O'Rourke 1995.

Methods	3 active arms, 1 placebo arm (stratified by urinary calcium level: <0.35 vs >0.35 mmol/mmol creatinine) Pain assessment: 10 cm VAS, patient reported Toxicity criteria: WHO
Participants	Any primary Bone metastases required No pain requirement Co‐intervention: unrestricted concomitant tumor therapy as clinically indicated Performance status criteria: life expectancy >1m Other criteria: exclude urinary calcium excretion <0.175mmol/mmol creatinine, radiotherapy within 1 month, chemotherapy/bisphosphonate within 3 months
Interventions	1. Active arm 1: Clodronate oral 400 mg /day x4 weeks 20 pts 2. Active arm 2: 1600mg 19 pts 3. Active arm 3: 3200mg 20 pts 4. Placebo control: May receive hormone/systemic chemotherapy if unchanged in previous 3 months 21 pts
Outcomes	1. Pain: No change in bone pain 2. Analgesics: No change in analgesic requirements Withdrawals 4 for whole study Adverse effects: Active arm 1: Nausea or vomiting: 3 Diarrhea: 1 Active arm 2: Nausea or vomiting: 3 Diarrhea: 3 Active arm 3: Nausea or vomiting: 4 Diarrhea: 1 Control arm: Nausea or vomiting: 6 Diarrhea: 1
Notes	QS = 3