Determinants of induction and duration of remission of Paget's disease of bone after bisphosphonate (olpadronate) therapy.

Bisphosphonates are the treatment of choice of Paget's disease of bone. For optimal patient care determinants of the induction and duration of remission of the disease after bisphosphonate therapy must be defined. We addressed these issues in a longitudinal study of 157 patients with biochemically active disease (serum alkaline phosphatase activity >120 U/L) treated with the bisphosphonate olpadronate and followed for a median period of 37 months (range 3-162, mean 46 +/- 30). Two different total doses of olpadronate were used: an effective dose (40 mg intravenously given over 5 or 10 consecutive days) and a high dose consisting of the effective dose followed by oral olpadronate 200 mg/day for 15 days. Treatment induced biochemical remission, defined as normalization of serum alkaline phosphatase activity, in 89.2% of the patients. There were no differences between the two treatment regimens. The only independent determinants of induction of remission were baseline serum alkaline phosphatase activity and number of affected bones. In contrast, duration of remission depended on the dose of olpadronate given (high versus effective dose, RR of relapse 0.49, 95% CI 0.27-0.89). Additional independent determinants of relapse were nadir value of serum alkaline phosphatase activity after treatment, number of previous therapies, and number of affected bones. Pain scores decreased with therapy in 88% of patients with pain complaints. Pain scores were significantly related to the probability of relapse (RR1.54, 95% CI 1.04-2.27). In this long-term study of a large cohort of patients with Paget's disease we confirmed the efficacy of olpadronate therapy. In addition, we identified and quantified determinants of the response to bisphosphonate that can help in improving the management of patients with Paget's disease with bisphosphonates.