IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-25 DOI: 10.1016/j.bone.2024.117264

Hongjiang Yang , Bo Li , Hailiang Li , Mi Zhou , Baicao Li , Junrui Guo , Hao Zhong , Song Liu , Qi Zhang , Cong Xing , Guangzhi Ning

Purpose

To assess the independent and joint effect of physical activity, sleep duration, and daily sitting time on bone mineral density (BMD), based on National Health and Nutrition Examination Survey (NHANES) 2007–2018.

Design

Cross-sectional design.

Methods

The primary outcome was risk of low BMD. All associations between lifestyle factors and the prevalence of low BMD were based on logistic regression, and dose-response relationships were further explored by restricted cubic spline (RCS). Finally, multiplicative and additive interaction was examined by P _interaction and relative excess risk due to interaction (RERI).

Results

10,346 individuals (N _{normal BMD} = 6353; N _{Low BMD} = 3993) were analyzed. Multivariate logistic regression indicated low intensity physical activity (odds ratio [OR] 0.84; 95 % confidence interval [95%CI] 0.78–0.90) and high intensity physical activity (0.67, 0.56–0.78) had protective impact on risk of low BMD, whereas short sleep (1.41, 1.20–1.64), long sleep (1.36, 1.03–1.79) and prolonged daily sitting (1.58, 1.32–1.88) had harmful effect. RCS revealed dose-response associations between physical activity (J-shaped), sleep duration (U-shaped), daily sitting time (positive-associated) and risk of low BMD. Multiplicative interaction between sleep duration and physical activity was observed (P _interaction = 0.003), while not between daily sitting time and physical activity (P _interaction = 0.600). Notably, negative additive interactions indicated that physical activity mitigated the increased risk of low BMD associated with irregular sleep patterns and prolonged sedentary behavior.

Conclusion

Increasing physical activity was presented as a modulating factor, potentially altering the relationship between independent variables that have deleterious effects on BMD like sleep duration and sedentary behavior. The study underscores the importance of lifestyle modifications in the prevention of early onset low BMD.

目的：根据2007-2018年美国国家健康与营养调查（NHANES），评估体力活动、睡眠时间和每日坐姿时间对骨矿物质密度（BMD）的独立和联合影响：设计：横断面设计：主要结果是低 BMD 风险。生活方式因素与低 BMD 患病率之间的所有关联均基于逻辑回归，剂量-反应关系则通过受限立方样条曲线（RCS）进一步探讨。最后，通过P交互作用和交互作用导致的相对超额风险（RERI）检验了乘法和加法交互作用：分析了 10346 人（正常 BMD = 6353 人；低 BMD = 3993 人）。多变量逻辑回归显示，低强度体力活动（几率比 [OR] 0.84；95% 置信区间 [95%CI] 0.78-0.90）和高强度体力活动（0.67，0.56-0.78）对低 BMD 风险具有保护作用，而短睡眠（1.41，1.20-1.64）、长睡眠（1.36，1.03-1.79）和每天久坐（1.58，1.32-1.88）则具有有害作用。RCS显示，体力活动（J形）、睡眠时间（U形）、每日久坐时间（正相关）与低BMD风险之间存在剂量-反应关系。睡眠时间与体力活动之间存在乘法交互作用（P 交互作用 = 0.003），而每日久坐时间与体力活动之间不存在乘法交互作用（P 交互作用 = 0.600）。值得注意的是，负相加相互作用表明，体育锻炼可减轻与不规律睡眠模式和长期久坐行为相关的低 BMD 风险的增加：增加体育锻炼是一个调节因素，有可能改变睡眠时间和久坐行为等对 BMD 有不利影响的自变量之间的关系。这项研究强调了改变生活方式对预防早发低 BMD 的重要性。

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引用次数: 0

Post-traumatic osteoarthritic-mediated changes in condylar shape do not covary with changes in the internal microstructure of the bone 创伤后骨关节炎引起的髁状突形状变化与骨骼内部微观结构的变化无关。

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-21 DOI: 10.1016/j.bone.2024.117263

Zach Skabelund , Dakshina Acharya , Jonathan Banks, Minahil Chaudhry, Chun-Chieh Huang, Christina Nicholas, David Reed

Post-traumatic osteoarthritis (PTOA) in the temporomandibular joint (TMJ) is associated with remodeling of the subchondral bone. This remodeling changes both the external appearance of the condylar bone and the internal bony microstructure. The external geometry can be quantified using shape, a multivariate mathematical measurement that contains all of the structure's geometric information with location, scale, and rotation effects removed. There is an important gap in knowledge related to how TMJ PTOA affects the shape of the mandible and if the external shape covaries with the internal bony microstructure. To evaluate these gaps, TMJ PTOA was induced in male and female skeletally mature mice using a surgical destabilization procedure. After four weeks, tissues were collected and characterized using a high-resolution μCT scanner. Shape was calculated from surface reconstructions of the mandibular condyle, and the internal bony microstructure was characterized by the region of interest including the subchondral trabeculae. The covariance of shape with and without corrections for allometric scaling and internal bony microstructure was calculated using a Procrustes ANOVA. The data illustrate that PTOA significantly alters the shape of the condyle in a sex-independent manner. PTOA does alter some aspects of the internal bony microstructure in a sex-dependent manner. Allometric scaling was a significant factor in the variance of shape. Shape including the effects of allometric scaling significantly covaries with some internal bony microstructure variables in both sexes. Shape scaled to remove the effects of allometric scaling does not covary with internal bony microstructure in either sex. These findings indicate that PTOA progression is associated with changes in the size and shape of the condyle but variance in trabecular bone remodeling is only associated with size related shape change. Thus, the allostatic response of subchondral bone is multimodal, coordinating two independent biological processes controlling size and shape. Since subchondral bone participates in and guides the progression of PTOA, these findings have implications for identifying select and specific mechanisms contributing to the progression and pathophysiology of the PTOA in the TMJ.

颞下颌关节（TMJ）创伤后骨关节炎（PTOA）与软骨下骨的重塑有关。这种重塑既改变了髁突骨的外部外观，也改变了内部骨质的微观结构。外部几何形状可以通过形状进行量化，形状是一种多元数学测量方法，它包含了结构的所有几何信息，并消除了位置、比例和旋转效应。关于颞下颌关节损伤如何影响下颌骨的形状，以及外部形状是否与内部骨性微观结构相关，目前还存在重要的知识空白。为了评估这些差距，我们使用外科手术失稳程序诱导骨骼成熟的雌雄小鼠进行颞下颌关节 PTOA 试验。四周后，收集组织并使用高分辨率μCT扫描仪进行特征描述。根据下颌骨髁状突的表面重建计算形状，并通过包括软骨下小梁在内的感兴趣区表征内部骨性微结构。使用 Procrustes 方差分析计算了经过和未经过异轴缩放和内部骨性微结构校正的形状协方差。数据表明，PTOA 显著改变了髁状突的形状，且与性别无关。PTOA 确实以性别依赖的方式改变了内部骨骼微观结构的某些方面。异轴缩放是造成形状差异的一个重要因素。包括异速缩放效应在内的形状与两性的某些内部骨骼微观结构变量有显著的共线关系。去除异速缩放效应的形状缩放与男女两性的内部骨骼微观结构均不相关。这些研究结果表明，PTOA 的进展与髁状突的大小和形状变化有关，但小梁骨重塑的变化仅与大小相关的形状变化有关。因此，软骨下骨的异位反应是多模式的，协调着控制尺寸和形状的两个独立生物过程。由于软骨下骨参与并引导了 PTOA 的进展，这些发现对确定导致颞下颌关节 PTOA 进展和病理生理学的特定机制具有重要意义。

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引用次数: 0

Preventive effects of transcutaneous CO2 application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model 经皮二氧化碳应用对大鼠后肢悬吊模型中废用性骨质疏松症和肌肉萎缩的预防作用

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-18 DOI: 10.1016/j.bone.2024.117262

Ryota Nishida , Tomoaki Fukui , Takahiro Niikura , Yohei Kumabe , Ryo Yoshikawa , Kyohei Takase , Yuya Yamamoto , Ryosuke Kuroda , Keisuke Oe

We previously demonstrated that transcutaneous CO₂ application promotes muscle fiber-type switching, fracture healing, and osteogenesis by increasing blood flow and angiogenesis. Here, we aimed to investigate the preventive effects of transcutaneous CO₂ application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model. Eleven-week-old male Sprague-Dawley rats were divided into hindlimb suspension (HS), HS with transcutaneous CO₂ application (HSCO₂), and control groups. HSCO₂ rats were administered transcutaneous 100 % CO₂ gas in their bilateral hindlimbs, five times a week for 20 min. After 3 weeks, we harvested the gastrocnemius, femur, and tibia for assessment. Histological analysis revealed a significant decrease in the gastrocnemius myofiber cross-sectional area in HS rats compared to the control rats, whereas HSCO₂ rats exhibited a significant increase compared to HS rats. Micro-computed tomography showed significant bone atrophy in the trabecular and cortical bones of the femur in HS rats compared to those of the control rats, whereas significant improvement was noted in HSCO₂ rats. Histological analysis of the proximal tibia revealed more marrow adipose tissue in the HS rats than in the control rats. However, in the HSCO₂ rats, fewer marrow adipose tissue and osteoclasts were observed. Moreover, HSCO₂ rats had more osteoblasts and higher expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and vascular endothelial growth factor (VEGF) than the HS rats. The gastrocnemius and distal femur of HSCO₂ rats also exhibited elevated PGC-1α and VEGF expression and upregulation of the myogenesis markers and osteogenesis markers compared to those of HS rats. This treatment effectively prevented disuse osteoporosis and muscle atrophy by promoting local angiogenesis and blood flow. PGC-1α is crucial for promoting this angiogenic pathway. Transcutaneous CO₂ application may be a novel preventive procedure for disuse osteoporosis and muscle atrophy, complementing medication and rehabilitation.

我们曾证实，经皮施用二氧化碳可通过增加血流量和血管生成促进肌肉纤维类型转换、骨折愈合和骨生成。在此，我们旨在研究经皮施用二氧化碳对大鼠后肢悬吊模型中废用性骨质疏松症和肌肉萎缩的预防作用。将 11 周大的雄性 Sprague-Dawley 大鼠分为后肢悬吊组（HS）、经皮施用二氧化碳的 HS 组（HSCO2）和对照组。HSCO2 组大鼠的双侧后肢经皮通入 100% CO2 气体，每周 5 次，每次 20 分钟。3 周后，我们采集腓肠肌、股骨和胫骨进行评估。组织学分析表明，与对照组大鼠相比，HS大鼠的腓肠肌肌纤维横截面积明显减少，而与HS大鼠相比，HSCO2大鼠的腓肠肌肌纤维横截面积明显增加。显微计算机断层扫描显示，与对照组大鼠相比，HS 大鼠股骨的骨小梁和皮质骨明显萎缩，而 HSCO2 大鼠则有明显改善。胫骨近端组织学分析显示，HS 大鼠的骨髓脂肪组织多于对照组大鼠。然而，在 HSCO2 大鼠中观察到的骨髓脂肪组织和破骨细胞较少。此外，与 HS 大鼠相比，HSCO2 大鼠有更多的成骨细胞，过氧化物酶体增殖激活受体γ辅助激活剂 1-α（PGC-1α）和血管内皮生长因子（VEGF）的表达量也更高。与 HS 大鼠相比，HSCO2 大鼠的腓肠肌和股骨远端也显示出 PGC-1α 和血管内皮生长因子表达的升高，以及肌生成标志物和骨生成标志物的上调。这种治疗方法通过促进局部血管生成和血流，有效预防了废用性骨质疏松症和肌肉萎缩。PGC-1α是促进这一血管生成途径的关键。经皮施用二氧化碳可能是一种新型的废用性骨质疏松症和肌肉萎缩的预防方法，可作为药物治疗和康复治疗的补充。

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引用次数: 0

The effects of all-trans retinoic acid on prednisolone-induced osteoporosis in zebrafish larvae 全反式维甲酸对泼尼松龙诱导的斑马鱼幼体骨质疏松症的影响

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-18 DOI: 10.1016/j.bone.2024.117261

Ting Yu , Manci Chen , Jing Wen , Juan Liu , Ke Li , Lei Jin , Jiang Yue , Zheqiong Yang , Jinlei Xi

Glucocorticoids (GCs) are extensively used as anti-inflammatory and immunosuppressive medications in the long-term treatment of rheumatic disorders, respiratory diseases, renal diseases, and organ transplantation. Prolonged use of GCs can reduce bone mineral density, leading to osteoporosis (Glucocorticoid Induced Osteoporosis, GIOP) and fracture. All-trans retinoic acid (ATRA) is an active vitamin A metabolite that regulates embryonic development and adult organ function. ATRA has been found in studies to enhance osteogenesis. To examine the interventional effects of ATRA on GIOP and the mechanisms of ATRA activities, we first performed bioinformatic analysis to identify potential gene targets of ATRA. Zebrafish larvae were recruited as experimental animals, and the frequently used GC, prednisolone, was administered to larvae to construct a GIOP model. We evaluated the influence of exogenous ATRA on the activities of bone metabolic enzymes, the expression of genes linked to osteoblasts and osteoclasts, and the restoration of bone mineral density and bone mass in GIOP zebrafish larvae. Furthermore, we studied the influence of RBM14, a transcriptional coactivator and negative reciprocal factor of ATRA, on the regulation of osteoblastic gene expression during the anti-GIOP process of ATRA using the morpholino knockdown approach. The findings of bone metabolic enzyme activity (alkaline phosphatase, ALP and tartrate-resistant acid phosphatase, TRAP) and expression assays of osteoblastic marker genes (Runx2a, Runx2b, SP7, Csf1a, RANKL, and CTSK) indicated that ATRA had bidirectional effects on osteogenesis. However, in the GIOP model, ATRA reversed the GIOP-induced osteoporosis phenotype by inhibiting the GIOP-induced suppression of osteoblastic metabolic enzyme (ALP) activities and osteoblastic marker gene expression (Runx2a, Runx2b, and SP7), and this antagonism was concentration-dependent. We also observed that ATRA inhibited RBM14 expression in zebrafish larvae, while ATRA alone and RBM14 knockdown showed a consistent induction of osteoblast marker gene expression, implying that ATRA's inhibitory effect on RBM14 expression may underlie ATRA's osteogenic effects. Based on these data, we postulated that ATRA may ameliorate GIOP by decreasing RBM14 expression, thereby enhancing osteoblastic marker gene expression.

糖皮质激素（GCs）被广泛用作抗炎和免疫抑制剂，长期用于治疗风湿性疾病、呼吸系统疾病、肾脏疾病和器官移植。长期使用糖皮质激素会降低骨质密度，导致骨质疏松症（糖皮质激素诱发骨质疏松症，GIOP）和骨折。全反式维甲酸（ATRA）是一种活性维生素 A 代谢物，可调节胚胎发育和成人器官功能。研究发现，ATRA 可促进骨生成。为了研究 ATRA 对 GIOP 的干预作用以及 ATRA 的活动机制，我们首先进行了生物信息学分析，以确定 ATRA 的潜在基因靶标。我们将斑马鱼幼体作为实验动物，并给幼体注射常用的GC--泼尼松龙来构建GIOP模型。我们评估了外源性 ATRA 对 GIOP 斑马鱼幼体骨代谢酶活性、成骨细胞和破骨细胞相关基因表达以及骨矿密度和骨量恢复的影响。此外，我们还利用吗啡基诺敲除法研究了 ATRA 在抗 GIOP 过程中转录辅激活剂和负互作因子 RBM14 对成骨细胞基因表达调控的影响。骨代谢酶活性（碱性磷酸酶（ALP）和耐酒石酸磷酸酶（TRAP））和成骨细胞标记基因（Runx2a、Runx2b、SP7、Csf1a、RANKL和CTSK）的表达检测结果表明，ATRA对成骨具有双向作用。然而，在 GIOP 模型中，ATRA 通过抑制 GIOP 诱导的成骨代谢酶（ALP）活性和成骨标志基因（Runx2a、Runx2b 和 SP7）表达，逆转了 GIOP 诱导的骨质疏松症表型，而且这种拮抗作用是浓度依赖性的。我们还观察到，ATRA 可抑制 RBM14 在斑马鱼幼体中的表达，而单独使用 ATRA 和 RBM14 基因敲除均可诱导成骨细胞标记基因的表达，这意味着 ATRA 对 RBM14 表达的抑制作用可能是 ATRA 成骨作用的基础。基于这些数据，我们推测 ATRA 可能通过降低 RBM14 的表达来改善 GIOP，从而增强成骨细胞标记基因的表达。

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引用次数: 0

Psoas muscle cross sectional area relates to bone density and microarchitecture in candidates for spine fusion surgery 腰肌横截面积与脊柱融合手术候选者骨密度和微结构的关系

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-18 DOI: 10.1016/j.bone.2024.117259

Joseph Raphael, Giavanna D'Erasmo, Jeri Nieves, Sravisht Iyer, Ryan Breighner, Alexander Dash, Emma Billings, Junho Song, Han Jo Kim, Sheeraz Qureshi, Matthew Cunningham, Emily Stein

Prior studies demonstrate that muscle and bone health are integrally related, and both independently impact orthopedic surgery outcomes. However, relationships between bone density, in vivo microarchitecture, and muscle area have not been previously investigated in orthopedic surgery patients. This study assessed associations between psoas cross sectional area (CSA), bone mineral density (BMD), and microstructure in a cohort undergoing spine fusion. Pre-operatively, bilateral psoas CSA was measured on axial lumbar spine CT in the L3-L4 disc space. To adjust for body size, Psoas Muscle Index (PMI) was calculated (CSA divided by the square of patient height). High resolution peripheral quantitative CT (HR-pQCT, XtremeCT2) assessed volumetric BMD (vBMD), cortical (Ct) and trabecular (Tb) microarchitecture at the distal radius and tibia. Areal BMD (aBMD) was measured by DXA at the lumbar spine (LS), total hip (TH), femoral neck (FN), and the 1/3 radius (1/3R). Pearson correlations related psoas CSA and bone imaging parameters before and after correcting for height and weight. Among 88 patients included, mean age was 63 ± 12 years, BMI was 28 ± 7 kg/m², 47 (53 %) were female. Larger psoas CSA was associated with higher vBMD, greater Ct thickness and better Tb microarchitecture (higher Tb number and lower Tb separation) at the tibia and radius. Larger psoas CSA was also associated with greater aBMD at TH and FN bilaterally and 1/3R (r 0.33 to 0.61; p < 0.002 for all comparisons). Psoas CSA was not associated with aBMD at the LS. Similar results were observed when relating PMI, and adjusting for age, height and weight to HR-pQCT and DXA measurements. Investigation of subgroups by sex demonstrated that relationships were similar magnitude among women but not the men. Patients who underwent primary compared to revision spine surgery had similar associations. Our results demonstrate a link between psoas muscle size and peripheral bone microarchitecture among patients undergoing posterior lumbar spinal fusion. Given the importance of both muscle and skeletal integrity to the success of spine surgery, further study regarding the associations between measurements of psoas muscle, bone microarchitecture, and surgical outcomes is warranted.

先前的研究表明，肌肉和骨骼的健康状况密切相关，两者都会对骨科手术的结果产生独立的影响。然而，此前尚未对骨科手术患者的骨密度、体内微结构和肌肉面积之间的关系进行过研究。本研究评估了接受脊柱融合术的人群中腰肌横截面积（CSA）、骨矿密度（BMD）和微结构之间的关系。术前，在 L3-L4 椎间盘间隙的轴向腰椎 CT 上测量双侧腰肌 CSA。为了调整体型，计算了腰肌指数（PMI）（CSA 除以患者身高的平方）。高分辨率外周定量 CT（HR-pQCT，XtremeCT2）评估了桡骨和胫骨远端的体积 BMD（vBMD）、皮质（Ct）和小梁（Tb）微结构。腰椎（LS）、全髋（TH）、股骨颈（FN）和桡骨1/3（1/3R）的面积BMD（aBMD）是通过DXA测量的。在校正身高和体重前后，腰肌CSA与骨成像参数之间存在皮尔逊相关性。88 名患者的平均年龄为 63 ± 12 岁，体重指数为 28 ± 7 kg/m2，其中 47 人（53%）为女性。腰肌CSA越大，胫骨和桡骨的vBMD越高、Ct厚度越大、Tb微结构越好（Tb数量越多、Tb分离度越低）。腰肌CSA越大，双侧TH和FN以及1/3R的aBMD也越大（r为0.33至0.61；所有比较的p均为0.002）。腰肌 CSA 与 LS 的 aBMD 无关。在将 PMI 与 HR-pQCT 和 DXA 测量值联系起来并对年龄、身高和体重进行调整后，也观察到了类似的结果。按性别划分的亚组调查显示，女性之间的关系程度相似，而男性之间的关系程度则不尽相同。接受初次脊柱手术的患者与接受翻修脊柱手术的患者之间的关系相似。我们的研究结果表明，在接受腰椎后路融合术的患者中，腰肌大小与外周骨骼微结构之间存在联系。鉴于肌肉和骨骼的完整性对脊柱手术的成功非常重要，因此有必要进一步研究腰肌、骨微结构和手术结果之间的关联。

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引用次数: 0

Cyclophilin D, regulator of the mitochondrial permeability transition, impacts bone development and fracture repair 线粒体通透性转换调节器环嗜蛋白 D 影响骨骼发育和骨折修复

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-18 DOI: 10.1016/j.bone.2024.117258

Rubens Sautchuk Jr , John Martinez , Sarah E. Catheline , Roman A. Eliseev

Mitochondrial Permeability Transition Pore (MPTP) and its key positive regulator, Cyclophilin D (CypD), control activity of cell oxidative metabolism important for differentiation of stem cells of various lineages including osteogenic lineage. Our previous work (Sautchuk et al., 2022) showed that CypD gene, Ppif, is transcriptionally repressed during osteogenic differentiation by regulatory Smad transcription factors in BMP canonical pathway, a major driver of osteoblast (OB) differentiation. Such a repression favors closure of the MPTP, priming OBs to higher usage of mitochondrial oxidative metabolism. The physiological role of CypD/MPTP regulation was demonstrated by its inverse correlation with BMP signaling in aging and bone fracture healing in addition to the negative effect of CypD gain-of-function (GOF) on bone maintenance. Here we show evidence that CypD GOF also negatively affects bone development and growth as well as fracture healing in adult mice. Developing craniofacial and long bones presented with delayed ossification and decreased growth rate, respectively, whereas in fracture, bony callus volume was diminished. Given that Genome Wide Association Studies showed that PPIF locus is associated with both body height and bone mineral density, our new data provide functional evidence for the role of PPIF gene product, CypD, and thus MPTP in bone growth and repair.

线粒体通透性转换孔（MPTP）及其关键正调控因子环嗜蛋白D（CypD）控制着细胞氧化代谢的活性，对包括成骨系在内的各种系的干细胞分化非常重要。我们之前的研究（Sautchuk 等人，2022 年）表明，在成骨分化过程中，CypD 基因 Ppif 会被成骨细胞（OB）分化的主要驱动因素 BMP 标准途径中的调控 Smad 转录因子转录抑制。这种抑制有利于 MPTP 的闭合，使 OB 更多利用线粒体氧化代谢。CypD/MPTP调节的生理作用体现在它与衰老和骨折愈合中的BMP信号的反相关性，以及CypD功能增益（GOF）对骨维持的负面影响。在这里，我们展示的证据表明，CypD GOF 也会对成年小鼠的骨骼发育和生长以及骨折愈合产生负面影响。发育中的颅面骨和长骨分别出现骨化延迟和生长速度下降的现象，而在骨折中，骨胼胝体体积减少。鉴于全基因组关联研究表明 PPIF 基因位点与身高和骨矿物质密度有关，我们的新数据为 PPIF 基因产物 CypD 以及 MPTP 在骨生长和修复中的作用提供了功能性证据。

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引用次数: 0

Corrigendum to “Interaction of high lipogenic states with titanium on osteogenesis” [Bone 188 (2024) 117242] 高脂生成态与钛对骨生成的相互作用"[Bone 188 (2024) 117242] 更正

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-18 DOI: 10.1016/j.bone.2024.117256

T.S. Pinto , B.C. van der Eerden , M. Schreuders-Koedam , J. van de Peppel , I. Ayada , Q. Pan , M.M. Verstegen , L.J. van der Laan , G.M. Fuhler , W.F. Zambuzzi , M.P. Peppelenbosch

引用次数: 0

The effects of endurance trainability phenotype, sex, and interval running training on bone collagen synthesis in adult rats 耐力训练表型、性别和间歇性跑步训练对成年大鼠骨胶原合成的影响。

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-17 DOI: 10.1016/j.bone.2024.117257

Rita Civil , Matthew S. Brook , Lívia Santos , Ian Varley , Kirsty J. Elliott-Sale , Sanna Lensu , Juha P. Ahtiainen , Heikki Kainulainen , Lauren G. Koch , Steven L. Britton , Daniel J. Wilkinson , Kenneth Smith , Philip J. Atherton , Craig Sale

Bone is influenced by many factors such as genetics and mechanical loading, but the short-term physiological effects of these factors on bone (re)modelling are not well characterised. This study investigated the effects of endurance trainability phenotype, sex, and interval running training (7-week intervention) on bone collagen formation in rats using a deuterium oxide stable isotope tracer method. Bone samples of the femur diaphysis, proximal tibia, mid-shaft tibia, and distal tibia were collected after necropsy from forty-six 9 ± 3-month male and female rats selectively bred for yielding low (LRT) or high (HRT) responses to endurance training. Bone collagen proteins were isolated and hydrolysed, and fractional synthetic rates (FSRs) were determined by the incorporation of deuterium into protein-bound alanine via GC-pyrolysis-IRMS. There was a significant large main effect of phenotype at the femur site (p < 0.001; η²_g = 0.473) with HRT rats showing greater bone collagen FSRs than LRT rats. There was a significant large main effect of phenotype (p = 0.008; η²_g = 0.178) and a significant large main effect of sex (p = 0.005; η²_g = 0.196) at the proximal site of the tibia with HRT rats showing greater bone collagen FSRs than LRT rats, and male rats showing greater bone collagen FSRs compared to female rats. There was a significant large main effect of training at the mid-shaft site of the tibia (p = 0.012; η²_g = 0.159), with rats that underwent interval running training having greater bone collagen FSRs than control rats. Similarly, there was a significant large main effect of training at the distal site of the tibia (p = 0.050; η²_g = 0.156), with rats in the interval running training group having greater bone collagen FSRs compared to rats in the control group. Collectively, this evidence highlights that bone responses to physiological effects are site-specific, indicating that interval running training has positive effects on bone collagen synthesis at the tibial mid-shaft and distal sites, whilst genetic factors affect bone collagen synthesis at the femur diaphysis (phenotype) and proximal tibia (phenotype and sex) in rats.

骨骼受遗传和机械负荷等多种因素的影响，但这些因素对骨骼（再）建模的短期生理影响尚未得到很好的描述。本研究采用氧化氘稳定同位素示踪法研究了耐力训练表型、性别和间歇性跑步训练（7 周干预）对大鼠骨胶原形成的影响。在对 46 只 9 ± 3 个月大的雄性和雌性大鼠进行尸检后收集了股骨干骺端、胫骨近端、胫骨中轴和胫骨远端的骨骼样本，这些大鼠经过选择性饲养，对耐力训练的反应较低（LRT）或较高（HRT）。分离并水解骨胶原蛋白，通过气相色谱-热解-质谱仪（GC-pyrolysis-IRMS）将氘掺入蛋白结合的丙氨酸中，测定分数合成率（FSR）。在股骨部位，HRT 大鼠比 LRT 大鼠显示出更大的骨胶原 FSR，表型的主效应非常明显（p 2g = 0.473）。表型（p = 0.008；η2g = 0.178）和性别（p = 0.005；η2g = 0.196）对胫骨近端部位有显著的大主效应，HRT 大鼠比 LRT 大鼠显示出更大的骨胶原 FSR，雄性大鼠比雌性大鼠显示出更大的骨胶原 FSR。在胫骨中轴部位，训练具有显著的大型主效应（p = 0.012；η2g = 0.159），接受间歇跑步训练的大鼠比对照组大鼠的骨胶原 FSR 更大。同样，胫骨远端部位的训练也存在显著的大主效应（p = 0.050；η2g = 0.156），与对照组大鼠相比，间歇跑训练组大鼠的骨胶原 FSR 更大。总之，这些证据突出表明，骨骼对生理效应的反应是有部位特异性的，表明间歇跑训练对胫骨中轴和远端部位的骨胶原合成有积极影响，而遗传因素则影响大鼠股骨干骺端（表型）和胫骨近端（表型和性别）的骨胶原合成。

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引用次数: 0

BDNF sensitizes bone and joint afferent neurons at different stages of MIA-induced osteoarthritis BDNF能在MIA诱发骨关节炎的不同阶段敏化骨和关节传入神经元。

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-17 DOI: 10.1016/j.bone.2024.117260

Michael Morgan , Vida Nazemian , Jenny Thai , Irene Lin , Susan Northfield , Jason J. Ivanusic

There is emerging evidence that Brain Derived Neurotrophic Factor (BDNF), and one of its receptors TrkB, play important roles in the pathogenesis of osteoarthritis (OA) pain. Whilst these studies clearly highlight the potential for targeting BDNF/TrkB signaling to treat OA pain, the mechanism for how BDNF/TrkB signaling contributes to OA pain remains unclear. In this study, we used an animal model of mono-iodoacetate (MIA)-induced OA, in combination with electrophysiology, behavioral testing, Western blot analysis, and retrograde tracing and immunohistochemistry, to identify roles for BDNF/TrkB signaling in the pathogenesis of OA pain. We found that: 1) TrkB is expressed in myelinated medium diameter neurons that innervate the knee joint and bone in naïve animals; 2) peripheral application of BDNF increases the sensitivity of Aδ, but not C knee joint and bone afferent neurons, in response to mechanical stimulation, in naïve animals; 3) BDNF expression increases in synovial tissue in early MIA-induced OA, when pathology is confined to the joint, and in the subchondral bone in late MIA-induced OA, when there is additional damage to the surrounding bone; and 4) TrkB inhibition reverses MIA-induced changes in the sensitivity of Aδ but not C knee joint afferent neurons early in MIA-induced OA, and Aδ but not C bone afferent neurons late in MIA-induced OA. Our findings suggest that BDNF/TrkB signaling may have a role to play in the pathogenesis of OA pain, through effects on knee joint afferent neurons early in disease when there is inflammation confined to the joint, and bone afferent neurons late in disease when there is involvement of damage to subchondral bone. Targeted manipulation of BDNF/TrkB signaling may provide therapeutic benefit for the management of OA pain.

越来越多的证据表明，脑源性神经营养因子（BDNF）及其受体之一TrkB在骨关节炎（OA）疼痛的发病机制中发挥着重要作用。虽然这些研究明确强调了靶向 BDNF/TrkB 信号转导治疗 OA 疼痛的潜力，但 BDNF/TrkB 信号转导如何导致 OA 疼痛的机制仍不清楚。在这项研究中，我们利用单碘醋酸（MIA）诱导的 OA 动物模型，结合电生理学、行为测试、Western 印迹分析、逆行追踪和免疫组织化学，确定了 BDNF/TrkB 信号在 OA 疼痛发病机制中的作用。我们发现1）TrkB表达于神经支配膝关节和骨的髓鞘中径神经元中；2）在外周应用BDNF可增加膝关节和骨传入神经元Aδ对机械刺激的敏感性，但不能增加C传入神经元对机械刺激的敏感性；3）在 MIA 引起的 OA 早期，滑膜组织中的 BDNF 表达增加，此时病变仅限于关节；在 MIA 引起的 OA 晚期，软骨下骨中的 BDNF 表达增加，此时周围骨质受到额外损伤；4）TrkB抑制可逆转MIA诱导的Aδ膝关节传入神经元（而非C膝关节传入神经元）在MIA诱导的OA早期的敏感性变化，以及Aδ骨传入神经元（而非C骨传入神经元）在MIA诱导的OA晚期的敏感性变化。我们的研究结果表明，当炎症局限于关节时，BDNF/TrkB 信号通过影响膝关节传入神经元，而当软骨下骨受损时，BDNF/TrkB 信号通过影响疾病晚期的骨传入神经元，可能在 OA 疼痛的发病机制中发挥作用。对 BDNF/TrkB 信号的靶向操作可能会为治疗 OA 疼痛带来疗效。

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引用次数: 0

Evaluating the role of biological age in osteoporosis risk among middle-aged and older adults: A nationwide perspective 评估生理年龄在中老年人骨质疏松症风险中的作用：全国视角

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2024-09-14 DOI: 10.1016/j.bone.2024.117255

Guomao Zhu , Buyu Guo , Jinqian Liang

Objectives

This study aimed to investigate the association between biological age acceleration and osteoporosis (OP) risk in middle-aged and older adults using data from the National Health and Nutrition Examination Survey (NHANES). The research focused on analyzing the relationship between two biological aging metrics, Klemera-Doubal Method Age (KDMAge) and Phenotypic Age (PhenoAge), and OP risk.

Methods

The study analyzed data from NHANES, which included 6550 participants aged 50 and above from survey cycles 2005–2010 and 2017–2018. Linear and logistic regression were used to investigate the relationship between biological age acceleration (KDMAgeAccel and PhenoAgeAccel) and OP. Subgroup analysis was performed by age, gender and other factors. Multivariable Cox regression analysis yielded Hazard Ratios (HRs) relating biological age acceleration to mortality were evaluated. The study also considered the mediating roles of body mass index (BMI).

Results

KDMAgeAccel (odds ratio [OR] = 2.34, 95 % CI, 1.72–3.18) and PhenoAgeAccel (OR = 2.03, 95 % CI, 1.48–2.78) were significantly associated with increased OP risk and reduced bone mineral density (BMD). Specifically, higher KDMAgeAccel and PhenoAgeAccel were linked to higher OP prevalence and lower BMD at multiple sites. Subgroup analyses indicated that the association between accelerated biological age acceleration and OP risk was consistent across different demographics. Mediation analysis revealed that BMI partially mediated the relationship between accelerated biological age and OP, although other mechanisms are likely involved. Statistical analysis indicated that individuals with higher biological age metrics had increased mortality risk related to OP.

Conclusion

The findings suggest that accelerated biological age is a robust predictor of OP risk and related mortality. KDMAgeAccel and PhenoAgeAccel could serve as valuable biomarkers for identifying individuals at high risk for OP, guiding preventive strategies.

目的本研究旨在利用美国国家健康与营养调查（NHANES）的数据，调查中老年人的生物年龄加速度与骨质疏松症（OP）风险之间的关系。研究重点分析了克莱默拉-杜巴法年龄（KDMAge）和表型年龄（Phenotypic Age，PhenoAge）这两个生物衰老指标与OP风险之间的关系。研究分析了NHANES的数据，其中包括2005-2010年和2017-2018年调查周期中6550名50岁及以上的参与者。研究采用线性回归和逻辑回归来探讨生物年龄加速度（KDMAgeAccel 和 PhenoAgeAccel）与 OP 之间的关系。根据年龄、性别和其他因素进行了分组分析。通过多变量考克斯回归分析，评估了生物年龄加速与死亡率之间的危险比（HRs）。研究还考虑了体重指数（BMI）的中介作用。结果KDMAgeAccel（比值比 [OR] = 2.34，95 % CI，1.72-3.18）和 PhenoAgeAccel（比值比 = 2.03，95 % CI，1.48-2.78）与 OP 风险增加和骨矿密度（BMD）降低显著相关。具体来说，较高的 KDMAgeAccel 和 PhenoAgeAccel 与 OP 患病率较高和多个部位的 BMD 较低有关。亚组分析表明，生物年龄加速与 OP 风险之间的关系在不同人口统计学中是一致的。中介分析显示，体重指数（BMI）在一定程度上中介了生物年龄加速与 OP 之间的关系，但也可能涉及其他机制。统计分析表明，生物年龄指标较高的个体与 OP 相关的死亡风险增加。KDMAgeAccel和PhenoAgeAccel可作为识别OP高风险人群的重要生物标记物，为预防策略提供指导。

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引用次数: 0

Bone最新文献

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