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Associations of Quantitative and Qualitative Muscle Parameters With Second Hip Fracture Risk in Older Women: A Prospective Cohort Study 定量和定性肌肉参数与老年妇女第二次髋部骨折风险的关系:前瞻性队列研究
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-25 DOI: 10.1002/jbm4.10834
Wenshuang Zhang, Yufeng Ge, Yandong Liu, Yi Yuan, Jian Geng, Fengyun Zhou, Pengju Huang, Jia Shi, Kangkang Ma, Zitong Cheng, Glen M. Blake, Minghui Yang, Xinbao Wu, Xiaoguang Cheng, Ling Wang

Older women with a first hip fracture exhibit heightened susceptibility and incidence of second fracture and potentially severe consequences. This prospective study was to compare the predictive power of qualitative and quantitative muscle parameters for a second hip fracture in older women with a first hip fracture. A total of 206 subjects were recruited from the longitudinal Chinese Second Hip Fracture Evaluation study. Hip computed tomography (CT) scans were obtained immediately after the first fracture. Muscle fat infiltration was assessed according to the Goutallier classification qualitatively. Quantitative parameters included cross-sectional area and density of gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) muscles. CT X-ray absorptiometry was used to measure the areal bone mineral density (aBMD) of the contralateral femur. Cox proportional hazards models were used to compute hazard ratios (HR) of second hip fracture risk. The mean age of subjects was 74.9 (±9.5) years at baseline. After 4.5 years, 35 had a second hip fracture, 153 without a second hip fracture, and 18 died. Except for the combined G.MinM Goutallier grade 3 and 4 groups before adjustment for covariates (HR = 5.83; 95% confidence interval [CI] 1.49–22.83), there were no significant HRs for qualitative classification to predict a second hip fracture. Among quantitative metrics, after adjustment for covariates, G.Med/MinM density was significant in the original (HR = 1.44; CI 1.02–2.04) and competing risk analyses (HR = 1.46; CI 1.02–2.07). After additional adjustment for femoral neck (FN) aBMD, G.Med/MinM density remained borderline significant for predicting a second hip fracture in competing risk analysis (HR = 1.43; CI 0.99–2.06; p = 0.057). Our study revealed that Goutallier classification was less effective than quantitative muscle metrics for predicting hip second fracture in this elderly female cohort. After adjustment for FN aBMD, G.Med/MinM density is a borderline independent predictor of second hip fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

首次髋部骨折的老年妇女更容易发生第二次骨折,并可能造成严重后果。这项前瞻性研究旨在比较肌肉定性和定量参数对首次髋部骨折老年妇女第二次髋部骨折的预测能力。该研究从中国第二次髋部骨折纵向评估研究中招募了 206 名受试者。首次骨折后立即进行髋部计算机断层扫描(CT)。根据 Goutallier 分类法对肌肉脂肪浸润进行定性评估。定量参数包括臀大肌(G.MaxM)、臀中肌和臀小肌(G.Med/MinM)的横截面积和密度。CT X 射线吸收测量法用于测量对侧股骨的骨矿密度(aBMD)。Cox比例危险模型用于计算第二次髋部骨折风险的危险比(HR)。基线受试者的平均年龄为 74.9 (±9.5) 岁。4.5 年后,35 人再次发生髋部骨折,153 人未再次发生髋部骨折,18 人死亡。除G.MinM Goutallier 3级和4级合并组在调整协变量(HR = 5.83;95% 置信区间 [CI] 1.49-22.83)之前,定性分类预测第二次髋部骨折的HR无显著性差异。在定量指标中,对协变量进行调整后,G.Med/MinM 密度在原始分析(HR = 1.44;CI 1.02-2.04)和竞争风险分析(HR = 1.46;CI 1.02-2.07)中具有显著性。在对股骨颈(FN)aBMD进行额外调整后,在竞争风险分析中,G.Med/MinM密度对预测第二次髋部骨折仍具有边缘显著性(HR = 1.43; CI 0.99-2.06; p = 0.057)。我们的研究表明,在这一老年女性队列中,Goutallier 分类在预测髋部二次骨折方面的效果不如定量肌肉指标。在对 FN aBMD 进行调整后,G.Med/MinM 密度是第二次髋部骨折风险的边缘独立预测指标。© 2023 作者。JBMR Plus 由 Wiley Periodicals LLC 代表美国骨与矿物质研究学会出版。
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引用次数: 0
Palovarotene Action Against Heterotopic Ossification Includes a Reduction of Local Participating Activin A-Expressing Cell Populations 帕罗伐汀对异位骨化的作用包括减少局部参与的表达活化素 A 的细胞群
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-19 DOI: 10.1002/jbm4.10821
Christina Mundy, Lutian Yao, Kelly A. Shaughnessy, Cheri Saunders, Eileen M. Shore, Eiki Koyama, Maurizio Pacifici

Heterotopic ossification (HO) consists of extraskeletal bone formation. One form of HO is acquired and instigated by traumas or surgery, and another form is genetic and characterizes fibrodysplasia ossificans progressiva (FOP). Recently, we and others showed that activin A promotes both acquired and genetic HO, and in previous studies we found that the retinoid agonist palovarotene inhibits both HO forms in mice. Here, we asked whether palovarotene's action against HO may include an interference with endogenous activin A expression and/or function. Using a standard mouse model of acquired HO, we found that activin A and its encoding RNA (Inhba) were prominent in chondrogenic cells within developing HO masses in untreated mice. Single-cell RNAseq (scRNAseq) assays verified that Inhba expression characterized chondroprogenitors and chondrocytes in untreated HO, in addition to its expected expression in inflammatory cells and macrophages. Palovarotene administration (4 mg/kg/d/gavage) caused a sharp inhibition of both HO and amounts of activin A and Inhba transcripts. Bioinformatic analyses of scRNAseq data sets indicated that the drug had reduced interactions and cross-talk among local cell populations. To determine if palovarotene inhibited Inhba expression directly, we assayed primary chondrocyte cultures. Drug treatment inhibited their cartilaginous phenotype but not Inhba expression. Our data reveal that palovarotene markedly reduces the number of local Inhba-expressing HO-forming cell populations. The data broaden the spectrum of HO culprits against which palovarotene acts, accounting for its therapeutic effectiveness. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

异位骨化(HO)包括骨骼外骨形成。一种异位骨化是获得性的,由创伤或手术引起;另一种是遗传性的,是渐进性骨纤维化症(FOP)的特征。最近,我们和其他研究人员发现,激活素 A 对获得性和遗传性 HO 均有促进作用,而在之前的研究中,我们发现视黄醇激动剂帕洛伐汀对小鼠的两种 HO 均有抑制作用。在此,我们提出了一个问题:帕洛伐汀对HO的作用是否可能包括干扰内源性激活素A的表达和/或功能?利用获得性HO的标准小鼠模型,我们发现在未经处理的小鼠中,活化素A及其编码RNA(Inhba)在发育中的HO肿块的软骨细胞中表现突出。单细胞 RNAseq(scRNAseq)检测验证了 Inhba 的表达除了在炎症细胞和巨噬细胞中的预期表达外,还具有未治疗 HO 中软骨生成细胞和软骨细胞的特征。帕洛伐汀给药(4 毫克/千克/天/灌胃)可显著抑制 HO 以及激活素 A 和 Inhba 转录物的数量。scRNAseq数据集的生物信息学分析表明,该药物减少了局部细胞群之间的相互作用和交叉对话。为了确定帕洛伐汀是否直接抑制了 Inhba 的表达,我们对原代软骨细胞培养物进行了检测。药物处理抑制了软骨表型,但没有抑制 Inhba 的表达。我们的数据显示,帕洛伐汀能显著减少局部表达 Inhba 的 HO 形成细胞群的数量。这些数据扩大了帕洛伐汀对HO罪魁祸首的作用范围,这也是其治疗效果的原因所在。© 2023 作者。JBMR Plus 由 Wiley Periodicals LLC 代表美国骨矿研究学会出版。
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引用次数: 0
Classification of Fracture Risk in Fallers Using Dual-Energy X-Ray Absorptiometry (DXA) Images and Deep Learning-Based Feature Extraction 利用双能量 X 射线吸收测量(DXA)图像和基于深度学习的特征提取对跌倒者的骨折风险进行分类
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-19 DOI: 10.1002/jbm4.10828
Damith Senanayake, Sachith Seneviratne, Mahdi Imani, Christel Harijanto, Myrla Sales, Peter Lee, Gustavo Duque, David C. Ackland

Dual-energy X-ray absorptiometry (DXA) scans are one of the most frequently used imaging techniques for calculating bone mineral density, yet calculating fracture risk using DXA image features is rarely performed. The objective of this study was to combine deep neural networks, together with DXA images and patient clinical information, to evaluate fracture risk in a cohort of adults with at least one known fall and age-matched healthy controls. DXA images of the entire body as, well as isolated images of the hip, forearm, and spine (1488 total), were obtained from 478 fallers and 48 non-faller controls. A modeling pipeline was developed for fracture risk prediction using the DXA images and clinical data. First, self-supervised pretraining of feature extractors was performed using a small vision transformer (ViT-S) and a convolutional neural network model (VGG-16 and Resnet-50). After pretraining, the feature extractors were then paired with a multilayer perceptron model, which was used for fracture risk classification. Classification was achieved with an average area under the receiver-operating characteristic curve (AUROC) score of 74.3%. This study demonstrates ViT-S as a promising neural network technique for fracture risk classification using DXA scans. The findings have future application as a fracture risk screening tool for older adults at risk of falls. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

双能 X 射线吸收测量(DXA)扫描是计算骨矿密度最常用的成像技术之一,但利用 DXA 图像特征计算骨折风险的方法却很少使用。本研究的目的是将深度神经网络与 DXA 图像和患者临床信息相结合,评估至少有一次已知跌倒的成年人和年龄匹配的健康对照组的骨折风险。研究人员从 478 名跌倒者和 48 名非跌倒者对照组中获取了全身的 DXA 图像,以及髋部、前臂和脊柱的单独图像(共 1488 张)。利用 DXA 图像和临床数据开发了一个用于预测骨折风险的建模管道。首先,使用小型视觉转换器(ViT-S)和卷积神经网络模型(VGG-16 和 Resnet-50)对特征提取器进行自监督预训练。经过预训练后,特征提取器与多层感知器模型配对,用于骨折风险分类。分类的平均接收者工作特征曲线下面积 (AUROC) 得分为 74.3%。这项研究表明,ViT-S 是利用 DXA 扫描进行骨折风险分类的一种很有前途的神经网络技术。研究结果未来可作为骨折风险筛查工具应用于有跌倒风险的老年人。© 2023 作者。JBMR Plus 由 Wiley Periodicals LLC 代表美国骨与矿物质研究学会出版。
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引用次数: 0
Bone Structure and Turnover in Postmenopausal Women With Long-Standing Type 1 Diabetes 长期患有1型糖尿病的绝经后妇女的骨结构和代谢
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-15 DOI: 10.1002/jbm4.10831
Viral N Shah, Shijing Qui, Jason Stoneback, Lubna Qamar, Virginia L Ferguson, Wendy M Kohrt, Janet K Snell-Bergeon, Sudhaker D Rao

Compromised bone structural and mechanical properties are implicated in the increased fracture risk in type 1 diabetes (T1D). We investigated bone structure and turnover by histomorphometry in postmenopausal women with T1D and controls without diabetes using tetracycline double-labeled transiliac bone biopsy. After in vivo tetracycline double labeling, postmenopausal women with T1D of at least 10 years and without diabetes underwent transiliac bone biopsy. An expert blinded to the study group performed histomorphometry. Static and dynamic histomorphometry measurements were performed and compared between the two groups. The analysis included 9 postmenopausal women with T1D (mean age 58.4 ± 7.1 years with 37.9 ± 10.9 years of diabetes and HbA1c 7.1% ± 0.4%) and 7 postmenopausal women without diabetes (mean age 60.9 ± 3.3 years and HbA1c 5.4% ± 0.2%). There were no significant differences in serum PTH (38.6 ± 8.1 versus 51.9 ± 23.9 pg/mL), CTX (0.4 ± 0.2 versus 0.51 ± 0.34 ng/mL), or P1NP (64.5 ± 26.2 versus 87.3 ± 45.3 ng/mL). Serum 25-hydroxyvitamin D levels were higher in T1D than in controls (53.1 ± 20.8 versus 30.9 ± 8.2 ng/mL, p < 0.05). Bone structure metrics (bone volume, trabecular thickness, trabecular number, and cortical thickness) were similar between the groups. Indices of bone formation (osteoid volume, osteoid surface, and bone formation rate) were 40% lower in T1D and associated with lower activation frequency. However, the differences in bone formation were not statistically significant. Long-standing T1D may affect bone turnover, mainly bone formation, without significantly affecting bone structure. Further research is needed to understand bone turnover and factors affecting bone turnover in people with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

1型糖尿病(T1D)患者骨折风险增加与骨骼结构和力学特性受损有关。我们使用四环素双标记经髂骨活检,通过组织形态学测量研究了绝经后T1D妇女和无糖尿病的对照组的骨结构和转换。在体内四环素双标记后,绝经后T1D至少10年且无糖尿病的妇女进行了经髂骨活检。一位对研究组不知情的专家进行了组织形态学测定。在两组之间进行静态和动态组织形态测量并进行比较。分析包括9名绝经后T1D妇女(平均年龄58.4±7.1岁,糖尿病37.9±10.9年,HbA1c 7.1%±0.4%)和7名绝经后无糖尿病妇女(平均年龄60.9±3.3岁,HbA1c 5.4%±0.2%)。血清PTH(38.6±8.1 vs . 51.9±23.9 pg/mL)、CTX(0.4±0.2 vs . 0.51±0.34 ng/mL)、P1NP(64.5±26.2 vs . 87.3±45.3 ng/mL)差异无统计学意义。T1D患者血清25-羟基维生素D水平高于对照组(53.1±20.8 ng/mL vs 30.9±8.2 ng/mL, p < 0.05)。骨结构指标(骨体积、骨小梁厚度、骨小梁数量和皮质厚度)在两组之间相似。T1D患者的骨形成指标(类骨体积、类骨表面和骨形成率)降低40%,且与较低的激活频率相关。然而,骨形成的差异没有统计学意义。长期存在的T1D可能影响骨转换,主要是骨形成,但对骨结构没有明显影响。需要进一步研究了解T1D患者的骨转换及影响骨转换的因素。©2023作者。JBMR Plus由Wiley期刊有限责任公司代表美国骨与矿物研究协会出版。
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引用次数: 0
Tensile Mechanical Properties of Dry Cortical Bone Extracellular Matrix: A Comparison Among Two Osteogenesis Imperfecta and One Healthy Control Iliac Crest Biopsies 干皮质骨细胞外基质的拉伸力学性能:两种成骨不全症和一种健康对照髂骨活检组织的比较
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-11 DOI: 10.1002/jbm4.10826
Michael Indermaur, Daniele Casari, Tatiana Kochetkova, Bettina M. Willie, Johann Michler, Jakob Schwiedrzik, Philippe Zysset

Osteogenesis imperfecta (OI) is a genetic, collagen-related bone disease that increases the incidence of bone fractures. Still, the origin of this brittle mechanical behavior remains unclear. The extracellular matrix (ECM) of OI bone exhibits a higher degree of bone mineralization (DBM), whereas compressive mechanical properties at the ECM level do not appear to be inferior to healthy bone. However, it is unknown if collagen defects alter ECM tensile properties. This study aims to quantify the tensile properties of healthy and OI bone ECM. In three transiliac biopsies (healthy n = 1, OI type I n = 1, OI type III n = 1), 23 microtensile specimens (gauge dimensions 10 × 5 × 2 μm3) were manufactured and loaded quasi-statically under tension in vacuum condition. The resulting loading modulus and ultimate strength were extracted. Interestingly, tensile properties in OI bone ECM were not inferior compared to controls. All specimens revealed a brittle failure behavior. Fracture surfaces were graded according to their mineralized collagen fibers (MCF) orientation into axial, mixed, and transversal fracture surface types (FST). Furthermore, tissue mineral density (TMD) of the biopsy cortices was extracted from micro–computed tomogra[hy (μCT) images. Both FST and TMD are significant factors to predict loading modulus and ultimate strength with an adjusted R2 of 0.556 (p = 2.65e−05) and 0.46 (p = 2.2e−04), respectively. The influence of MCF orientation and DBM on the mechanical properties of the neighboring ECM was further verified with quantitative polarized Raman spectroscopy (qPRS) and site-matched nanoindentation. MCF orientation and DBM were extracted from the qPRS spectrum, and a second mechanical model was developed to predict the indentation modulus with MCF orientation and DBM (R2 = 67.4%, p = 7.73e−07). The tensile mechanical properties of the cortical bone ECM of two OI iliac crest biopsies are not lower than the one from a healthy and are primarily dependent on MCF orientation and DBM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

成骨不全症(OI)是一种与胶原蛋白有关的遗传性骨病,会增加骨折的发生率。然而,这种脆性机械行为的起源仍不清楚。成骨不全症骨骼的细胞外基质(ECM)显示出较高的骨矿化度(DBM),而 ECM 水平的压缩机械性能似乎并不低于健康骨骼。然而,胶原缺陷是否会改变 ECM 的拉伸特性尚不得而知。本研究旨在量化健康骨和 OI 骨 ECM 的拉伸特性。在三个经髂活检组织(健康 n = 1、OI I 型 n = 1、OI III 型 n = 1)中,制作了 23 个微拉试样(规格尺寸为 10 × 5 × 2 μm3),并在真空条件下进行准静态拉伸加载。结果提取了加载模量和极限强度。有趣的是,与对照组相比,OI 骨 ECM 的拉伸性能并不逊色。所有试样都显示出脆性破坏行为。根据矿化胶原纤维 (MCF) 的取向,将断裂面分为轴向、混合和横向断裂面类型 (FST)。此外,还从微计算机断层扫描(μCT)图像中提取了活检皮质的组织矿物质密度(TMD)。FST和TMD都是预测加载模量和极限强度的重要因素,调整后的R2分别为0.556(p = 2.65e-05)和0.46(p = 2.2e-04)。定量偏振拉曼光谱 (qPRS) 和位点匹配纳米压痕法进一步验证了 MCF 取向和 DBM 对邻近 ECM 力学性能的影响。从 qPRS 光谱中提取了 MCF 取向和 DBM,并建立了第二个力学模型来预测 MCF 取向和 DBM 的压痕模量(R2 = 67.4%,p = 7.73e-07)。两个 OI 髂嵴活检组织皮质骨 ECM 的拉伸力学性能并不比健康组织的低,而且主要取决于 MCF 取向和 DBM。© 2023 作者。JBMR Plus 由 Wiley Periodicals LLC 代表美国骨与矿物质研究学会出版。
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引用次数: 0
Zucker Diabetic-Sprague Dawley Rats Have Impaired Peri-Implant Bone Formation, Matrix Composition, and Implant Fixation Strength Zucker糖尿病- sprague - Dawley大鼠的种植体周围骨形成、基质成分和种植体固定强度受损
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-11 DOI: 10.1002/jbm4.10819
Kyle D Anderson, Christian Beckmann, Saskia Heermant, Frank C Ko, Bryan Dulion, Imad Tarhoni, Jeffrey A Borgia, Amarjit S Virdi, Markus A Wimmer, D Rick Sumner, Ryan D Ross

An increasing number of patients with type 2 diabetes (T2DM) will require total joint replacement (TJR) in the next decade. T2DM patients are at increased risk for TJR failure, but the mechanisms are not well understood. The current study used the Zucker Diabetic-Sprague Dawley (ZDSD) rat model of T2DM with Sprague Dawley (SPD) controls to investigate the effects of intramedullary implant placement on osseointegration, peri-implant bone structure and matrix composition, and fixation strength at 2 and 10 weeks post-implant placement. Postoperative inflammation was assessed with circulating MCP-1 and IL-10 2 days post-implant placement. In addition to comparing the two groups, stepwise linear regression modeling was performed to determine the relative contribution of glucose, cytokines, bone formation, bone structure, and bone matrix composition on osseointegration and implant fixation strength. ZDSD rats had decreased peri-implant bone formation and reduced trabecular bone volume per total volume compared with SPD controls. The osseointegrated bone matrix of ZDSD rats had decreased mineral-to-matrix and increased crystallinity compared with SPD controls. Osseointegrated bone volume per total volume was not different between the groups, whereas implant fixation was significantly decreased in ZDSD at 2 weeks but not at 10 weeks. A combination of trabecular mineral apposition rate and postoperative MCP-1 levels explained 55.6% of the variance in osseointegration, whereas cortical thickness, osseointegration mineral apposition rate, and matrix compositional parameters explained 69.2% of the variance in implant fixation strength. The results support the growing recognition that both peri-implant structure and matrix composition affect implant fixation and suggest that postoperative inflammation may contribute to poor outcomes after TJR surgeries in T2DM patients. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

在未来十年,越来越多的2型糖尿病(T2DM)患者将需要全关节置换术(TJR)。T2DM患者TJR衰竭的风险增加,但其机制尚不清楚。本研究采用Zucker糖尿病-Sprague Dawley (ZDSD) T2DM大鼠模型和Sprague Dawley (SPD)对照,研究髓内种植体植入后2周和10周对骨整合、种植体周围骨结构和基质组成以及固定强度的影响。植入后2天用循环MCP-1和IL-10评估术后炎症。除了对两组进行比较外,还采用逐步线性回归模型来确定葡萄糖、细胞因子、骨形成、骨结构和骨基质组成对骨整合和种植体固定强度的相对贡献。与SPD对照组相比,ZDSD大鼠种植体周围骨形成减少,每总体积小梁骨体积减少。与SPD对照组相比,ZDSD大鼠骨整合基质的矿物-基质含量降低,结晶度增加。两组间每总容积的骨整合体积没有差异,而种植体固定在2周时明显减少,而在10周时则没有。骨小梁矿物附着率和术后MCP-1水平的结合解释了55.6%的骨整合差异,而皮质厚度、骨整合矿物附着率和基质成分参数解释了69.2%的种植体固定强度差异。研究结果支持了越来越多的认识,即种植体周围结构和基质组成都会影响种植体固定,并提示术后炎症可能导致T2DM患者TJR手术后预后不良。©2023作者。JBMR Plus由Wiley期刊有限责任公司代表美国骨骼和矿物研究协会出版。
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引用次数: 0
Interrogating Causal Effects of Body Composition and Puberty-Related Risk Factors on Adolescent Idiopathic Scoliosis: A Two-Sample Mendelian Randomization Study 探究身体成分和青春期相关风险因素对青少年特发性脊柱侧凸的因果效应:双样本孟德尔随机研究
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-05 DOI: 10.1002/jbm4.10830
Faegheh Ghanbari, Nao Otomo, Isabel Gamache, Takuro Iwami, Yoshinao Koike, Anas M. Khanshour, Shiro Ikegawa, Carol A. Wise, Chikashi Terao, Despoina Manousaki

Adolescent idiopathic scoliosis (AIS) is the most common form of pediatric musculoskeletal disorder. Observational studies have pointed to several risk factors for AIS, but almost no evidence exists to support their causal association with AIS. Here, we applied Mendelian randomization (MR), known to limit bias from confounding and reverse causation, to investigate causal associations between body composition and puberty-related exposures and AIS risk in Europeans and Asians. For our two-sample MR studies, we used single nucleotide polymorphisms (SNPs) associated with body mass index (BMI), waist-hip ratio, lean mass, childhood obesity, bone mineral density (BMD), 25-hydroxyvitamin D (25OHD), age at menarche, and pubertal growth in large European genome-wide association studies (GWAS), and with adult osteoporosis risk and age of menarche in Biobank Japan. We extracted estimates of the aforementioned SNPs on AIS risk from the European or Asian subsets of the largest multiancestry AIS GWAS (N = 7956 cases/88,459 controls). The results of our inverse variance-weighted (IVW) MR estimates suggest no causal association between the aforementioned risk factors and risk of AIS. Pleiotropy-sensitive MR methods yielded similar results. However, restricting our analysis to European females with AIS, we observed a causal association between estimated BMD and the risk of AIS (IVW odds ratio for AIS = 0.1, 95% confidence interval 0.01 to 0.7, p = 0.02 per SD increase in estimated BMD), but this association was no longer significant after adjusting for BMI, body fat mass, and 25OHD and remained significant after adjusting for age at menarche in multivariable MR. In conclusion, we demonstrated a protective causal effect of BMD on AIS risk in females of European ancestry, but this effect was modified by BMI, body fat mass, and 25OHD levels. Future MR studies using larger AIS GWAS are needed to investigate small effects of the aforementioned exposures on AIS. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

青少年特发性脊柱侧凸(AIS)是最常见的儿科肌肉骨骼疾病。观察性研究指出了导致 AIS 的几个风险因素,但几乎没有证据支持这些因素与 AIS 的因果关系。众所周知,孟德尔随机法(Mendelian randomization,MR)可限制混杂和反向因果关系造成的偏差,在此,我们采用该方法研究了欧洲人和亚洲人的身体成分、青春期相关暴露与 AIS 风险之间的因果关系。在我们的双样本 MR 研究中,我们使用了欧洲大型全基因组关联研究(GWAS)中与体重指数(BMI)、腰臀比、瘦体重、儿童肥胖、骨矿物质密度(BMD)、25-羟维生素 D(25OHD)、初潮年龄和青春期发育相关的单核苷酸多态性(SNPs),以及日本生物数据库中与成人骨质疏松症风险和初潮年龄相关的单核苷酸多态性。我们从最大的多种族 AIS 全基因组关联研究的欧洲或亚洲子集中提取了上述 SNPs 对 AIS 风险的估计值(N = 7956 例/88459 例对照)。我们的反方差加权(IVW)MR 估计结果表明,上述风险因素与 AIS 风险之间没有因果关系。对多态性敏感的磁共振方法也得出了类似的结果。然而,将我们的分析局限于患有 AIS 的欧洲女性,我们观察到估计 BMD 与 AIS 风险之间存在因果关系(AIS 的 IVW 机率比 = 0.1,95% 置信区间为 0.01 至 0.7,估计 BMD 每增加 SD,p = 0.02),但在调整 BMI、体脂量和 25OHD 后,这种关系不再显著,而在多变量 MR 中调整初潮年龄后,这种关系仍然显著。总之,我们证明了 BMD 对欧洲血统女性 AIS 风险的保护性因果效应,但这种效应受 BMI、体脂量和 25OHD 水平的影响。未来需要使用更大规模的 AIS GWAS 进行 MR 研究,以调查上述暴露对 AIS 的微小影响。© 2023 作者。JBMR Plus 由 Wiley Periodicals LLC 代表美国骨与矿物质研究学会出版。
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引用次数: 0
Abstracts from the 50th International Musculoskeletal Biology Workshop, July 22 – 27, 2023, Midway, Utah 第50届国际肌肉骨骼生物学研讨会摘要,2023年7月22-27日,犹他州中途岛
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-03 DOI: 10.1002/jbm4.10827

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引用次数: 0
Reduced Bone Regeneration in Rats With Type 2 Diabetes Mellitus as a Result of Impaired Stromal Cell and Osteoblast Function—A Computer Modeling Study 基质细胞和成骨细胞功能受损导致2型糖尿病大鼠骨再生减少——计算机模型研究
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-10-02 DOI: 10.1002/jbm4.10809
Mahdi Jaber, Lorenz C Hofbauer, Christine Hofbauer, Georg N Duda, Sara Checa

Bone has the fascinating ability to self-regenerate. However, under certain conditions, such as type 2 diabetes mellitus (T2DM), this ability is impaired. T2DM is a chronic metabolic disease known by the presence of elevated blood glucose levels that is associated with reduced bone regeneration capability, high fracture risk, and eventual non-union risk after a fracture. Several mechanical and biological factors relevant to bone regeneration have been shown to be affected in a diabetic environment. However, whether impaired bone regeneration in T2DM can be explained due to mechanical or biological alterations remains unknown. To elucidate the relevance of either one, the aim of this study was to investigate the relative contribution of T2DM-related alterations on either cellular activity or mechanical stimuli driving bone regeneration. A previously validated in silico computer modeling approach that was capable of explaining bone regeneration in uneventful conditions of healing was further developed to investigate bone regeneration in T2DM. Aspects analyzed included the presence of mesenchymal stromal cells (MSCs), cellular migration, proliferation, differentiation, apoptosis, and cellular mechanosensitivity. To further verify the computer model findings against in vivo data, an experimental setup was replicated, in which regeneration was compared in healthy and diabetic after a rat femur bone osteotomy stabilized with plate fixation. We found that mechanical alterations had little effect on the reduced bone regeneration in T2DM and that alterations in MSC proliferation, MSC migration, and osteoblast differentiation had the highest effect. In silico predictions of regenerated bone in T2DM matched qualitatively and quantitatively those from ex vivo μCT at 12 weeks post-surgery when reduced cellular activities reported in previous in vitro and in vivo studies were included in the model. The presented findings here could have clinical implications in the treatment of bone fractures in patients with T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

骨头具有自我再生的神奇能力。然而,在某些情况下,如2型糖尿病(T2DM),这种能力受损。T2DM是一种慢性代谢性疾病,血糖水平升高与骨再生能力降低、骨折风险高以及骨折后最终不愈合风险相关。一些与骨再生相关的机械和生物因素已被证明在糖尿病环境中受到影响。然而,T2DM患者骨再生受损是否可以由机械或生物学改变来解释仍不清楚。为了阐明两者之间的相关性,本研究的目的是研究t2dm相关改变对驱动骨再生的细胞活性或机械刺激的相对贡献。一种先前经过验证的计算机模拟方法能够解释在平稳愈合条件下的骨再生,该方法进一步发展用于研究T2DM的骨再生。分析的方面包括间充质间质细胞(MSCs)的存在、细胞迁移、增殖、分化、凋亡和细胞机械敏感性。为了进一步验证计算机模型的结果与体内数据的对比,我们复制了一个实验装置,比较了健康大鼠股骨截骨和钢板固定稳定后的再生情况。我们发现,机械改变对T2DM患者骨再生减少的影响很小,而MSC增殖、MSC迁移和成骨细胞分化的改变影响最大。2型糖尿病患者再生骨的计算机预测在定性和定量上与手术后12周的离体μCT结果相匹配,模型中包括了先前体外和体内研究中报告的细胞活性降低。本研究结果可能对治疗2型糖尿病患者骨折具有临床意义。©2023作者。JBMR Plus由Wiley期刊有限责任公司代表美国骨骼和矿物研究协会出版。
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引用次数: 0
The Association between Sleep and Bone Mineral Density: Cross-Sectional Study Using Health Check-up Data in a Local Hospital in Japan 睡眠与骨矿物质密度之间的关系:利用日本一家地方医院的健康检查数据开展的横断面研究
IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-09-30 DOI: 10.1002/jbm4.10820
Reiko Yamaura, Hideko Kasahara, Satoshi Iimuro, Tsutomu Yamazaki

This study aimed to investigate the association between daily sleep duration of <7 hours and lower bone mineral density (BMD) using data from annual health check-ups conducted in Japan between 2020 and 2022. Multivariate regression models were used, where BMD was the objective variable and daily sleep duration (<5 hours, 5 to <7 hours, 7 to <9 hours [reference], ≥9 hours) was the exposure variable adjusted for age, body mass index, physical activity, smoking status, and alcohol intake for men and women and further adjusted for menopausal status for women. The association between insomnia and BMD was also investigated. BMD was determined using calcaneal quantitative ultrasound and expressed as a percentage of the young adult mean (%YAM). In total, 896 men and 821 women were included. Median age was 54 years (interquartile range [IQR]: 46 to 64) for men and 55 years (IQR: 46 to 64) for women). Median BMD for men and women was 79%YAM (IQR: 71 to 89) and 75%YAM (IQR: 68 to 84), respectively. Approximately 80% of men and women slept <7 hours daily. Multivariate regression showed no association between sleep duration and BMD in men. However, women who slept 5 to <7 hours daily had significantly higher BMD by 3.9% compared with those who slept 7 to<9 hours (p = 0.004). No association between insomnia and BMD was found. Overall, a daily sleep duration of <7 hours was not independently associated with lower BMD compared to those who slept 7 to <9 hours in men and women. However, as there is evidence of both shorter and longer sleep durations being associated with an increased risk of adverse events, including cardiovascular events, our result needs to be interpreted with caution. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

本研究旨在利用 2020 年至 2022 年期间在日本进行的年度健康体检数据,研究每日睡眠时间为 7 小时与骨矿物质密度(BMD)降低之间的关系。研究采用了多变量回归模型,其中骨密度是客观变量,每日睡眠时间(5小时、5至7小时、7至9小时[参考]、≥9小时)是暴露变量,并对男性和女性的年龄、体重指数、体力活动、吸烟状况和酒精摄入量进行了调整,还对女性的绝经状况进行了进一步调整。此外,还研究了失眠与骨密度之间的关系。骨密度是通过小腿骨定量超声波测定的,并以占青壮年平均值的百分比(%YAM)表示。共纳入了 896 名男性和 821 名女性。男性的中位年龄为 54 岁(四分位数间距 [IQR]:46 至 64 岁),女性为 55 岁(四分位数间距 [IQR]:46 至 64 岁)。男性和女性的 BMD 中位数分别为 79%YAM(IQR:71 至 89)和 75%YAM(IQR:68 至 84)。约 80% 的男性和女性每天睡 7 小时。多变量回归显示,男性睡眠时间与 BMD 之间没有关联。然而,与睡眠时间为 7 至 9 小时的女性相比,每天睡眠 5 至 7 小时的女性的 BMD 明显增加了 3.9%(p = 0.004)。失眠与 BMD 之间没有关联。总体而言,与睡眠时间为 7 到 9 小时的男性和女性相比,每天睡眠时间为 7 小时的男性和女性与较低的 BMD 无关。不过,由于有证据表明,睡眠时间的长短与不良事件(包括心血管事件)的风险增加有关,因此需要谨慎解释我们的结果。© 2023 作者。JBMR Plus 由 Wiley Periodicals LLC 代表美国骨矿研究学会出版。
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引用次数: 0
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