Risedronate - A review of its pharmacological properties and clinical use in resorptive bone disease

Risedronate is a novel orally administered pyridinyl bisphosphonate indicat ed for the prevention or treatment of postmenopausal and glucocorticoid-ind uced osteoporosis and Paget's disease. The drug reduces bone turnover and d ecreases resorption chiefly through osteoclastic effects, with no undesirab le effects on cortical porosity or thickness or on cancellous bone volume. Four randomised. double-blind trials have been carried out in 4873 patients with postmenopausal osteoporosis. In 2 of these studies, the primary end-p oint of vertebral fracture incidence was reduced by risedronate 5mg once da ily by up to 65 and 49% relative to placebo after 1 and 3 years, respective ly. Across all 4 trials, risedronate improved lumbar spine, femoral neck an d femoral trochanter bone mineral density (BMD) statistically significantly relative to placebo. The drug also prevented bone loss in a study in 383 w omen with recent menopause, and reduced the risk of hip fracture in elderly women with confirmed osteoporosis in a trial involving a total of 9331 pat ients. Risedronate 5 mg/day plus estrogen has been shown to be superior to estrogen alone in a 12-month double-blind study in 524 women with at least 1-year's history of menopause. Two randomised, double-blind and placebo-controlled 12-month studies in a t otal of 518 patients have shown risedronate 5 mg/day to prevent or reverse bone loss in patients receiving glucocorticoid therapy. Risedronate 30 mg/day was associated with statistically significant reducti ons in mean serum levels of alkaline phosphatase (ALP) in noncomparative st udies in patients with Pager's disease. ALP normalisation rates ranged from 53.8 to 65% across two 84-day treatment cycles in 2 of these trials in 180 patients. In a randomised, double-blind study in 123 patients, risedronate 30 mg/day for 2 months evoked significantly greater serum ALP responses th an etidronate 400 mg/day for 6 months. The overall tolerability profile of risedronate was similar to that of plac ebo in clinical studies, with no evidence of acute-phase reactions or miner alisation defects, or excess incidence of upper GI lesions, in patients rec eiving the drug. Conclusions: Risedronate is an effective and well tolerated novel bisphosph onate that is suitable for first-line therapy in Paget's disease. The rapid and sustained reductions in vertebral fracture incidence and BMD changes s een in patients with postmenopausal and glucocorticoid-induced osteoporosis indicate the drug to be a valuable treatment option with first-line potent ial, particularly in patients for whom hormonal therapy is inappropriate. T he effects of the drug on hip fracture incidence in elderly women with conf irmed osteoporosis point to a particular role in older patients, or those w ith more advanced disease.