AntiRANKL

antiRANKL refers to therapies that inhibit the receptor activator of nuclear factor-kappa B ligand (RANKL), a cytokine essential for osteoclast formation, function, and survival. RANKL is produced by osteoblasts and other stromal cells and binds to RANK on osteoclast precursors to promote bone resorption. By neutralizing RANKL, antiRANKL agents reduce osteoclast-mediated bone loss, helping to preserve bone mass. These therapies are typically monoclonal antibodies that act as decoy inhibitors, functionally opposing the natural osteoprotegerin pathway.

The most clinically used antiRANKL drug is denosumab. It is administered as a subcutaneous injection and is approved for osteoporosis in individuals at risk of fracture, for prevention of skeletal-related events in patients with solid tumors or multiple myeloma with bone involvement, and for treating hypercalcemia of malignancy. Dosing varies by indication, with osteoporosis regimens commonly every six months and cancer-related indications requiring more frequent administration.

Safety and monitoring considerations include potential hypocalcemia, infections, and dermatologic reactions. Notable procedure-related risks include osteonecrosis of the jaw and atypical femoral fractures, particularly with long-term use. Prior to and during treatment, calcium and vitamin D levels should be corrected, and dental assessment is often advised to mitigate jaw-related risks. Discontinuation can lead to rebound bone loss and vertebral fractures, so planning for transition to another therapy is important. Compared with bisphosphonates, antiRANKL therapies are not renally cleared and are given by injection, offering advantages for some patients but requiring ongoing monitoring of calcium status.