Denosumab has been proven to be at least as effective with respect to zoledronic acid in preventing skeletal-related events in patients with bone metastases from solid tumors. Although denosumab can be considered to have a more favorable toxicity profile compared to zoledronic acid in terms of kidney toxicity and flu-like symptoms, hypocalcemia is twice as frequent with denosumab. Importantly, denosumab is not metabolized by the kidney and it may be employed even in patients with severe kidney failure. Like zoledronic acid, denosumab is administered with oral calcium and vitamin D. As conversion of vitamin D to its active form is progressively impaired with a creatinine clearance < 70 ml/min, we speculate that calcitriol may be a better option than vitamin D in denosumab-treated patients with impaired kidney function.