Cheng Xinyi, Chen Yida, Zhou Xichao, Gu Qiaoli, Zhao Huan, Wan Chao, Chen Mimi, Yang Huilin, Shi Qin
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute of Soochow University, 899 Pinghai Road, Suzhou, 215031, Jiangsu, China.
Key Laboratory of Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China.
J Orthop Translat. 2025 Jul 25;53:325-335. doi: 10.1016/j.jot.2025.06.015. eCollection 2025 Jul.
Osteoporosis (OP) is a serious public health problem affecting the elderly worldwide. The immune system is well-known to play an important role in bone metabolism and formation. However, immunosenescence, defined as the gradual deterioration of immune system function with aging, has become one of the key factors that drive OP, referred to as immunoporosis. Immune cells may experience substantial functional and phenotypic alterations with aging, disturbing the intricate balance between bone formation and resorption, ultimately leading to bone loss and fragility. These alterations promote osteoclastogenesis and impair osteogenesis through the release of senescence-associated secretory phenotype (SASP) factors and other signaling pathways, a phenomenon referred to as "inflammaging". Accordingly, the present review summarizes the latest findings on the interplay between immunosenescence and bone biology, with a purpose to shed light on the molecular and cellular processes that drive the development of OP. This study is anticipated to provide potential reference for developing innovative therapeutic strategies targeting immunosenescence to rescue bone fragility and enhance skeletal health in older adults. The Translational potential statement: This review highlights the role of immunosenescence in the development of OP and suggests it as a possible treatment target. We summarize the mechanisms of senescent immune cells affecting bone metabolism balance and removing these cells or blocking their secretions [e.g., SASPs] in reducing bone loss. Several preclinical studies have shown that drugs targeting immunosenescence can improve bone health in animal models. Recent clinical studies also report links between immunosenescence markers (e.g., CD4 CD28 T cells, TNF-α, and IL 6) and low bone mineral density. These findings support the idea of using immunosenescence features to identify high risk patients and guide early treatment. By combining basic research with clinical data, this review may provide valuable insights for future immune based therapies for OP.
骨质疏松症(OP)是一个严重的公共卫生问题,影响着全球老年人。众所周知,免疫系统在骨骼代谢和形成中起着重要作用。然而,免疫衰老,即免疫系统功能随年龄增长而逐渐衰退,已成为导致OP(称为免疫性骨质疏松症)的关键因素之一。免疫细胞可能会随着年龄增长而经历大量功能和表型改变,扰乱骨形成与骨吸收之间的复杂平衡,最终导致骨质流失和骨骼脆弱。这些改变通过衰老相关分泌表型(SASP)因子的释放和其他信号通路促进破骨细胞生成并损害成骨作用,这种现象称为“炎症衰老”。因此,本综述总结了免疫衰老与骨生物学相互作用的最新研究结果,旨在阐明驱动OP发展的分子和细胞过程。预计这项研究将为开发针对免疫衰老的创新治疗策略提供潜在参考,以挽救老年人的骨骼脆弱并增强骨骼健康。转化潜力声明:本综述强调了免疫衰老在OP发展中的作用,并将其作为一个可能的治疗靶点。我们总结了衰老免疫细胞影响骨代谢平衡的机制,以及清除这些细胞或阻断其分泌[如SASP]以减少骨质流失的机制。几项临床前研究表明,针对免疫衰老的药物可以改善动物模型中的骨骼健康。最近的临床研究也报告了免疫衰老标志物(如CD4 CD28 T细胞、TNF-α和IL 6)与低骨密度之间的联系。这些发现支持利用免疫衰老特征识别高危患者并指导早期治疗的观点。通过将基础研究与临床数据相结合,本综述可能为未来基于免疫的OP治疗提供有价值的见解。