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

Bone, Henry G.; Greenspan, Susan L.; McKeever, Clark; Bell, Norman; Davidson, Michael; Downs, Robert W.; Emkey, Ronald; Meunier, Pierre J.; Miller, Sam S.; Mulloy, Anthony L.; Recker, Robert R.; Weiss, Stuart R.; Heyden, Norman; Musliner, Thomas; Suryawanshi, Shailaja; Yates, A. John; Lombardi, Antonio

Affiliations

¹Michigan Bone and Mineral Clinic, Detroit, Michigan 48236

²General Clinical Research Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215

³ReSearch for Health, Houston, Texas 77024

⁴Veterans Administration Medical Center, Charleston, South Carolina 29401

⁵Chicago Center for Clinical Research, Chicago, Illinois 60610

⁶Medical College of Virginia, Richmond, Virginia 23298

⁷Bone Research Center, Reading, Pennsylvania 19611

⁸Edouard Herriot Hopital, Lyon, France

⁹SAM Clinical Research, San Antonio, Texas 78229

¹⁰Medical College of Georgia, Augusta, Georgia 30912

¹¹Creighton University, Omaha, Nebraska 68131

¹²San Diego Endocrine Clinic, San Diego, California 92108

¹³Merck Research Laboratories, Rahway, New Jersey 07065

Abstract and keywords

The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis. Acting by different mechanisms, these two agents decrease bone resorption and thereby increase or preserve bone mineral density (BMD). The comparative and combined effects of these medications have not been rigorously studied. This prospective, double blind, placebo-controlled, randomized clinical trial examined the effects of oral alendronate and conjugated estrogen, in combination and separately, on BMD, biochemical markers of bone turnover, safety, and tolerability in 425 hysterectomized postmenopausal women with low bone mass. In addition, bone biopsy with histomorphometry was performed in a subset of subjects. Treatment included placebo, alendronate (10 mg daily), conjugated equine 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 alendronate, CEE, and alendronate plus CEE of 6.0% (P < 0.001 vs. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and CEE; P = 0.022 vs. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alendronate, estrogen, alendronate plus estrogen, and placebo groups, respectively. Both alendronate and CEE significantly decreased biochemical markers of bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone, but the mean absolute values remained within the normal premenopausal range. Alendronate, alone or in combination with CEE, was well tolerated. In the subset of patients who underwent bone biopsies, histomorphometry showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group.

Thus, alendronate and estrogen produced favorable effects on BMD. Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated.

Keywords:

Links

DOI: 10.1210/jc.85.2.720

PubMed: 10690882

WoS: 000085377700046

History

Received: 1999-05-06

Revised: 1999-11-04

Accepted: 1999-11-08

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2019	Bouxsein ML, Eastell R, Lui L-Y, Wu LA, de Papp AE, Grauer A, Marin F, Cauley JA, Bauer DC, Black DM; FNIH Bone Quality Project. Change in bone density and reduction in fracture risk: a meta-regression of published trials. J Bone Miner Res. April 2019;34(4):632-642.
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