BonePub Date : 2026-04-01Epub Date: 2026-01-26DOI: 10.1016/j.bone.2026.117805
Jessica L. Puranda , Vinicius M.R. Weber , Éric Doucet , Kristi B. Adamo
{"title":"Calcium, FSH, and the changing bones of menopause: A longitudinal look at the silent transformation","authors":"Jessica L. Puranda , Vinicius M.R. Weber , Éric Doucet , Kristi B. Adamo","doi":"10.1016/j.bone.2026.117805","DOIUrl":"10.1016/j.bone.2026.117805","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoporosis poses a health risk to post-menopausal females. The menopause transition is associated with hormone fluctuations (e.g., follicle-stimulating hormone (FSH), estrogen), and other biochemical and physiological changes that contribute a decline in bone mineral density (BMD). This will investigate the relationship between biochemical and physiological markers of BMD across the menopause transition.</div></div><div><h3>Methods</h3><div>Fifty-six middle-aged females who completed their menopause transition were included in this longitudinal sub-analysis. Participants were recruited from the Ottawa/Gatineau region. Menopause status was classified using menstrual history and FSH plasma levels. BMD and body composition were assessed using dual-energy x-ray absorptiometry (DXA). Additional measures included BMI, cardiorespiratory fitness (VO<sub>2max</sub>), diet calcium and Vitamin D, and biochemical markers (i.e., FSH, cortisol, calcium). Statistical analysis included repeated measures analysis of variance, linear mixed modeling, and group-based trajectory modeling to identify distinct FSH trajectory groups and their associations with BMD changes over time.</div></div><div><h3>Results</h3><div>Serum calcium was negatively associated with BMD at the lumbar spine [β: −0.0799, 95% confidence interval (CI): −0.139; −0.020, <em>p</em> = 0.009]. Further, the high FSH trajectory group experienced a greater decrease in BMD across the 5-year period, at the femur neck [β: 0.067, CI: 0.050; 0.084 vs. β: 0.035, CI: 0.021; 0.048; <em>p</em> = 0.003] and total body [β: 0.045, CI: 0.035; 0.055 vs. β: 0.028, CI: 0.020; 0.036; <em>p</em> = 0.007] than the low FSH trajectory group.</div></div><div><h3>Conclusion</h3><div>Associations between serum calcium and lumbar spine BMD, and a greater BMD decline in individuals with high FSH levels were revealed. This information suggests that serum calcium and FSH should be monitored throughout the menopause transition to protect BMD.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117805"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073887","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}
BonePub Date : 2026-04-01Epub Date: 2026-01-14DOI: 10.1016/j.bone.2026.117795
Yiwen Zou , Ning Zhao , Hongyuan Huang , Ying Zhou , Yuanning Yang , Qiao Qiao , Qingxiang Li , Jianhua Zhu , Yifei Wang , Yuxing Guo
{"title":"Combined antiresorptive and antiangiogenic therapy versus antiresorptive monotherapy: Impact on the surgical prognosis of MRONJ patients with advanced malignancies","authors":"Yiwen Zou , Ning Zhao , Hongyuan Huang , Ying Zhou , Yuanning Yang , Qiao Qiao , Qingxiang Li , Jianhua Zhu , Yifei Wang , Yuxing Guo","doi":"10.1016/j.bone.2026.117795","DOIUrl":"10.1016/j.bone.2026.117795","url":null,"abstract":"<div><div>For patients with advanced cancer and bone metastasis, antiresorptive medications (ARMs) and antiangiogenic medications (AGMs) are commonly employed to manage tumor progression and skeletal complications. This study evaluates the effects of distinct pharmacotherapeutic strategies—ARM monotherapy versus ARM+AGM combined therapy on surgical outcomes of medication-related osteonecrosis of the jaw (MRONJ) in this population.</div><div>A retrospective cohort analysis was conducted on 157 patients: 106 received ARM monotherapy, and 51 underwent combined ARM+AGM treatment. Demographic data, MRONJ clinical characteristics, and quality of life (QoL) metrics were systematically collected and analyzed using univariate and multivariate statistical methods.</div><div>Univariate analysis revealed that the ARM group had a higher proportion of females, longer antiresorptive therapy duration, and more favorable outcomes, including reduced postoperative pain and improved QoL compared to the ARM+AGM group. Multivariate analysis demonstrated that the ARM+AGM group exhibited a 2.8-fold recurrence risk relative to the ARM group, with prognosis significantly influenced by medication strategy, disease stage, and surgical approach.</div><div>These findings indicate that combined ARM+AGM therapy is associated with a poorer prognosis and heightened recurrence risk in MRONJ patients compared to ARM monotherapy.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117795"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992184","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}
BonePub Date : 2026-04-01Epub Date: 2026-01-22DOI: 10.1016/j.bone.2026.117804
Fernanda Perin Maia Starck , Barbara C. Silva , Victória Zeghbi Cochenski Borba
{"title":"Impact of abdominal adiposity correction on trabecular bone score (TBS) in obese women: A comparative study of software versions 3.0 and 4.0 with a predictive model","authors":"Fernanda Perin Maia Starck , Barbara C. Silva , Victória Zeghbi Cochenski Borba","doi":"10.1016/j.bone.2026.117804","DOIUrl":"10.1016/j.bone.2026.117804","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the impact of soft-tissue thickness correction on trabecular bone score (TBS) in obese women across different BMI categories, comparing software versions 3.0 and 4.0, and to examine their associations with bone mineral density (BMD), fracture occurrence, and clinical variables.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 247 obese women (BMI ≥30 kg/m<sup>2</sup>) who underwent lumbar spine densitometry with TBS assessment using versions 3.0 and 4.0 of the TBS iNsight® software. Demographic, anthropometric, and BMD data were analyzed. Correlations and multivariate linear regression models were used to assess associations between TBS 4.0, BMD, fractures, and clinical parameters.</div></div><div><h3>Results</h3><div>TBS 4.0 were lower than TBS 3.0 across all BMI categories (<em>p</em> < 0.001), with the largest reductions observed in women with BMI ≥ 37 kg/m<sup>2</sup>. Classification of TBS changed in 34% of cases when using version 4.0, with a greater proportion reclassified to degraded categories. TBS 4.0 showed a positive correlation with lumbar spine BMD (<em>r</em> = 0.51, <em>p</em> < 0.001) and BMI (<em>r</em> = 0.17, <em>p</em> = 0.007), but showed no significant correlation with abdominal wall thickness (<em>r</em> = −0.08, <em>p</em> = 0.229). The correlation between TBS and BMI was stronger for version 3.0 than for version 4.0 (<em>r</em> = 0.32 vs. <em>r</em> = 0.17, respectively). In multivariate analysis, abdominal wall thickness emerged as an independent predictor of TBS 4.0. A multivariate regression model including TBS 3.0, age, L1–L4 BMD, and abdominal wall thickness explained 86% of the variability in TBS 4.0, enabling estimation of TBS 4.0 from clinical variables and the earlier software version. Women with fractures showed lower TBS values, though not significant.</div></div><div><h3>Conclusions</h3><div>The TBS 4.0, by incorporating automatic correction for soft-tissue thickness, provides lower values that possibly better characterize trabecular microarchitecture in individuals with obesity, especially in those with higher BMIs, and mitigates the bias attributable to differences in body composition observed with previous versions of the TBS software.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117804"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044416","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}
BonePub Date : 2026-03-01Epub Date: 2025-12-08DOI: 10.1016/j.bone.2025.117757
Soo-Young Choi, Mi-Kyung Lee
{"title":"Fermented mealworm extract prevents concurrent bone and muscle loss by modulating RANKL-NFκB/MAPK signaling in ovariectomized mice","authors":"Soo-Young Choi, Mi-Kyung Lee","doi":"10.1016/j.bone.2025.117757","DOIUrl":"10.1016/j.bone.2025.117757","url":null,"abstract":"<div><div>This study investigated whether fermented mealworms extract (FME) can simultaneously improve postmenopausal osteoporosis and muscle atrophy, along with the underlying mechanisms. Female C57BL/6 N mice were divided into five groups: sham-operated, ovariectomized (OVX), OVX treated with two doses of FME (200 and 500 mg/kg, oral), and OVX treated with alendronate (Alen, 500 μg/kg, oral) as a positive control, for 15 weeks. FME500 significantly increased grip strength, whereas FME200 showed no significant improvement compared to the OVX group. Muscle cross-sectional area significantly increased in both FME groups compared to the OVX group. FME500 also enhanced muscle protein synthesis markers (MyoD1 and MHC) and more effectively suppressed muscle degradation markers (MuRF-1, atrogin-1, myostatin, and polyubiquitinated proteins) than FME200. In bone, both FME doses improved bone density and serum levels of RANKL and CTX-1 compared to the OVX group. FME500 more effectively downregulated RANKL, IL-6, and TNF-α expression in both bone and muscle than FME200 in OVX group. Mechanistic analyses were performed mainly in the FME500 group, which downregulated NFκB/MAPK and upregulated IGF-1-PI3K-Akt in both bone and muscle. These results indicate that FME suppresses the postmenopausal concurrent bone and muscle loss by regulating RANKL-NFκB/MAPK and IGF-1-PI3K-Akt signaling pathways.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117757"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727611","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}
BonePub Date : 2026-03-01Epub Date: 2025-12-03DOI: 10.1016/j.bone.2025.117753
Suzanne M. Tabbaa , Emily A. Davidson , Theodore Miclau , Ashraf El Naga
{"title":"Does irradiation adversely impact bone forming properties of demineralized bone matrix and allograft bone? A systematic review of the literature","authors":"Suzanne M. Tabbaa , Emily A. Davidson , Theodore Miclau , Ashraf El Naga","doi":"10.1016/j.bone.2025.117753","DOIUrl":"10.1016/j.bone.2025.117753","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117753"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688759","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}
BonePub Date : 2026-03-01Epub Date: 2025-12-15DOI: 10.1016/j.bone.2025.117758
Tiffany Y. Kim , Trisha F. Hue , Susan K. Ewing , Xiaojuan Li , Sigurdur Sigurdsson , Vilmundur Gudnason , Annegreet G. Vlug , Deborah M. Kado , Eric Vittinghoff , Karin C. Wu , Eileen H. Koh , Clifford J. Rosen , Mone Zaidi , Ann V. Schwartz , Anne L. Schafer
{"title":"FSH and longitudinal changes in bone marrow adipose tissue composition in older adults","authors":"Tiffany Y. Kim , Trisha F. Hue , Susan K. Ewing , Xiaojuan Li , Sigurdur Sigurdsson , Vilmundur Gudnason , Annegreet G. Vlug , Deborah M. Kado , Eric Vittinghoff , Karin C. Wu , Eileen H. Koh , Clifford J. Rosen , Mone Zaidi , Ann V. Schwartz , 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":"2026-03-01","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}
BonePub Date : 2026-03-01Epub Date: 2025-12-12DOI: 10.1016/j.bone.2025.117760
Kenichiro Doi , Dina Moazamian , Yuanshan Wu , Takuaki Yamamoto , Amy Leu , Salem Alenezi , James H. Flint , Karen Y. Cheng , Yajun Ma , Saeed Jerban
{"title":"Evaluation of trabecular and subentheseal bone volume density in calcaneus with dual-echo ultrashort echo time magnetic resonance imaging: In vivo feasibility study","authors":"Kenichiro Doi , Dina Moazamian , Yuanshan Wu , Takuaki Yamamoto , Amy Leu , Salem Alenezi , James H. Flint , Karen Y. Cheng , Yajun Ma , Saeed Jerban","doi":"10.1016/j.bone.2025.117760","DOIUrl":"10.1016/j.bone.2025.117760","url":null,"abstract":"<div><div>Trabecular and entheseal bone quantity in the calcaneus may relate to general bone health and physical activity levels of patients. Magnetic resonance imaging (MRI) has been increasingly used for bone evaluation, to avoid ionizing radiation and enable simultaneous evaluation of surrounding soft tissue. A rapid quantitative MRI-based method to estimate bone volume to total volume (BV/TV), <sup>without re</sup>solving <sup>trabecular-level f</sup>eatures, has been developed utilizing a dual echo ultrashort echo time (UTE) sequence that can directly acquire bone and free water signal for further quantification. This <sup>study i</sup>nvestigated the feasibility of using dual echo UTE for trabecular and subentheseal BV/TV evaluation in the calcaneus. Ankle joints of 32 healthy subjects (12 women and 20 men, 35.0 ± 6.8<!--> <!-->years old) were scanned in the sagittal plane using dual echo UTE <sup>(TE=0.03 and 2.2 ms) on a clinical 3T MRI scanner</sup> with 3 min scan time. BV/TV was measured in four regions of interest (ROIs); proximal calcaneal crescent (ROI 1), plantar calcaneal crescent (ROI 2), deep calcaneal bone (ROI 3), and subentheseal bone (ROI 4). Differences were examined with Kruskal Wallis test. Spearman's correlations of BV/TV with age, weight, height, and BMI were calculated. BVTV was significantly different (<em>p</em> < 0.05) between regions (mean ± SD of 42.8 ± 4.3, 41.7 ± 3.2,38.4 ± 3.3, and 37.8 ± 3.2 for subentheseal bone, proximal calcaneal crescent, plantar calcaneal crescent, and deep trabecular regions, respectively). BV/TV showed significant positive correlations with age and weight in all regions. This study highlights the <sup>feasibi</sup>lity of dual echo UTE technique for rapid MRI-based evaluation of BV/TV in patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117760"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758770","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}
BonePub Date : 2026-03-01Epub Date: 2025-12-13DOI: 10.1016/j.bone.2025.117761
Annabel R. Bugbird , Steven K. Boyd
{"title":"Predicting skeletal age from HR-pQCT imaging","authors":"Annabel R. Bugbird , Steven K. Boyd","doi":"10.1016/j.bone.2025.117761","DOIUrl":"10.1016/j.bone.2025.117761","url":null,"abstract":"<div><h3>Introduction:</h3><div>High-resolution peripheral quantitative computed tomography (HR-pQCT) provides detailed bone microarchitecture assessments, but the interpretability of its many complex parameters remains challenging. This study aimed to develop a deep learning model to estimate skeletal age from HR-pQCT scans, offering an interpretable, quantitative summary of bone health relative to chronological age.</div></div><div><h3>Methods:</h3><div>The <em>training</em> dataset included 1236 adults (62.1% female) from a normative cohort, and an independent <em>test</em> set of 460 adults (69.3% female). HR-pQCT scans of the distal radius and tibia were acquired for all participants. Five models were trained: 2D models using a single radius (<em>2DRad</em>) and tibia (<em>2DTib</em>) slice from the middle of the scan; 3D models using full volumetric radius (<em>3DRad</em>) and tibia (<em>3DTib</em>); and a combined 2D model (<em>2DRadTib</em>) applying linear regression to the 2D outputs.</div></div><div><h3>Results:</h3><div>The <em>2DRadTib</em> model achieved the best performance, with a <em>validation</em> mean absolute error (MAE) of 5.29 ± 4.60 years (R<span><math><msup><mrow></mrow><mrow><mn>2</mn></mrow></msup></math></span> = 0.85) and <em>test</em> MAE of 5.34 ± 4.38 years (R<span><math><msup><mrow></mrow><mrow><mn>2</mn></mrow></msup></math></span> = 0.85). Saliency maps revealed cortical bone was most influential in younger individuals, while both cortical and trabecular features contributed in older participants. Predicted skeletal age was strongly correlated with established HR-pQCT parameters, particularly cortical and density measures (<span><math><mi>ρ</mi></math></span> = –0.51 to 0.85), indicating the model relies on key bone features.</div></div><div><h3>Conclusion:</h3><div>We present a novel deep learning framework for skeletal age prediction from HR-pQCT, providing a concise and interpretable summary measure of bone health. This approach may enhance the clinical utility of HR-pQCT by improving interpretability and supporting early identification of accelerated skeletal aging.</div></div><div><h3>Lay Summary</h3><div>High-resolution peripheral quantitative computed tomography (HR-pQCT) provides detailed images of bone structure, but the volume and complexity of data can make interpretation difficult. In this study, we developed a deep learning model to estimate skeletal age from HR-pQCT scans, offering a simplified and interpretable measure of bone health. By translating complex imaging data into an age-based summary, this approach may enhance clinical use of HR-pQCT, support early identification of individuals at risk of accelerated bone loss, and improve patient understanding by providing a relatable measure of skeletal integrity.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117761"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758701","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":"Development of an explainable machine learning model to reproduce and interpret expert pharmacological decisions in osteoporosis treatment","authors":"Yutaro Sugawara , Tomohiro Shimizu , Hotaka Ishizu , Kosuke Arita , Yusuke Ohashi , Shu Yamazaki , Terufumi Kokabu , Katsuhisa Yamada , Norimasa Iwasaki","doi":"10.1016/j.bone.2025.117745","DOIUrl":"10.1016/j.bone.2025.117745","url":null,"abstract":"<div><div>The management of osteoporosis in real-world clinical practice is highly heterogeneous, reflecting the complexity and variability inherent in therapeutic decision-making. Although artificial intelligence (AI)-based tools have been developed to support diagnosis, limited research has investigated their potential to elucidate the rationale underlying treatment choices. This study applied explainable machine learning to replicate and interpret pharmacological treatment decisions made by two board-certified osteoporosis specialists. We retrospectively analyzed 1481 patients who underwent dual-energy X-ray absorptiometry (DXA) and lateral spine radiography between 2020 and 2023 at Hokkaido University Hospital and two affiliated institutions. Two specialists independently assigned patients to one of five non-overlapping treatment categories. External validation was performed in 372 outpatients from three independent hospitals in 2024. The LightGBM model demonstrated the highest predictive performance. To interpret this model, we analyzed feature importance and applied SHapley Additive exPlanations (SHAP) to identify the most influential clinical factors driving treatment decisions.</div><div>The LightGBM model achieved an accuracy of 0.90 and an F1-score of 0.90 in external validation. SHAP analysis revealed that femoral neck bone mineral density (BMD) and severity of vertebral fractures (especially grade 3) were the most influential factors in treatment selection. These patterns mirrored the expert reasoning, highlighting the prioritization of objective imaging data in therapeutic decisions. This study demonstrated that explainable AI can clarify the clinical reasoning behind osteoporosis treatment decisions. Bone mineral density and vertebral fracture severity are key determinants, supporting a transparent and reproducible framework for future decision support tools that assist clinicians in making consistent therapeutic decisions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117745"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145672516","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}
BonePub Date : 2026-03-01Epub Date: 2025-12-18DOI: 10.1016/j.bone.2025.117765
Asier Muñoz, Annalisa De Paolis, Luis Cardoso, Alessandra Carriero
{"title":"Multiaxial physiological loading generates complex fluid flow and strain patterns in the osteocyte lacunar-canalicular system","authors":"Asier Muñoz, Annalisa De Paolis, Luis Cardoso, 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":"2026-03-01","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}