A double-blind dose-ranging study of risedronate in Japanese patients with
osteoporosis (a study by the Risedronate Late Phase II Research Group).
Author(s): Shiraki M, Fukunaga M, Kushida K, Kishimoto H, Taketani Y, Minaguchi H, Inoue T,
Morita R, Morii H, Yamamoto K, Ohashi Y, Orimo H.
Affiliation(s): Research Institute and Practice for Involutional Diseases, 1610-1 Meisei,
Misato-Mura, 399-8101, Minamiazumi-gun, Nagano Prefecture, Japan.
Publication date & source: 2003, Osteoporos Int. , 14(3):225-34
To determine the clinical recommended dosage regimen of risedronate for the
treatment of involutional osteoporosis in Japanese patients, dose-response
relationships for the efficacy and safety of this drug were investigated using a
multi-center, randomized, double-blind, parallel group comparative design with
four dose levels of risedronate (placebo, 1 mg, 2.5 mg and 5 mg per day). A total
of 211 patients diagnosed with involutional osteoporosis according to the
criteria proposed by the Japanese Society for Bone and Mineral Research were
randomized and received one of the four doses once daily for 36 weeks. All
patients were supplemented with 200 mg of calcium daily in the form of calcium
lactate. The primary efficacy endpoint was the percent change in bone mineral
density of the lumbar spine (L2-L4 BMD) determined by dual-energy X-ray
absorptiometry (DXA) from baseline to the time of final evaluation. Changes in
biochemical markers of bone turnover and safety profile were also compared.
Percent changes in L2-L4 BMD at final evaluation in the placebo, and 1-, 2.5-,
and 5-mg risedronate groups were 0.79+/-5.30, 2.71+/-4.93, 5.29+/-3.96, and
5.15+/-4.25% (mean+/-SD), respectively. A linear dose-response relationship was
obtained up to a dose of 2.5 mg, whereas no further increase in BMD was observed
at 5 mg. The decrease in bone turnover markers, including N-terminal osteocalcin,
phosphorus, and urinary deoxypyridinoline, also showed a linear dose-response
relationship up to a dose of 2.5 mg. Alkaline phosphatase level decreased
linearly up to a dose of 5 mg. Risedronate was well tolerated in this 36-week
study with 1- to 5-mg doses. Neither the overall incidence of adverse events nor
the percentage of patients without problem in overall safety assessment differed
significantly among the dose groups including the placebo group. Based on these
results, a once-daily dose of 2.5 mg of risedronate, which is half that used in
Caucasians, is recommended for the treatment of involutional osteoporosis in
Japanese patients.
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