Alendronate and estrogen effects in postmenopausal women with low bone mineral density

The bisphosphonate alendronate and conjugated equine estrogens are both wid ely used for the treatment of postmenopausal osteoporosis. Acting by differ ent mechanisms, these two agents decrease bone resorption and thereby incre ase or preserve bone mineral density (BMD). The comparative and combined ef fects of these medications have not been rigorously studied. This prospecti ve, double blind, placebo-controlled, randomized clinical trial examined th e effects of oral alendronate and conjugated estrogen, in combination and s eparately, on BMD, biochemical markers of bone turnover, safety, and tolera bility in 425 hysterectomized postmenopausal women with low bone mass. In a ddition, bane biopsy with histomorphometry was performed in a subset of sub jects. Treatment included placebo, alendronate(10 mg daily), conjugated equ ine estrogen (CEE; 0.625 mg daily), or alendronate (10 mg daily) plus CEE ( 0.625 mg daily) for 2 yr. All of the women received a supplement of 500 mg calcium daily. At 2 yr, placebo-treated patients showed a mean 0.6% loss in lumbar spine BMD, compared with mean increases in women receiving alendron ate, GEE, and alendronate plus CEE of 6.0% (P < 0.001 us. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and GEE; P = 0.022 c s. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alen dronate, estrogen, alendronate plus estrogen, and placebo groups, respectiv ely. Both alendronate and CEE significantly decreased biochemical markers o f bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combinat ion produced slightly greater decreases in these markers than either treatm ent alone, but the mean absolute values remained within the normal premenop ausal range. Alendronate, alone or in combination with GEE, was well tolera ted. In the subset of patients who underwent bone biopsies, histomorphometr y showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group. Thus, alendro nate and estrogen produced favorable effects on BMD. Combined use of alendr onate and estrogen produced somewhat larger increases in BMD than either ag ent alone and was well tolerated.