IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-29 DOI: 10.1016/j.bone.2025.117738

Xiaoyue Sun , Binqian Liu , Zetong Li , Songqin Zhou , Zijun Wang , Jingjing Yu , Qing Nie , Lingxin Zhu

Aseptic craniofacial osteolysis around the implant-bone interface, induced by wear particles, leads to the loosening and failure of dental implants, temporomandibular joint prostheses and internal fixation during maxillofacial reconstruction. Osteoclasts, as terminally differentiated multinucleated giant cells and the exclusive bone resorptive cells, play an important role in this pathological process. The PINK1/Parkin pathway is involved in mitochondrial quality control; however, its effects on osteoclast-mediated physiological bone homeostasis and the therapeutic potential on craniofacial osteolysis remains unexplored. We generated the mutant mice in which Parkin was conditionally deleted in myeloid lineage cells (LysM-Cre/Park2^flox/flox; Park2^ΔM/ΔM). Unexpectedly, the Park2^ΔM/ΔM mice displayed no overall skeletal phenotype. In tandem, upon osteoclastogenic induction, Park2^ΔM/ΔM macrophages undergone RANKL-induced osteoclastogenesis normally with compensated increased PINK1 expression. Notably, Mdivi-1 remarkably simultaneously inhibited the PINK1 and Parkin expression, leading to significant attenuated osteoclastogenesis in a concentration-dependent manner. The aseptic titanium particle-induced calvaria erosion model was constructed to simulate craniofacial osteolysis. Importantly, Mdivi-1 effectively alleviated the bone resorption and trabecular structure destruction induced by titanium particles, and blocked the osteoclast accumulation in the lesions. Taken together, Mdivi-1 alleviated titanium particle-induced aseptic craniofacial osteolysis via inhibition of PINK1/Parkin-dependent mitophagy. In summary, while myeloid lineage conditionally deletion of Park2 does not interfere with osteoclast differentiation and physiological bone homeostasis in mice probably due to the compensation by PINK1 expression, Mdivi-1 as the inhibitor of PINK1/Parkin-dependent mitophagy may provide a novel therapeutic strategy towards aseptic craniofacial osteolysis.

在颌面部重建过程中，由于磨损颗粒导致种植体-骨界面周围发生无菌性颅面骨溶解，导致种植体、颞下颌关节假体和内固定松动失效。破骨细胞作为终末分化的多核巨细胞和唯一的骨吸收细胞，在这一病理过程中发挥了重要作用。PINK1/Parkin通路参与线粒体质量控制；然而，其对破骨细胞介导的生理性骨稳态的影响以及对颅面骨溶解的治疗潜力仍未被探索。我们在髓系细胞中产生了Parkin被有条件地删除的突变小鼠（LysM-Cre/Park2flox/flox; Park2ΔM/ΔM）。出乎意料的是，Park2ΔM/ΔM小鼠没有表现出整体骨骼表型。同时，在诱导破骨后，Park2ΔM/ΔM巨噬细胞正常经历rankl诱导的破骨发生，同时补偿性地增加PINK1表达。值得注意的是，Mdivi-1显著同时抑制了PINK1和Parkin的表达，导致破骨细胞的发生以浓度依赖性的方式显著减弱。建立无菌钛颗粒致颅骨侵蚀模型，模拟颅面骨溶解。重要的是，Mdivi-1能有效缓解钛颗粒诱导的骨吸收和骨小梁结构破坏，阻断破骨细胞在病变部位的堆积。综上所述，Mdivi-1通过抑制PINK1/帕金森依赖性线粒体自噬来减轻钛颗粒诱导的无菌性颅面骨溶解。综上所述，骨髓系有条件地缺失Park2不会干扰小鼠破骨细胞分化和生理骨稳态，这可能是由于PINK1表达的补偿，而Mdivi-1作为PINK1/帕金森依赖性线粒体自噬的抑制剂可能为无菌颅面骨溶解提供一种新的治疗策略。

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引用次数: 0

Atypical periprosthetic femoral fractures around cemented stems: Radiographic features and clinical implications from a multicenter study 骨水泥柄周围非典型股骨假体周围骨折：一项多中心研究的影像学特征和临床意义。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-28 DOI: 10.1016/j.bone.2025.117741

Ken Tashiro , Tomonori Baba , Hiroshi Fujita , Hiroaki Iwase , Hirotsugu Ohashi , Kenichi Oe , Makoto Otsuka , Shintaro Iwai , Suguru Nakamura , Takeru Morimoto , Takeshi Sawaguchi , Yosuke Nagai , Yosuke Otsuki , Youngwoo Kim , Muneaki Ishijima

Atypical periprosthetic femoral fracture (APFF) is a rare but increasingly recognized complication of hip arthroplasty. Although cemented stems are generally considered protective against fractures, APFFs have also been reported around these implants. However, their clinical and radiographic characteristics remain poorly understood. This multicenter retrospective study aimed to clarify the features of APFFs occurring around cemented stems. Twenty hips from 19 patients were identified, based on the revised criteria of the American Society for Bone and Mineral Research Task Force, without excluding periprosthetic fractures. Fracture location was classified by distance from the stem tip: beyond 25 mm proximally as subtrochanteric type, within 25 mm as stem tip-type, and beyond 25 mm distally as femoral shaft type. Stem tip-type fractures were most common (15 hips, 75 %), followed by femoral shaft type (four hips, 20 %) and subtrochanteric type (one hip, 5 %). All varus aligned stems (four hips) and 83 % of neutrally aligned stems (10 of 12 hips) were stem tip-type fractures. Beaking or flaring of the lateral cortex was present in 76 % (13 of 17 hips) with pre-fracture radiographs. Prodromal pain was reported in 40 % (eight hips) and bisphosphonate use was identified in 94 % (16 of 17 hips) with available medication data. Surgical treatment was performed in 85 % (17 hips), including internal fixation (10 hips) and revision arthroplasty (seven hips); 15 % (three hips) were managed conservatively. Cemented APFFs frequently occur around the stem tip and are often preceded by radiographic changes and symptoms. Early recognition may support timely diagnosis and intervention.

非典型股骨假体周围骨折（APFF）是一种罕见但越来越被认识到的髋关节置换术并发症。虽然骨水泥通常被认为可以防止骨折，但在这些植入物周围也有APFFs的报道。然而，他们的临床和放射学特征仍然知之甚少。本多中心回顾性研究旨在阐明骨水泥茎周围发生apff的特征。根据美国骨与矿物研究工作组的修订标准，不排除假体周围骨折，确定了19例患者的20个髋关节。骨折位置根据距茎尖的距离进行分类：近端超过25 mm为粗隆下型，25 mm为茎尖型，远端超过25 mm为股骨干型。茎尖型骨折最常见（15髋，75 %），其次是股骨干型（4髋，20 %）和转子下型（1髋，5 %）。所有内翻对准的茎（4髋）和83% %的中性对准的茎（10髋）为茎尖型骨折。骨折前x线片显示76%（ %）（17髋中的13髋）侧皮质呈喙状或扁平状。40% %（8髋）的患者报告了前驱疼痛，94% %（17髋中的16髋）的患者使用了双膦酸盐。手术治疗占85% %（17髋），包括内固定（10髋）和翻修关节置换术（7髋）；15 %（3髋）保守处理。骨水泥APFFs经常发生在茎尖周围，通常在放射学改变和症状之前发生。早期识别有助于及时诊断和干预。

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引用次数: 0

Effects of exercise on the cortical bone of the proximal femur in women: a systematic review and meta-analysis 运动对女性股骨近端皮质骨的影响：系统回顾和荟萃分析

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-27 DOI: 10.1016/j.bone.2025.117740

Norifumi Fujii , Takeshi Imura , Tsubasa Mitsutake , Kenta Hirohama , Nobukazu Okimoto , Manabu Tsukamoto , Ryo Tanaka

Objective

The incidence of hip fractures is higher in women. Thus, preventive interventions (e.g., exercise) are important. According to research, the strength of the proximal femur, which affects hip fractures, is more important in the cortical bone than in the cancellous bone. This study aimed to evaluate the presence and quality of evidence of exercise on the cortical bone of the proximal femur in women.

Methods

A literature search was performed using the following databases: PubMed, Physiotherapy Evidence Database, Cochrane Central Register of Controlled Trials, and Scopus. Six articles that met the inclusion and exclusion criteria were selected for systematic review and meta-analysis.

Results

Only one study included premenopausal women, and the meta-analysis was performed only on studies in postmenopausal women. Exercise significantly improved the femoral neck cortical thickness in postmenopausal women (I² = 82 %, p < 0.01; random-effects model standardized mean difference [SMD] = 0.61 [95 % confidence interval {CI}: 0.07–1.15]). However, it did not significantly improve the femoral neck cross-sectional area (I² = 95 %, p < 0.01; random-effects model SMD = 0.72 [95 % CI: −0.43–1.87]).

Conclusion

The meta-analysis revealed that high-intensity resistance training combined with high-impact training for 8 months or more improved the femoral neck cortical thickness in postmenopausal women.

目的女性髋部骨折的发生率较高。因此，预防性干预（如锻炼）是重要的。根据研究，影响髋部骨折的股骨近端强度在皮质骨中比在松质骨中更为重要。本研究旨在评估女性股骨近端皮质骨运动证据的存在和质量。方法采用PubMed、物理治疗证据数据库、Cochrane中央对照试验注册库和Scopus进行文献检索。选择符合纳入和排除标准的6篇文章进行系统评价和荟萃分析。结果只有一项研究纳入了绝经前妇女，并且荟萃分析仅对绝经后妇女进行了研究。运动显著改善绝经后妇女股骨颈皮质厚度（I2 = 82%, p < 0.01；随机效应模型标准化平均差[SMD] = 0.61[95%可信区间{CI}: 0.07-1.15]）。然而，它并没有显著改善股骨颈横截面积（I2 = 95%, p < 0.01；随机效应模型SMD = 0.72 [95% CI:−0.43-1.87]）。结论荟萃分析显示，高强度阻力训练结合8个月或更长时间的高冲击训练可改善绝经后妇女股骨颈皮质厚度。

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引用次数: 0

Association of metabolic score for visceral fat with fragility fracture risk: The combined and mediating roles of arterial stiffness 内脏脂肪代谢评分与脆性骨折风险的关联：动脉硬度的联合和中介作用

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-25 DOI: 10.1016/j.bone.2025.117739

Lu Guo , Shaoxuan Wei , Qian Liu , Wenqi Xu , Guodong Wang , Wenchao Yao , Nan Zhang , Man Gui , Xiaoli Hou , Shuohua Chen , Bin Wang , Xinhao Fan , Liu Zhang , Jingyuan Gao , Lei Xing , Shouling Wu , Faming Tian

Objectives

To investigate the combined effect of the metabolic score for visceral fat (METS-VF) and arterial stiffness on fragility fractures, and to further examine whether arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV), mediates the association between METS-VF and fragility fractures.

Methods

The study included 42,256 participants (mean age, 49.42 ± 13.05 years, 73.36 % male) from the Kailuan cohort, with complete baPWV and METS-VF data, followed until 2022. METS-VF ≥ 6.86 was defined as the high group and < 6.86 as the low group, while baPWV ≥1800 cm/s was defined as the arterial stiffness group and < 1800 cm/s as the normal group. Participants were further classified into four combined groups, with the low METS-VF and normal baPWV group serving as the reference group. Multiplicative and additive interaction analyses were applied, and Cox regression models estimated hazard ratios (HRs) with 95 % confidence intervals (CIs). Mediation analysis assessed the role of baPWV.

Results

During a mean follow-up of 7.47 years, 367 participants experienced fragility fractures. A significant additive interaction between METS-VF and baPWV was observed. (Additive: relative excess risk due to the interaction [RERI] = 0.51, 95 % CI 0.04–0.98; Multiplicative, HR = 0.73, 95 % CI 0.69–1.71). After adjusting for covariates, HRs for incident fractures compared to the reference group were 1.39 (95 % CI, 1.02–1.90) for Group 2, 2.21 (95 % CI, 1.60–3.04) for Group 3, and 3.32 (95 % CI, 2.40–4.57) for Group 4. Additionally, baPWV mediated 13.08 % of the association between METS-VF and fracture risk.

Conclusions

Higher METS-VF and arterial stiffness levels were associated with an increased risk of fragility fractures, and arterial stiffness, assessed by baPWV, partly mediated this association.

目的探讨内脏脂肪代谢评分（METS-VF）和动脉僵硬度对脆性骨折的联合作用，并进一步探讨肱-踝脉波速度（baPWV）测量的动脉僵硬度是否介导METS-VF与脆性骨折的关系。方法该研究纳入开滦队列42,256名参与者（平均年龄49.42±13.05岁，男性73.36%），具有完整的baPWV和METS-VF数据，随访至2022年。met - vf≥6.86定义为高组，<； 6.86定义为低组，baPWV≥1800 cm/s定义为动脉僵硬组，<； 1800 cm/s定义为正常组。参与者进一步分为四组，以低met - vf组和正常baPWV组作为参照组。应用乘法和加性相互作用分析，并用Cox回归模型估计95%置信区间（ci）的风险比（hr）。中介分析评估baPWV的作用。结果在平均7.47年的随访期间，367名参与者经历了脆性骨折。发现met - vf与baPWV之间存在显著的加性相互作用。（加性：相互作用导致的相对过量风险[rei] = 0.51, 95% CI 0.04-0.98；乘法，HR = 0.73, 95% CI 0.69-1.71）。调整协变量后，与参考组相比，第2组发生骨折的hr为1.39 (95% CI, 1.02-1.90)，第3组为2.21 (95% CI, 1.60-3.04)，第4组为3.32 （95% CI, 2.40-4.57）。此外，baPWV介导了met - vf与骨折风险之间13.08%的关联。结论较高的METS-VF和动脉硬度水平与脆性骨折的风险增加有关，而baPWV评估的动脉硬度在一定程度上介导了这种关联。

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引用次数: 0

Inosine ameliorated bone destruction and inflammation in rheumatoid arthritis via inhibiting osteclastogenesis and synovial fibroblasts activation 肌苷通过抑制成骨细胞生成和滑膜成纤维细胞活化改善类风湿关节炎的骨破坏和炎症

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-25 DOI: 10.1016/j.bone.2025.117734

Xia-nan Wu , Ke Dong , Li Liu , Fang Lin , Xi Wang , Zhao-wei Gao , Xiao-ming Zhu

This study aim to investigate the effects of inosine on rheumatoid arthritis (RA) disease and explore the potential mechanism. Collagen-Induced Arthritis (CIA) rats were used to investigate the effects of inosine on bone destruction and inflammation. Micro-CT scan was used to detect the bone injury. H&E and Safranin O staining were used to evaluate the synovial inflammation and cartilage damage. RANKL-induced osteoclasts differentiation assay was used to investigate the effects of inosine on osteclastogenesis. CCK-8 and transwell experiments were performed to investigate the RA synovioblast (RASFs) proliferation and invasion. We observed that inosine intraperitoneal injection led to significant reduction in arthritis score of CIA rats. Micro-CT scan showed the decreased degree of bone destruction and increased bone mass in inosine treated CIA-rats. H&E and Safranin O staining showed that inosine significantly inhibited the inflammation and cartilage erosion in CIA-rats. The IL-6 and IL-8 levels in synovial tissues were lower in inosine treated CIA-rats than that in vehicle group. Furthermore, TRAP staining showed that the osteoclasts numbers were decreased in inosine treated CIA-rats. In vitro, inosine led to the decrease of osteoclasts numbers, F-actin ring and the expression of osteoclasts-specific markers. Furthermore, we found that inosine inhibited osteoclastogenesis via down-regulating OPN. OPN supplementation could counteract the inhibiting effect of inosine on osteoclastogenesis. Additionally, we observed that inosine significantly inhibited proliferation, invasion and inflammatory cytokines secretion of RASFs. In conclusion, inosine alleviated bone destruction and inflammation in CIA-rats by inhibiting osteoclastogenesis and RASFs activation. Hence, inosine supplementation may be a potential strategy for RA therapy.

本研究旨在探讨肌苷在类风湿关节炎（RA）中的作用及其可能的机制。以胶原性关节炎（CIA）大鼠为研究对象，探讨肌苷对骨破坏和炎症的影响。显微ct扫描检测骨损伤。采用H&；E和红花红素O染色评估滑膜炎症和软骨损伤。采用rankl诱导破骨细胞分化实验研究肌苷对成骨细胞发生的影响。采用CCK-8和transwell实验观察RA滑膜母细胞（rasf）的增殖和侵袭。我们观察到肌苷腹腔注射可显著降低CIA大鼠关节炎评分。Micro-CT扫描显示肌苷处理的cia大鼠骨破坏程度降低，骨量增加。H&；E和红花素O染色显示肌苷能显著抑制cia大鼠的炎症和软骨侵蚀。肌苷处理的cia大鼠滑膜组织中IL-6、IL-8水平明显低于对照组。此外，TRAP染色显示肌苷处理的cia大鼠破骨细胞数量减少。在体外，肌苷导致破骨细胞数量减少，f -肌动蛋白环减少，破骨细胞特异性标志物表达减少。此外，我们发现肌苷通过下调OPN抑制破骨细胞的形成。补充OPN可以抵消肌苷对破骨细胞形成的抑制作用。此外，我们观察到肌苷显著抑制rasf的增殖、侵袭和炎症细胞因子的分泌。综上所述，肌苷通过抑制破骨细胞生成和rasf激活来减轻cia大鼠的骨破坏和炎症。因此，补充肌苷可能是治疗类风湿性关节炎的一种潜在策略。

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引用次数: 0

ED-71 alleviates OVX-induced osteoporosis by inhibiting macrophage senescence through SIRT1/PGC-1α pathway: A potential therapeutic approach ED-71通过SIRT1/PGC-1α途径抑制巨噬细胞衰老，减轻ovx诱导的骨质疏松症：一种潜在的治疗方法

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-23 DOI: 10.1016/j.bone.2025.117737

Yaqiu Fu , Lingxiao Meng , Minglei Zhang , Lingshuang Li , Hongrui Liu , Wanli Ma , Minqi Li

Postmenopausal osteoporosis (PMOP) is a prevalent condition among postmenopausal women, closely linked to estrogen deficiency, aging, and oxidative stress. Cellular senescence, through mechanisms such as the senescence-associated secretory phenotype (SASP) and bone marrow stromal cells (BMSCs) differentiation imbalance, disrupts bone homeostasis in PMOP. Macrophages play a critical role in maintaining bone homeostasis. However, the extent of macrophage senescence in PMOP and the mechanisms by which it disrupts bone homeostasis have not yet been elucidated. Eldecalcitol (ED-71), a novel drug, has shown potential in osteoporosis treatment, though its effects on macrophage are not fully elucidated. In this study, using hydrogen peroxide (H₂O₂), we induced senescence in macrophages and assessed senescence-associated markers by SA-β-gal staining, Western blotting, and RT-qPCR. We then employed an indirect co-culture system to investigate the paracrine impact of these senescent macrophages on the osteogenic differentiation of BMSCs. The PMOP model was established using ovariectomy (OVX) in mice, followed by histological evaluation. Both 17β-Estradiol (E2) and ED-71 effectively reduced cellular senescence-related indicators such as p16, p53 and β-galactosidase in macrophages, suggesting E2 can alleviate macrophage senescence, and ED-71 may serve as an alternative. Co-culture systems revealed that senescent macrophages impaired BMSCs osteogenic differentiation, an effect reversed by ED-71. SIRT1 inhibition with EX-527 disrupted ED-71's anti-senescence action. Additionally, ED-71 improved bone mass and aging in OVX mice. In conclusion, ED-71 alleviates macrophage senescence via the SIRT1/PGC-1α signaling axis, thereby enhancing BMSC osteogenic potential and mitigating bone loss in OVX-induced osteoporosis.

绝经后骨质疏松症（PMOP）是绝经后妇女的常见病，与雌激素缺乏、衰老和氧化应激密切相关。细胞衰老，通过衰老相关分泌表型（SASP）和骨髓基质细胞（BMSCs）分化失衡等机制，破坏了ppu的骨稳态。巨噬细胞在维持骨稳态中起关键作用。然而，巨噬细胞衰老的程度及其破坏骨稳态的机制尚未阐明。Eldecalcitol （ED-71）是一种新型药物，虽然其对巨噬细胞的作用尚未完全阐明，但已显示出治疗骨质疏松症的潜力。在这项研究中，我们使用过氧化氢（H₂O₂）诱导巨噬细胞衰老，并通过SA-β-gal染色，Western blotting和RT-qPCR评估衰老相关标志物。然后，我们采用间接共培养系统来研究这些衰老巨噬细胞对骨髓间充质干细胞成骨分化的旁分泌影响。采用小鼠卵巢切除术（OVX）建立PMOP模型，并进行组织学评价。17β-雌二醇（E2）和ED-71均能有效降低巨噬细胞中p16、p53、β-半乳糖苷酶等细胞衰老相关指标，提示E2可缓解巨噬细胞衰老，ED-71可能起到替代作用。共培养系统显示，衰老巨噬细胞损害了骨髓间充质干细胞的成骨分化，ED-71逆转了这一作用。EX-527抑制SIRT1破坏ED-71的抗衰老作用。此外，ED-71还能改善OVX小鼠的骨量和衰老。综上所述，ED-71通过SIRT1/PGC-1α信号轴缓解巨噬细胞衰老，从而增强骨髓间充质干细胞成骨潜能，减轻ovx所致骨质疏松症的骨质流失。

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引用次数: 0

Pain intensity in patients with genetic metabolic bone diseases: an observational study 遗传代谢性骨病患者的疼痛强度：一项观察性研究

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-22 DOI: 10.1016/j.bone.2025.117736

Mattia Morri , Morena Tremosini , Cristiana Forni , Elena Pedrini , Alice Moroni , Maria Gnoli , Alessia Di Cecco , Luca Sangiorgi

Objective

The aim of this study was to describe the intensity of the pain in patients with genetic metabolic bone disease and to identify possible risk factors.

Design

Retrospective cohort study.

Setting

The patients were recruited through the outpatient register of the Centre for Rare Skeletal Diseases between 2017 and 2022 from a dedicated orthopedic hospital in northern Italy.

Subjects

All patients with a diagnosis of genetic metabolic bone disease were enrolled. The diagnosis of the pathology was based on the clinical data and the outcome of any genetic tests.

Methods

Pain intensity (0-10) at the first exam was collected and two comparison groups were made: no/ mild pain and moderate/severe pain. Through medical and nursing clinical records, a set of clinical data was collected.

Results

The analysis was performed on 68 patients. The median age was 32.1 years, osteogenesis imperfecta was present in 72.1 % of cases and the median pain score was 2. Logistic regression showed that the independent risk factors of pain were age with a 5 % increase in risk for each year of age (p value = 0.010), a previous surgical intervention (OR = 10.16; CI95%: 2.07–49.89) and the presence of muscle anomalies (OR = 5.91; CI95% 1.09–31.88). The median pain score in the osteogenesis imperfecta group was 1, whereas in the other group it was 2, with a non-significant difference.

Conclusions

In genetic metabolic bone diseases, pain is a relevant symptom. Increased age, surgical intervention and the presence of muscular problems are risk factors in determining higher levels of pain and require targeted treatments.

目的：本研究的目的是描述遗传代谢性骨病患者的疼痛强度，并确定可能的危险因素。设计：回顾性队列研究。环境：患者是通过2017年至2022年意大利北部一家专门骨科医院的罕见骨骼疾病中心门诊登记处招募的。研究对象：所有诊断为遗传代谢性骨病的患者均入组。病理诊断是基于临床资料和任何基因测试的结果。方法：收集第一次检查时疼痛强度（0-10），分为无/轻度疼痛组和中度/重度疼痛组。通过医疗护理临床记录，收集一组临床资料。结果：对68例患者进行了分析。中位年龄为32.1 岁，72.1 %的病例存在成骨不全，中位疼痛评分为2。Logistic回归分析显示，疼痛的独立危险因素为年龄，年龄越大风险增加5 % （p值 = 0.010）、既往手术（OR = 10.16;CI95%: 2.07-49.89）和存在肌肉异常（OR = 5.91;CI95% 1.09-31.88）。成骨不全组疼痛评分中位数为1分，而成骨不全组疼痛评分中位数为2分，差异无统计学意义。结论：在遗传代谢性骨病中，疼痛是一种相关症状。年龄的增长，手术干预和肌肉问题的存在是决定更高程度疼痛的危险因素，需要有针对性的治疗。

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引用次数: 0

AI-supported opportunistic detection of vertebral fractures on routine CT scans: Diagnostic performance and clinical relevance 在常规CT扫描中人工智能支持的椎体骨折机会检测：诊断性能和临床相关性。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-21 DOI: 10.1016/j.bone.2025.117735

Martina Behanova , Anton Sokhan , Judith Haschka , Shahin Zandieh , Christoph Salzlechner , Richard Ljuhar , Jochen Zwerina , Roland Kocijan

Background

Vertebral fractures (VFs) are among the most common osteoporotic fractures, yet they are frequently underdiagnosed and left untreated. The use of an artificial intelligence (AI) tool may support improved detection rates. This study aimed to evaluate the diagnostic performance of the AI-based software (IB Lab FLAMINGO) in identifying VFs on thoracic and abdominal CT scans, using radiologist assessment as the reference standard.

Methods

This was a monocentric, retrospective cross-sectional study. 205 patients with CT scans performed for non-skeletal indications were randomly selected. Sensitivity, specificity, and accuracy were calculated at the vertebra and patient level. We examined the proportion of false positive AI-identified fractures that might represent overlooked fractures upon re-evaluation.

Results

Among 205 patients (59 % male; mean age 67.9 ± 9.5 years), VFs were initially identified in 11.2 % by the radiologist, most frequently at the thoracolumbar junction. Females showed more thoracic (T4–T7) fractures, while males more commonly had lumbar (L1–L4) fractures. The AI analyzed 190 patients (92.7 %), detecting fractures in 24.7 %. At the patient level, IB Lab FLAMINGO showed 81 % accuracy, 74 % sensitivity and 82 % specificity. Vertebra-level performance (N = 3040) demonstrated high accuracy (97 %) and specificity (97 %). As a result of re-evaluation, fractures were confirmed in 29 of 30 AI-positively flagged patients, increasing sensitivity to 88.5 %, specificity to 99.3 %, and the overall presence of VFs to 25 %.

Discussion

The performance metrics support potential use of AI IB Lab FLAMINGO as a screening aid and as a quality assurance tool, taking into account the proportion of missed diagnoses by the radiologist.

背景：椎体骨折（VFs）是最常见的骨质疏松性骨折之一，但它们经常被误诊和未得到治疗。使用人工智能（AI）工具可以提高检测率。本研究旨在评估基于ai的软件（IB Lab FLAMINGO）在识别胸部和腹部CT扫描上的VFs方面的诊断性能，以放射科医生的评估作为参考标准。方法：这是一项单中心、回顾性的横断面研究。随机选择205例进行非骨骼适应症CT扫描的患者。在椎体和患者水平上计算灵敏度、特异性和准确性。我们检查了人工智能识别的假阳性骨折的比例，这些骨折可能代表了重新评估时被忽视的骨折。结果：在205例患者中（59 %男性，平均年龄67.9 ± 9.5 岁），VFs最初被放射科医生发现的比例为11.2 %，最常见的是在胸腰椎交界处。女性多见于胸椎（T4-T7）骨折，而男性多见于腰椎（L1-L4）骨折。AI分析了190例患者（92.7 %），检测到24.7 %的骨折。在患者水平上，IB Lab FLAMINGO的准确率为81 %，灵敏度为74 %，特异性为82 %。椎骨水平的表现（N = 3040）显示出较高的准确性（97 %）和特异性（97 %）。作为重新评估的结果，30例ai阳性标记患者中有29例确诊骨折，敏感性增加到88.5 %，特异性增加到99.3 %，VFs的总体存在率增加到25 %。讨论：考虑到放射科医生漏诊的比例，性能指标支持AI IB Lab FLAMINGO作为筛查辅助和质量保证工具的潜在使用。

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引用次数: 0

Influence of pressure on mandibular angiosomes: What implications for decellularization? 压力对下颌血管小体的影响：对脱细胞有什么影响？

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-19 DOI: 10.1016/j.bone.2025.117733

Corentin Serra , Romain Monchaux , Benjamin Salmon , Lara Nokovitch , Natacha Kadlub , Jean Boisson

The vascularization of bone still holds several unknowns, crucial to future developments in reconstructive surgery: both for bone transplantation and decellularized allograft. This study introduces a novel method to analyze pressure-dependent vascular territories in the human mandible, with direct implications for the optimization of decellularization by perfusion protocols. Traditional anatomical approaches have struggled to delineate perfusion territories due to the complexity of multiple arterial inputs and the dynamic nature of blood flow. Our methodology integrates pressure-controlled perfusion with 3D imaging to map vascular distribution within the mandibular bone under varying perfusion pressures. We conducted controlled perfusions on human cadaveric mandibles, progressively increasing pressure while monitoring the expansion of perfused territories using contrast-enhanced cone beam computed tomography. A custom segmentation pipeline allowed for the reconstruction of pressure maps detailing the minimal pressure required to perfuse different regions of the mandible. Our results demonstrate a low-pressure anastomosis of the maxillary artery to the facial artery through the mental artery, suggesting the equivalence of intraosseous territories, followed by a radial perfusion pattern from the inferior alveolar artery, with increasing resistance at the cortical bone. Perfusion saturation was achieved at approximately 100–125 hPa, in accordance with physiological arterial pressures. Furthermore, cortical bone exhibited higher perfusion thresholds than cancellous bone, emphasizing differential vascular resistance across bone structures.

These findings suggest that pressure-driven perfusion analysis can provide crucial insights into bone vascularization. By optimizing pressure parameters, it may be possible to achieve more effective decellularization by perfusion in massive bone allografts, improving graft integration and long-term viability. This study also underscores the need for pressure-controlled anatomical studies, as perfusion territories vary significantly with applied pressure, challenging traditional static angiosoma models. Future research should explore the applicability of these findings in living tissues and refine decellularization techniques based on controlled perfusion dynamics.

骨血管化仍有几个未知数，这对骨移植和脱细胞异体移植重建手术的未来发展至关重要。本研究介绍了一种分析人类下颌骨压力依赖性血管区域的新方法，这对通过灌注方案优化脱细胞具有直接意义。由于多动脉输入的复杂性和血流的动态性，传统的解剖学方法难以描绘灌注区域。我们的方法将压力控制灌注与3D成像相结合，以绘制不同灌注压力下下颌骨内的血管分布。我们对人类尸体下颌骨进行控制灌注，逐步增加压力，同时使用对比增强锥束计算机断层扫描监测灌注区域的扩张。自定义分割管道允许重建压力图，详细说明灌注下颌骨不同区域所需的最小压力。我们的研究结果表明，上颌动脉通过颏动脉与面动脉的低压吻合，表明骨内区域的等效性，其次是来自下牙槽动脉的径向灌注模式，在皮质骨处阻力增加。灌注饱和达到约100-125 hPa，符合生理动脉压。此外，皮质骨比松质骨表现出更高的灌注阈值，强调了骨结构间血管阻力的差异。这些发现表明，压力驱动的灌注分析可以为骨血管化提供重要的见解。通过优化压力参数，可以在大量同种异体骨移植物中通过灌注实现更有效的脱细胞，提高移植物的整合和长期生存能力。该研究还强调了压力控制解剖学研究的必要性，因为灌注区域随着施加压力而显著变化，挑战了传统的静态血管瘤模型。未来的研究应探索这些发现在活体组织中的适用性，并完善基于受控灌注动力学的脱细胞技术。

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引用次数: 0

Enhanced fracture repair in p21−/− mice is mediated through increased callus mineralization p21-/-小鼠骨折修复的增强是通过增加骨痂矿化介导的。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-11-18 DOI: 10.1016/j.bone.2025.117732

Alexandra Olsen , Priyatha Premnath , Scott Brunet , Leila Larijani , Sarah L. Manske , Leah Ferrie , Neil A. Duncan , Derrick E. Rancourt , Ralph S. Marcucio , Roman Krawetz

Fracture healing is a complex, multi-phase process involving mesenchymal progenitor cell (MPC) recruitment, chondrogenesis, osteogenesis and bone remodelling. The cyclin-dependent kinase inhibitor p21 is known to regulate cell cycle progression and has been implicated in tissue regeneration. Here, we investigated the role of p21 in endochondral fracture repair using a transverse tibial fracture model in physiologically normal mice. Prx1CreERT2-GFP;R26RTdtomato mice on C57BL/6 and p21^−/− backgrounds enabled lineage tracing of MPCs. Longitudinal in vivo micro-CT, histological analysis, tissue cytometry and mechanical testing were used to assess callus formation, cellular composition, and mechanical integrity.

Our results demonstrate that p21^−/− mice exhibit enhanced bone regeneration, with significantly higher bone mineral density (BMD) and bone volume fraction (BV/TV) in the fracture callus at 2 and 4 weeks post-fracture (wpf). Histology revealed increased Prx1⁺ cell recruitment, along with greater expression of chondrogenic (Sox9) and osteogenic (BSP) markers in p21^−/− mice at 2wpf. Biomechanical testing showed that despite similar strength, p21^−/− calluses had reduced toughness, suggesting altered matrix remodelling.

Collectively, our findings highlight p21 as a negative regulator of bone regeneration, likely through modulation of MPC recruitment and differentiation. Together, these data suggest therapeutic targeting of p21 may enhance fracture healing and counteract osteoporosis in terms of bone remodelling and repair.

骨折愈合是一个复杂的多阶段过程，涉及间充质祖细胞（MPC）募集、软骨形成、成骨和骨重塑。已知周期蛋白依赖性激酶抑制剂p21调节细胞周期进程，并与组织再生有关。本研究采用生理正常小鼠胫骨横骨折模型研究p21在软骨内骨折修复中的作用。Prx1CreERT2-GFP;C57BL/6和p21-/-背景的R26RTdtomato小鼠实现了MPCs的谱系追踪。纵向体内显微ct、组织学分析、组织细胞术和力学测试用于评估愈伤组织的形成、细胞组成和力学完整性。我们的研究结果表明，p21-/-小鼠在骨折后2周和4周（wpf）表现出增强的骨再生，骨折痂的骨矿物质密度（BMD）和骨体积分数（BV/TV）显著提高。组织学显示p21-/-小鼠在2wpf时Prx1+细胞募集增加，同时软骨生成（Sox9）和成骨（BSP）标记物表达增加。生物力学测试显示，尽管强度相似，但p21-/-老茧的韧性降低，表明基质重塑发生了改变。总的来说，我们的研究结果强调p21是骨再生的负调节因子，可能通过调节MPC的募集和分化。综上所述，这些数据表明p21的靶向治疗可以促进骨折愈合，并在骨重塑和修复方面对抗骨质疏松症。

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引用次数: 0

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