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Calcium, FSH, and the changing bones of menopause: A longitudinal look at the silent transformation 钙、卵泡刺激素和更年期骨骼的变化:对沉默转变的纵向观察
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-04-01 Epub Date: 2026-01-26 DOI: 10.1016/j.bone.2026.117805
Jessica L. Puranda , Vinicius M.R. Weber , Éric Doucet , Kristi B. Adamo

Introduction

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.

Methods

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 (VO2max), 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.

Results

Serum calcium was negatively associated with BMD at the lumbar spine [β: −0.0799, 95% confidence interval (CI): −0.139; −0.020, p = 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; p = 0.003] and total body [β: 0.045, CI: 0.035; 0.055 vs. β: 0.028, CI: 0.020; 0.036; p = 0.007] than the low FSH trajectory group.

Conclusion

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.
骨质疏松症对绝经后女性的健康构成威胁。更年期过渡与激素波动(例如,促卵泡激素(FSH),雌激素)以及其他导致骨矿物质密度(BMD)下降的生化和生理变化有关。本研究将探讨绝经过渡期骨密度的生化和生理指标之间的关系。方法对56名完成更年期过渡的中年女性进行纵向亚分析。参与者是从渥太华/加蒂诺地区招募的。使用月经史和FSH血浆水平对绝经状态进行分类。采用双能x线吸收仪(DXA)评估骨密度和体成分。其他测量包括BMI、心肺功能(最大摄氧量)、饮食中的钙和维生素D,以及生化指标(即FSH、皮质醇、钙)。统计分析包括重复测量方差分析、线性混合建模和基于组的轨迹建模,以确定不同的FSH轨迹组及其与BMD随时间变化的关系。结果血清钙与腰椎骨密度呈负相关[β: - 0.0799, 95%可信区间(CI): - 0.139;−0.020,p = 0.009]。此外,高FSH轨迹组在5年期间股骨颈的骨密度下降幅度更大[β: 0.067, CI: 0.050;0.084 vs. β: 0.035, CI: 0.021;0.048;p = 0.003]和全身[β: 0.045, CI: 0.035;0.055 vs. β: 0.028, CI: 0.020;0.036;p = 0.007]高于低FSH轨迹组。结论血清钙与腰椎骨密度之间存在关联,且FSH水平高的个体骨密度下降更大。这一信息表明,在绝经过渡期应监测血清钙和卵泡刺激素,以保护骨密度。
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引用次数: 0
Combined antiresorptive and antiangiogenic therapy versus antiresorptive monotherapy: Impact on the surgical prognosis of MRONJ patients with advanced malignancies 联合抗吸收和抗血管生成治疗与单一抗吸收治疗:对晚期恶性肿瘤MRONJ患者手术预后的影响。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-04-01 Epub Date: 2026-01-14 DOI: 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
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.
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.
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.
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.
对于晚期癌症和骨转移患者,抗吸收药物(ARMs)和抗血管生成药物(AGMs)通常用于控制肿瘤进展和骨骼并发症。本研究评估了不同的药物治疗策略-ARM单药治疗与ARM/AGM联合治疗对该人群药物相关性颌骨骨坏死(MRONJ)手术结果的影响。对157例患者进行回顾性队列分析:106例接受ARM单药治疗,51例接受ARM/AGM联合治疗。采用单变量和多变量统计方法系统收集和分析人口统计学数据、MRONJ特征和生活质量(QoL)指标。单因素分析显示,与ARM+AGM组相比,ARM组女性比例更高,抗吸收治疗持续时间更长,预后更佳,包括术后疼痛减轻和生活质量改善。多因素分析显示,与ARM组相比,ARM+AGM组的复发风险增加了2.8倍,其结果受药物治疗策略、疾病分期和手术方式的显著影响。这些发现表明,与ARM单药治疗相比,ARM+AGM联合治疗与MRONJ患者的预后较差和复发风险增加相关。
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引用次数: 0
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 腹部脂肪矫正对肥胖女性小梁骨评分(TBS)的影响:软件版本3.0和4.0与预测模型的比较研究
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-04-01 Epub Date: 2026-01-22 DOI: 10.1016/j.bone.2026.117804
Fernanda Perin Maia Starck , Barbara C. Silva , Victória Zeghbi Cochenski Borba

Purpose

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.

Methods

This cross-sectional study included 247 obese women (BMI ≥30 kg/m2) 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.

Results

TBS 4.0 were lower than TBS 3.0 across all BMI categories (p < 0.001), with the largest reductions observed in women with BMI ≥ 37 kg/m2. 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 (r = 0.51, p < 0.001) and BMI (r = 0.17, p = 0.007), but showed no significant correlation with abdominal wall thickness (r = −0.08, p = 0.229). The correlation between TBS and BMI was stronger for version 3.0 than for version 4.0 (r = 0.32 vs. r = 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.

Conclusions

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.
目的:通过比较软件版本3.0和4.0,评估软组织厚度矫正对不同BMI类别肥胖女性小梁骨评分(TBS)的影响,并研究其与骨密度(BMD)、骨折发生率和临床变量的关系。方法:本横断面研究纳入247名肥胖女性(BMI≥30 kg/m2),使用TBS iNsight®软件3.0和4.0版本进行腰椎密度测量和TBS评估。对人口统计学、人体测量学和骨密度数据进行分析。采用相关性和多元线性回归模型评估TBS 4.0、骨密度、骨折和临床参数之间的关系。结果:TBS 4.0在所有BMI分类中均低于TBS 3.0 (p 2)。使用4.0版本时,34%的TBS分类发生了变化,更大比例的TBS被重新分类为降级类别。TBS 4.0与腰椎骨密度呈正相关(r = 0.51,p )结论:TBS 4.0通过对软组织厚度的自动校正,提供了较低的值,可能更好地表征肥胖个体的小梁微结构,特别是那些bmi较高的人,并减轻了由于与以前版本的TBS软件观察到的身体组成差异而引起的偏差。
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引用次数: 0
Fermented mealworm extract prevents concurrent bone and muscle loss by modulating RANKL-NFκB/MAPK signaling in ovariectomized mice 发酵粉虫提取物通过调节去卵巢小鼠RANKL-NFκB/MAPK信号通路防止骨和肌肉同时丢失。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-01 Epub Date: 2025-12-08 DOI: 10.1016/j.bone.2025.117757
Soo-Young Choi, Mi-Kyung Lee
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.
本研究探讨发酵粉虫提取物(FME)是否能同时改善绝经后骨质疏松和肌肉萎缩,并探讨其机制。雌性C57BL/6 N小鼠分为5组:假手术、去卵巢(OVX)、两剂量FME(200和500 mg/kg,口服)和阳性对照阿仑膦酸钠(Alen, 500 μg/kg,口服)治疗,持续15 周。与OVX组相比,FME500显著增加了握力,而FME200没有显著改善。与OVX组相比,FME组和OVX组的肌肉横截面积均显著增加。与FME200相比,FME500还增强了肌肉蛋白合成标志物(MyoD1和MHC),并更有效地抑制了肌肉降解标志物(MuRF-1、萎缩素-1、肌肉生长抑制素和多泛素化蛋白)。在骨骼方面,与OVX组相比,两种FME剂量都改善了骨密度和RANKL和CTX-1的血清水平。在OVX组中,FME500比FME200更有效地下调骨和肌肉中RANKL、IL-6和TNF-α的表达。机制分析主要在FME500组进行,FME500组在骨和肌肉中下调NFκB/MAPK和上调IGF-1-PI3K-Akt。这些结果表明FME通过调节RANKL-NFκB/MAPK和IGF-1-PI3K-Akt信号通路抑制绝经后并发骨骼肌损失。
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引用次数: 0
Does irradiation adversely impact bone forming properties of demineralized bone matrix and allograft bone? A systematic review of the literature 辐照对脱矿骨基质和同种异体骨的成骨性能有不利影响吗?对文献的系统回顾。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-01 Epub Date: 2025-12-03 DOI: 10.1016/j.bone.2025.117753
Suzanne M. Tabbaa , Emily A. Davidson , Theodore Miclau , Ashraf El Naga
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引用次数: 0
FSH and longitudinal changes in bone marrow adipose tissue composition in older adults 老年人骨髓脂肪组织组成的FSH和纵向变化。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-01 Epub Date: 2025-12-15 DOI: 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
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.
骨髓脂肪组织(BMAT)扩张和不同的BMAT组成谱,包括较低的不饱和水平,在横切面上与年龄有关。BMAT组成随年龄的变化和血清促卵泡激素(FSH)的作用(FSH影响骨和脂肪代谢)的未来变化尚不清楚。我们在AGES-Reykjavik骨髓脂肪队列中检查了这些关联,使用性别分层线性回归模型调整了包括雌二醇和睾酮在内的协变量。基线时,236名女性和245名男性的平均年龄分别为81岁(SD 4)和83岁(4)。154名女性平均3.3 岁,151名男性平均2.6 岁,总体或饱和BMAT没有显著变化。然而,女性的平均不饱和BMAT增加(+0.26 %/年,95 % CI +0.21 %/年至+0.32 %/年),男性增加(+0.24 %/年,95 % CI +0.18 %/年至+0.30 %/年)。在女性中,不饱和骨密度的增加与椎骨小梁体积骨密度的显著降低相关。基线时,FSH最高的四分位数的女性有最高的总(66.6% %,95 % CI 64.3 %-69.0 %)和饱和BMAT(95 % CI 49.3 %,47.5% %- 51.0% %)。女性FSH和不饱和BMAT之间没有关系,男性BMAT结果也没有关系。纵向上,在女性中,较高的FSH与不饱和BMAT的增加有关。FSH与女性总BMAT或饱和BMAT的变化之间没有关系,男性的结果也没有任何变化。在老年人中,总BMAT是稳定的,但BMAT的组成随着不饱和BMAT的增加而改变。在女性中,较高的FSH横断面与较高的饱和BMAT相关,但纵向上与较高的不饱和BMAT相关。这些新发现为进一步的纵向研究提供了依据,以更好地表征BMAT的变化和FSH的作用。
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引用次数: 0
Evaluation of trabecular and subentheseal bone volume density in calcaneus with dual-echo ultrashort echo time magnetic resonance imaging: In vivo feasibility study 双回波超短回波时间磁共振成像评价跟骨骨小梁和骨骺下骨体积密度:体内可行性研究。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-01 Epub Date: 2025-12-12 DOI: 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
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), without resolving trabecular-level features, 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 study investigated 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 (TE=0.03 and 2.2 ms) on a clinical 3T MRI scanner 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 (p < 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 feasibility of dual echo UTE technique for rapid MRI-based evaluation of BV/TV in patients.
跟骨的骨小梁和骨骺量可能与患者的总体骨骼健康和身体活动水平有关。磁共振成像(MRI)已越来越多地用于骨评估,以避免电离辐射和能够同时评估周围软组织。利用双回波超短回波时间(UTE)序列,开发了一种基于mri的快速定量估计骨体积/总体积(BV/TV)的方法,无需解析小梁水平特征,该方法可以直接获取骨和自由水信号,以便进一步量化。本研究探讨了双回声超声超声对跟骨小梁和跟骨下BV/TV评估的可行性。32例健康受试者(女性12例,男性20例,年龄35.0 ± 6.8岁)在临床3T MRI扫描仪上采用双回声UTE (TE=0.03, 2.2 ms)扫描踝关节矢状面,扫描时间为3 min。在四个兴趣区域(roi)中测量BV/TV;近端跟骨月牙(ROI 1)、足底跟骨月牙(ROI 2)、跟骨深骨(ROI 3)和跟骨下骨(ROI 4)。用Kruskal Wallis检验差异。计算BV/TV与年龄、体重、身高和BMI的Spearman相关性。双回声UTE技术用于快速评估患者BV/TV的可行性(p )。
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引用次数: 0
Predicting skeletal age from HR-pQCT imaging 从HR-pQCT成像预测骨骼年龄。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-01 Epub Date: 2025-12-13 DOI: 10.1016/j.bone.2025.117761
Annabel R. Bugbird , Steven K. Boyd

Introduction:

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.

Methods:

The training dataset included 1236 adults (62.1% female) from a normative cohort, and an independent test 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 (2DRad) and tibia (2DTib) slice from the middle of the scan; 3D models using full volumetric radius (3DRad) and tibia (3DTib); and a combined 2D model (2DRadTib) applying linear regression to the 2D outputs.

Results:

The 2DRadTib model achieved the best performance, with a validation mean absolute error (MAE) of 5.29 ± 4.60 years (R2 = 0.85) and test MAE of 5.34 ± 4.38 years (R2 = 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 (ρ = –0.51 to 0.85), indicating the model relies on key bone features.

Conclusion:

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.

Lay Summary

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.
高分辨率外周定量计算机断层扫描(HR-pQCT)提供了详细的骨微结构评估,但其许多复杂参数的可解释性仍然具有挑战性。本研究旨在开发一种深度学习模型,从HR-pQCT扫描中估计骨骼年龄,提供相对于实足年龄的可解释的、定量的骨骼健康总结。方法:训练数据集包括来自规范队列的1236名成年人(女性占62.1%)和460名成年人(女性占69.3%)的独立测试数据集。所有参与者都获得了远端桡骨和胫骨的HR-pQCT扫描。五个模型被训练:2D模型使用单一的半径(2DRad)和胫骨(2DTib)切片从扫描的中间;使用全体积半径(3DRad)和胫骨(3DTib)的3D模型;以及对2D输出应用线性回归的组合2D模型(2DRadTib)。结果:2DRadTib模型表现最佳,验证平均绝对误差(MAE)为5.29±4.60年(R2 = 0.85),检验MAE为5.34±4.38年(R2 = 0.85)。显著性图显示,皮质骨对年轻人的影响最大,而皮质骨和小梁骨的特征对老年人的影响都很大。预测的骨骼年龄与已建立的HR-pQCT参数密切相关,特别是皮质和密度测量(ρ = -0.51至0.85),表明该模型依赖于关键的骨骼特征。结论:我们提出了一个新的深度学习框架,用于从HR-pQCT中预测骨骼年龄,提供了一个简洁且可解释的骨骼健康总结测量。这种方法可以提高HR-pQCT的可解释性,并支持骨骼加速老化的早期识别,从而提高其临床应用价值。摘要:高分辨率外周定量计算机断层扫描(HR-pQCT)提供了骨骼结构的详细图像,但数据的体积和复杂性给解释带来困难。在本研究中,我们开发了一种深度学习模型,从HR-pQCT扫描中估计骨骼年龄,提供了一种简化且可解释的骨骼健康测量方法。通过将复杂的成像数据转化为基于年龄的摘要,该方法可以增强HR-pQCT的临床应用,支持早期识别有加速骨质流失风险的个体,并通过提供相关的骨骼完整性测量来提高患者的理解。
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引用次数: 0
Development of an explainable machine learning model to reproduce and interpret expert pharmacological decisions in osteoporosis treatment 开发可解释的机器学习模型,以重现和解释骨质疏松症治疗中的专家药理学决策。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-01 Epub Date: 2025-12-01 DOI: 10.1016/j.bone.2025.117745
Yutaro Sugawara , Tomohiro Shimizu , Hotaka Ishizu , Kosuke Arita , Yusuke Ohashi , Shu Yamazaki , Terufumi Kokabu , Katsuhisa Yamada , Norimasa Iwasaki
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.
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.
在现实世界的临床实践中,骨质疏松症的管理是高度异质性的,反映了治疗决策的复杂性和可变性。尽管基于人工智能(AI)的工具已经开发出来支持诊断,但有限的研究调查了它们阐明治疗选择基本原理的潜力。本研究应用可解释的机器学习来复制和解释由两位董事会认证的骨质疏松症专家做出的药物治疗决定。我们回顾性分析了2020年至2023年间在北海道大学医院和两个附属机构接受双能x线吸收仪(DXA)和侧位脊柱x线摄影的1481例患者。两名专家独立地将患者分配到五种不重叠的治疗类别之一。2024年对3家独立医院的372例门诊患者进行外部验证。LightGBM模型表现出最高的预测性能。为了解释这个模型,我们分析了特征重要性,并应用SHapley加性解释(SHAP)来确定驱动治疗决策的最具影响力的临床因素。在外部验证中,LightGBM模型的准确率为0.90,f1评分为0.90。SHAP分析显示,股骨颈骨密度(BMD)和椎体骨折严重程度(尤其是3级)是影响治疗选择的最重要因素。这些模式反映了专家的推理,突出了客观成像数据在治疗决策中的优先级。本研究表明,可解释的人工智能可以阐明骨质疏松症治疗决策背后的临床原因。骨密度和椎体骨折严重程度是关键的决定因素,为未来的决策支持工具提供透明和可重复的框架,帮助临床医生做出一致的治疗决策。
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引用次数: 0
Multiaxial physiological loading generates complex fluid flow and strain patterns in the osteocyte lacunar-canalicular system 多轴生理载荷在骨细胞腔隙-小管系统中产生复杂的流体流动和应变模式。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-01 Epub Date: 2025-12-18 DOI: 10.1016/j.bone.2025.117765
Asier Muñoz, Annalisa De Paolis, Luis Cardoso, Alessandra Carriero
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.
骨细胞嵌入骨腔管系统中,在感知机械刺激和指导骨适应中发挥核心作用。流固相互作用(FSI)模型已经成为模拟骨细胞周围机械环境的有价值的工具,但在计算机上的研究依赖于理想化的加载条件来简化骨细胞可能在体内暴露的复杂的多轴加载。在本研究中,我们通过将Lanyon等人(1975)[1]在步行和跑步过程中实验测量的人类胫骨张力纳入到三维骨细胞尺度的FSI模拟中,利用多轴生理学相关的加载条件,模拟腔隙-管系统内的机械环境。我们在此评估由生理负荷产生的间质液流动和骨细胞应变模式与使用简化的单轴正弦负荷获得的结果有何不同。研究结果表明,尽管间隙流体速度大小相似,但在多轴生理载荷下的空间流动肯定更为复杂。多轴生理载荷产生的流体速度和应变是高度不均匀的,并随着时间的推移而改变方向,树枝状应变超过细胞体的应变一个数量级以上。相反,单轴正弦加载产生与主加载轴对齐的均匀周期性流动,垂直于主加载轴的枝晶应变最小。值得注意的是,多轴生理负荷在小管内诱导局部再循环区和更广泛的速度分布——极低的雷诺数证实了层流,排除了真正的湍流——这可以放大骨细胞的机械敏感信号。这些在单轴正弦加载中没有观察到。这些发现突出了单轴正弦载荷作为骨细胞生理力学模型的局限性。
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Bone
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