Bone最新文献_第3页

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

Bone

Pub 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 (R

^{2}

= 0.85) and test MAE of 5.34 ± 4.38 years (R

^{2}

= 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

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

Bone

Pub 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 re}solving ^{trabecular-level f}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 ^{study i}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 ^{(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

Association of body fat distribution with bone mineral density: evidence from observational and mendelian randomization analyses 体脂分布与骨密度的关联：来自观察性和孟德尔随机化分析的证据。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-12-10 DOI: 10.1016/j.bone.2025.117742

Qichao Sun , Lijia Cui , Yuxi Liu , Qianqian Pang , Yue Chi , Ruizhi Jiajue , Wei Liu , Yan Jiang , Ou Wang , Mei Li , Xiaoping Xing , Weibo Xia

Background

Although higher body weight is generally considered protective against low bone mineral density (BMD), the influence of body fat distribution on BMD remains unclear. We aimed to investigate whether specific adipose tissue depots have differential associations with BMD and to assess causality using Mendelian randomization (MR).

Methods

We conducted a cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) data to evaluate associations between regional fat depots (gynoid, android, visceral, abdominal subcutaneous fat, and total fat percentage) and BMD at total body, femoral neck, and lumbar spine. Multivariable linear regression was used to evaluate these relationships. To assess potential causal effects, we performed two-sample MR using genome-wide association study summary statistics for fat distribution traits and BMD.

Results

Gynoid fat was positively associated with BMD at the total body, femoral neck, and lumbar spine, while visceral and total body fat showed consistent inverse associations across these regions. Two-sample MR analysis supported a causal effect of gynoid fat on BMD but found no evidence of causality for visceral or total body fat.

Conclusions

Gynoid fat shows a beneficial and causal effect on BMD, whereas the inverse associations observed for visceral and total body fat appear to be non-causal. These findings underscore the importance of considering fat distribution, not merely total body fat or weight, when evaluating bone health.

背景：虽然较高的体重通常被认为对低骨密度（BMD）有保护作用，但体脂分布对骨密度的影响尚不清楚。我们的目的是研究特定的脂肪组织储存是否与骨密度有不同的关联，并使用孟德尔随机化（MR）来评估因果关系。方法：我们使用全国健康与营养调查（NHANES）数据进行了横断面分析，以评估全身、股骨颈和腰椎的区域脂肪储存库（雌性、雌性、内脏、腹部皮下脂肪和总脂肪百分比）与骨密度之间的关系。使用多变量线性回归来评估这些关系。为了评估潜在的因果关系，我们使用脂肪分布特征和骨密度的全基因组关联研究汇总统计数据进行了两样本MR。结果：雌性脂肪与全身、股骨颈和腰椎的骨密度呈正相关，而内脏脂肪和全身脂肪在这些区域表现出一致的负相关。双样本磁共振分析支持雌性脂肪对骨密度的因果关系，但没有发现内脏脂肪或全身脂肪的因果关系。结论：雌性脂肪对骨密度有有益的因果关系，而内脏脂肪和全身脂肪的负相关关系似乎没有因果关系。这些发现强调了在评估骨骼健康时考虑脂肪分布的重要性，而不仅仅是全身脂肪或体重。

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引用次数: 0

Region-specific variation in trapeziometacarpal joint bone microarchitecture in females with osteoarthritis assessed using HR-pQCT 使用HR-pQCT评估女性骨关节炎患者的骨微结构区域特异性差异

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-12-09 DOI: 10.1016/j.bone.2025.117759

Michael T. Kuczynski , Charley Hasselaar , Gurpreet Dhaliwal , Christina Hiscox , Neil J. White , Danielle E. Whittier , Sarah L. Manske

The trapeziometacarpal (TMC) joint is commonly affected by osteoarthritis (OA), and its unique morphology creates localized loading patterns that cause regional bone adaption. Radiographic OA is more prevalent than symptomatic OA, highlighting the disconnect between structural features and clinical disease. Ex vivo studies have demonstrated regional changes in trapezial bone microarchitecture but are limited to cadaveric specimen with advanced disease. In vivo studies are needed to characterize regional bone microarchitecture in symptomatic TMC OA. We investigated regional bone microarchitecture in females with TMC OA using high-resolution peripheral quantitative computed tomography (HR-pQCT), and whether these changes differed from those associated with ageing. HR-pQCT scans of the TMC joint were acquired from 13 females with TMC OA, 12 controls matched groupwise by age and sex, and 15 sex-matched young controls. Total bone mineral density, bone volume fraction (Tt.BV/TV), thickness, and separation were quantified by quadrant in the first metacarpal and trapezium. A mixed ANOVA assessed group, quadrant, and group-by-quadrant effects. Significant interaction effects were observed for all parameters in the trapezium and separation in the first metacarpal (p < 0.001). In OA, trapezial separation was higher, and Tt.BV/TV was lower in the ulnar-volar quadrant, while separation was lower in the radial-volar quadrant compared to young controls (p < 0.05). In the first metacarpal, radial-volar separation was lower in OA than young controls (p < 0.05). These results suggest that OA may disrupt the normal variation in first metacarpal and trapezial bone microarchitecture, highlighting the utility of HR-pQCT in early detection of structural bone changes in hand OA.

骨关节炎（OA）通常会影响到斜骨掌骨（TMC）关节，其独特的形态形成了局部的负荷模式，导致区域骨适应。影像学上的骨性关节炎比症状性骨性关节炎更普遍，突出了结构特征与临床疾病之间的脱节。离体研究已经证明了梯形骨微结构的局部改变，但仅限于晚期疾病的尸体标本。需要在体内研究来表征症状性TMC OA的局部骨微结构。我们使用高分辨率外围定量计算机断层扫描（HR-pQCT）研究了患有TMC OA的女性的局部骨微结构，并研究了这些变化是否与衰老相关的变化不同。从13名患有TMC OA的女性患者、12名按年龄和性别分组匹配的对照组和15名性别匹配的年轻对照组中获得了TMC关节的HR-pQCT扫描。总骨矿物质密度，骨体积分数(Tt。BV/TV)、厚度、分离用第一掌骨和斜方骨象限进行量化。混合方差分析评估组效应、象限效应和逐象限效应。在斜方骨的所有参数和第一掌骨的分离中观察到显著的相互作用效应（p < 0.001）。在OA中，斜向分离较高，Tt。BV/TV在尺掌象限较低，而在桡掌象限的分离较低（p < 0.05）。在第一掌骨，骨性关节炎患者桡骨-掌侧分离低于年轻对照组（p < 0.05）。这些结果表明OA可能会破坏第一掌骨和斜骨微结构的正常变化，突出了HR-pQCT在早期检测手部OA的骨结构变化中的应用。

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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

Bone

Pub 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

Expression of proteins secreted by osteocytes in bone biopsies of patients with chronic kidney disease and iron overload, before and after treatment with deferoxamine 去铁胺治疗前后慢性肾脏病和铁超载患者骨活检中骨细胞分泌蛋白的表达

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-12-04 DOI: 10.1016/j.bone.2025.117754

Hanna Karla Andrade Guapyassu Machado , Luciene Machado dos Reis , Lucas Acatauassu Nunes , Ivone B. Oliveira , Cleonice Silva , Wagner V. Dominguez , Rosilene M. Elias , Rosa M. Moysés , Melani Custódio , Vanda Jorgetti

Introduction: Individuals with CKD can develop anemia, as well as mineral and bone disorder. Anemia is treated with recombinant erythropoietin and iron supplementation, which can result iron overload in various organs. Little is known about the effects of iron overload and its treatment on bone remodeling and osteocyte expression of relevant proteins. The objective of this study was to evaluate the effects that iron overload and treatment with the iron chelator deferoxamine have on parameters of iron metabolism in bone tissue and on osteocyte protein expression. Methods: This was an observational study of individuals with CKD and iron overload who underwent bone biopsy and were treated with deferoxamine. Biochemical analysis, histomorphometry, and immunohistochemistry were performed. The results were compared with those obtained for controls. Results: Deferoxamine treatment reduced all parameters of iron metabolism decreased calcium, increased alkaline phosphatase, and decreased (intact and c-terminal) fibroblast growth factor 23 levels. After treatment, trabecular separation increased, and osteoblast surface decreased. DFO treatment increased the expression of DMP-1, decreased the expression of DKK-1, PHEX and the RAGE proteins involved in bone remodeling and oxidative stress. Comparison of the expression of osteocyte proteins before and after DFO treatment with their expression in normal bone tissue, there was also increased expression of proteins that act in the formation of dendrites and cytoskeleton, such as E11 and CD44. Conclusion: In patients with CKD and iron overload, deferoxamine treatment modulates bone remodeling and expression of osteocyte proteins, which also play a role in the process.

CKD患者可能会出现贫血，以及矿物质和骨骼紊乱。贫血是用重组红细胞生成素和补铁治疗的，这可能导致各器官铁超载。目前对铁超载及其治疗对骨重塑和骨细胞相关蛋白表达的影响知之甚少。本研究的目的是评估铁超载和铁螯合剂去铁胺治疗对骨组织铁代谢参数和骨细胞蛋白表达的影响。方法：这是一项观察性研究，对CKD和铁超载患者进行骨活检并接受去铁胺治疗。进行生化分析、组织形态测定和免疫组织化学。结果与对照组进行了比较。结果：去铁胺处理降低了铁代谢的所有参数，降低了钙，增加了碱性磷酸酶，降低了（完整的和c端）成纤维细胞生长因子23的水平。治疗后小梁分离增加，成骨细胞表面减少。DFO处理增加了DMP-1的表达，降低了DKK-1、PHEX和参与骨重塑和氧化应激的RAGE蛋白的表达。与正常骨组织相比，DFO处理前后骨细胞蛋白的表达也有所增加，参与树突和细胞骨架形成的蛋白如E11和CD44的表达也有所增加。结论：在CKD和铁超载患者中，去铁胺治疗可调节骨重塑和骨细胞蛋白的表达，骨细胞蛋白也在这一过程中发挥作用。

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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

Bone

Pub Date : 2025-12-03 DOI: 10.1016/j.bone.2025.117753

Suzanne M. Tabbaa , Emily A. Davidson , Theodore Miclau , Ashraf El Naga

引用次数: 0

Pro-osteogenic effects of green Rooibos (Aspalathus linearis) against different dietary backgrounds in male Wistar rats 绿色路易波士对不同饮食背景下雄性Wistar大鼠的促成骨作用。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-12-02 DOI: 10.1016/j.bone.2025.117743

J. Khan , H. Sadie-Van Gijsen , L.M. Kotzé-Hörstmann , S.H. Kotze , S.L. Windvogel , T.N. Brink , J.I. Layman-Lemphane

Previous in vitro studies have demonstrated direct effects of Rooibos (Aspalathus linearis) on bone cell populations, notably osteoblasts and osteoclasts, but in vivo evidence of Rooibos effects on bone remain scant. Here, we compared the effects of a green (minimally oxidized) Rooibos extract (GRT) on the femora of male Wistar rats, against the background of a medium-fat/high-sugar (MF/HS) and a high-fat/high-fructose (HF/Fr) diet. Male Wistar rats were maintained for 17 weeks on one of three diets: control (CON), MF/HS (OB1) or HF/Fr (OB2) (n = 24 each). From weeks 11–17, n = 12 animals in each group received oral GRT supplementation (60 mg/kg body weight daily). Femoral bone mineral content and density (BMC, BMD) were analysed by densitometry; cortical and cancellous bone microarchitecture was assessed using micro-computed tomography (μCT); and osteoblast (N.Ob), osteoclast (N.Oc), adipocyte (N.Ad) and chondrocyte numbers (N.Ch) were quantified histomorphometrically. GRT supplementation did not affect femur weight, BMC or BMD, but improved trabecular measurements were observed in the CON-GRT group, compared to all other groups. GRT increased N.Ob/mm² and decreased N.Oc/mm² in the CON and OB2 dietary groups. Notably, GRT reversed the OB2 diet-associated increase in N.Oc/mm² in both cortical and cancellous bone. Although GRT had no effect on serum malondialdehyde (MDA) levels as a measure of systemic oxidative stress status, serum MDA levels were nevertheless positively correlated with cortical and cancellous N.Oc/mm² and negatively correlated with cortical N.Ob/mm². Overall, GRT supplementation had pro-osteogenic and anti-osteoclastogenic effects in vivo, indicating that green Rooibos should be further explored as a bone-supporting nutraceutical.

先前的体外研究已经证明了路易波士对骨细胞群，特别是成骨细胞和破骨细胞的直接影响，但在体内路易波士对骨的影响仍然缺乏证据。在此，我们比较了绿色（最低氧化）路易波士提取物（GRT）在中脂肪/高糖（MF/HS）和高脂肪/高果糖（HF/Fr）饮食背景下对雄性Wistar大鼠股骨的影响。雄性Wistar大鼠在对照（CON）、MF/HS （OB1）或HF/Fr （OB2）三种饮食中的一种维持17 周（各 = 24）。从第11-17周开始，n = 每组12只动物口服GRT（每天60 mg/kg体重）。用密度法分析股骨骨矿物质含量和骨密度（BMC、BMD）；采用微计算机断层扫描（μCT）评估骨皮质和松质骨微结构；对成骨细胞（N.Ob）、破骨细胞（N.Oc）、脂肪细胞（N.Ad）和软骨细胞数量（N.Ch）进行组织形态学定量。补充GRT不影响股骨重量、BMC或BMD，但与所有其他组相比，在CON-GRT组中观察到改善的小梁测量。在CON和OB2饲粮组，GRT提高了N.Ob/mm2，降低了N.Oc/mm2。值得注意的是，GRT逆转了与OB2饮食相关的皮质骨和松质骨N.Oc/mm2的增加。尽管GRT对测量全身氧化应激状态的血清丙二醛（MDA）水平没有影响，但血清MDA水平与皮质和松质N.Oc/mm2呈正相关，与皮质N.Ob/mm2负相关。综上所述，在体内补充GRT具有促骨和抗破骨作用，表明绿色路易波士作为一种支持骨骼的营养保健品有待进一步探索。

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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

Bone

Pub 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

Genetic contributors to osteoporosis in pregnancy and lactation associated osteoporosis (PLO) 妊娠和哺乳期骨质疏松症（PLO）的遗传因素。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-30 DOI: 10.1016/j.bone.2025.117744

Lauren Lynch , Patrick R. Shea , Natalie Vena , Wendy K. Chung , Elizabeth Shane , Mafo Kamanda-Kosseh , Jordan Barry , Dany El-Najjar , Sanchita Agarwal , Ananya Kondapalli , Ivelisse Colon , Mariana Bucovsky , Adi Cohen

Pregnancy- and lactation-associated osteoporosis (PLO) describes a fragility fracture presentation around pregnancy/lactation. Presentation often includes multiple vertebral fractures, but can also involve hip, sacral/pelvic, or other fractures. Substantial bone structural deficits and low bone formation rate have been documented. Most have no known secondary cause. Many have a history of childhood fracture and/or family history of osteoporosis. These characteristics, together with early onset and disease severity, lead to the hypothesis that genetic factors may contribute to PLO.

We enrolled 110 women with PLO (mean #fractures = 6, vertebral fractures in 88 %) in an exome sequencing (ES) study. Analyses identified rare (<1 % allele frequency in gnomAD) predicted deleterious variants (RPDV) in 33/110 (30 %) women. All were heterozygous; two participants had multiple RPDV. No RPDV in COL1A1/COL1A2 were identified. 28/110 (25 %) had RPDV in genes related to WNT signaling, critical to bone formation: LRP5 (n = 19), LRP6 (n = 6), WNT1 (n = 2) or WNT1&LRP5 (n = 1). Seven had RPDV related to renal/calcium handling (SLC34A1, SLC34A3, SLC9A3), or other osteoporosis mechanisms (PLS3 (n = 3), HGD (n = 1)). Those with RPDV did not differ from those without in terms of BMD, fracture characteristics, and most clinical characteristics.

Among 110 PLO women, exome sequencing analyses identified a potential genetic osteoporosis contribution in 30 %, suggesting that many genetic contributors to PLO have yet to be elucidated. The finding of variants related to WNT signaling in 25 % of the cohort is consistent with the predominantly low bone formation phenotype of PLO and may have implications for prognosis and treatment response.

妊娠和哺乳期相关骨质疏松症（PLO）描述了妊娠/哺乳期的脆性骨折表现。表现通常包括多处椎体骨折，但也可包括髋部、骶骨/骨盆或其他骨折。大量的骨结构缺陷和低骨形成率已被记录。大多数没有已知的继发原因。许多患者有童年骨折史和/或骨质疏松家族史。这些特点，加上发病早和疾病严重程度，导致遗传因素可能导致PLO的假设。我们在一项外显子组测序（ES）研究中招募了110名患有PLO的女性（平均骨折数 = 6，椎体骨折88 %）。分析发现罕见的(

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引用次数: 0