A 2-YEAR PHASE-II STUDY WITH 1-YEAR OF FOLLOW-UP OF RISEDRONATE (NE-58095) IN POSTMENOPAUSAL OSTEOPOROSIS

This paper presents the results of a two-center, double-masked, placeb o-controlled, randomized, oral-dose study of risedronate treatment in postmenopausal osteoporosis. Patients had at least one, but no more th an four prevalent vertebral fractures at baseline. They received eithe r 2.5 mg continuous risedronate, 2.5 mg cyclic risedronate, or placebo for 2 years. Both risedronate and placebo were formulated as hard gel atin capsules. All women furthermore received a daily calcium suppleme nt of 1 g which was taken separately from the study drug. During the 1 -year of follow-up, all women received only a daily calcium supplement of 1 g. A total of 132 patients were enrolled (44 in each treatment g roup), of which 73% completed the 2-year treatment period and 70% all 3 years. Generally the outcome of the study was negative. Lumbar spine bone mineral density (BMD) increased 1.2% (NS) and 0.8% (NS) and afte r 2 and 3 years in the group treated with continuous risedronate, 1.7% (NS) and 2.3% (p < 0.05) in the group treated with cyclic risedronate , and 0.6% (NS) and 1.7% (NS) in the placebo group. BMD in the femoral neck increased 2.9% (p < 0.05) and 0.9% (NS) after 2 and 3 years in t he group treated with continuous risedronate, 1.3% (NS) and 2.4% (p < 0.01) in the group treated with cyclic risedronate, and 1.3% (NS) and 2.6% (p ( 0.01) in the placebo group. The differences between all thre e groups in spinal and femoral BMD after 2 years were not statisticall y significant, but reached statistical significance after 3 years (p < 0.01) in the femoral neck. Only minor changes were observed in the me asured markers of bone turnover. Both the incidence and rate of new ve rtebral fractures showed no overall differences between the groups. Th e distribution of adverse events was similar across treatment groups. None of the serious adverse events were considered causally related to risedronate. The lack of effect shown in the present study may be exp lained by insufficient dose regimen and/or impaired absorption from th e intestinal tract. Further investigations (ongoing phase III trials) are needed to define future dose regimens in order to validate the eff ect on bone mass, fracture rate and biochemical markers. In these stud ies another formulation of the drug and other dosing instructions are used.