Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial.

CONTEXT

Data on the efficacy and safety of ipriflavone for prevention of postmenopausal bone loss are conflicting.

OBJECTIVES

To investigate the effect of oral ipriflavone on prevention of postmenopausal bone loss and to assess the safety profile of long-term treatment with ipriflavone in postmenopausal osteoporotic women.

DESIGN AND SETTING

Prospective, randomized, double-blind, placebo-controlled, 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 mg 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 BMD and biochemical markers of bone resorption (urinary hydroxyproline corrected for creatinine and urinary CrossLaps [Osteometer Biotech, Herlev, Denmark] corrected for creatinine), assessed every 6 months. Laboratory safety measures and adverse events were recorded every 3 months.

RESULTS

Based on intent-to-treat analysis, after 36 months of treatment, the annual percentage change from baseline in BMD of the lumbar spine for ipriflavone 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 measured, did not differ significantly between groups. The response in biochemical 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% CI, 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 nearly so in the 2 groups at all time points. Lymphocyte concentrations decreased significantly (500/microL (0.5 x 10(9)/L]) in women treated with ipriflavone. Thirty-one women (13.2%) in the ipriflavone group developed subclinical lymphocytopenia, of whom 29 developed it during ipriflavone treatment. Of 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 or affect biochemical markers of bone metabolism. Additionally, ipriflavone induces lymphocytopenia in a significant number of women.