Bone最新文献

{"title":"Temporal transcriptomic profiling of bone autograft healing reveals dynamic immune, vascular, and osteogenic programs","authors":"Jared A. Mereness ,&nbsp;Sayantani Basu ,&nbsp;Lauren Benoodt ,&nbsp;Danielle S.W. Benoit","doi":"10.1016/j.bone.2025.117771","DOIUrl":"10.1016/j.bone.2025.117771","url":null,"abstract":"<div><div>Bone autograft healing is a highly orchestrated process that integrates immune activation, vascular ingrowth, and osteogenic remodeling. To define the molecular and cellular programs driving early autograft integration, bulk and single-cell RNA sequencing was used to analyze graft-associated tissues over 14 days in a murine periosteal-mediated autograft model. Global transcriptomic analysis revealed rapid and dynamic remodeling, with maximal gene expression changes occurring within the first week. The first 48 h were dominated by pro-inflammatory signaling, including TNF, IL-1, TLR, and MAPK pathways, accompanied by transcriptional signatures of phagocytosis and cellular clearance. These early inflammatory programs gave way to pro-regenerative signals, including activation of HIF-1, PI3K-AKT, Wnt, and BMP pathways, coincident with angiogenesis, osteogenesis, and matrix deposition. By day 14, extracellular matrix production and remodeling predominated, marked by metalloproteinase activity and structural matrix gene enrichment. Single-cell RNA sequencing revealed that donor-derived (eGFP⁺) graft cells were rare and transient, whereas host-derived immune cells were progressively replaced by myofibroblasts, endothelial cells, and neurogenic cell types, including GABAergic neurons and IGSF21⁺ dendritic cells, suggesting active neurovascular crosstalk during healing. Together, these data define a temporal immune-to-regenerative cascade in bone autograft repair and highlight candidate cellular and molecular targets to enhance graft performance.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117771"},"PeriodicalIF":3.6,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Akt2 regulates autophagy and osteogenesis in diabetic osteoporosis via PI3K/AKT/mTOR signaling axis","authors":"Qiaonan Ye ,&nbsp;Ting Fu ,&nbsp;Peixuan Li ,&nbsp;Xuemei Long ,&nbsp;Zhiyuan Zhang ,&nbsp;Luwen Ye ,&nbsp;Yanqiu Zhou ,&nbsp;Shuanglin Peng ,&nbsp;Qianke Tao ,&nbsp;Jingang Xiao","doi":"10.1016/j.bone.2025.117770","DOIUrl":"10.1016/j.bone.2025.117770","url":null,"abstract":"<div><div>Adipose-derived stem cells (ASCs) are crucial seed cells for bone defect repair. In diabetic osteoporosis (DOP), however, their osteogenic potential is impaired. This study found that ASCs from a pre-clinical DOP model, established in C57BL/6 J mice using a high-fat/high-sucrose diet combined with streptozotocin-induced insulin deficiency, exhibited suppressed osteogenic differentiation and impaired autophagy flux. This was accompanied by hyperactivation of the PI3K/AKT/mTOR signaling, particularly elevated AKT2 phosphorylation. Transcriptomic analysis confirmed enrichment of related pathways. Mechanistically, <em>Akt2</em> overexpression suppressed osteogenesis and autophagy, while its knockdown restored both. Crucially, implanting sh<em>Akt2</em>-treated DOP-ASCs into calvarial defects of DOP mice enhanced bone regeneration, improving bone volume, trabecular number, and collagen deposition. These findings identify <em>Akt2</em> as a key regulator of ASC dysfunction in DOP and demonstrate that its targeted inhibition rescues osteogenic potential, offering a promising therapeutic strategy for diabetic osteoporotic bone repair.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117770"},"PeriodicalIF":3.6,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing osteoporosis medications for other diseases: a narrative review by the European Calcified Tissue Society (ECTS)","authors":"Polyzois Makras ,&nbsp;Maria P. Yavropoulou ,&nbsp;Athanasios D. Anastasilakis ,&nbsp;Natasha M. Appelman-Dijkstra ,&nbsp;John J. Carey ,&nbsp;Anda Mihaela Naciu ,&nbsp;Julien Paccou ,&nbsp;Tim Rolvien ,&nbsp;Elizabeth M. Winter ,&nbsp;Socrates E. Papapoulos ,&nbsp;Willem F. Lems","doi":"10.1016/j.bone.2025.117769","DOIUrl":"10.1016/j.bone.2025.117769","url":null,"abstract":"<div><h3>Purpose</h3><div>This narrative review explores the therapeutic potential of repurposing medications originally developed or approved for osteoporosis to treat non-osteoporotic conditions. Given their pharmacologic profiles and safety data, these agents offer promising therapeutic alternatives in both rare and common diseases with unmet clinical needs.</div></div><div><h3>Principal results</h3><div>Evidence from preclinical models, observational data, and randomised trials supports the repositioning of several osteoporosis drugs. Cyclic etidronate has shown efficacy in halting arterial calcification progression in pseudoxanthoma elasticum. Pamidronate has demonstrated symptom improvement in adult chronic nonbacterial osteitis. Neridronate is approved only in Italy for complex regional pain syndrome type I. Denosumab has shown therapeutic effects in Langerhans cell histiocytosis and has structural benefits in erosive hand osteoarthritis and rheumatoid arthritis. Parathyroid hormone analogues (rhPTH [1–84] and teriparatide) improve calcium-phosphate homeostasis in chronic and genetic hypoparathyroidism. Calcilytics, though originally discontinued for osteoporosis, show emerging promise in autosomal dominant hypoparathyroidism. In contrast, zoledronic acid has not demonstrated consistent clinical benefit in knee osteoarthritis. Strontium ranelate, despite showing structure-modifying effects in osteoarthritis, is no longer marketed due to safety concerns. Alendronate and denosumab in fibrous dysplasia yielded mixed results, with concerns about rebound effects after denosumab withdrawal.</div></div><div><h3>Conclusions</h3><div>Repurposing osteoporosis medications represents a cost-effective, timely strategy to expand treatment options across diverse clinical indications. While promising outcomes have been demonstrated—particularly in rare diseases—rigorous, indication-specific clinical trials are essential to confirm efficacy, safety, and long-term outcomes. The accumulated pharmacologic and clinical experience with these agents offers a strong foundation for their continued exploration beyond osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117769"},"PeriodicalIF":3.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary trabecular bone formation in vitro by the OmGFP66 osteogenic cell line: Multiscale symmetry breaking and characterization in 3D","authors":"Benazir Khurshid ,&nbsp;Aisha Mousa ,&nbsp;Sarah L. Dallas ,&nbsp;Joseph Deering ,&nbsp;Natalie Reznikov ,&nbsp;Marc D. McKee","doi":"10.1016/j.bone.2025.117767","DOIUrl":"10.1016/j.bone.2025.117767","url":null,"abstract":"<div><div>Osteocytes are abundant bone cells that serve as central regulators of skeletal homeostasis. Within mineralized bone tissue, osteocytes and their cell processes/dendrites maintain cell connectivity through a lacunocanalicular network morphologically positioned for executing myriad cell signaling pathways, including those related to mechanosensation, mineral ion homeostasis, and extracellular matrix mineralization. Given the complexity of osteocyte morphological transitions within mineralized bone, there are few robust <em>in vitro</em> models that reproduce the mineralized bone microenvironment. A recently developed mouse calvarial osteocyte cell line, OmGFP66, overcomes many of these limitations. Here we provide a comprehensive 3D multiscale characterization of mineralized, primary bone-like trabeculae formed by OmGFP66 cells <em>in vitro</em>, with a comparison to mouse calvariae. Submicron X-ray microcomputed tomography (μCT) was used to image and reveal quantitative features of thousands of discrete, variably shaped trabeculae formed by OmGFP66 cells with osteocyte lacunae having features quantitatively similar to those of neonatal mouse calvarial primary bone. Moreover, FIB-SEM and TEM analyses revealed the 3D ultrastructure of an extended lacunocanalicular network formed by the OmGFP66 cells within mineralized extracellular matrix and extending through an osteoid layer to osteoblasts at the surface, comparable to bone <em>in vivo</em>. At the nanoscale-to-microscale, again like bone, OmGFP66 trabeculae exhibit a 3D crossfibrillar mineral tessellation pattern. We also fit OmGFP66 trabecular morphology patterning and mineralization to the Gray-Scott model of oscillating reaction-diffusion patterns to describe symmetry breaking that initiates and facilitates mineralization through the combined dynamics of diffusing mineral ions and inhibitors. Together, these findings establish OmGFP66 cell cultures as a powerful <em>in vitro</em> bone model for studying osteocyte differentiation, matrix mineralization, and pattern formation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117767"},"PeriodicalIF":3.6,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 micro-CT grayscale analysis for early detection and staging of osteoporosis in rats","authors":"Yajun Zhang ,&nbsp;Hanwen Cheng ,&nbsp;Jiuxu Deng ,&nbsp;Bo Chen ,&nbsp;Yuyang Ran ,&nbsp;Yuhui Kou ,&nbsp;Baoguo Jiang","doi":"10.1016/j.bone.2025.117768","DOIUrl":"10.1016/j.bone.2025.117768","url":null,"abstract":"<div><h3>Background</h3><div>Rat models are widely used in preclinical osteoporosis research to study disease mechanisms and evaluate therapies. Current Micro-CT studies mostly rely on cross-sectional comparisons at a single time point, and there is a lack of standardized reference data across multiple time points. To address this gap, the present study provides standardized reference data from multiple time points using a deep learning-based Micro-CT grayscale analysis, enabling early detection and precise staging of osteoporosis.</div></div><div><h3>Methods</h3><div>A standardized osteoporosis model was established in ovariectomized Sprague–Dawley rats (<em>n</em> = 32) with a sham-operated group (n = 32). Femurs were harvested at 4, 8, 16, and 24 weeks post-surgery. The proximal 0–250 slice region adjacent to the growth plate was defined as the region of interest (ROI), and six representative slices per femur were analyzed. Voxels within each ROI were classified into four grayscale regions: 0–50 (non-bone), 51–100 (bone–nonbone transition), 101–150 (defined bone), and 151–255 (highly mineralized bone). The percentage areas of the four regions across the six slices (4 × 6 input) were used to train a custom deep learning model. Diagnostic performance for early osteoporosis detection and staging was compared with conventional trabecular parameters.</div></div><div><h3>Results</h3><div>Both the grayscale-based algorithm and conventional Micro-CT parameters distinguished Sham and OVX rats at 4 weeks, enabling early detection, whereas DXA only detected differences at 16 weeks. In osteoporosis staging within the OVX group, the grayscale-based model achieved higher accuracy (88.4 % ± 6.4 %) than conventional parameters (55.9 % ± 8.4 %, <em>p</em> &lt; 0.05). For single-time-point osteoporosis diagnosis, the grayscale-based algorithm (98.3 % ± 3.4 %) also outperformed conventional parameters (85.3 % ± 3.4 %, p &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>The grayscale-based deep learning method allows sensitive early detection and more accurate staging of osteoporosis, providing a robust quantitative tool for assessment of osteoporotic progression in OVX rats.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117768"},"PeriodicalIF":3.6,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiaxial physiological loading generates complex fluid flow and strain patterns in the osteocyte lacunar-canalicular system","authors":"Asier Muñoz,&nbsp;Annalisa De Paolis,&nbsp;Luis Cardoso,&nbsp;Alessandra Carriero","doi":"10.1016/j.bone.2025.117765","DOIUrl":"10.1016/j.bone.2025.117765","url":null,"abstract":"<div><div>Osteocytes, embedded within the lacunar-canalicular system in bone, play a central role in sensing mechanical stimuli and directing bone adaptation. Fluid–structure interaction (FSI) models have emerged as valuable tools to simulate the mechanical environment surrounding osteocytes, but in silico studies have relied on idealized loading conditions to simplify the complex, multiaxial loading that osteocytes are likely exposed to in vivo. In this study, we model the mechanical environment within the lacunar-canalicular system using multiaxial physiologically relevant loading conditions, by incorporating human tibia strains experimentally measured during walking and running by Lanyon et al. (1975) [1], into 3D osteocyte-scale FSI simulations. We here evaluate how interstitial fluid flow and osteocyte strain patterns generated by physiological loading differ from those obtained using a simplified uniaxial sinusoidal loading. Our findings show that despite similar interstitial fluid velocity magnitude, the spatial flow under multiaxial physiological loading is definitely more complex. Multiaxial physiological loading generates fluid velocities and strains that are highly heterogeneous and shift in direction over time, with dendritic strain exceeding by over an order of magnitude the ones of the cell body. Instead, uniaxial sinusoidal loading produces uniform, periodic flows aligned with the primary loading axis, with minimal strain in dendrites perpendicular to this axis. Notably, multiaxial physiological loading induces localized recirculation zones and broader velocity distributions within canaliculi - with extremely low Reynolds number confirming the laminar flow and excluding true turbulence - that can amplify osteocyte mechanosensitive signals. These are not observed in uniaxial sinusoidal loading. These findings highlight the limitations of uniaxial sinusoidal loading as a model of physiological osteocyte mechanics.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117765"},"PeriodicalIF":3.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of bisphosphonate treatment on the oim mouse middle ear ossicles' structure, composition and hearing","authors":"Maialen Ugarteburu ,&nbsp;Michael Doube ,&nbsp;Christoph Rau ,&nbsp;Olga Antipova ,&nbsp;Lu Xi Li ,&nbsp;Stuart R. Stock ,&nbsp;Xiaodong Tan ,&nbsp;Luis Cardoso ,&nbsp;Claus-Peter Richter ,&nbsp;Alessandra Carriero","doi":"10.1016/j.bone.2025.117764","DOIUrl":"10.1016/j.bone.2025.117764","url":null,"abstract":"<div><div>Hearing loss is common in people with osteogenesis imperfecta (OI or <em>brittle bone disease</em>). Bisphosphonates are widely used to treat long bone fragility in children with OI. However, its impact on the bone quality of the middle ear ossicles and hearing remains unknown. This study determines whether bisphosphonates treatment itself may contribute to hearing loss in OI by evaluating its effects in the <em>oim/oim</em> mouse model of severe OI having normal auditory function. Specifically, this study reports the effects of alendronate (ALN), a nitrogen-containing bisphosphonate, on ossicle morphology, porosity, and elemental composition in 14-week-old <em>oim/oim</em> mice treated weekly, starting at 2 weeks of age. The ossicles were examined using synchrotron microtomography and X-ray fluorescence microscopy (XFM). Hearing was assessed longitudinally until 26 weeks of age by determining auditory brainstem response (ABR) thresholds in another group of mice also treated weekly starting at 2 weeks of age. ALN treatment further reduces in size the already small <em>oim/oim</em> ossicles, specifically in female mice. Porosity, bone composition, and hearing function, however, were generally not affected by the ALN treatment. Furthermore, ALN does not prevent joint fusions, excessive bone formations, or enlarged joint spaces in WT or <em>oim/oim</em> experimental groups. One ALN-treated <em>oim/oim</em> mouse with a bone formation in the interior of the footplate, and one ALN-treated WT mouse with a fixed footplate had frequency-specific hearing loss. Since footplate abnormalities are not observed in PBS-treated mice in this study, it remains unclear whether ALN fails to prevent these changes or contributes to their development. Future studies should investigate the mechanisms of ossicular abnormalities and bisphosphonates modulatory role in the ossicles.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117764"},"PeriodicalIF":3.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between advanced glycation end products and bone mineral density in Mexican population","authors":"Diana I. Aparicio-Bautista ,&nbsp;Jorge Salmerón ,&nbsp;Rogelio F. Jiménez-Ortega ,&nbsp;Tania V. López-Pérez ,&nbsp;Adriana Becerra-Cervera ,&nbsp;Rafael Velázquez-Cruz ,&nbsp;Berenice Rivera-Paredez","doi":"10.1016/j.bone.2025.117763","DOIUrl":"10.1016/j.bone.2025.117763","url":null,"abstract":"<div><h3>Background</h3><div>Evidence shows that advanced glycation end products (AGEs) play a key role in skeletal deterioration by impacting bone quality and strength. However, there is limited long-term research on their association with bone mineral density (BMD), especially among different sexes and age groups.</div></div><div><h3>Objective</h3><div>To evaluate the longitudinal association between serum AGEs and BMD in adults, stratified by sex and age groups (&lt;45 years and ≥45 years).</div></div><div><h3>Methods</h3><div>We conducted a longitudinal analysis using data from 1138 adults enrolled in the Health Workers Cohort Study, followed over a six-year period (2004–2010). BMD (g/cm²) was measured at various skeletal sites using dual-energy X-ray absorptiometry. Generalized estimating equations (GEE) and fixed-effects models were employed, stratified by sex and age group, and adjusted for potential confounders.</div></div><div><h3>Results</h3><div>In GEE models, a 100 μU/mL increase in AGEs was significantly associated with lower BMD at the hip, femoral neck, and lumbar spine in women aged ≥45 years (β = −0.003, β = −0.004, β = −0.011, respectively). Among men ≥45 years, higher AGEs were also associated with lower BMD at the hip and femoral neck (β = −0.004 and β = −0.006, respectively). In women &lt;45 years, AGEs were inversely associated with hip and femoral neck BMD (β = −0.003 for both). Fixed-effects models yielded consistent results, particularly among women ≥45 years. No significant associations were observed in men &lt;45 years.</div></div><div><h3>Conclusions</h3><div>Elevated serum AGEs levels are associated with lower BMD over time, particularly among women. These findings suggest a potential role of AGEs in bone deterioration and their relevance in clinical risk assessment.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117763"},"PeriodicalIF":3.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FSH and longitudinal changes in bone marrow adipose tissue composition in older adults","authors":"Tiffany Y. Kim ,&nbsp;Trisha F. Hue ,&nbsp;Susan K. Ewing ,&nbsp;Xiaojuan Li ,&nbsp;Sigurdur Sigurdsson ,&nbsp;Vilmundur Gudnason ,&nbsp;Annegreet G. Vlug ,&nbsp;Deborah M. Kado ,&nbsp;Eric Vittinghoff ,&nbsp;Karin C. Wu ,&nbsp;Eileen H. Koh ,&nbsp;Clifford J. Rosen ,&nbsp;Mone Zaidi ,&nbsp;Ann V. Schwartz ,&nbsp;Anne L. Schafer","doi":"10.1016/j.bone.2025.117758","DOIUrl":"10.1016/j.bone.2025.117758","url":null,"abstract":"<div><div>Bone marrow adipose tissue (BMAT) expansion and distinct BMAT composition profiles, including lower unsaturated levels, are cross-sectionally associated with older age. Prospective changes in BMAT composition with aging and the effect of serum follicle stimulating hormone (FSH), which influences both bone and fat metabolism, are unknown. We examined these associations in the AGES-Reykjavik Bone Marrow Adipose cohort, using sex-stratified linear regression models adjusted for covariates including estradiol and testosterone. At baseline, 236 women and 245 men had mean age 81 (SD 4) and 83 (4) years, respectively. Over a mean 3.3 years for 154 women and 2.6 years for 151 men, there was no significant change in total or saturated BMAT. However, mean unsaturated BMAT increased in women (+0.26 %/year, 95 % CI +0.21 %/year to +0.32 %/year) and men (+0.24 %/year, 95 % CI +0.18 %/year to +0.30 %/year). Among women, greater increases in unsaturated BMAT were associated with significantly greater reductions in vertebral trabecular volumetric BMD. At baseline, women in the highest FSH quartile had highest total (66.6 %, 95 % CI 64.3 %–69.0 %) and saturated BMAT (95 % CI 49.3 %, 47.5 %–51.0 %). No relationship existed between FSH and unsaturated BMAT in women or any BMAT outcome in men. Longitudinally, in women, higher FSH was associated with greater increase in unsaturated BMAT. There was no relationship between FSH and change in total or saturated BMAT in women or any change outcome in men. In older adults, total BMAT was stable, but BMAT composition changed with increases in unsaturated BMAT. In women, higher FSH correlated cross-sectionally with higher saturated BMAT but longitudinally with greater gain in unsaturated BMAT. These novel findings warrant further longitudinal studies to better characterize BMAT changes and the role of FSH.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117758"},"PeriodicalIF":3.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Craniofacial and whole-skeleton fracture patterns in osteogenesis imperfecta: Findings from a nationwide U.S. insurance claims database","authors":"Hsiao H. Sung ,&nbsp;Daniel G. Whitney ,&nbsp;Kenneth M. Kozloff ,&nbsp;Michelle S. Caird","doi":"10.1016/j.bone.2025.117762","DOIUrl":"10.1016/j.bone.2025.117762","url":null,"abstract":"<div><h3>Background</h3><div>Osteogenesis imperfecta (OI) is an inherited connective tissue disease characterized by lifelong skeletal fragility and recurrent fractures. While most prior research has focused on long bone fractures in selected clinical cohorts, population-based estimates of craniofacial and site-specific fracture risk in OI remain largely limited. This study used insurance claims data to quantify the period prevalence, anatomical distribution, and predictors of fractures in individuals with versus without OI.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using the IBM® MarketScan® Multi-State Medicaid (2016–2022, all ages) and Commercial Databases (2016–2022, &lt; 65 years old). Diagnosis of OI and all fractures were identified using ICD and CPT codes recorded during healthcare encounters. The first full year of enrollment was used to determine 1-year period prevalence and counts of fractures overall and by site, stratified by age (&lt;5, 6–9, 10–13, 14–18, 19–25, ten-year intervals to &gt;55). Differences between cohorts were estimated using relative risk (RR). Associations with demographic and clinical factors were assessed via logistic regression. Proxy measures of OI severity and medical device use were applied, as clinical classification and exposure to treatments could not be directly adjudicated.</div></div><div><h3>Results</h3><div>Among 4294 individuals with OI and approximately 54.8 million controls, the overall fracture prevalence was 33.9 % in the OI cohort versus 2.5 % in controls (RR 13.6), with elevated rates observed at all anatomical sites. Jaw (craniofacial) fractures were nearly seven times more frequent in OI (0.40 % vs. 0.06 %; RR 6.7), while femur fractures showed the greatest disparity (RR 119.4). Age-specific analysis revealed the highest fracture risk for individuals with OI in early childhood, particularly at craniofacial and axial sites, with risk increasing further in those with greater proxy-measured disease severity. Female was associated with lower odds of fracture compared to males, and Medicaid coverage correlated with increased risk at select skeletal sites. Limitations include inability to distinguish fracture etiology (spontaneous, traumatic, or iatrogenic), unmeasured exposure to treatments, inability to apply clinical OI classifications, and exclusion of uninsured individuals.</div></div><div><h3>Conclusions</h3><div>Individuals with OI face a markedly greater and distinctive burden of fractures, including craniofacial involvement, than the general population. This work provides the first large-scale, population-based estimates of craniofacial fracture burden in OI, highlighting distinct age- and site-specific risk patterns. These findings reinforce the importance of ongoing, site-specific monitoring and integrated multidisciplinary care for individuals with OI, supporting clinicians in anticipatory guidance and tailored prevention strategies.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117762"},"PeriodicalIF":3.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}