Low dose estrogen and calcium have an additive effect on bone resorption in older women

Previous studies have shown that treatment with estrogen or calcium decreas es bone turnover in older women. The mechanisms by which estrogen and calci um exert their effects are probably different. We therefore examined the po ssibility of an additive or synergistic effect of combined treatment with c alcium and low dose estrogen on bone turnover in older women, using biochem ical markers. Thirty-one healthy women over 70 yr of age were randomized to 12 weeks of t reatment with either micronized 17 beta-estradiol [0.5 mg/day Estrace (E-2) ] or 1500 mg/day elemental calcium, given as carbonate plus Vitamin D (800 IU/day; Ca+D). At the end of the initial 12-week treatment period, both gro ups received both Ca+D and E-2 for an additional 12 weeks. Eleven older wom en were followed for 36 weeks without any treatment and served as a control group. Serum and urine were collected at baseline, at 12 and 24 weeks on treatment , and at 12 weeks after treatment was terminated far measurement of biochem ical markers of bone turnover. Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I procollagen peptide; markers of bone resorption were urinary crosslinked C-telopeptides and N-telopeptides of ty pe I collagen, serum cross-linked N-telopeptides of type I collagen, urinar y free deoxypyridinoline cross-links, and serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in bone turnover measures ove r time by group. All markers of bone resorption decreased with initial treatment and decreas ed further with combination therapy (P < 0.001). Markers of bone formation decreased with Ca+D treatment, but not with E-2 alone; there was no additio nal effect of combination therapy on formation markers compared to Ca+D alo ne. Neither markers of formation nor resorption changed in the control grou p. These results suggest that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation, in older women. Thus, the combination of low dose estrogen plus calcium is likely to be mo re effective in alder women than either treatment alone.