help button home button Endocrine Society JCEM JCEM Call for Nominations for EIC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bone, H. G.
Right arrow Articles by Lombardi, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bone, H. G.
Right arrow Articles by Lombardi, A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ESTROGENIC SUBSTANCES, CONJUGATED
The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 2 720-726
Copyright © 2000 by The Endocrine Society

Original Studies

Alendronate and Estrogen Effects in Postmenopausal Women with Low Bone Mineral Density1

Henry G. Bone, Susan L. Greenspan, Clark McKeever, Norman Bell, Michael Davidson, Robert W. Downs, Ronald Emkey, Pierre J. Meunier, Sam S. Miller, Anthony L. Mulloy, Robert R. Recker, Stuart R. Weiss, Norman Heyden, Thomas Musliner, Shailaja Suryawanshi, A. John Yates, Antonio Lombardi and for the alendronate/estrogen study group2

Michigan Bone and Mineral Clinic (H.G.B.), Detroit, Michigan 48236; General Clinical Research Center, Beth Israel Deaconess Medical Center (S.L.G.), Boston, Massachusetts 02215; ReSearch for Health (C.M.), Houston, Texas 77024; Veterans Administration Medical Center (N.B.), Charleston, South Carolina 29401; Chicago Center for Clinical Research (M.D.), Chicago, Illinois 60610; Medical College of Virginia (R.W.D.), Richmond, Virginia 23298; Bone Research Center (R.E.), Reading, Pennsylvania 19611; Edouard Herriot Hopital (P.J.M.), Lyon, France; SAM Clinical Research (S.S.M.), San Antonio, Texas 78229; Medical College of Georgia (A.L.M.), Augusta, Georgia 30912; Creighton University (R.R.R.), Omaha, Nebraska 68131; San Diego Endocrine Clinic (S.R.W.), San Diego, California 92108; and Merck Research Laboratories (N.H., T.M., S.S., A.J.Y., A.L.), Rahway, New Jersey 07065

Address all correspondence and requests for reprints to: Dr. Henry G. Bone, Michigan Bone and Mineral Clinic (H.G.B.), Detroit, Michigan 48236.

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.




This article has been cited by other articles:


Home page
 Am J Health Syst PharmHome page
E. J. MacLaughlin and C. L. Raehl
ASHP Therapeutic Position Statement on the Prevention and Treatment of Osteoporosis in Adults
Am. J. Health Syst. Pharm., February 15, 2008; 65(4): 343 - 357.
[Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
C. MacLean, S. Newberry, M. Maglione, M. McMahon, V. Ranganath, M. Suttorp, W. Mojica, M. Timmer, A. Alexander, M. McNamara, et al.
Systematic Review: Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women with Low Bone Density or Osteoporosis
Ann Intern Med, February 5, 2008; 148(3): 197 - 213.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
I. LAMBRINOUDAKI, G. CHRISTODOULAKOS, and D. BOTSIS
Bisphosphonates
Ann. N.Y. Acad. Sci., December 1, 2006; 1092(1): 397 - 402.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. V. Odvina, J. E. Zerwekh, D. S. Rao, N. Maalouf, F. A. Gottschalk, and C. Y. C. Pak
Severely Suppressed Bone Turnover: A Potential Complication of Alendronate Therapy
J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1294 - 1301.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. I. Plotkin, J. I. Aguirre, S. Kousteni, S. C. Manolagas, and T. Bellido
Bisphosphonates and Estrogens Inhibit Osteocyte Apoptosis via Distinct Molecular Mechanisms Downstream of Extracellular Signal-regulated Kinase Activation
J. Biol. Chem., February 25, 2005; 280(8): 7317 - 7325.
[Abstract] [Full Text] [PDF]

Home page
 Obstet GynecolHome page
Osteoporosis
Obstet. Gynecol., October 1, 2004; 104(4_suppl): 66S - 76S.
[Full Text] [PDF]

Home page
 NEJMHome page
H. G. Bone, D. Hosking, J.-P. Devogelaer, J. R. Tucci, R. D. Emkey, R. P. Tonino, J. A. Rodriguez-Portales, R. W. Downs, J. Gupta, A. C. Santora, et al.
Ten Years' Experience with Alendronate for Osteoporosis in Postmenopausal Women
N. Engl. J. Med., March 18, 2004; 350(12): 1189 - 1199.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Evio, A. Tiitinen, K. Laitinen, O. Ylikorkala, and M. J. Valimaki
Effects of Alendronate and Hormone Replacement Therapy, Alone and in Combination, on Bone Mass and Markers of Bone Turnover in Elderly Women with Osteoporosis
J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 626 - 631.
[Abstract] [Full Text] [PDF]

Home page
 Clin. DiabetesHome page
S. A. Brown and J. L. Sharpless
Osteoporosis: An Under-appreciated Complication of Diabetes
Clin. Diabetes, January 1, 2004; 22(1): 10 - 20.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. Doren, J.-A. Nilsson, and O. Johnell
Effects of specific post-menopausal hormone therapies on bone mineral density in post-menopausal women: a meta-analysis
Hum. Reprod., August 1, 2003; 18(8): 1737 - 1746.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
S. L. Greenspan, N. M. Resnick, and R. A. Parker
Combination Therapy With Hormone Replacement and Alendronate for Prevention of Bone Loss in Elderly Women: A Randomized Controlled Trial
JAMA, May 21, 2003; 289(19): 2525 - 2533.
[Abstract] [Full Text] [PDF]

Home page
 Arch Intern MedHome page
B. H. Ascott-Evans, N. Guanabens, S. Kivinen, B. G. A. Stuckey, C. H. Magaril, K. Vandormael, B. Stych, and M. E. Melton
Alendronate Prevents Loss of Bone Density Associated With Discontinuation of Hormone Replacement Therapy: A Randomized Controlled Trial
Arch Intern Med, April 14, 2003; 163(7): 789 - 794.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
J. P. Brown and R. G. Josse
Lignes directrices de pratique clinique 2002 pour le diagnostic et le traitement de l'osteoporose au Canada
Can. Med. Assoc. J., March 18, 2003; 168(90060): SF1 - 38.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
S. L. Greenspan, R. D. Emkey, H. G. Bone III, S. R. Weiss, N. H. Bell, R. W. Downs Jr., C. McKeever, S. S. Miller, M. Davidson, M. A. Bolognese, et al.
Significant Differential Effects of Alendronate, Estrogen, or Combination Therapy on the Rate of Bone Loss after Discontinuation of Treatment of Postmenopausal Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Trial
Ann Intern Med, December 3, 2002; 137(11): 875 - 883.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
J. P. Brown and R. G. Josse
2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada
Can. Med. Assoc. J., November 12, 2002; 167(90100): s1 - 34.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
N. H. Bell, J. P. Bilezikian, H. G. Bone III, A. Kaur, A. Maragoto, and A. C. Santora
Alendronate Increases Bone Mass and Reduces Bone Markers in Postmenopausal African-American Women
J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2792 - 2797.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
D. Grady
A 60-Year-Old Woman Trying to Discontinue Hormone Replacement Therapy
JAMA, April 24, 2002; 287(16): 2130 - 2137.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Palomba, F. Orio Jr., A. Colao, C. di Carlo, T. Sena, G. Lombardi, F. Zullo, and P. Mastrantonio
Effect of Estrogen Replacement Plus Low-Dose Alendronate Treatment on Bone Density in Surgically Postmenopausal Women with Osteoporosis
J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1502 - 1508.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. C. Hochberg, S. Greenspan, R. D. Wasnich, P. Miller, D. E. Thompson, and P. D. Ross
Changes in Bone Density and Turnover Explain the Reductions in Incidence of Nonvertebral Fractures that Occur during Treatment with Antiresorptive Agents
J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1586 - 1592.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
B. Ettinger and J. P. Bilezikian
For Osteoporosis, Are Two Antiresorptive Drugs Better Than One?
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 983 - 984.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
O. Johnell, W. H. Scheele, Y. Lu, J.-Y. Reginster, A. G. Need, and E. Seeman
Additive Effects of Raloxifene and Alendronate on Bone Density and Biochemical Markers of Bone Remodeling in Postmenopausal Women with Osteoporosis
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 985 - 992.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
D. G. Altman, D. J. Torgerson, and S. E. M. Bell-Syer
A Meta-analysis of Hormone Replacement Therapy for Fracture Prevention
JAMA, November 7, 2001; 286(17): 2096 - 2097.
[Full Text] [PDF]

Home page
 DTBHome page
Bisphosphonates for osteoporosis
DTB, September 1, 2001; 39(9): 68 - 72.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. C. Gallagher, S. E. Fowler, J. R. Detter, and S. S. Sherman
Combination Treatment with Estrogen and Calcitriol in the Prevention of Age-Related Bone Loss
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3618 - 3628.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. R. Recker and R. P. Heaney
The Role of Combination Treatment for Osteoporosis
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1888 - 1889.
[Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. T. Harris, E. F. Eriksen, M. Davidson, M. P. Ettinger, A. H. Moffett Jr., D. J. Baylink, C. E. Crusan, and A. A. Chines
Effect of Combined Risedronate and Hormone Replacement Therapies on Bone Mineral Density in Postmenopausal Women
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1890 - 1897.
[Abstract] [Full Text]

Home page
 JAMAHome page
D. Altkorn and T. Vokes
Treatment of Postmenopausal Osteoporosis
JAMA, March 21, 2001; 285(11): 1415 - 1418.
[Full Text] [PDF]

Home page
 Arch Intern MedHome page
C. Crandall
Risedronate: A Clinical Review
Arch Intern Med, February 12, 2001; 161(3): 353 - 360.
[Abstract] [Full Text] [PDF]

Home page
 JWatch Women's HealthHome page
Estrogen, Alendronate, or Both for Osteoporosis?
Journal Watch Women's Health, June 1, 2000; 2000(601): 6 - 6.
[Full Text]

Home page
 JWatch GastroenterologyHome page
Estrogen, Alendronate, or Both for Osteoporosis?
Journal Watch Gastroenterology, May 1, 2000; 2000(501): 19 - 19.
[Full Text]

Home page
 JWatch GeneralHome page
Estrogen, Alendronate, or Both for Osteoporosis?
Journal Watch (General), March 14, 2000; 2000(314): 1 - 1.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2000 by The Endocrine Society