Risedronate, a highly effective, short-term oral treatment for Paget's disease: A dose-response study

Risedronate is a potent pyridinyl bisphosphonate being developed for bone d iseases such as Paget's disease and osteoporosis, In this study, we compare d the efficacy, safety, and tolerability of three different doses of oral r isedronate in 62 patients with severe Paget's disease of bone [serum alkali ne phosphatase (AP) >3 times the upper limit of normal]. Patients were trea ted at six study centers with either 10, 20, or 30 mg oral risedronate dail y for 28 days and followed up to day 85. The primary efficacy parameter was percentage change from baseline in AP excess. The data show that there is a dose-response with risedronate: patients who received 30 mg oral risedron ate for 28 days benefited most, with a mean percentage decrease in AP exces s of 72.2% (20 mg: 57.9%; 10 mg: 48.0%). Time to response-the first time po int when there was a greater than or equal to 30% reduction from baseline i n AP excess and greater than or equal to 50% reduction from baseline in uri nary hydroxyproline (HP)/creatinine-was also significantly shorter (median 29 days) in the 30 mg group compared with the other two groups (20 mg: 43 d ays and 10 mg: 71 days). Long-term follow-up data up to 33 months from the start of the study indicated that AP remained below baseline levels for all patients. Histologic evaluation of bone formed during risedronate therapy demonstrated that normal lamellar bone was formed as opposed to woven paget ic bone, with no evidence of osteomalacia. Risedronate was well tolerated, Transient decreases in serum calcium and increases in serum intact parathyr oid hormone were observed, consistent with the pharmacology of risedronate. In conclusion, risedronate administered at daily doses of 10, 20, and 30 m g for 28 days was effective in reducing the biochemical indices of disease activity in patients with severe Paget's disease of bone. A daily dose of 3 0 mg was most effective without compromising safety or tolerability.