Effect of RANKL-specific denosumab on osteoclast number and function: a potential friend or foe?

The antiresorptive effect of a single 60-mg injection of the RANKL (receptor activator of NFkappaB ligand)-specific mAb, denosumab, substantially exceeds the effects of alendronic acid (70 mg weekly) yet increases in bone mass at the lumbar spine are identical for both agents. Important experimental and clinical observations illustrating some of the potential consequences of osteoclast deficiency and low-rate bone resorption for osteoblast function, bone mineralization, bone quality and related mechanical properties are summarized. This review also discusses whether the benefits for bone health can be improved when aggressively pushing the limits with novel antiresorptive medications.