Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies

Inclusion Criteria: * Age ≥ 18 years. * Histologically proven mRCC. * Administration of one of the systemic agents in use for the treatment of mRCC (no more than three prior systemic therapy regimens). Patients with at least 6 months of 1st line treatment and a bone event may be included. * More than 1 bone metastasis. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2. * Adequate renal function (serum creatinine ≤ 200 mmol/L or creatinine clearance ≥ 30 mL/min according to Cockroft formula or MDRD formula for patients older than 65 years). * Covered by a medical insurance. * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. * Signed informed consent. * Accepting to use effective contraception during study treatment and within 5 months after final dose of study therapy. Exclusion Criteria: * Prior bisphosphonate or denosumab treatment in the year before inclusion. * Imminent or ongoing nerve or spinal compression as per the investigator's judgement. * Ongoing first-line therapy, started for less than 6 months (patients with BM at time of metastases diagnosis will initially benefit from the angiogenesis targeted agents used and are not at higher risk). * Anticancer treatment under investigation. * Paraneoplastic hypercalcemia (corrected total calcium \> 2.7 mmol/L). * Grade 4 toxicity under previous targeted agents. * Liver failure (AST and/or ALT ≥ 5.0 x upper limit of normal (ULN) or total bilirubin beyond normal limits). * Severe hypocalcaemia \> 2.8 mmol/l. * Fructose intolerance. * Invasive dental procedure (i.e. tooth extraction, dental implants, oral surgery) within the 10 days prior to randomization or required dental procedures at the pre-inclusion dental examination. * Psychological, familial, sociological, geographical conditions that would limit compliance with study protocol requirements. * Pregnant or breastfeeding woman. Females of child-bearing potential must have a negative serum pregnancy test within 7 days prior inclusion. * Life expectancy ≤ 3 months. * Participation to another clinical trial that might interfere with the evaluation of the main criterion. * Known hypersensitivity to the active substance or to any of the excipients of bisphosphonate or denosumab.