumor-induced osteomalacia. There are currently no data on its efficacy and safety in fibrous dysplasia/MAS patients. A 27-yr-old male with MAS was under the care of the Endocrinology Department for persistent hypophosphatemia and skeletal complications despite treatment with oral phosphate supplements and calcitriol. He started treatment with burosumab (1 mg/kg s.c. every 4 wk) and achieved normalization of calcium-phosphate metabolism (phosphate 0.83 mmol/L vs 0.38 mmol/L; PTH 70.4 pg/mL vs 177 pg/mL) and significant reduction in alkaline phosphatase activity (ALP 620 IU/L vs 1182 IU/L) and bone fraction of alkaline phosphatase activity (BALP 327 IU/L vs 603 IU/L). No further fractures were observed during 24 mo of treatment. The patient reported a reduction in bone pain and improved well-being. No adverse effects were reported during treatment. This is the first reported case of burosumab treatment in an adult patient with fibrous dysplasia/MAS. The therapy had positive effects on the patient's well-being, calcium-phosphate balance, and bone markers. However, longer follow-up and further safety studies are needed before routine use in adult fibrous dysplasia/MAS patients.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 9","pages":"ziaf125"},"PeriodicalIF":2.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954610","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":"Mortality from vertebral fractures in White women aged 65+ with osteoporosis: a CDC database trend analysis from 1999 to 2020.","authors":"Muhammad Hammad Zaheer, Hamza Zaheer, Arslan Tariq","doi":"10.1093/jbmrpl/ziaf121","DOIUrl":"10.1093/jbmrpl/ziaf121","url":null,"abstract":"<p><p>Osteoporotic vertebral fractures represent a significant yet underdiagnosed manifestation of osteoporosis, particularly affecting older White women. While vertebral fractures are among the most common osteoporotic fractures, their contribution to mortality has received less attention compared to hip fractures, creating a critical knowledge gap. This study analyzed temporal trends in age-adjusted mortality rates from osteoporotic vertebral fractures among White women aged 65 and older in the United States from 1999 to 2020. We conducted a retrospective analysis using Centers for Disease Control and Prevention's Multiple Cause of Death files, identifying cases where both vertebral fractures and osteoporosis were listed as causes of death using specific ICD-10 codes. Age-adjusted mortality rates per 100 000 population were calculated using the 2000 US standard population, and joinpoint regression analysis identified significant changes in mortality trends over the 22-yr study period. Our findings revealed a concerning 87.5% increase in age-adjusted mortality rates, rising from 0.24 per 100 000 in 1999 to 0.45 per 100 000 in 2020. Joinpoint regression identified three distinct trend segments: a non-significant decline from 1999 to 2004, followed by a statistically significant increase from 2004 to 2009 with an annual percent change (APC) of 13.93%, and a more modest upward trend from 2009 to 2020. The overall average APC was 4.21%, indicating a highly significant upward trend in mortality rates. The pronounced increase during 2004-2009 coincides with important developments in osteoporosis management, including declining hormone replacement therapy use following Women's Health Initiative findings and emerging bisphosphonate safety concerns. These findings underscore vertebral fractures as potentially life-threatening complications requiring aggressive prevention and management strategies. As the population ages, our results highlight the urgent need for improved osteoporosis screening, enhanced fracture risk assessment, and optimized treatment approaches to reduce the growing burden of vertebral fracture-related mortality in this vulnerable population.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 9","pages":"ziaf121"},"PeriodicalIF":2.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954318","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":"Cortical bone mechanics technology signal quality maintains robustness across a range of biometric profiles.","authors":"Andrew Dick, Max Stoeckel, Massimo Ruzzenne, Tony von Sadovszky, Janet E Simon, Leatha A Clark, Stuart J Warden, Todd M Manini, Charalampos Lyssikatos, Tiffani Hart, Brian C Clark","doi":"10.1093/jbmrpl/ziaf116","DOIUrl":"10.1093/jbmrpl/ziaf116","url":null,"abstract":"<p><p>Current methods of diagnosing osteoporosis, such as DXA, have limitations in predicting fracture risk. Cortical bone mechanics technology (CBMT) offers a novel approach by using a three-point bend test with multifrequency vibration analysis to directly measure ulnar bending stiffness and calculate flexural rigidity, a mechanical property highly predictive of whole-bone strength under bending conditions. Cortical bone mechanics technology targets the diaphyseal ulna, a site composed primarily of cortical bone, enhancing its specificity for cortical bone quality. In this study of 388 postmenopausal women, we developed and validated a 20-point signal quality indicator (SQI) scoring system to quantify CBMT signal quality and evaluated its relationship to biometric characteristics. The SQI was developed through expert assessment of representative frequency response function (vibration data) trials and refined over 17 iterations. The final system achieved excellent classification performance (AUC = 0.974; sensitivity, specificity, and accuracy all >97%). A total of 22 740 trials were collected across 758 total arm tests, sampling 10 ulnar sites per arm under three vibration amplitudes. Two expert analysts evaluated signal features associated with high signal quality. The resulting SQI is fully automated and provides real-time feedback. All correlations between SQI scores and biometric attributes were weak or very weak (|ρ| < 0.30). The correlations with body weight (ρ = -0.11), BMI (ρ = -0.12), ulnar BMD (ρ = -0.17), CBMT-derived flexural rigidity (ρ = -0.28), and grip strength (ρ = 0.17) were statistically significant (<i>p</i> < .05) but remained small in magnitude. SQI scores were modestly lower in individuals with higher BMI or flexural rigidity (~2 to 3 points), but values remained in the acceptable-to-good range. This study introduces a robust, automated CBMT signal quality metric and demonstrates that its performance remains stable across a broad range of biometric profiles, supporting its application in both clinical and research settings.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 9","pages":"ziaf116"},"PeriodicalIF":2.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953990","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}