Vol. 11, Issue 3 (2025)

Denosumab, a monoclonal antibody targeting receptor activator of nuclear factor kappa-B ligand (RANKL), has emerged as a promising therapeutic agent in orthopaedics beyond its initial indication for osteoporosis. Denosumab effectively reduces bone resorption and increases bone mass by inhibiting osteoclast formation and function. Recent studies have demonstrated its potential in fracture healing with no significant delay in radiological or clinical healing. Denosumab's antiresorptive properties also make it a viable candidate for preventing periprosthetic bone loss and improving implant longevity. In orthopaedic oncology, denosumab has shown remarkable efficacy in the treatment of giant cell tumors of the bone (GCTB), facilitating en bloc resection, reducing surgical morbidity, and improving tumor resectability. However, Denosumab therapy is associated with risks including a rebound effect upon discontinuation, hypocalcemia, atypical femur fractures, and osteonecrosis of the jaw. Careful monitoring of the duration of therapy and tapering are crucial for mitigating adverse effects. Future research should explore the potential of denosumab in enhancing spinal fusion, preventing aseptic loosening, and as an adjunct in bone cyst management. With growing evidence and expanding indications, denosumab is poised to become an integral part of the orthopaedic pharmacological arsenal; however, its use warrants caution and further long-term safety data.