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

H. G. Bone, S. L. Greenspan, C. McKeever, N. Bell, M. Davidson, R. W. Downs, R. Emkey, P. J. Meunier, S. S. Miller, A. L. Mulloy, R. R. Recker, S. R. Weiss, N. Heyden, T. Musliner, S. Suryawanshi, A. J. Yates, A. Lombardi

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)720-726
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume85
Issue number2
DOIs
StatePublished - Dec 1 2000

Fingerprint

Alendronate
Bone Density
Minerals
Bone
Estrogens
Placebos
Conjugated (USP) Estrogens
Bone Remodeling
Bone and Bones
Biopsy
Biomarkers
Postmenopausal Osteoporosis
Histology
Diphosphonates
Bone Resorption
Collagen Type I
Femur

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Bone, H. G., Greenspan, S. L., McKeever, C., Bell, N., Davidson, M., Downs, R. W., ... Lombardi, A. (2000). Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Journal of Clinical Endocrinology and Metabolism, 85(2), 720-726. https://doi.org/10.1210/jc.85.2.720

Alendronate and estrogen effects in postmenopausal women with low bone mineral density. / Bone, H. G.; Greenspan, S. L.; McKeever, C.; Bell, N.; Davidson, M.; Downs, R. W.; Emkey, R.; Meunier, P. J.; Miller, S. S.; Mulloy, A. L.; Recker, R. R.; Weiss, S. R.; Heyden, N.; Musliner, T.; Suryawanshi, S.; Yates, A. J.; Lombardi, A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 2, 01.12.2000, p. 720-726.

Research output: Contribution to journalArticle

Bone, HG, Greenspan, SL, McKeever, C, Bell, N, Davidson, M, Downs, RW, Emkey, R, Meunier, PJ, Miller, SS, Mulloy, AL, Recker, RR, Weiss, SR, Heyden, N, Musliner, T, Suryawanshi, S, Yates, AJ & Lombardi, A 2000, 'Alendronate and estrogen effects in postmenopausal women with low bone mineral density', Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 2, pp. 720-726. https://doi.org/10.1210/jc.85.2.720
Bone, H. G. ; Greenspan, S. L. ; McKeever, C. ; Bell, N. ; Davidson, M. ; Downs, R. W. ; Emkey, R. ; Meunier, P. J. ; Miller, S. S. ; Mulloy, A. L. ; Recker, R. R. ; Weiss, S. R. ; Heyden, N. ; Musliner, T. ; Suryawanshi, S. ; Yates, A. J. ; Lombardi, A. / Alendronate and estrogen effects in postmenopausal women with low bone mineral density. In: Journal of Clinical Endocrinology and Metabolism. 2000 ; Vol. 85, No. 2. pp. 720-726.
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AU - Downs, R. W.

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N2 - 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.

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