The aim of the study was to assess the effects of 2 yr of treatment with two dose levels of tibolone on bone mineral density and bio-chemical markers of bone metabolism in late postmenopause. Ninety-one healthy women, more than 10 yr after menopause, entered a 2-yr double blind, randomized, placebo-controlled study of treatment with either 1.25 mg/day (n = 36) or 2.5 mg/day (n = 35) Tibolone or placebo (n = 20). Densitometry and determinations of biochemical markers of bone metabolism in serum and urine were performed before randomization and every 3 months during the study. The results revealed a steady and equal increase in bone mineral density in both tibolone groups at the bone sites studied. Gains in BMD spine of 5.9 +/- 0.9% in the 1.25 mg group, 5.1 +/- 0.9% in the 2.5 mg group, and 0.4 +/- 1.1% in the placebo group were found. In the forearm, increases of 2.2 +/- 0.7% in the 1.25 mg group and 1.9 +/- 1.1% in the 2.5 mg group were detected, whereas the placebo group lost 2.1 +/- 1.0%. This was fully supported by changes in biochemical markers of bone resorption (urinary excretion of fragments from the osteoclastic degradation of the alpha 1-chain of the C telopeptides of type 1 collagen and hydroxyproline) and bone formation (serum osteocalcin), respectively. In conclusion, within 2 yr of treatment, tibolone increases bone mass in the spine and prevents bone loss in the forearm in late postmenopausal women determined by densitometry and several biochemical parameters of bone turnover. Tibolone at two doses (1.25 and 2.5 mg/day) had similar effects, indicating that even lower doses may be efficacious.