IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-29 DOI: 10.1016/j.bone.2026.117813

Paccou Julien , Badr Sammy , Ramdane Nassima , Michou Laetitia , Courbon Guillaume , Mentaverri Romuald

Context

Experimental studies have suggested that the autocrine/paracrine effects of bone-derived Fibroblast Growth Factor 23 (FGF23) inhibit adipogenesis and promote osteoblastic differentiation of bone marrow stroma cells.

Objective

To examine whether there is relationship between circulating levels of FGF23 and bone marrow adiposity assessed by MRI.

Design

This cross-sectional study included 199 postmenopausal women without apparent disorders in phosphate homeostasis.

Setting

University Hospital of Lille, France.

Main outcome measure(s)

C-terminal FGF23 (cFGF23, relative units (RU)/ml) and intact FGF23 (iFGF23, pg/ml). The Proton Density Fat Fraction (PDFF) of the lumbar spine and the proximal femur was assessed using MRI with chemical shift-based water-fat separation (WFI) and DXA of the hip and spine. Our main goal was to explore the relationships between PDFF, cFGF23, and iFGF23 levels in women who are postmenopausal. The relationships between cFG23, iFGF23, and body composition metrics were subsequently analyzed.

Results

A significant positive correlation was observed between cFGF23 and iFGF23 (R = 0.534, p < 0.0001). Significant inverse associations were found between cFGF23, iFGF23, and femoral neck PDFF (reciprocally, coefficient β (95%CI), −1.35 (−2.49 to −0.21), p = 0.020 and − 1.66 (−3.00 to −0.32), p = 0.016) after adjustment for age, recent fragility fracture, BMI, eGFR, and BMD. Conversely, there were no notable associations identified between cFGF23, iFGF23, and lumbar spine PDFF, regardless of whether adjustment models were applied. No significant associations were found between cFGF23, iFGF23, and body composition parameters (total body fat and visceral adipose tissue).

Conclusions

An inverse association was found between cFGF23, iFGF23, and proximal femur PDFF (particularly femoral neck PDFF), but not with lumbar spine PDFF. Moreover, cFGF23 and iFGF23 levels were not associated with other adipose deposits.

背景：实验研究表明，骨源性成纤维细胞生长因子23 （FGF23）的自分泌/旁分泌作用抑制脂肪生成，促进骨髓基质细胞成骨分化。目的：探讨FGF23循环水平与MRI评估骨髓肥胖之间的关系。设计：这项横断面研究包括199名无明显磷酸盐稳态紊乱的绝经后妇女。单位：法国里尔大学医院。主要观察指标：c端FGF23 （cFGF23，相对单位(RU)/ml）和完整FGF23 （iFGF23, pg/ml）。采用基于化学位移的水-脂肪分离（WFI）和髋关节和脊柱DXA的MRI评估腰椎和股骨近端质子密度脂肪分数（PDFF）。我们的主要目的是探讨绝经后妇女PDFF、cFGF23和iFGF23水平之间的关系。随后分析了cFG23、iFGF23与体成分指标之间的关系。结果：cFGF23与iFGF23呈正相关（R = 0.534,p ）。结论：cFGF23、iFGF23与股骨近端PDFF（尤其是股骨颈PDFF）呈负相关，但与腰椎PDFF无关。此外，cFGF23和iFGF23水平与其他脂肪沉积无关。

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引用次数: 0

Clec4a2 deficiency promotes post-fission osteoclast cell death and suppresses acute inflammation-induced bone loss in the mouse Clec4a2缺乏促进小鼠裂变后破骨细胞死亡并抑制急性炎症诱导的骨质流失。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 10.1016/j.bone.2026.117797

Hirofumi Fujita , Yuma Tai , Kenji Takahashi , Yuto Ueda , Wakana Kitagawa , Mitsuaki Ono , Toshitaka Oohashi , Hideyo Ohuchi

To achieve efficient bone resorption by osteoclasts, the specialized innate immune cells, it is important not only to promote osteoclast differentiation and activation but also to maintain their survival. C-type lectin (CLEC) receptors recognize pathogen ligands and altered self-tissues, comprising activating and inhibitory types whose balance eliminates pathogens while preventing excessive immune responses. However, roles of CLEC receptors in osteoclast differentiation, function, and survival remain unclear. We established knockout (KO) mice of CLEC receptor genes highly expressed by osteoclast and analyzed osteoclast features and bone morphology. We conducted comprehensive in silico screening of osteoclast lineage-specific CLEC receptors utilizing a mouse gene expression dataset and generated single and double KO (DKO) mice of Clec4a2 and Clec4d using a multi-targeted CRISPR-Cas9 system. Clec4a2 KO and DKO enhanced osteoclast differentiation in vitro, and Clec4a2 KO also stimulated enlargement of osteoclasts. Clec4d KO slightly reduced trabecular bone thickness in the femur, while Clec4a2 KO and DKO did not affect bone morphology under physiological conditions. Contrary to conventional understanding that enhanced osteoclast differentiation leads to increased bone resorption, our time-lapse analysis revealed that Clec4a2 KO paradoxically increased osteoclast formation while reducing resorption efficiency due to cell death of osteoclasts and its daughter cells after fission. Clec4a2 KO provided protection against inflammatory bone loss induced by lipopolysaccharide, demonstrating the first evidence that Clec4a2 could serve as therapeutic targets for inflammatory osteolytic diseases. This study introduces a novel paradigm that osteoclast survival regulation by Clec4a2 is fundamental for efficient bone resorption.

破骨细胞是一种特化的先天免疫细胞，要实现破骨细胞的高效骨吸收，不仅要促进破骨细胞的分化和活化，而且要维持破骨细胞的存活。c型凝集素（CLEC）受体识别病原体配体和改变的自身组织，包括激活型和抑制性，其平衡消除病原体，同时防止过度的免疫反应。然而，CLEC受体在破骨细胞分化、功能和存活中的作用尚不清楚。我们建立了高表达破骨细胞CLEC受体的敲除（KO）小鼠，并分析了破骨细胞的特征和骨形态。我们利用小鼠基因表达数据集对破骨细胞谱系特异性CLEC受体进行了全面的硅筛选，并使用多靶点CRISPR-Cas9系统生成了Clec4a2和Clec4d的单和双KO （DKO）小鼠。Clec4a2 KO和DKO均能促进破骨细胞的体外分化，同时Clec4a2 KO也能刺激破骨细胞的增大。Clec4d KO轻微降低股骨小梁骨厚度，而Clec4a2 KO和DKO在生理条件下对骨形态没有影响。与传统的理解相反，增强破骨细胞分化导致骨吸收增加，我们的延时分析显示，由于破骨细胞及其子细胞在裂变后的细胞死亡，Clec4a2 KO矛盾地增加了破骨细胞的形成，同时降低了骨吸收效率。Clec4a2 KO对脂多糖诱导的炎症性骨质流失具有保护作用，首次证明了Clec4a2可以作为炎症性溶骨性疾病的治疗靶点。本研究引入了一种新的范式，即Clec4a2对破骨细胞存活的调节是有效骨吸收的基础。

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引用次数: 0

Quantitative analysis of osseointegration of glass fiber-reinforced composite-bioactive glass cranial implants 玻璃纤维增强复合材料-生物活性玻璃颅骨植入物骨整合的定量分析。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-10 DOI: 10.1016/j.bone.2026.117790

Vita M. Klieverik , Marvick S.M. Muradin , N. Nicolai , J. Kortes , Pierre A. Robe , Peter A. Woerdeman

Background

Glass fiber-reinforced composite-bioactive glass (FRC-BG) implants are emerging as an alternative to autologous bone grafts with the potential for new bone formation and ingrowth from the surrounding skull. However, clinical evidence of osseointegration remains to be demonstrated.

Objective

To evaluate radiological measures of osseointegration of FRC-BG implants used for cranioplasty.

Methods

A retrospective cohort study was conducted including adult patients who underwent cranioplasty with FRC-BG implants between 2016 and 2021. Sequential non-contrast head CT-scans were obtained within 24 h postoperatively and after one year of follow-up. Using three-dimensional (3D) segmentation and analysis software, changes in bone volume (in cm³) and bone density (in Hounsfield units [HU]) of a standardized one cm-wide region of skull bone surrounding the margins of the FRC-BG implants were quantified. Paired samples t-tests assessed differences between baseline and after one year of follow-up.

Results

A total of 38 patients were included (mean age 50.2 ± 18.4 years). After one year of follow-up, significant increases were observed in both skull bone volume (mean difference 6.04 cm³, 95% confidence interval [CI] 4.65–7.43, p < 0.001) and skull bone density (mean difference 45.84 HU, 95% CI 1.15–90.52, p = 0.045) surrounding the FRC-BG implants.

Conclusion

The present study shows radiological signs of osseointegration of FRC-BG implants used for cranioplasty.

背景：玻璃纤维增强复合生物活性玻璃（FRC-BG）植入物作为自体骨移植的一种替代品正在兴起，具有从周围颅骨形成新骨和向内生长的潜力。然而，骨融合的临床证据仍有待证实。目的：探讨FRC-BG假体颅骨成形术中骨融合的影像学指标。方法：回顾性队列研究包括2016年至2021年间接受FRC-BG植入物颅骨成形术的成年患者。术后24 h内和随访1年后进行序贯非对比头部ct扫描。使用三维（3D）分割和分析软件，量化FRC-BG植入物边缘周围标准化1厘米宽颅骨区域的骨体积（cm3）和骨密度（Hounsfield单位[HU]）的变化。配对样本t检验评估基线和随访一年后的差异。结果：共纳入38例患者（平均年龄50.2 ± 18.4 岁）。随访一年后，观察到两组颅骨体积显著增加（平均差6.04 cm3, 95%可信区间[CI] 4.65-7.43, p ）。结论：本研究显示用于颅骨成形术的FRC-BG植入物具有骨融合的影像学征像。

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引用次数: 0

Electroacupuncture remodels brain functional connectivity and improves bone metabolism in ovariectomized rats 电针重塑去卵巢大鼠脑功能连接并改善骨代谢。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-13 DOI: 10.1016/j.bone.2025.117774

Lu Zhang , Yi Rong , Xiaoxue Wang , Yanan Chen , Maoting Xu , Cai Tang , Yuan Yang , Guiquan Chen , Sheng Li

Electroacupuncture has demonstrated established efficacy in treating postmenopausal osteoporosis, yet the central mechanisms underlying its action via the brain-bone axis remain incompletely understood. This study employed multimodal resting-state functional magnetic resonance imaging to investigate neurofunctional changes induced by electroacupuncture in a rat model of postmenopausal osteoporosis. Twenty-four female Sprague-Dawley rats were randomly allocated to electroacupuncture, sham, and model (ovariectomized) groups. The electroacupuncture group received an 8-week intervention at acupoints GB30, GB34, and GB39. We assessed brain function through amplitude of low-frequency fluctuation, regional homogeneity, and region-of-interest functional connectivity, while simultaneously measuring serum bone turnover markers via enzyme-linked immunosorbent assay. Our results demonstrated that electroacupuncture significantly improved bone microstructure and reduced bone resorption marker levels. Neuroimaging revealed enhanced cerebellar neural activity which correlated negatively with bone resorption, alongside decreased neural synchronization in the entorhinal cortex. Furthermore, strengthened functional connectivity between entorhinal and visual cortices positively correlated with bone formation markers, while weakened somatosensory-cerebellar connectivity correlated with reduced bone resorption. Bayesian mediation analysis provided strong statistical evidence for the role of the entorhinal-visual pathway involvement in bone formation regulation and cerebellar mediation of bone resorption suppression. These findings systematically reveal the association between electroacupuncture-induced brain functional reorganization and bone metabolic improvements, offering new insights into the role of the brain-bone axis in osteoporosis management.

电针治疗绝经后骨质疏松症的疗效已得到证实，但其通过脑-骨轴作用的中枢机制仍不完全清楚。本研究采用多模态静息状态功能磁共振成像研究电针对绝经后骨质疏松大鼠模型的神经功能改变。24只雌性Sprague-Dawley大鼠随机分为电针组、假手术组和去卵巢模型组。电针组在GB30、GB34、GB39穴位进行为期8周的干预。我们通过低频波动幅度、区域均匀性和感兴趣区域功能连通性来评估脑功能，同时通过酶联免疫吸附法测量血清骨转换标志物。我们的研究结果表明，电针显著改善骨微结构和降低骨吸收标志物水平。神经影像学显示小脑神经活动增强，与骨吸收呈负相关，同时内嗅皮质神经同步性降低。此外，内嗅皮层和视觉皮层之间的功能连接增强与骨形成标志物正相关，而体感-小脑连接减弱与骨吸收减少相关。贝叶斯中介分析为内视通路参与骨形成调控和小脑介导骨吸收抑制的作用提供了有力的统计证据。这些发现系统地揭示了电针诱导的脑功能重组与骨代谢改善之间的关系，为脑-骨轴在骨质疏松症治疗中的作用提供了新的见解。

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引用次数: 0

Corrigendum to “Pulsed electromagnetic fields inhibit human osteoclast formation and gene expression via osteoblasts” [Bone 106 (2018) 194–203 (ISSN: 8756-3282)] “脉冲电磁场通过成骨细胞抑制人类破骨细胞的形成和基因表达”的更正[骨106 (2018)194-203 (ISSN: 8756-3282)]。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-22 DOI: 10.1016/j.bone.2026.117794

Zhiming He , Nagarajan Selvamurugan , Johanna Warshaw , Nicola C. Partridge

引用次数: 0

Association between systemic redox balance and osteoporosis: prospective evidence, polygenic modification, and proteomic and inflammatory mediation in the UK Biobank 系统性氧化还原平衡与骨质疏松症之间的关联：前瞻性证据、多基因修饰、蛋白质组学和炎症介导。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bone.2026.117802

Yuanpeng Zhu , Di Liu , Xiangjie Yin , Terry Jianguo Zhang , Nan Wu

Purpose

Redox signaling governs bone remodeling, but whether systemic redox balance is associated with incident osteoporosis, genetic susceptibility, and proteomic/inflammatory pathways at population scale remains unclear.

Methods

We analyzed UK Biobank participants free of osteoporosis at baseline. Serum redox balance score (SRBS) combined albumin, total bilirubin, and γ-glutamyl transferase. Cox proportional hazards models adjusted for prespecified covariates. Effect modification by an osteoporosis polygenic risk score (PRS) was tested on multiplicative and additive scales. Mediation was evaluated in a proteomics subset and an inflammatory-panel subset using counterfactual mediation with multiple-testing control.

Results

Over a median follow-up of 12.8 years (IQR, 11.7–13.7), 12,893 incident osteoporosis cases were observed. SRBS demonstrated a nonlinear inverse association with osteoporosis, displaying a J-shaped pattern: relative to Q1, multivariable hazard ratios (95% CIs) were 0.82 (0.78–0.86) for Q2, 0.75 (0.71–0.78) for Q3, and 0.72 (0.68–0.75) for Q4; the per–standard-deviation increase corresponded to an HR of 0.85 (0.83–0.87). Cumulative-incidence curves diverged early and showed a stepwise gradient across quartiles. Associations were stronger among men and physically inactive participants. SRBS interacted with the osteoporosis PRS on the multiplicative scale (interaction HR, 1.03; 95% CI, 1.02–1.04), whereas evidence for additive interaction was limited. Proteomic mediation implicated EGFR, TNFRSF10A, CBLN4, CD27, and IGDCC4 (≈8–11% each); inflammatory mediation implicated C-reactive protein (≈8%), platelets (≈4%), and neutrophils (≈4%).

Conclusion

Systemic redox balance values were linked to osteoporosis risk, with partial mediation through plasma-protein and inflammatory pathways and only modest modification by polygenic risk.

目的：氧化还原信号控制骨重塑，但在人群规模上，系统性氧化还原平衡是否与骨质疏松症、遗传易感性和蛋白质组学/炎症途径相关尚不清楚。方法：我们分析了基线时无骨质疏松症的英国生物银行参与者。血清氧化还原平衡评分（SRBS）联合白蛋白、总胆红素和γ-谷氨酰转移酶。根据预先设定的协变量调整的Cox比例风险模型。骨质疏松多基因风险评分（PRS）在乘法和加性量表上进行了效果修正测试。在蛋白质组学亚组和炎症组亚组中使用多重测试控制的反事实调解来评估调解。结果：中位随访时间为12.8 年（IQR, 11.7-13.7），共观察到12893例骨质疏松事件。SRBS与骨质疏松呈非线性负相关，呈j型模式：相对于Q1， Q2的多变量风险比（95% ci）为0.82 (0.78-0.86)，Q3为0.75 (0.71-0.78)，Q4为0.72 (0.68-0.75)；每标准差增加对应的HR为0.85（0.83-0.87）。累积发生率曲线较早偏离，并在四分位数上呈逐步梯度。这种关联在男性和缺乏运动的参与者中更为明显。SRBS与骨质疏松PRS在乘法尺度上相互作用（相互作用HR， 1.03; 95% CI, 1.02-1.04），而加性相互作用的证据有限。蛋白质组学介导涉及EGFR、TNFRSF10A、CBLN4、CD27和IGDCC4（各≈8-11%）；炎症介导涉及c反应蛋白（≈8%）、血小板（≈4%）和中性粒细胞（≈4%）。结论：系统性氧化还原平衡值与骨质疏松症风险相关，部分通过血浆蛋白和炎症途径介导，多基因风险仅适度改变。

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引用次数: 0

Cellular alterations in trabecular bone following monocrotaline-induced right heart failure in rats 大鼠右心衰后小梁骨的细胞改变

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-29 DOI: 10.1016/j.bone.2026.117807

Akinori Kaneguchi, Rena Takagi, Sakura Sunagawa, Yuichiro Azuma, Koki Ishinaka, Takuya Umehara, Kaoru Yamaoka, Junya Ozawa

Heart failure is associated with bone deterioration, consequently increasing the risk of fractures. Fractures occurring in patients with heart failure are associated with increased hospitalization and mortality rates, making the prevention of bone deterioration a critical clinical concern. The cellular alterations associated with heart failure-related bone deterioration remain largely unexplored. This study aimed to investigate histological changes in trabecular bone following heart failure, with a focus on characterizing cellular alterations associated with bone deterioration. Male Wistar rats were assigned to either a control or heart failure group. The heart failure group was administered monocrotaline intraperitoneally, while the control group received a vehicle injection. Twenty-eight days post-injection, histological analyses were conducted on the proximal humerus, proximal femur, distal femur, and proximal tibia. Compared to controls, rats in the heart failure group exhibited a significant reduction in trabecular bone volume at all examined sites. In parallel, they showed a significant increase in the number of osteoclasts, an increased empty lacuna ratio (indicative of osteocyte loss), and a greater proportion of caspase-3–positive osteocytes (a marker of apoptosis). These changes were consistently observed across all anatomical locations. These findings suggest that heart failure induces osteocyte apoptosis, which may drive osteoclastogenesis and lead to trabecular bone loss. The fact that similar changes were observed consistently across all anatomical sites suggests that systemic factors associated with heart failure, rather than localized influences, are likely the primary contributors to bone deterioration. Understanding these processes could inform novel therapeutic strategies to prevent bone loss following heart failure.

心力衰竭与骨质退化有关，从而增加骨折的风险。心力衰竭患者发生骨折与住院率和死亡率增加有关，因此预防骨骼恶化是一个重要的临床问题。与心力衰竭相关的骨退化相关的细胞改变在很大程度上仍未被探索。本研究旨在研究心力衰竭后小梁骨的组织学变化，重点研究与骨退化相关的细胞改变。雄性Wistar大鼠被分为对照组和心力衰竭组。心力衰竭组患者腹腔注射野鬼碱，对照组患者腹腔注射载药。注射后28天，对肱骨近端、股骨近端、股骨远端和胫骨近端进行组织学分析。与对照组相比，心力衰竭组的大鼠在所有检查部位的骨小梁体积都明显减少。同时，它们显示破骨细胞数量显著增加，空腔率增加（表明骨细胞丢失），caspase-3阳性骨细胞比例增加（细胞凋亡的标志）。这些变化在所有解剖部位都一致地被观察到。这些发现提示心力衰竭可诱导骨细胞凋亡，从而驱动破骨细胞发生并导致骨小梁骨丢失。事实上，在所有解剖部位都观察到类似的变化，这表明与心力衰竭相关的全身因素，而不是局部影响，可能是导致骨骼退化的主要因素。了解这些过程可以为预防心力衰竭后骨质流失提供新的治疗策略。

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引用次数: 0

o-Vanillin enhances bone health and fracture healing by inhibiting cellular senescence in aging mice 香兰素通过抑制衰老小鼠的细胞衰老来促进骨骼健康和骨折愈合

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2025-12-30 DOI: 10.1016/j.bone.2025.117773

Xiao Ouyang , Shuo Geng , Muhammad Abdullah , Yan Geng , Ke Heng , Liangwei Sha , Yinuo Geng , Peiru Nie , Fanshuo Liu , Juan Zhai , Xingchen Song , Huaiyuan Zhai , Junli Huang , Guoqiang Wang , Rui Geng , Kui Xue , Qilong Wang , Wanying Huang , Huanyu Zhang , Ying Geng , Qinghe Geng

Aging is associated with skeletal fragility driven by impaired bone remodeling, increased oxidative stress, and the accumulation of senescent cells. To determine whether ortho-vanillin (o-Vanillin) can alleviate age-related deficits in bone, we examined femoral bone microarchitecture, biomechanical properties, bone turnover, bone marrow adiposity, oxidative stress, DNA damage, osteocyte senescence, and femoral fracture healing in C57BL/6 J mice. DEXA was additionally used to assess bone mineral density and content at the femur, tibia, spine, and whole body. Aged mice displayed substantial deterioration in femoral trabecular and cortical structure, reduced mechanical strength, diminished osteogenic activity, enhanced osteoclastogenesis, and increased marrow adiposity. Aging also elevated oxidative stress, lipid peroxidation, and DNA damage, and induced significant osteocyte senescence with upregulation of SASP factors. o-Vanillin administration attenuated these changes, improving femoral bone microarchitecture and strength, restoring osteoblast function, suppressing osteoclast activity and adipogenesis, reducing oxidative stress and γH2AX accumulation, and decreasing osteocyte senescence and SASP expression. In a mid-diaphyseal femoral fracture model, aged mice exhibited impaired callus formation and delayed healing, whereas o-Vanillin partially improved early cartilage formation, osteoblast activity, and mechanical strength of the healing callus. These findings demonstrate that o-Vanillin mitigates multiple age-related impairments in the femur and partially restores fracture healing capacity, supporting its potential as a senescence-targeting approach to improve skeletal health during aging.

由于骨骼重塑受损、氧化应激增加和衰老细胞的积累，衰老与骨骼脆弱有关。为了确定邻香兰素（o-Vanillin）是否可以缓解与年龄相关的骨缺损，我们检测了C57BL/6 J小鼠股骨骨微结构、生物力学特性、骨转换、骨髓脂肪、氧化应激、DNA损伤、骨细胞衰老和股骨骨折愈合。DEXA还用于评估股骨、胫骨、脊柱和全身的骨矿物质密度和含量。老年小鼠表现出股骨小梁和皮质结构的严重退化，机械强度降低，成骨活性减弱，破骨细胞生成增强，骨髓脂肪增加。衰老还会增加氧化应激、脂质过氧化和DNA损伤，并通过上调SASP因子诱导骨细胞明显衰老。o-香兰素可减轻这些变化，改善股骨骨微结构和强度，恢复成骨细胞功能，抑制破骨细胞活性和脂肪生成，减少氧化应激和γ - h2ax积累，减少骨细胞衰老和SASP表达。在股骨中骨干骨折模型中，老年小鼠表现出骨痂形成受损和愈合延迟，而o-香兰素部分改善了早期软骨形成、成骨细胞活性和愈合的骨痂的机械强度。这些发现表明，o-香兰素可以减轻股骨中多种与年龄相关的损伤，并部分恢复骨折愈合能力，支持其作为衰老靶向方法改善衰老过程中骨骼健康的潜力。

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引用次数: 0

Hyperbaric oxygen therapy for osteoporosis: A systematic review of preclinical evidence and mechanisms 高压氧治疗骨质疏松症：临床前证据和机制的系统综述

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-02 DOI: 10.1016/j.bone.2025.117772

Hao Wang , Xiao Ma , Yang Sun , Zhihao Guo , Jincheng Wang , Mingli Sun

Hyperbaric oxygen therapy (HBOT) has been proposed as a direct anti-osteoporotic intervention rather than solely an adjunctive therapy. We systematically synthesized preclinical in vivo evidence and underlying mechanisms following PRISMA, with prospective registration (PROSPERO CRD42024525038), by searching PubMed, Embase, Cochrane Library, and Web of Science to November 2025. Of 3281 records, six studies (2016–2025) met inclusion across ovariectomy, hindlimb unloading, spinal cord transection, and D-galactose–induced aging models in Wistar and Sprague-Dawley rats. HBOT protocols most used 2.0–2.2 atm absolute with 85–100 % oxygen for 40–60 min per session. Across studies, HBOT improved bone mineral density and trabecular microarchitecture (e.g., BV/TV, Tb.Th, Tb.N), enhanced biomechanical strength, increased formation markers (e.g., procollagen type I N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin), and reduced resorption markers (e.g., C-terminal telopeptide of type I collagen, tartrate-resistant acid phosphatase-5b). Mechanistic signals converged on remodeling and vascular–metabolic pathways: modulation of the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis; restoration of Wnt/β-catenin signaling with reduced sclerostin; attenuation of oxidative and inflammatory stress (e.g., tumor necrosis factor-α); pro-angiogenic support (vascular endothelial growth factor, basic fibroblast growth factor); and neuropeptide-related effects (calcitonin gene-related peptide). Risk-of-bias profiles were mixed and heterogeneity precluded meta-analysis. Collectively, preclinical data indicate that HBOT mitigates osteoporotic bone loss primarily through coordinated, mechanisms of action that rebalance bone remodeling and improve the osteovascular milieu, while underscoring the need for standardized dosing parameters and rigorously designed human studies powered for clinically meaningful endpoints.

高压氧治疗（HBOT）已被认为是一种直接的抗骨质疏松干预措施，而不仅仅是一种辅助治疗。我们通过检索PubMed、Embase、Cochrane Library和Web of Science到2025年11月，系统地综合了PRISMA的临床前体内证据和潜在机制，并进行了前瞻性注册（PROSPERO CRD42024525038）。在3281项记录中，有6项研究（2016-2025）在Wistar和Sprague-Dawley大鼠的卵巢切除术、后肢切除、脊髓横断和d -半乳糖诱导衰老模型中被纳入。HBOT协议大多数使用2.0-2.2 atm绝对温度，85 - 100%氧气，每次会话40-60分钟。在研究中，HBOT改善了骨矿物质密度和小梁微结构(如BV/TV， Tb。Th,结核病。N)，增强生物力学强度，增加形成标志物（例如，I型前胶原N端前肽，骨特异性碱性磷酸酶，骨钙素），减少吸收标志物（例如，I型胶原c端端肽，抗酒石酸酸性磷酸酶5b）。骨保护素(OPG)/核因子-κB配体受体激活因子（RANKL）轴的调控通过减少硬化蛋白来恢复Wnt/β-catenin信号；氧化应激和炎症应激的减弱（如肿瘤坏死因子-α）；促血管生成支持（血管内皮生长因子，碱性成纤维细胞生长因子）；以及神经肽相关作用（降钙素基因相关肽）。风险偏倚概况是混合的，异质性排除了荟萃分析。总的来说，临床前数据表明，HBOT减轻骨质疏松性骨质流失主要是通过协调的作用机制，重新平衡骨重塑和改善骨血管环境，同时强调需要标准化的剂量参数和严格设计的人体研究，为临床有意义的终点提供支持。

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引用次数: 0

Sex chromosome and gonadal contributions to body composition and skeletal mass and strength in aged four core genotypes (FCG) mice 老龄四种核心基因型（FCG）小鼠的性染色体和性腺对身体组成、骨骼质量和力量的影响。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-04-01 Epub Date: 2026-01-09 DOI: 10.1016/j.bone.2026.117785

Paola Ortiz Gonzalez , Alix Teal , Lakshmi Chellaganapathy , Gabriel Ramirez , Roquelina Pianeta , Dyann M. Segvich , Ziyue Liu , Joseph M. Wallace , Lilian I. Plotkin

Sex differences in musculoskeletal aging are often attributed to gonadal hormones, but the independent role of sex chromosomes remains unclear. Using the Four Core Genotype mouse model, which dissociates sex chromosomes (XX vs. XY) from gonadal sex (ovaries vs. testes), our goal was to examine sex chromosomes and gonads independent and interactive effects on bone, muscle and organ phenotypes from 8 to 20 months of age in XXO, XYO, XXT, and XYT mice. XYO mice showed high mortality (38.7%-survival by 20 months) when compared with other genotypes (67–86.7%). Between 8 and 20 months, XYO mice showed increases in lean mass and femoral BMD and improved bone structural parameters, yet lower cortical tissue mineral density. XXO mice displayed pronounced late-life gains in body weight, lean and fat mass not observed in other genotypes, although lean mass differed only versus XXT mice at 20 months. Total and spine BMD declined in XXO mice, accompanied with lower structural parameters and higher tissue mineral density than XYO mice. XXT mice displayed bone loss at all skeletal sites, whereas XYT mice showed a selective decline in spine BMD. Overall, chromosome sex adversely affected bone and muscle mass in XX versus XY mice, while gonadal sex influenced bone structure and absolute muscle mass, with mice bearing ovaries generally exhibiting lower muscle mass. Organ weight effects were modest and limited to spleen (XYO > XXO/XYT) and brain (XYT > XXT). Collectively, these findings reveal a previously unrecognized, tissue-specific contribution of sex chromosomes to musculoskeletal aging, independent of gonadal sex.

肌肉骨骼老化中的性别差异通常归因于性腺激素，但性染色体的独立作用尚不清楚。使用四核心基因型小鼠模型，将性染色体（XX vs. XY）与性腺性别（卵巢vs.睾丸）分离，我们的目标是检查性染色体和性腺在XXO， XYO， XXT和XYT小鼠8至20 月龄期间对骨骼，肌肉和器官表型的独立和相互作用。与其他基因型（67-86.7%）相比，XYO小鼠的死亡率高（38.7%-存活20 个月）。在8至20 个月期间，XYO小鼠瘦体重和股骨骨密度增加，骨结构参数改善，但皮质组织矿物质密度降低。在其他基因型中没有观察到，XXO小鼠在晚年体重、瘦体重和脂肪量方面表现出明显的增加，尽管瘦体重仅在20 个月时与XXT小鼠不同。与XYO小鼠相比，XXO小鼠总骨密度和脊柱骨密度下降，结构参数降低，组织矿物质密度升高。XXT小鼠表现出所有骨骼部位的骨质流失，而XYT小鼠表现出脊柱骨密度的选择性下降。总体而言，染色体性别对XX小鼠和XY小鼠的骨骼和肌肉质量产生不利影响，而性腺性别影响骨骼结构和绝对肌肉质量，有卵巢的小鼠通常表现出较低的肌肉质量。器官重量的影响是适度的，仅限于脾脏（XYT > XXO/XYT）和大脑（XYT > XXT）。总的来说，这些发现揭示了以前未被认识到的，性染色体对肌肉骨骼衰老的组织特异性贡献，独立于性腺性别。

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