Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised rat

The dose-dependent bone-sparing effects of dietary isoflavones (IF) were in vestigated in adult (7-month-old) Wistar rats. Forty animals were ovariecto mised, allocated into four groups of ten rats each, and immediately treated orally with IF at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) mug/g body we ight per d for 91 d; ten sham-operated (SH) controls received the same diet without added IF. Animals were killed on day 91. Both femoral failure load and total femoral, diaphyseal or metaphyseal bone mineral densities (BMD) were lower in OVX animals than in SH animals. Urinary deoxypyridinoline (DP D) excretion, a marker of bone resorption, and plasma osteocalcin (OC) leve ls, a marker of osteoblast activity, were higher in OVX animals than in SH animals. Total femoral and diaphyseal BMD and femoral failure load were sim ilar in IF-treated rats and SH rats. Although metaphyseal BMD in IF40 or IF 80 rats was similar to that in SH rats, its value was lower in IF20 rats th an in controls, The day 91 urinary DPD excretion in IF40 and IF80 rats, but not in IF20 rats, was similar to that in SH rats. Day 91 plasma OC concent rations in IF-treated rats were similar to day 45 values, but were decrease d in OVX and SH rats. Thus, daily IF consumption prevented ovariectomy-indu ced bone loss, both by depressing bone resorption and stimulating osteoblas t activity. Moreover, as only the highest IF level induced a weak uterotrop hic activity, the optimal IF dose which preserves both cancellous and corti cal bone, but exhibits no oestrogen-like effects on the uterus, was 40 mug/ g body weight per d.