[Inhibition of RANK ligand to treat bone metastases]

Bone is the most common metastatic site. The skeleton is also the preferential initial metastatic site in breast and prostate carcinomas. Objective complications of bone metastases are named « skeletal-related events » (SREs) and generally include the need for radiotherapy on bone, surgery to bone, pathologic fracture and spinal cord compression. Recent phase III double-blind trials have demonstrated the superiority of denosumab to zoledronic acid for delaying the time to first SRE in patients with breast or prostate cancer and bone metastases. Non-inferiority was shown in the trial including other solid tumors and multiple myeloma. The overall burden of the disease was also significantly reduced in the breast and prostate cancer studies, and in the pre-specified integrated analysis that included all three comparative trials. Denosumab is conveniently administered by subcutaneous injections and is devoid of renal toxicity. However, denosumab induces more cases of hypocalcaemia than zoledronate. Calcium and vitamin D supplementation is recommended during therapy and it is advised to regularly monitor calcium levels during denosumab long-term treatment. There are numerically more cases of osteonecrosis of the jaw, but the differences are not statistically significant between zoledronate and denosumab, whether in the individual studies or in the integrated analysis. Treatment with these potent inhibitors of bone resorption should be progressively 'individualized' to better define the place of intermittent treatments, to decrease the occurrence of toxic effects and to improve the cost-effectiveness ratio of new compounds.