Abstract
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.