BIOCHEMICAL BONE MARKERS AND BONE-MINERAL DENSITY DURING POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY WITH AND WITHOUT VITAMIN-D-3 - A PROSPECTIVE, CONTROLLED, RANDOMIZED STUDY

The effects of postmenopausal hormone replacement therapy (KRT) and vi tamin D on the serum concentrations of three bone biochemical markers and their associations with bone mineral density (BMD) were studied in a population-based 1-yr follow-up study. A total of 72 healthy postme nopausal women were randomized into 4 treatment groups: HRT group (seq uential combination of 2 mg estradiol valerate and 1 mg cyproterone ac etate), D group (vitamin D-3, 300 IU/day), HRT+D group (both of the ab ove), and placebo group (calcium lactate, 500 mg/day). Serum concentra tions of osteocalcin (OC)and bone-specific alkaline phosphatase (BAP) were measured as biochemical markers of bone formation, and serum type I collagen carboxy-terminal telopeptide was measured as a marker of b one resorption at baseline and after 6 and 12 months of treatment. To investigate the associations of these markets with BMD, lumbar (L2-L3) and femoral neck BMDs were determined by dual x-ray absorptiometry at baseline and after 2.5 yr of treatment. In both hormone groups, the s erum concentrations of the three bone metabolic markers had decreased after 12 months. Those of OC decreased by 29.2% (P = 0.017) in the HRT group and by 37.3% (P = 0.004) in the HRT+D group, and BAP concentrat ions decreased by 34.4% (P < 0.001) in the HRT group and by 36.2% (P < 0.001) in the HRT+D group. Serum type I collagen carboxy-terminal tel opeptide concentrations had decreased by 21.6% (P = 0.012) in HRT grou p and by 14.1% (P = 0.011) in the HRT+D group. In the D group, the ser um concentrations of BAP had decreased by 11.7% (P = 0.040) after 12 m onths, but the other two markers showed no change. The only change see n in the placebo group was a 19.2% increase in OC concentrations (P =: 0.041) after 6 months, but at 12 months, the mean OC level was simila r to that at baseline. After 2.5 yr, both lumbar and femoral BMD had d ecreased in the D group [2.1% (P = 0.022) and 3.6% (P = 0.019, respect ively] and in the placebo group [3.3% (P = 0.009) and 2.7% (P = 0.010) , respectively], whereas no significant changes occurred in the hormon e groups. There were significant inverse correlations between the chan ges in lumbar and femoral BMDs and changes in all three biochemical ma rkers (r = -0.240 through -0.336; P = 0.005-0.064). Our results sugges t that HRT counteracts the biochemical changes caused by increased bon e turnover associated with menopause. Importantly, the changes in bone markers correlate with long term changes in BMDs of lumbar spine and femoral neck. Low dose vitamin D treatment, however, seems to have onl y marginal effects on bone metabolism in early postmenopausal healthy women.