Inhibition of RANKL: a new approach to the treatment of osteoporosis

Osteoporosis affects > 10 million people in the US. Although there are a range of drugs available to treat osteoporosis, adherence to these agents is poor, leaving patients at risk of fracture. Receptor activator of nuclear-κB ligand (RANKL) is essential for the function of the bone-resorbing osteoclasts. Denosumab is a humanised monoclonal antibody to RANKL that can be administered subcutaneously every 3 or 6 months. With this protocol, denosumab increased bone mineral density in the lumbar spine and total hip of postmenopausal women with osteoporosis over 1 year. This confirms that inhibition of RANKL is a new and potentially useful approach to the treatment of osteoporosis. The long-term safety of denosumab, and the effect of denosumab on the incidence of fractures, needs to be evaluated, especially as there is, as yet, no indication that denosumab decreases the incidence of fractures. Comparative studies with denosumab, once-weekly alendronate and once-yearly zoledronate, evaluating their effects on bone mineral density and fractures and the degree of adherence, also need to be considered.