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 354:821-831 February 23, 2006 Number 8 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Whyte, M. P. 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 Receptor activator of nuclear factor-B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action.

Methods The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of –1.8 to –4.0 at the lumbar spine or –1.8 to –3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase.

Results Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent.

Conclusions In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186 [ClinicalTrials.gov] .)

Source Information

From Providence Portland Medical Center, Portland, Oreg. (M.R.M.); New Mexico Clinical Research and Osteoporosis Center, Albuquerque (E.M.L.); Radiant Research, Dallas (S.B.C.); Bethesda Health Research Center, Bethesda, Md. (M.A.B.); Atlanta Research Center, Decatur, Ga. (G.C.W.); OB-GYN Associates of Mid Florida, Leesburg, Fla. (A.H.M.); Indiana University School of Medicine, Indianapolis (M.P.); Colorado Center for Bone Research, Lakewood (P.D.M.); Radiant Research, Lake Worth, Fla. (S.N.L.); University of Washington Medical Center, Seattle(C.H.C.); Arthritis Associates and Osteoporosis Center of Colorado Springs, Colorado Springs, Colo. (D.L.); Altoona Center for Clinical Research, Duncansville, Pa. (A.J.K.); and Amgen, Thousand Oaks, Calif. (D.L.H., C.Z., M.C.P., P.J.B.).

Address reprint requests to Dr. McClung at the Oregon Osteoporosis Center, 5050 NE Hoyt St., Suite 651, Portland, OR 97213, or at mmcclung{at}orost.com.

Full Text of this Article

Related Letters:

Denosumab in Postmenopausal Women with Low Bone Mineral Density
Schwartzman J., Yazici Y., Rifkin W. D., McClung M. R.
Extract | Full Text | PDF  
N Engl J Med 2006; 354:2390-2391, Jun 1, 2006. Correspondence

This article has been cited by other articles:

• Cole, Z., Dennison, E., Cooper, C. (2008). Update on the treatment of post-menopausal osteoporosis. Br Med Bull 0: ldn017v1-15 [Abstract] [Full Text]  
• Hirschhorn, J. N., Gennari, L. (2008). Bona Fide Genetic Associations with Bone Mineral Density. NEJM 0: NEJMe0803046v1-1 [Full Text]  
• Kearns, A. E., Khosla, S., Kostenuik, P. J. (2008). Receptor Activator of Nuclear Factor {kappa}B Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease. Endocr. Rev. 29: 155-192 [Abstract] [Full Text]  
• Lloyd, S. A.J., Travis, N. D., Lu, T., Bateman, T. A. (2008). Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse. J. Appl. Physiol. 104: 729-738 [Abstract] [Full Text]  
• MacLaughlin, E. J., Raehl, C. L. (2008). ASHP Therapeutic Position Statement on the Prevention and Treatment of Osteoporosis in Adults. Am J Health Syst Pharm 65: 343-357 [Full Text]  
• MacLean, C., Newberry, S., Maglione, M., McMahon, M., Ranganath, V., Suttorp, M., Mojica, W., Timmer, M., Alexander, A., McNamara, M., Desai, S. B., Zhou, A., Chen, S., Carter, J., Tringale, C., Valentine, D., Johnsen, B., Grossman, J. (2008). Systematic Review: Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women with Low Bone Density or Osteoporosis. ANN INTERN MED 148: 197-213 [Abstract] [Full Text]  
• Jadoul, M. (2007). Towards the prevention of bone fractures in dialysed patients?. Nephrol Dial Transplant 22: 3377-3380 [Full Text]  
• Vega, D., Maalouf, N. M., Sakhaee, K. (2007). The Role of Receptor Activator of Nuclear Factor-{kappa}B (RANK)/RANK Ligand/Osteoprotegerin: Clinical Implications. J. Clin. Endocrinol. Metab. 92: 4514-4521 [Abstract] [Full Text]  
• Tauchmanova, L., Colao, A., Lombardi, G., Rotoli, B., Selleri, C. (2007). REVIEW: Bone Loss and Its Management in Long-Term Survivors from Allogeneic Stem Cell Transplantation. J. Clin. Endocrinol. Metab. 92: 4536-4545 [Abstract] [Full Text]  
• Martin, T. J., Ng, K. W. (2007). New Agents for the Treatment of Osteoporosis. IBMS BoneKEy 4: 287-298 [Abstract] [Full Text]  
• Schlechte, J. A. (2007). Update in Endocrinology. ANN INTERN MED 147: 563-572 [Full Text]  
• Chu, C. R., McMahon, M. S., Ueki, Y., Fyhrie, D. P. (2007). On the Horizon From the ORS. J Am Acad Orthop Surg 15: 636-638 [Full Text]  
• Kiechl, S., Schett, G., Schwaiger, J., Seppi, K., Eder, P., Egger, G., Santer, P., Mayr, A., Xu, Q., Willeit, J. (2007). Soluble Receptor Activator of Nuclear Factor-{kappa}B Ligand and Risk for Cardiovascular Disease. Circulation 116: 385-391 [Abstract] [Full Text]  
• Samadfam, R., Xia, Q., Goltzman, D. (2007). Pretreatment with Anticatabolic Agents Blunts But Does Not Eliminate the Skeletal Anabolic Response to Parathyroid Hormone in Oophorectomized Mice. Endocrinology 148: 2778-2787 [Abstract] [Full Text]  
• Minisola, S., Pepe, J., Romagnoli, E., Blade, J. (2007). Monoclonal Gammopathy of Undetermined Significance. NEJM 356: 2223-2224 [Full Text]  
• Shoback, D. (2007). Update in Osteoporosis and Metabolic Bone Disorders. J. Clin. Endocrinol. Metab. 92: 747-753 [Abstract] [Full Text]  
• Yaccoby, S., Ling, W., Zhan, F., Walker, R., Barlogie, B., Shaughnessy, J. D. Jr (2007). Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 109: 2106-2111 [Abstract] [Full Text]  
• Lentle, B., Worsley, D. (2006). Osteoporosis Redux. JNM 47: 1945-1959 [Full Text]  
• Sato, K., Suematsu, A., Okamoto, K., Yamaguchi, A., Morishita, Y., Kadono, Y., Tanaka, S., Kodama, T., Akira, S., Iwakura, Y., Cua, D. J., Takayanagi, H. (2006). Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J. Exp. Med. 203: 2673-2682 [Abstract] [Full Text]  
• Smith, M. R. (2006). Bisphosphonates for Metastatic Bone Disease -- Too Much of a Good Thing?. IBMS BoneKEy 3: 24-27 [Full Text]  
• Westenfeld, R., Ketteler, M., Brandenburg, V. M. (2006). Anti-RANKL therapy--implications for the bone-vascular-axis in CKD? Denosumab in post-menopausal women with low bone mineral density. Nephrol Dial Transplant 21: 2075-2077 [Full Text]  
• Schwartzman, J., Yazici, Y., Rifkin, W. D., McClung, M. R. (2006). Denosumab in postmenopausal women with low bone mineral density.. NEJM 354: 2390-2391 [Full Text]  
• Martin, T. J. (2006). Current, New and Emerging Anti-Resorptive Drugs; Antibody Blockade Of RANKL Action. IBMS BoneKEy 3: 42-46 [Full Text]  
• (2006). A New Approach to Treating Osteoporosis?. JWatch Women's Health 2006: 1-1 [Full Text]  
• (2006). Endocrinology & Metabolism News, April 2006. J. Clin. Endocrinol. Metab. 91: 17a-17a [Full Text]  
• Tonks, A. (2006). What's new in the other general journals.. BMJ 332: 536-537 [Full Text]  
• Whyte, M. P. (2006). The long and the short of bone therapy.. NEJM 354: 860-863 [Full Text]