Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females

With the aim of preventing postmenopausal bone loss, a placebo-controlled double-blind trial of 2 years duration was performed. We randomized 315 healthy volunteers in their early natural menopause to seven treatment and three placebo groups: 17 beta-oestradiol, oestriol and sequential norethisteron (hormones); bendroflumethiazide 5 mg/day (thiazide); hormones and thiazide; sodium fluoride 20 mg/day; vitamin D3 2000 IU/day (D3); fluoride and D3; and 1 alpha (OH) vitamin D3 0.25 microgram/day (1 alpha D3). All participants were given daily calcium supplement of 500 mg. Every 3 months we measured the bone mineral content (BMC) of both forearms by photon absorptiometry and chemical quantities in blood and 48 h urinary collections. The study was completed by 264 (84%). The combined placebo groups showed a linear fall in BMC reaching 3.3% after 2 years (P < 0.001). Hormones and hormones and thiazide led to a 2.5% gain in BMC (P < 0.01). Thiazide alone postponed the BMC fall for 6 months. After 2 years the thiazide group showed a BMC fall of 1.5% (P < 0.05), less than that of the placebo group (P < 0.05). BMC declined by 3.6%, 4.5%, 3.7% and 3.7% during the respective use of fluoride, D3, fluoride and D3 and 1 alpha D3. Nevertheless, the urinary calcium excretion during 1 alpha D3 and D3 treatment was 1--1.5 mmol/day higher than in the placebo groups. Apparently, there is no real alternative to oestrogen/gestagen in the prevention of postmenopausal osteoporosis.