FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 350:1189-1199 March 18, 2004 Number 12 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Strewler, G. J. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years.

Methods The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study.

Results Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit.

Conclusions The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.

Source Information

From Michigan Bone and Mineral Clinic, Detroit (H.G.B.); Medical Research Center, Nottingham City Hospital, Nottingham, United Kingdom (D.H.); Saint-Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium (J.-P.D.); Department of Medicine, Roger Williams General Hospital, Providence, R.I. (J.R.T.); Radiant Research–Reading, Wyomissing, Pa. (R.D.E.); Good Health Associates in Adult Medicine, South Burlington, Vt. (R.P.T.); Departamento de Endocrinologia, Escuela de Medicina, Universidad Catolica de Chile, Santiago, Chile (J.A.R.-P.); Virginia Commonwealth University, Richmond (R.W.D.); Merck Research Laboratories, Rahway, N.J. (J.G., A.C.S.); and Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah-Tikva, Israel (U.A.L.).

Address reprint requests to Dr. Bone at the Michigan Bone and Mineral Clinic, 22201 Moross Rd., Suite 260, Detroit, MI 48236.

Full Text of this Article

Related Letters:

Ten Years of Alendronate Treatment for Osteoporosis in Postmenopausal Women
Bjarnason N. H., Chan A. S., Ott S. M., Ruggiero S. L., Mehrotra B., Bone H. G., Santora A. C.
Extract | Full Text | PDF  
N Engl J Med 2004; 351:190-192, Jul 8, 2004. Correspondence

This article has been cited by other articles:

• Ferrari, S. (2009). Continuous broad protection against osteoporotic fractures with strontium ranelate. Rheumatology (Oxford) 48: iv20-iv24 [Abstract] [Full Text]  
• Pozzi, S., Vallet, S., Mukherjee, S., Cirstea, D., Vaghela, N., Santo, L., Rosen, E., Ikeda, H., Okawa, Y., Kiziltepe, T., Schoonmaker, J., Xie, W., Hideshima, T., Weller, E., Bouxsein, M. L., Munshi, N. C., Anderson, K. C., Raje, N. (2009). High-Dose Zoledronic Acid Impacts Bone Remodeling with Effects on Osteoblastic Lineage and Bone Mechanical Properties. Clin. Cancer Res. 15: 5829-5839 [Abstract] [Full Text]  
• Graat-Verboom, L., Wouters, E. F. M., Smeenk, F. W. J. M., van den Borne, B. E. E. M., Lunde, R., Spruit, M. A. (2009). Current status of research on osteoporosis in COPD: a systematic review. Eur Respir J 34: 209-218 [Abstract] [Full Text]  
• Kennel, K. A., Drake, M. T. (2009). Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management. Mayo Clin Proc. 84: 632-638 [Abstract] [Full Text]  
• Lorincz, C., Manske, S. L., Zernicke, R. (2009). Bone Health: Part 1, Nutrition. Sports Health: A Multidisciplinary Approach 1: 253-260 [Abstract] [Full Text]  
• Recker, R. R. (2009). Should We Be Concerned About Giant Osteoclasts?. IBMS BoneKEy 6: 157-158 [Full Text]  
• Bachrach, L. K., Ward, L. M. (2009). Clinical Review: Bisphosphonate Use in Childhood Osteoporosis. J. Clin. Endocrinol. Metab. 94: 400-409 [Abstract] [Full Text]  
• Majumdar, S. R., Lier, D. A., Beaupre, L. A., Hanley, D. A., Maksymowych, W. P., Juby, A. G., Bell, N. R., Morrish, D. W. (2009). Osteoporosis Case Manager for Patients With Hip Fractures: Results of a Cost-effectiveness Analysis Conducted Alongside a Randomized Trial. Arch Intern Med 169: 25-31 [Abstract] [Full Text]  
• Weinstein, R. S., Roberson, P. K., Manolagas, S. C. (2009). Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy. NEJM 360: 53-62 [Abstract] [Full Text]  
• CAREY, J. J., PALOMO, L. (2008). Bisphosphonates and osteonecrosis of the jaw: Innocent association or significant risk?. Cleveland Clinic Journal of Medicine 75: 871-879 [Abstract] [Full Text]  
• Sampath, T. K., Simic, P., Moreno, S., Bukanov, N., Draca, N., Kufner, V., Tikvica, A., Blair, A., Semenski, D., Brncic, M., Burke, S. K., Vukicevic, S. (2008). Sevelamer Restores Bone Volume and Improves Bone Microarchitecture and Strength in Aged Ovariectomized Rats. Endocrinology 149: 6092-6102 [Abstract] [Full Text]  
• Papaioannou, A., Kennedy, C. C., Freitag, A., Ioannidis, G., O'Neill, J., Webber, C., Pui, M., Berthiaume, Y., Rabin, H. R., Paterson, N., Jeanneret, A., Matouk, E., Villeneuve, J., Nixon, M., Adachi, J. D. (2008). Alendronate Once Weekly for the Prevention and Treatment of Bone Loss in Canadian Adult Cystic Fibrosis Patients (CFOS Trial). Chest 134: 794-800 [Abstract] [Full Text]  
• Berenson, J. R., Yellin, O., Boccia, R. V., Flam, M., Wong, S.-F., Batuman, O., Moezi, M. M., Woytowitz, D., Duvivier, H., Nassir, Y., Swift, R. A. (2008). Zoledronic Acid Markedly Improves Bone Mineral Density for Patients with Monoclonal Gammopathy of Undetermined Significance and Bone Loss. Clin. Cancer Res. 14: 6289-6295 [Abstract] [Full Text]  
• Voskaridou, E., Christoulas, D., Konstantinidou, M., Tsiftsakis, E., Alexakos, P., Terpos, E. (2008). Continuous improvement of bone mineral density two years post zoledronic acid discontinuation in patients with thalassemia-induced osteoporosis: long-term follow-up of a randomized, placebo-controlled trial. haematol 93: 1588-1590 [Full Text]  
• Greenspan, S. L., Nelson, J. B., Trump, D. L., Wagner, J. M., Miller, M. E., Perera, S., Resnick, N. M. (2008). Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy. JCO 26: 4426-4434 [Abstract] [Full Text]  
• Drake, M. T., Clarke, B. L., Khosla, S. (2008). Bisphosphonates: Mechanism of Action and Role in Clinical Practice. Mayo Clin Proc. 83: 1032-1045 [Abstract] [Full Text]  
• Visekruna, M., Wilson, D., McKiernan, F. E. (2008). Severely Suppressed Bone Turnover and Atypical Skeletal Fragility. J. Clin. Endocrinol. Metab. 93: 2948-2952 [Abstract] [Full Text]  
• Heikkinen, J., Vaheri, R., Haapalahti, J., Timonen, U. (2008). A 10-year follow-up of the effect of continuous-combined hormone replacement therapy and its discontinuation on bone in postmenopausal women. Menopause Int 14: 70-77 [Abstract] [Full Text]  
• Gehrig, L., Lane, J., O'Connor, M. I. (2008). Osteoporosis: Management and Treatment Strategies for Orthopaedic Surgeons. JBJS 90: 1362-1374 [Full Text]  
• Black, D. M., Bouxsein, M. L., Palermo, L., McGowan, J. A., Newitt, D. C., Rosen, E., Majumdar, S., Rosen, C. J., for the PTH Once-Weekly Research (POWR) Group, (2008). Randomized Trial of Once-Weekly Parathyroid Hormone (1-84) on Bone Mineral Density and Remodeling. J. Clin. Endocrinol. Metab. 93: 2166-2172 [Abstract] [Full Text]  
• Cole, Z., Dennison, E., Cooper, C. (2008). Update on the treatment of post-menopausal osteoporosis. Br Med Bull 86: 129-143 [Abstract] [Full Text]  
• Papapoulos, S E, Schimmer, R C (2008). Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate. Postgrad. Med. J. 84: 307-312 [Abstract] [Full Text]  
• Edwards, B. J., Migliorati, C. A. (2008). Osteoporosis and Its Implications for Dental Patients. Journal of the American Dental Association 139: 545-552 [Abstract] [Full Text]  
• Raje, N., Woo, S.-B., Hande, K., Yap, J. T., Richardson, P. G., Vallet, S., Treister, N., Hideshima, T., Sheehy, N., Chhetri, S., Connell, B., Xie, W., Tai, Y.-T., Szot-Barnes, A., Tian, M., Schlossman, R. L., Weller, E., Munshi, N. C., Van Den Abbeele, A. D., Anderson, K. C. (2008). Clinical, Radiographic, and Biochemical Characterization of Multiple Myeloma Patients with Osteonecrosis of the Jaw. Clin. Cancer Res. 14: 2387-2395 [Abstract] [Full Text]  
• Dodson, T. B., Raje, N. S., Caruso, P. A., Rosenberg, A. E. (2008). Case 9-2008 -- A 65-Year-Old Woman with a Nonhealing Ulcer of the Jaw. NEJM 358: 1283-1291 [Full Text]  
• Reid, I. R. (2008). Pathogenesis of Osteonecrosis of the Jaw. IBMS BoneKEy 5: 69-77 [Abstract] [Full Text]  
• Ruggiero, S.L., Drew, S.J. (2007). Osteonecrosis of the Jaws and Bisphosphonate Therapy. JDR 86: 1013-1021 [Abstract] [Full Text]  
• Wilkinson, G. S., Kuo, Y.-F., Freeman, J. L., Goodwin, J. S. (2007). Intravenous Bisphosphonate Therapy and Inflammatory Conditions or Surgery of the Jaw: A Population-Based Analysis. JNCI J Natl Cancer Inst 99: 1016-1024 [Abstract] [Full Text]  
• Papapoulos, S E, Schimmer, R C (2007). Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate. Ann Rheum Dis 66: 853-858 [Abstract] [Full Text]  
• Papapoulos, S. E., Cremers, S. C.L.M. (2007). Prolonged Bisphosphonate Release after Treatment in Children. NEJM 356: 1075-1076 [Full Text]  
• Goh, S.-K., Yang, K. Y., Koh, J. S. B., Wong, M. K., Chua, S. Y., Chua, D. T. C., Howe, T. S. (2007). Subtrochanteric insufficiency fractures in patients on alendronate therapy: A CAUTION. J Bone Joint Surg Br 89-B: 349-353 [Abstract] [Full Text]  
• Russell, R. G. G. (2007). Bisphosphonates: Mode of Action and Pharmacology. Pediatrics 119: S150-S162 [Abstract] [Full Text]  
• McClung, M. R. (2007). Bisphosphonate Therapy: To Stop or Not to Stop?. IBMS BoneKEy 4: 78-82 [Full Text]  
• Krueger, C. D, West, P. M, Sargent, M., Lodolce, A. E, Pickard, A S. (2007). Bisphosphonate-Induced Osteonecrosis of the Jaw. The Annals of Pharmacotherapy 41: 276-284 [Abstract] [Full Text]  
• Moroni, A., Faldini, C., Hoang-Kim, A., Pegreffi, F., Giannini, S. (2007). Alendronate Improves Screw Fixation in Osteoporotic Bone. JBJS 89: 96-101 [Abstract] [Full Text]  
• Black, D. M., Schwartz, A. V., Ensrud, K. E., Cauley, J. A., Levis, S., Quandt, S. A., Satterfield, S., Wallace, R. B., Bauer, D. C., Palermo, L., Wehren, L. E., Lombardi, A., Santora, A. C., Cummings, S. R., for the FLEX Research Group, (2006). Effects of Continuing or Stopping Alendronate After 5 Years of Treatment: The Fracture Intervention Trial Long-term Extension (FLEX): A Randomized Trial. JAMA 296: 2927-2938 [Abstract] [Full Text]  
• Colon-Emeric, C. S. (2006). Ten vs Five Years of Bisphosphonate Treatment for Postmenopausal Osteoporosis: Enough of a Good Thing. JAMA 296: 2968-2969 [Full Text]  
• Cummings, S. R. (2006). A 55-Year-Old Woman With Osteopenia. JAMA 296: 2601-2610 [Abstract] [Full Text]  
• Watts, N. B., Harris, S. T., McClung, M. R., Bilezikian, J. P., Greenspan, S. L., Luckey, M. M. (2006). Bisphosphonates and osteonecrosis of the jaw.. ANN INTERN MED 145: 791-792 [Full Text]  
• Armamento-Villareal, R., Napoli, N., Panwar, V., Novack, D. (2006). Suppressed Bone Turnover during Alendronate Therapy for High-Turnover Osteoporosis. NEJM 355: 2048-2050 [Full Text]  
• Liu, H., Michaud, K., Nayak, S., Karpf, D. B., Owens, D. K., Garber, A. M. (2006). The Cost-effectiveness of Therapy With Teriparatide and Alendronate in Women With Severe Osteoporosis.. Arch Intern Med 166: 1209-1217 [Abstract] [Full Text]  
• Reginster, J-Y, Adami, S, Lakatos, P, Greenwald, M, Stepan, J J, Silverman, S L, Christiansen, C, Rowell, L, Mairon, N, Bonvoisin, B, Drezner, M K, Emkey, R, Felsenberg, D, Cooper, C, Delmas, P D, Miller, P D (2006). Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis 65: 654-661 [Abstract] [Full Text]  
• Rauch, F., Munns, C., Land, C., Glorieux, F. H. (2006). Pamidronate in Children and Adolescents with Osteogenesis Imperfecta: Effect of Treatment Discontinuation. J. Clin. Endocrinol. Metab. 91: 1268-1274 [Abstract] [Full Text]  
• Michaud, L. B., Goodin, S. (2006). Cancer-treatment-induced bone loss, part 2. Am J Health Syst Pharm 63: 534-546 [Abstract] [Full Text]  
• Michalska, D., Stepan, J. J., Basson, B. R., Pavo, I. (2006). The Effect of Raloxifene after Discontinuation of Long-Term Alendronate Treatment of Postmenopausal Osteoporosis. J. Clin. Endocrinol. Metab. 91: 870-877 [Abstract] [Full Text]  
• Crandall, C., Pregler, J. P. (2005). Update in Women's Health. ANN INTERN MED 143: 823-829 [Full Text]  
• Lai, K.-A., Shen, W.-J., Yang, C.-Y., Shao, C.-J., Hsu, J.-T., Lin, R.-M. (2005). The Use of Alendronate to Prevent Early Collapse of the Femoral Head in Patients with Nontraumatic Osteonecrosis. A Randomized Clinical Study. JBJS 87: 2155-2159 [Abstract] [Full Text]  
• Cosman, F., Nieves, J., Zion, M., Woelfert, L., Luckey, M., Lindsay, R. (2005). Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate. NEJM 353: 566-575 [Abstract] [Full Text]  
• Morris, C. D., Einhorn, T. A. (2005). Bisphosphonates in Orthopaedic Surgery. JBJS 87: 1609-1618 [Abstract] [Full Text]  
• Schousboe, J. T., Nyman, J. A., Kane, R. L., Ensrud, K. E. (2005). Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal Women. ANN INTERN MED 142: 734-741 [Abstract] [Full Text]  
• Licata, A. A (2005). Discovery, Clinical Development, and Therapeutic Uses of Bisphosphonates. The Annals of Pharmacotherapy 39: 668-677 [Abstract] [Full Text]  
• Ott, S. M. (2005). Long-Term Safety of Bisphosphonates. J. Clin. Endocrinol. Metab. 90: 1897-1899 [Full Text]  
• Odvina, C. V., Zerwekh, J. E., Rao, D. S., Maalouf, N., Gottschalk, F. A., Pak, C. Y. C. (2005). Severely Suppressed Bone Turnover: A Potential Complication of Alendronate Therapy. J. Clin. Endocrinol. Metab. 90: 1294-1301 [Abstract] [Full Text]  
• Epstein, S. (2005). The Roles of Bone Mineral Density, Bone Turnover, and Other Properties in Reducing Fracture Risk During Antiresorptive Therapy. Mayo Clin Proc. 80: 379-388 [Abstract]  
• Strewler, G. J. (2005). Long-Term Bisphosphonates for Osteoporosis: An Introduction. IBMS BoneKEy 2: 6-9 [Full Text]  
• Reid, I. R. (2005). Long-Term Use of Alendronate. IBMS BoneKEy 2: 10-12 [Full Text]  
• Papapoulos, S. E. (2005). Long-Term Therapy of Osteoporosis with Bisphosphonates: Evidence and Implications for Daily Practice. IBMS BoneKEy 2: 13-19 [Full Text]  
• Alekel, D. L. (2004). Isoflavones and Postmenopausal Women. JAMA 292: 2336-2336 [Full Text]  
• McClung, M. R., Wasnich, R. D., Hosking, D. J., Christiansen, C., Ravn, P., Wu, M., Mantz, A. M., Yates, J., Ross, P. D., Santora, A. C. II, on behalf of the Early Postmenopausal Intervention, (2004). Prevention of Postmenopausal Bone Loss: Six-Year Results from the Early Postmenopausal Intervention Cohort Study. J. Clin. Endocrinol. Metab. 89: 4879-4885 [Abstract] [Full Text]  
• Di Munno, O, Mazzantini, M, Sedie, A D., Mosca, M, Bombardieri, S (2004). Risk factors for osteoporosis in female patients with systemic lupus erythematosus. Lupus 13: 724-730 [Abstract]  
• Rodeo, S. A., Maher, S. A., Hidaka, C. (2004). What's New in Orthopaedic Research. JBJS 86: 2085-2095 [Full Text]  
• Bjarnason, N. H., Chan, A. S., Ott, S. M., Ruggiero, S. L., Mehrotra, B., Bone, H. G., Santora, A. C. (2004). Ten Years of Alendronate Treatment for Osteoporosis in Postmenopausal Women. NEJM 351: 190-192 [Full Text]  
• (2004). Alendronate: Safe and Effective During One Decade of Use. JWatch Women's Health 2004: 6-6 [Full Text]  
• (2004). 10-Year Experience with Alendronate for Osteoporosis. JWatch General 2004: 1-1 [Full Text]