Denosumab: A bone antiresorptive drug

Bone remodeling is the continuous process by which old bone is removed by bone-resorbing cells, the osteoclasts and replaced by new bone synthesized by bone forming cells, the osteoblasts. Osteoporosis is characterized by a progressive loss of bone mass and microarchitecture, which leads to increased fracture risk. Denosumab, a human monoclonal antibody resembling natural IgG2 immunoglobulin, has antiresorptive activity and is distinguished from other antiresorptive drugs. It mimics osteoprotegerin (OPG) that binds to RANKL and hence does not allow RANKL to bind with RANK receptor, thereby inhibiting osteoclast differentiation, activation and survival exerting primarily antiresorptive action. Denosumab trials have shown its efficacy in postmenopausal women with osteoporosis, unresectable giant cell tumor of bone and significant effect in non-metastatic prostate cancer and delay in the time-to-first skeletal related events (SRE) and subsequent SRE with denosumab than zoledronic acid in patients. It is available as 60 mg/ml in pre-filled syringes and approved for osteoporosis in postmenopausal women (60 mg s.c. twice yearly), unresectable giant cell tumor of bone in adults and skeletally mature adolescents (120 mh s.c. monthly), prevention of skeletal-related events and to increase bone mass in patients at high risk for fracture including androgen deprivation therapy for non-metastatic prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer. Denosumab offers advantages of twice yearly dosing in osteoporosis and monthly dosing in giant cell tumor of bone with its novel mechanism of action and better tolerability.