Rheumatoid Arthritis and Osteoporosis as Prototypes of Immunosenescence in Osteoimmunology: Molecular Pathways of Inflammaging and Targeted Therapies.

Immunosenescence refers to the set of immunoendocrinological alterations underlying the progressive decline in innate and adaptive immune function that occurs with aging. It is closely linked to the concept of inflammaging, a state of low-grade chronic systemic inflammation that contributes to age-related diseases. In the elderly, key features of diseases such as rheumatoid arthritis, particularly in its elderly onset form, and senile osteoporosis are characterized by a decline in sex hormones and the immunoregulatory IL-2; an increase in serum autoantibodies and pro-inflammatory mediators such as TNF-α, IL-6; and upregulation of bone-related factors RANKL, DKK1, and sclerostin, including the dysregulation of the IL-33/IL-31 axis. The aim of this review is to examine the key molecular pathways of immunosenescence in osteoimmunology, as well as the potential for therapeutic modulation of inflammaging through biologic and target synthetic disease-modifying antirheumatic drugs, denosumab and romosozumab, with particular attention to their management in elderly patients.