Ipriflavone in the treatment of postmenopausal osteoporosis - A randomizedcontrolled trial

Context Data on the efficacy and safety of ipriflavone for prevention of po stmenopausal bone loss are conflicting. Objectives To investigate the effect of oral ipriflavone on prevention of p ostmenopausal bone loss and to assess the safety profile of long-term treat ment with ipriflavone in postmenopausal osteoporotic women. Design and Setting Prospective, randomized, double-blind, placebo-controlle d, 4-year study conducted in 4 centers in Belgium, Denmark, and Italy from August 1994 to July 1998. Participants Four hundred seventy-four postmenopausal white women, aged 45 to 75 years, with bone mineral densities (BMDs) of less than 0.86 g/cm(2). Interventions Patients were randomly assigned to receive ipriflavone, 200 m g 3 times per day (n = 234), or placebo (n = 240); all received 500 mg/d of calcium. Main Outcome Measures Efficacy measures included spine, hip, and forearm BM D and biochemical markers of bone resorption (urinary hydroxyproline correc ted for creatinine and urinary CrossLaps [Osteometer Biotech, Herlev, Denma rk] corrected for creatinine), assessed every 6 months, Laboratory safety m easures and adverse events were recorded every 3 months. Results Based on intent-to-treat analysis, after 36 months of treatment, th e annual percentage change from baseline in BMD of the lumbar spine for ipr iflavone vs placebo (0.1% [95% confidence interval {CI}, -7.9% to 8.1%] vs 0.8% [95% CI, -9.1% to 10.7%]; P =.14), or in any of the other sites measur ed, did not differ significantly between groups. The response in biochemica l markers was also similar between groups (eg, for hydroxyproline corrected for creatinine, 20.13 mg/g [95% CI, 18.85-21.41 mg/g] vs 20.67 mg/g [95% C I, 19.41-21.92 mg/g]; P =.96); urinary CrossLaps corrected for creatinine, 268 mg/mol (95% CI, 249-288 mg/mol) vs 268 mg/mol (95% CI, 254-282 mg/mol); P =.81. The number of women with new vertebral fracture was identical or n early so in the 2 groups at all time points. Lymphocyte concentrations decr eased significantly (500/muL (0.5 x 10(9)/L]) in women treated with iprifla vone. Thirty-one women (13.2%) in the ipriflavone group developed subclinic al lymphocytopenia, of whom 29 developed it during ipriflavone treatment. O f these, 15 (52%) of 29 had recovered spontaneously by 1 year and 22 (81 %) of 29 by 2 years. Conclusions Our data indicate that ipriflavone does not prevent bone loss o r affect biochemical markers of bone metabolism. Additionally, ipriflavone induces lymphocytopenia in a significant number of women.