Abstract

Over 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration of bone structure is associated with impaired bone healing. Fracture healing is a dynamic process which can be divided into four stages. While the initial hematoma generates an inflammatory environment in which mesenchymal stem cells and macrophages orchestrate the framework for repair, angiogenesis and cartilage formation mark the second healing period. In the central region, endochondral ossification favors soft callus development while next to the fractured bony ends, intramembranous ossification directly forms woven bone. The third stage is characterized by removal and calcification of the endochondral cartilage. Finally, the chronic remodeling phase concludes the healing process.Impaired fracture healing due to aging is related to detrimental changes at the cellular level. Macrophages, osteocytes and chondrocytes express markers of senescence, leading to reduced self-renewal and proliferative capacity. A prolonged phase of “inflammaging” results in an extended remodeling phase, characterized by a senescent microenvironment and deteriorating healing capacity. Although there is evidence that in the setting of injury, at least in some tissues, senescent cells may play a beneficial role in facilitating tissue repair, recent data demonstrate that clearing senescent cells enhances fracture repair. In this review, we summarize the physiological as well as pathological processes during fracture healing in endocrine disease and aging in order to establish a broad understanding of the biomechanical as well as molecular mechanisms involved in bone repair.

中文翻译：

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内分泌疾病、衰老和细胞衰老背景下的骨折愈合

摘要

美国每年发生超过 210 万例与年龄相关的骨折，造成巨大的社会经济负担。重要的是，与年龄相关的骨结构退化与骨愈合受损有关。骨折愈合是一个动态过程，可分为四个阶段。虽然最初的血肿会产生炎症环境，间充质干细胞和巨噬细胞在其中协调修复框架，但血管生成和软骨形成标志着第二个愈合期。在中央区域，软骨内骨化有利于软愈伤组织的发育，而在骨折骨端附近，膜内骨化直接形成编织骨。第三阶段的特征是软骨内软骨的去除和钙化。最后，慢性重塑阶段结束了愈合过程。老化导致的骨折愈合受损与细胞水平的有害变化有关。巨噬细胞、骨细胞和软骨细胞表达衰老标志物，导致自我更新和增殖能力降低。延长的“炎症”阶段会导致延长的重塑阶段，其特征是微环境衰老和愈合能力恶化。尽管有证据表明在受伤的情况下，至少在某些组织中，衰老细胞可能在促进组织修复方面发挥有益作用，但最近的数据表明，清除衰老细胞可增强骨折修复。在这篇评论中，