With Comments by Adriane Fugh-Berman, MD
Ipriflavone for Osteoporosis
July 2001; Volume 3; 56
Source: Alexandersen P, et al. Ipriflavone in the treatment of postmenopausal osteoporosis. JAMA 2001;285:1482-1488.
Design and Setting: A randomized, double-blind, placebo-controlled, multicenter trial (The Ipriflavone Multicenter European Fracture Study) conducted in Belgium, Denmark, and Italy.
Subjects: 474 postmenopausal white women (age 45-75) with osteoporosis (< 0.86 g/cm2) of the lumbar spine. Exclusion criteria included body mass index lower than 30 kg/m2, previous vertebral fractures, significant concomitant disease, alcohol abuse, or use of any medication known to affect bone metabolism. Two hundred ninety-two women completed the study.
Treatment Dose/Route/Duration: Ipriflavone, 200 mg tid for three years. Both treatment and placebo groups received 500 mg/d of calcium.
Outcome Measures: Bone mineral density at spine, hip, and forearm (assessed by dual-energy radiograph absorptiometry) and biochemical markers of bone resorption (including serum alkaline phosphatase, fasting urinary hydroxy- proline corrected by creatinine, serum calcium, serum phosphorus, and urinary excretion of calcium corrected for creatinine) assessed every six months. Adverse events, hematology, blood chemistry, and urinalysis were assessed every three months. Non-traumatic vertebral fractures were assessed by lateral radiography at years 1, 2, and 3.
Results: Intent-to-treat analysis showed no difference in annual percentage change in bone mineral density at any site (compared to baseline) between the treated group and the placebo group (lumbar spine ipriflavone 0.1% [95% CI -7.9% to 8.1%] vs. 0.8% [95% CI -9.1% to 10.7%], P = 0.14). Biochemical markers were similar between groups as were new vertebral fractures. The ipriflavone-treated group experienced a significant decrease in lymphocyte concentrations; this effect occurred after six months of treatment. Twenty-nine women in the ipriflavone group developed lymphocytopenia (< 500 mcL) during the study; two additional subjects had lymphocytopenia at 36 months. After discontinuation of ipriflavone, 52% recovered by one year and 81% by two years. The lymphocytopenia was subclinical; there were no significant differences in opportunistic infections, cancers, or other adverse effects between the two groups. Compliance was similar between groups.
Funding: Cheisi Farmaceutici, SpA, which manufactures ipriflavone.
Comments: Ipriflavone, a synthetic isoflavone available over-the-counter as a dietary supplement, has been promoted for prevention and treatment of osteoporosis. Previous smaller trials have indicated a benefit for ipriflavone (see Alternative Therapies in Women’s Health, September 2000, pp. 67-70.) but this trial is the largest, longest, and methodologically the best of all trials performed to date. There appears to be no benefit of using ipriflavone in postmenopausal women with osteoporosis, and lymphocytopenia is a significant adverse effect. Patients should be counseled against using this dietary supplement.