The current Rethinking Clinical Trials (REaCT) trial will compare two schedules(12- vs. 4-weekly) of bone-targeting agents (BTAs) to evaluate quality of life, pain and skeletal events within the Canadian Health Care System. This study will use an "integrated consent model" that involves "oral consent" rather than a written informed consent writing process as the study is comparing standard schedules and not a new administration schedule.

Bone metastases are common in patients with advanced breast and prostate cancers. Skeletal metastases can be associated with reduced Quality of Life (QoL), pain and skeletal-related events (SREs) (defined as pathological fractures, surgery/radiotherapy to bone, spinal cord compression and hypercalcaemia). Maintaining QoL while avoiding or delaying SREs are the main goals of therapy. Patients therefore receive bone-targeted agents (e.g. pamidronate, zoledronate and denosumab) which are typically given every 4 weeks. However, this 4 week dosing is based on convenience so the treatment could be given concurrently with chemotherapy. The half-life of these drugs in the bone is many months or even years. Hence studies have been performed evaluating 12-weekly therapy. These have confirmed similar palliative outcomes in the 4 vs 12-weekly groups for both breast and prostate cancer patients. However, there remains clinical equipoise about which dosing interval physicians prescribe. The current trial will compare these two schedules of bone-targeting agents (12- vs. 4-weekly) to evaluate quality of life, pain and skeletal events within the Canadian Health Care System. This study will use an "integrated consent model" that involves "oral consent" rather than a written informed consent writing process as the study is comparing standard schedules and not a new administration schedule.

Inclusion Criteria:

• Patients with either radiologically and/or histologically confirmed bone metastases from castrate resistant prostate cancer (36) or breast cancer.
• About to start or currently receiving BTA therapy.
• Serum creatinine >30 ml/min and corrected serum calcium ≥ 2 mmol/l
• Age ≥ 18 years.
• Able to provide verbal consent

Exclusion Criteria:

• For CRPC patients - Definite contraindication for denosumab at baseline (e.g. hypocalcaemia [Albumin-corrected serum calcium < 2.0 mmol/l]).
• History of or current evidence of osteonecrosis of the jaw.
• Radiotherapy or surgery to the bone planned within 4 weeks after randomization.
• Known hypersensitivity to trial drug or hypersensitivity to any other component of the trial drug (e.g. fructose).
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol.

There is no plan to make individual participant data available.