| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
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:
 |
|
 |
|
  A. Qaseem, V. Snow, P. Shekelle, R. Hopkins Jr., M. A. Forciea, D. K. Owens, and for the Clinical Efficacy Assessment Subcommittee Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians Ann Intern Med, September 16, 2008; 149(6): 404 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Visekruna, D. Wilson, and F. E. McKiernan Severely Suppressed Bone Turnover and Atypical Skeletal Fragility J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 2948 - 2952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 B. Cryer and D. C. Bauer Oral Bisphosphonates and Upper Gastrointestinal Tract Problems: What Is the Evidence? Mayo Clin. Proc., October 1, 2002; 77(10): 1031 - 1043. [Abstract] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. Grady A 60-Year-Old Woman Trying to Discontinue Hormone Replacement Therapy JAMA, April 24, 2002; 287(16): 2130 - 2137. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 Bisphosphonates for osteoporosis DTB, September 1, 2001; 39(9): 68 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. Altkorn and T. Vokes Treatment of Postmenopausal Osteoporosis JAMA, March 21, 2001; 285(11): 1415 - 1418. [Full Text] [PDF]
|
|
|
|
|
|
C. Crandall Risedronate: A Clinical Review Arch Intern Med, February 12, 2001; 161(3): 353 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Estrogen, Alendronate, or Both for Osteoporosis? Journal Watch Women's Health, June 1, 2000; 2000(601): 6 - 6. [Full Text]
|
|
|
|
 |
|
 Estrogen, Alendronate, or Both for Osteoporosis? Journal Watch Gastroenterology, May 1, 2000; 2000(501): 19 - 19. [Full Text]
|
|
|
|
 |
|
 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 |
