Seventy-four patients with chronic knee pain from knee osteoarthritis, who received intramuscular clodronate 200 mg/day for 15 days, were randomized into receiving clodronate once/week for the next 11.5 months or once/week for the next 2.5 months. The primary outcome of interest was pain on a Visual Analogue Scale (VAS). Secondary outcomes of interest included the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index pain, stiffness and physical function scores, paracetamol consumption, and the Whole Organ Magnetic Resonance Imaging Score (WORMS) for bone marrow edema. All outcomes were measured and 30 days, 3 months, 6 months , 9 months, and 12 months follow up, except for WORMS which was measured at 12 months only. Statistically significant differences in favour of the 11.5 month group were observed in VAS pain scores, WOMAC pain scores and WOMAC function at 6, 9 and 12 months (p<0.05 for all). Furthermore, WOMAC stiffness scores were significantly in favour of the 11.5 month group at 9 and 12 months follow-up (p<0.01 for both). Similarly WORMS scores at 12 months were statistically significantly different in favour of the 11.5 month group. Clinical outcomes in both groups improved during treatment, however in the 2.5 month group, clinical outcomes began to worsen and trend towards pre-intervention levels following cessation of treatment. Paracetamol consumption decreased in both groups up to 3 months; the 11.5 month group continued to demonstrate reductions in paracetamol consumption up to 12 months, while the 2.5 month group demonstrated increased paracetamol consumption from 6 to 12 months. No adverse events were observed in both groups.