Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA.
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
J Bone Miner Res. 2022 Aug;37(8):1417-1434. doi: 10.1002/jbmr.4643. Epub 2022 Jul 28.
Disuse and aging are known risk factors associated with low bone mass and quality deterioration, resulting in increased fracture risk. Indeed, current and emerging evidence implicate a large number of shared skeletal manifestations between disuse and aging scenarios. This review provides a detailed overview of current preclinical models of musculoskeletal disuse and the clinical scenarios they seek to recapitulate. We also explore and summarize the major similarities between bone loss after extreme disuse and advanced aging at multiple length scales, including at the organ/tissue, cellular, and molecular level. Specifically, shared structural and material alterations of bone loss are presented between disuse and aging, including preferential loss of bone at cancellous sites, cortical thinning, and loss of bone strength due to enhanced fragility. At the cellular level bone loss is accompanied, during disuse and aging, by increased bone resorption, decreased formation, and enhanced adipogenesis due to altered gap junction intercellular communication, WNT/β-catenin and RANKL/OPG signaling. Major differences between extreme short-term disuse and aging are discussed, including anatomical specificity, differences in bone turnover rates, periosteal modeling, and the influence of subject sex and genetic variability. The examination also identifies potential shared mechanisms underlying bone loss in aging and disuse that warrant further study such as collagen cross-linking, advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling, reactive oxygen species (ROS) and nuclear factor κB (NF-κB) signaling, cellular senescence, and altered lacunar-canalicular connectivity (mechanosensation). Understanding the shared structural alterations, changes in bone cell function, and molecular mechanisms common to both extreme disuse and aging are paramount to discovering therapies to combat both age-related and disuse-induced osteoporosis. © 2022 American Society for Bone and Mineral Research (ASBMR).
废用和衰老已知是与低骨量和质量恶化相关的风险因素，导致骨折风险增加。事实上，目前和新出现的证据表明，废用和衰老情况下存在大量共同的骨骼表现。这篇综述详细概述了肌肉骨骼废用的当前临床前模型及其试图重现的临床情况。我们还探索并总结了在多个长度尺度上，包括器官/组织、细胞和分子水平上，极端废用后和高级衰老之间骨丢失的主要相似性。具体来说，在废用和衰老之间呈现了骨丢失的共同结构和材料改变，包括松质骨部位的骨丢失优先、皮质变薄以及由于脆性增加而导致骨强度丧失。在细胞水平上，废用和衰老期间伴随着骨吸收增加、形成减少和脂肪生成增加，这是由于细胞间隙连接细胞间通讯、WNT/β-catenin 和 RANKL/OPG 信号的改变所致。讨论了极端短期废用和衰老之间的主要差异，包括解剖学特异性、骨转换率、骨膜建模以及受试者性别和遗传变异性的影响。该检查还确定了衰老和废用导致骨丢失的潜在共同机制，这些机制值得进一步研究，例如胶原交联、晚期糖基化终产物/晚期糖基化终产物受体 (AGE-RAGE) 信号、活性氧 (ROS) 和核因子 kB (NF-κB) 信号、细胞衰老和腔隙-小管连通性改变（机械感觉）。了解极端废用和衰老共有的结构改变、骨细胞功能变化和分子机制对于发现治疗年龄相关性和废用性骨质疏松症的疗法至关重要。© 2022 美国骨骼矿物质研究协会 (ASBMR)。
