Revolutionizing osteoporosis management: the emerging role of immunotherapeutic and next-generation therapies

Osteoporosis (OsP) is a bone-associated pathologic state defined by low bone mass and reduced bone mineral density (BMD) with susceptibility to fracture. However, conventional therapies have mainly relied on hormonal therapy and resorptive or anabolic drugs. As a novel scientific discipline, osteoimmunology has shown the immune system's role in bone tissue turnover. Osteoclastogenesis can be influenced by pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1beta ( IL-1β), and IL-6. Meanwhile, OsP has been considered a protective factor comprising anti-inflammatory cytokines such as IL-10 and transforming growth factor beta (TGF-beta) and regulatory T cells (Tregs). Therefore, novel immunotherapeutic approaches that are presently available include the use of monoclonal antibodies (mAbs) against the receptor activator of nuclear factor-kappa B (RANK)/RANKL/osteoprotegerin (OPG) system, cytokine manipulation, and Treg expansion. Possible avenues for future research are the ability to manipulate the gut-immune axis using probiotics, the potential cross-talk between bisphosphonates and the immune system, as well as targeting Tregs, macrophages, and mesenchymal stem cells (MSCs). However, there are still concerns about these treatments' effectiveness and side effects. Nevertheless, the patient's immunological status is not constant, and the relationship between aging and immune dysfunction is not fully understood. This review article offers an update on the current understanding of immunotherapeutic approaches in managing OsP and next-generation strategies that aim to develop tailored therapies for bone disorders.