A Double Blind, Placebo-Controlled Trial of Ipriflavone for Prevention of Postmenopausal Spinal Bone Loss

Abstract.

One hundred ninety-eight postmenopausal women (aged 50–65 years) with vertebral bone density (VBD) 1 SD below the mean value for normal, age-matched, postmenopausal subjects were enrolled in six Italian centers and 134 completed 2 years of treatment. All subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d.) or a matching placebo, according to a double-blind, parallel group design. All patients also received an oral daily calcium supplement of 1 g as calcium carbonate. VBD and markers of bone turnover were measured at baseline, and every 6 months. A complete routine analysis of liver and kidney functions along with hematological parameters were measured before and at the end of treatment period. The valid completers analysis showed a significant increase of VBD in ipriflavone-treated women with average percent changes of +1.4 after 1 year, and +1% at the end of treatment period (P < 0.05). The placebo group presented a significant decrease of VBD after 2 years of treatment (P < 0.05). The difference between treatments was significant (P < 0.01). The intention to treat analysis confirmed the significant decrease of VBD in the placebo group, with no changes in ipriflavone-treated women. Skeletal ALP significantly decreased in ipriflavone-treated women (P < 0.05). Serum BGP and urine HOP/Cr showed a significant decrease only in ipriflavone-treated women, suggesting an inhibitory effect on bone turnover rate. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups. The evaluation of patients' compliance, assessed by residual tablets count, revealed a drug intake of more than 80% after 2 years in 92.5% and 92.8% of patients treated with ipriflavone or placebo, respectively. This study demonstrates that ipriflavone can prevent bone loss in postmenopausal women with low bone mass.