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Dual inhibition of sclerostin and Notum induces synergistic osteoanabolic action in mice 双抑制硬化蛋白和Notum诱导小鼠骨合成代谢的协同作用

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-02-03 DOI: 10.1016/j.bone.2026.117816

Roy B. Choi , April M. Hoggatt , Daniel J. Horan , Connor J. Cunningham , Robert Brommage , David R. Powell , Alexander G. Robling

Expanding the number of clinically approved choices for osteoanabolic therapy represents the next hurdle on the osteoporosis treatment horizon. The WNT pathway is involved in stimulating new bone formation, and the most recent FDA-approved anabolic therapy—sclerostin neutralizing antibody—works by stimulating the WNT pathway in bone. The challenge with all current osteoanabolic therapies is the short treatment window in which they are efficacious. One strategy to dealing with this limited anabolic window is to further maximize bone formation during the window, using combination therapy. For example, simultaneous pharmacological or genetic inhibition of the WNT antagonists sclerostin and DKK1 potentiate the already strong effects of sclerostin inhibition alone, particularly in cancellous bone. Considerable interest has emerged regarding other candidates that might be co-inhibited along with sclerostin to potentiate its effects in bone, with specific action on cortical bone. In this communication, partnering sclerostin inhibition with the inhibition of another secreted WNT antagonist, NOTUM, is explored. NOTUM is a secreted WNT deacylase that inactivates WNT ligands and has preferential effects on cortical bone. To evaluate combination therapy involving sclerostin/NOTUM inhibition, double knockout mice for Sost and Notum (Sost^−/−;Notum^−/−) were generated and compared to single knockouts and WT controls. Further experiments were conducted using pharmacologic inhibitors, rather than genomic mutations, for sclerostin (sclerostin neutralizing antibody) and a small molecule inhibitor of NOTUM (LP-922056). Each experiment included evaluation by DXA-derived radiography, μCT, biomechanical testing and bone dynamic histomorphometry. Deletion of Notum alone had mild cortical effects but co-deletion of Sost and Notum improved cortical and some cancellous parameters significantly beyond Sost^−/− mice. Co-inhibition of the protein products with antibody/small molecule were less synergistic, with only a small cortical effect, particularly in younger mice. Taken together, the results suggest the potential to improve efficacy of sclerostin inhibition using NOTUM inhibition is promising, but development of additional NOTUM inhibiting tools and optimization of current tools might be necessary to strengthen the partnership.

扩大临床批准的骨合成代谢疗法的选择数量代表了骨质疏松症治疗领域的下一个障碍。WNT通路参与刺激新骨形成，最近fda批准的合成代谢疗法-硬化蛋白中和抗体-通过刺激骨中的WNT通路起作用。目前所有骨合成代谢疗法面临的挑战是它们有效的治疗窗口时间短。处理这个有限的合成代谢窗口的一个策略是在窗口期间进一步最大化骨形成，使用联合治疗。例如，WNT拮抗剂硬化蛋白（sclerostin）和DKK1的同时药理或遗传抑制增强了硬化蛋白单独抑制的强大作用，特别是在松质骨中。对于其他可能与硬化蛋白共同抑制以增强其在骨中的作用的候选物质，以及对皮质骨的特异性作用，人们产生了相当大的兴趣。在这篇文章中，我们探讨了与另一种分泌的WNT拮抗剂NOTUM合作抑制硬化蛋白的作用。NOTUM是一种分泌的WNT去乙酰化酶，可使WNT配体失活，并对皮质骨有优先作用。为了评估涉及硬化蛋白/NOTUM抑制的联合治疗，生成Sost和NOTUM双敲除小鼠（Sost−/−;NOTUM−/−），并与单敲除和WT对照进行比较。进一步的实验使用药理学抑制剂，而不是基因组突变，用于硬化蛋白（硬化蛋白中和抗体）和NOTUM的小分子抑制剂（LP-922056）。每个实验包括dxa衍生x线片、μCT、生物力学测试和骨动态组织形态测量。单独删除Notum对皮质有轻微的影响，但共同删除Sost和Notum对皮质和一些松质参数的改善明显超过Sost - / -小鼠。蛋白产物与抗体/小分子共抑制的协同作用较小，仅对皮质产生较小的影响，特别是在年轻小鼠中。综上所示，研究结果表明，利用NOTUM抑制剂提高硬化蛋白抑制效果的潜力是有希望的，但开发额外的NOTUM抑制剂工具和优化现有工具可能是加强合作的必要条件。

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引用次数: 0

Quantitative assessment of the alignment between human trabecular microstructural orientation and mechanical anisotropy: Implications for Wolff's Law 定量评估人类小梁微观结构取向和力学各向异性之间的对齐：对沃尔夫定律的影响

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-02-02 DOI: 10.1016/j.bone.2026.117817

Pengwei Xiao

Trabecular bone exhibits a highly organized microarchitecture that adapts to its mechanical loading environment, a concept fundamentally described by Wolff's law. However, direct quantitative evidence linking the trabecular microstructural orientation with mechanical anisotropy remains limited. In this study, we quantitatively assessed the alignment between trabecular microstructural orientation and the apparent stiffness tensor using a micro-CT-based finite element (μFE) framework. Fabric tensors and the orientations of individual trabecular plates and rods were derived using the Mean Intercept Length (MIL) method and Individual Trabecula segmentation (ITS) analysis, respectively. The apparent stiffness tensors were obtained through μFE models subjected to three uniaxial compression and three pure shear loading cases. The results demonstrated a strong alignment between the fabric tensor and the apparent stiffness tensor, with an overall alignment index (

\bar{λ}

) of 0.92 (IQR: 0.09). Trabecular plates exhibited a high degree of alignment with the apparent stiffness tensor (

\bar{λ}

: 0.88, IQR: 0.15), whereas trabecular rods demonstrated a substantially lower degree of alignment (

\bar{λ}

: 0.36, IQR: 0.19). Moreover, the alignment between the principal axis of trabecular plates and the apparent stiffness tensor increased with the degree of anisotropy (DA), while the alignment of trabecular rods decreased with increasing DA. These findings provide quantitative evidence supporting Wolff's law, confirming that trabecular bone architecture is structurally optimized to align with habitual mechanical stress pathways, and highlight the dominant role of trabecular plates in governing the mechanical competence of cancellous bone.

小梁骨表现出高度组织化的微结构，以适应其机械负载环境，这一概念基本上由沃尔夫定律描述。然而，将小梁微观结构取向与力学各向异性联系起来的直接定量证据仍然有限。在这项研究中，我们使用基于微ct的有限元（μFE）框架定量评估了小梁微观结构取向与表观刚度张量之间的对齐。利用平均截距长度（MIL）方法和个体小梁分割（ITS）分析分别得到了织物张量和单个小梁板和棒的方向。通过三种单轴压缩和三种纯剪切加载情况下的μ有限元模型获得了表观刚度张量。结果表明，织物张量与表观刚度张量之间具有较强的准直性，总体准直指数（λ¯）为0.92 （IQR: 0.09）。小梁板与表观刚度张量的对齐程度较高（λ¯：0.88,IQR: 0.15），而小梁棒的对齐程度较低（λ¯：0.36,IQR: 0.19）。随着各向异性（DA）的增加，小梁板主轴与视刚度张量之间的对齐度增加，而小梁棒的对齐度随DA的增加而降低。这些发现为Wolff定律提供了定量证据，证实了骨小梁结构在结构上经过优化以适应习惯性的机械应力途径，并强调了骨小梁板在控制松质骨的机械能力方面的主导作用。

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引用次数: 0

Multiexon COL1A2 deletion as a rare mechanism in osteogenesis imperfecta: Case report and literature review 多外显子COL1A2缺失是成骨不全的罕见机制：病例报告和文献复习。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-01-29 DOI: 10.1016/j.bone.2026.117810

Daniela Oliveira , Pedro M. Almeida , Sofia Franco , Raquel Pina , Rita Cerqueira , Silvia Modamio-Hoybjor , Karen E. Heath , Sérgio B. Sousa , Fabiana Ramos

Background

Osteogenesis imperfecta (OI) is mostly caused by pathogenic variants in COL1A1/COL1A2; while single nucleotide variants predominate, multiexon copy number variants (CNVs) remain under-recognised contributors with incompletely defined phenotypic impacts.

Methods

We investigated a fetus presenting severe skeletal dysplasia using NGS with CNV calling and MLPA, clinical and radiologic assessments, and transcript analysis of maternal fibroblasts. We also reviewed the literature and curated databases for reported multiexon COL1A2 deletions.

Results

The fetus exhibited lethal OI type II features, including progressive long bone shortening and bowing, multiple fractures, diffuse hypomineralisation, and a bell-shaped thorax. Genetic analysis revealed a heterozygous in-frame COL1A2 exons 4–17 deletion. Maternal testing identified low-level mosaicism for this large deletion alongside a germline in-frame deletion of exons 12–17. Detailed breakpoint analysis of the exon 12–17 deletion revealed a complex rearrangement characterised by the insertion of an inverted duplicated segment of exon 3 and intron 3 at the deletion junction. Despite these findings, the mother showed only joint hypermobility and a family history of osteoporosis, without overt features of OI.

Conclusions

N-terminal in-frame COL1A2 deletions show variable expressivity, including perinatal lethality. We report a novel, complex and likely unstable genomic rearrangement which probably predisposed to a secondary, larger deletion. Integrated CNV analysis and parental studies are crucial to ensure accurate recurrence risk counselling.

背景：成骨不全症（Osteogenesis imperfecta， OI）主要由COL1A1/COL1A2的致病变异引起；虽然单核苷酸变异占主导地位，但多外显子拷贝数变异（CNVs）仍未被充分认识，其表型影响尚未完全确定。方法：我们使用NGS、CNV呼叫和MLPA、临床和放射学评估以及母体成纤维细胞转录分析研究了一例出现严重骨骼发育不良的胎儿。我们还回顾了文献和数据库中报道的COL1A2多外显子缺失。结果：胎儿表现出致死性II型成骨不全特征，包括进行性长骨缩短和弯曲，多发骨折，弥漫性低矿化和钟形胸。遗传分析显示COL1A2外显子4-17存在杂合缺失。母体检测发现这种低水平的嵌合性缺失伴随着种系框架内外显子12-17的缺失。外显子12-17缺失的详细断点分析揭示了一个复杂的重排，其特征是在缺失连接处插入了外显子3和内含子3的反向重复片段。尽管有这些发现，但母亲仅表现出关节活动过度和骨质疏松家族史，没有明显的成骨不全特征。结论：框架内n端COL1A2缺失具有不同的表达性，包括围产期致死率。我们报告了一个新的，复杂的和可能不稳定的基因组重排，这可能会导致二次，更大的缺失。综合CNV分析和家长研究对于确保准确的复发风险咨询至关重要。

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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 : 2026-01-29 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

COVID-19 increases the risk for hip fractures in older subjects – A register-based Swedish population study 2019冠状病毒病增加老年受试者髋部骨折的风险——一项基于登记的瑞典人口研究

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-01-29 DOI: 10.1016/j.bone.2026.117811

Kristina Kajba , Yiyi Xu , Ailiana Santosa , Maria Bygdell , Claes Ohlsson , Fredrik Nyberg , Huiqi Li

Hip fractures are a significant public health concern, associated with high morbidity and mortality. This population-based cohort study investigated whether COVID-19 increased hip fracture risk in Swedish adults. The study included 3,931,893 Swedish residents aged ≥50 years as of January 1st 2020, and recorded 50,883 incident hip fractures during follow-up, until the end of 2022. The exposure of interest was COVID-19 confirmed via national registries during the study period, with 711,879 (18.1%) identified cases. The primary outcome was hip fracture incidence. Secondary outcomes included fractures of the proximal humerus and wrist. Association between COVID-19 and fractures was estimated using Cox proportional hazards regression with time-varying exposure, adjusting for demographic and socioeconomic characteristics, frailty index, previous comorbidities, prior medication use, and COVID-19 vaccination status. Results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). In fully adjusted models, COVID-19 was associated with a 43% higher risk of hip fractures (HR 1.43, 95% CI 1.36–1.50), with stronger association observed in men (HR 1.57, 95% CI 1.45–1.71) than in women (HR 1.36, 95% CI 1.28–1.45). Age-stratified analyses revealed significant associations in individuals aged ≥65 years (men: HR 1.68, 95% CI 1.54–1.82; women: HR 1.42, 95% CI 1.33–1.51), but not in those aged 50–65 years. Associations with proximal humerus and wrist fractures were less pronounced. These findings suggest that COVID-19 is associated with a substantially increased risk of hip fracture, especially among individuals aged ≥65 years old, underscoring the importance of targeted fracture prevention in this group after COVID-19.

髋部骨折是一个重要的公共卫生问题，与高发病率和死亡率有关。这项基于人群的队列研究调查了COVID-19是否会增加瑞典成年人髋部骨折的风险。该研究纳入了截至2020年1月1日年龄≥50岁的3,931,893名瑞典居民，并在随访期间记录了50,883例髋部骨折事件，直到2022年底。在研究期间，通过国家登记处确认了感兴趣的COVID-19暴露，确定了711,879例（18.1%）病例。主要观察指标为髋部骨折发生率。次要结局包括肱骨近端和腕关节骨折。使用随时间变化暴露的Cox比例风险回归，调整人口统计学和社会经济特征、虚弱指数、既往合并症、既往用药和COVID-19疫苗接种状况，估计COVID-19与骨折之间的关联。结果以95%置信区间（ci）的风险比（hr）表示。在完全调整的模型中，COVID-19与髋部骨折的风险高出43% (HR 1.43, 95% CI 1.36 - 1.50)，男性（HR 1.57, 95% CI 1.45-1.71）比女性（HR 1.36, 95% CI 1.28-1.45）的相关性更强。年龄分层分析显示，年龄≥65岁的个体有显著相关性（男性：HR 1.68, 95% CI 1.54-1.82；女性：HR 1.42, 95% CI 1.33-1.51），但50-65岁的个体无显著相关性。与肱骨近端和腕部骨折的关联不太明显。这些研究结果表明，COVID-19与髋部骨折风险大幅增加有关，特别是在年龄≥65岁的人群中，这强调了在COVID-19后对这一人群进行针对性骨折预防的重要性。

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引用次数: 0

Bone mineral density in rheumatoid arthritis patients on antirheumatic therapies: a systematic review 抗风湿治疗对类风湿关节炎患者骨密度的影响：系统综述。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-01-28 DOI: 10.1016/j.bone.2026.117812

Owen Taylor-Williams , Ross Godwin , Reece Carvallio , Michaela Taylor-Williams , Christine Barrett , Charles Inderjeeth

Rheumatoid Arthritis (RA) is associated with increased fracture risk due to systemic bone loss. Whilst new disease modifying antirheumatic drugs (DMARD) have improved disease control, their impacts on bone mineral density (BMD) remains controversial. This systematic review investigates the effects of conventional synthetic (cs), biologic (b), and targeted synthetic (ts) DMARDs on BMD in RA patients. 13,340 records were screened, with 46 studies meeting the inclusion and exclusion criteria, published on PROSPERO (CRD42024534452). Included studies were analysed by their use of specific DMARD, glucocorticosteroids (GCS), antiosteoporotic therapy (AOT) and disease activity. csDMARD appear beneficial to BMD, and on the balance of evidence bDMARD and tsDMARD appear to have a greater effect on BMD. Encouragingly, early data suggests some csDMARD, bDMARD, tsDMARD may be superior to others, however, further research is required to confirm this. Future researchers should consider DMARD mechanism of action on BMD and examine the role of specific csDMARD, bDMARD, and tsDMARD in large cohort studies and trials.

类风湿性关节炎（RA）与系统性骨质流失导致的骨折风险增加有关。虽然新的疾病调节抗风湿药物（DMARD）改善了疾病控制，但它们对骨矿物质密度（BMD）的影响仍存在争议。本系统综述调查了常规合成（cs）、生物合成(b)和靶向合成（ts） DMARDs对RA患者骨密度的影响。筛选了13340条记录，其中46项研究符合纳入和排除标准，发表在PROSPERO （CRD42024534452）上。纳入的研究通过使用特异性DMARD、糖皮质激素（GCS）、抗骨质疏松治疗（AOT）和疾病活动性进行分析。csDMARD似乎对BMD有益，在证据的平衡上，bDMARD和tsDMARD似乎对BMD有更大的影响。令人鼓舞的是，早期数据显示一些csDMARD， bDMARD， tsDMARD可能优于其他的，然而，需要进一步的研究来证实这一点。未来的研究人员应该考虑DMARD对BMD的作用机制，并在大型队列研究和试验中检查特异性csDMARD、bDMARD和tsDMARD的作用。

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引用次数: 0

Sclerostin-targeted delivery of PCSK9 siRNA reverses osteoporosis in OVX mice 以硬化蛋白为靶点的PCSK9 siRNA递送可逆转OVX小鼠的骨质疏松症

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-01-27 DOI: 10.1016/j.bone.2026.117808

Hongling Wu , Liyuan Huang , Fangfang Song , Yueli Zhou , Yanru Wu , Jiqi Zheng , Zhengrong Yin , Yanyang Wei , Hualing Sun , Cui Huang

The role of PCSK9 in bone metabolism has recently emerged as a critical area of research. This study identifies a significant upregulation of PCSK9, approximately 1.2-fold in ovariectomized (OVX) mice serum, approximately 3-fold in OVX mice bone marrow stem cells, which correlates strongly with decreased bone mineral density, implicating PCSK9 in estrogen deficiency-induced bone loss. Genetic knockout of PCSK9 was found to ameliorate osteoporosis by improving bone microarchitecture, increasing trabecular bone volume fraction (BV/TV) by 50%, enhancing bone formation (serum PINP increased by 30%), and bone resorption (serum β-CTX increased by 10%), confirming its dual regulatory function. Based on these findings, we engineered a bone-targeted exosome delivery system by surface functionalizing exosomes with an anti-sclerostin (anti-SCL) fragment. This novel system facilitated efficient bone-specific enrichment (fluorescence intensity in bone increased by 60%) and the successful delivery of siPCSK9, resulting in potent silencing of bone marrow PCSK9 expression. In OVX osteoporotic mice, this targeted intervention markedly attenuated bone loss. A 2-fold increase in bone mass was observed relative to the untreated OVX group. Our work not only elucidates a pivotal role of PCSK9 in osteoporosis pathogenesis but also provides a compelling proof-of-concept for exosome-based precision therapy, offering substantial potential for clinical translation.

PCSK9在骨代谢中的作用最近成为一个重要的研究领域。本研究发现PCSK9显著上调，在卵巢切除（OVX）小鼠血清中上调约1.2倍，在OVX小鼠骨髓干细胞中上调约3倍，这与骨密度下降密切相关，暗示PCSK9与雌激素缺乏诱导的骨质流失有关。研究发现，基因敲除PCSK9可通过改善骨微结构、提高骨小梁体积分数（BV/TV） 50%、促进骨形成（血清PINP增加30%）和骨吸收（血清β-CTX增加10%）改善骨质疏松症，证实其双重调节功能。基于这些发现，我们设计了一种骨靶向外泌体递送系统，通过表面功能化带有抗硬化蛋白（anti-SCL）片段的外泌体。这种新系统促进了高效的骨特异性富集（骨中的荧光强度增加了60%）和siPCSK9的成功递送，导致骨髓PCSK9表达的有效沉默。在OVX骨质疏松小鼠中，这种靶向干预明显减轻了骨质流失。与未治疗的OVX组相比，骨量增加了2倍。我们的工作不仅阐明了PCSK9在骨质疏松发病机制中的关键作用，而且为基于外泌体的精确治疗提供了令人信服的概念证明，为临床转化提供了巨大的潜力。

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引用次数: 0

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

Bone

Pub 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 (VO_2max), 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

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

Bone

Pub 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

Development of a novel anthropomorphic bone phantoms for mimicking osteoporosis in medical imaging development 一种新型拟人化骨幻象在医学影像发展中模拟骨质疏松症。

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2026-01-20 DOI: 10.1016/j.bone.2026.117803

Jingrui Hu , Junning Chen , Steve Wells , Karen Knapp

Osteoporosis (OP) is characterised by loss of bone mineral density (BMD) and deterioration of trabecular microarchitecture, yet routine clinical imaging techniques remain limited in their ability to fully characterise bone microarchitecture. As new imaging technologies are developed, the potential for point of care bone assessment with both density and microarchitectural parameters of bone becomes a reality. Although advanced imaging modalities such as high-resolution peripheral quantitative computed tomography (HR-pQCT) offers improved sensitivity to bone structure, this is primarily focused on research settings. The development of higher resolution digital tomosynthesis (DT), required rethinking of phantoms, otherwise development and pre-clinical validation are constrained by the lack of reproducible, structure-controlled reference standards. In this study, we present a novel anthropomorphic bone phantom designed as a preclinical platform for calibration, benchmarking, and validation of bone imaging systems and quantitative analysis methods. The phantom integrates digital-twin trabecular models derived from micro-computed tomography (μ-CT), enabling parametric control of trabecular thickness and bone volume fraction to represent healthy and osteoporotic conditions. BMD is independently controlled using calibrated contrast agent (PVP-BaSO₄), while moulded lean and adipose soft-tissue equivalents are incorporated to provide realistic X-ray attenuation for projection-based imaging. The phantoms were evaluated using multiple imaging modalities, including X-ray, DXA, pQCT, DT, and μCT, to verify their fidelity in reproducing both BMD and trabecular microstructural features. Imaging-derived parameters showed strong correlations with controlled variations in trabecular architecture and BMD, demonstrating the utility of the phantom as a source of controlled ground truth for cross-modality comparison. This reproducible platform enables systematic evaluation of imaging systems and facilitates early osteoporosis detection by bridging structure-density relationships. Our phantom serves as a valuable tool for preclinical diagnostic validation, imaging quality assurance, and the development of bone health biomarkers, thereby reducing reliance on animal or cadaveric studies.

骨质疏松症（OP）的特征是骨密度（BMD）的丧失和小梁微结构的恶化，然而常规的临床成像技术在充分表征骨微结构方面的能力仍然有限。随着新的成像技术的发展，利用骨的密度和微结构参数进行骨评估的潜力成为现实。尽管高分辨率外围定量计算机断层扫描（HR-pQCT）等先进的成像方式提高了对骨骼结构的敏感性，但这主要集中在研究环境中。更高分辨率的数字断层合成（DT）的发展需要对幻影进行重新思考，否则由于缺乏可重复的、结构可控的参考标准，开发和临床前验证受到限制。在这项研究中，我们提出了一种新的拟人化骨幻影设计作为临床前平台，用于骨成像系统和定量分析方法的校准，基准测试和验证。该模型集成了来自微计算机断层扫描（μ-CT）的数字孪生小梁模型，能够参数控制小梁厚度和骨体积分数，以代表健康和骨质疏松状况。使用校准造影剂（PVP-BaSO4）独立控制BMD，同时结合建模的瘦肉和脂肪软组织等效物，为基于投影的成像提供真实的x射线衰减。使用x射线、DXA、pQ-CT、DT和μ-CT等多种成像方式对模型进行评估，以验证其再现BMD和小梁微观结构特征的保真度。成像衍生参数显示与小梁结构和BMD的受控变化有很强的相关性，证明了幻像作为跨模态比较的受控地面真相来源的实用性。这个可重复的平台能够系统地评估成像系统，并通过桥接结构-密度关系促进早期骨质疏松症的检测。我们的假体是临床前诊断验证、成像质量保证和骨骼健康生物标志物开发的宝贵工具，从而减少了对动物或尸体研究的依赖。

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引用次数: 0