MARKERS OF BONE TURNOVER AND RATES OF BONE LOSS DURING 3 YEARS COMBINED HORMONE REPLACEMENT THERAPY

Seventy-five women who had had their last menstrual period 6 months to 3 years previously were randomized to continuous treatment with 2 mg estradiol valerate (E(2)V) and 1 mg cyproterone acetate (CPA), sequent ial treatment with 2 mg E(w)V and 75 mg levonorgestrel (LNG), or place bo, Both, treatment regimens prevented bone loss from the axial and pe ripheral skeleton, and the effect was maintained throughout the entire study period. The 3-year changes in bone loss in the two hone compart ments were significantly related (r = 0.56; p < 0.001). The 3-year cha nges in bone mass of both bone compartments were furthermore significa ntly related lo the changes after 6 and 12 months in both a specific b one resorption marker (fasting urinary cross-links corrected for creat inine) (r = -0.75 to -0.79, p < 0.001 for the forearm, r = -0.31 to -0 .34, p < 0.05 to 0.07 for the spine) and a bone formation marker (BGP) (r = -0.40 to -0.46, p < 0.05 to 0.01 for the forearm; r = -0.40 to - 0.45, p < 0.05 to 0.01 for the spine). Stratification of the participa nts according to reduction in bone turnover markers showed significant differences in rates of bone loss from both the forearm (p < 0.001 to 0.01) and the spine (p < 0.01 to 0.05). Menopausal complaints were re duced with both treatments, but the reduction was unrelated to the res ponse in the skeleton. In conclusion, continuous treatment with 2 mg E (2)V/1 mg CPA and sequential treatment with 2 mg E(2)V and 75 mg LNG a re effective in preventing postmenopausal bone loss for greater than o r equal to 3 years and in reducing menopausal symptoms. Furthermore, t he responses in the axial and peripheral skeleton an highly correlated , and follow-up call be done accurately by caking measurements in one bone compartment only. The skeletal response is reflected by changes i n markers of bone turnover, bur measurements of a few markers are not clinically useful in monitoring the effects of hormone replacement the rapy.