Online citations, reference lists, and bibliographies.
← Back to Search

Denosumab For Prevention Of Fractures In Postmenopausal Women With Osteoporosis.

S. Cummings, J. S. San Martin, M. Mcclung, E. Siris, R. Eastell, I. Reid, P. Delmas, H. Zoog, M. Austin, Andrea Wang, Š. Kutílek, S. Adami, J. Zanchetta, C. Libanati, S. Siddhanti, C. Christiansen
Published 2009 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
BACKGROUND Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis. METHODS We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures. RESULTS As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0.41; P<0.001)--a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04)--a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01)--a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab. CONCLUSIONS Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791.)
This paper references
10.1359/jbmr.2003.18.6.1160
Osteoporosis Panel Summary
A. Capron (2003)
10.5694/j.1326-5377.1977.tb130872.x
THE LONG AND THE SHORT
R. Vines (1977)
10.1359/jbmr.080301
Considerations for Development of Surrogate Endpoints for Antifracture Efficacy of New Treatments in Osteoporosis: A Perspective
M. Bouxsein (2008)
Effect of denosumab on
PD Miller
Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis
J Reginster (2000)
10.1001/JAMA.280.24.2077
Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.
S. Cummings (1998)
Am J Med
(1993)
10.1016/S0140-6736(02)08657-9
Epidemiology and outcomes of osteoporotic fractures
S. Cummings (2002)
10.1002/14651858.CD004523.pub3
Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.
G. Wells (2008)
Downloaded from www.nejm.org at RIVERSIDE CO REGL MED CTR on
(2009)
10.1007/s00198-007-0540-8
Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy
R. Russell (2007)
For personal use only. No other uses without permission. Copyright © 2009 Massachusetts Medical Society
(2011)
10.1038/nature01658
Osteoclast differentiation and activation
W. Boyle (2003)
Bouxsein ML, Delmas PD. Consider- 28
(2005)
10.1016/j.bone.2008.04.007
Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial.
P. Miller (2008)
10.1056/NEJM200105103441904
Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.
R. Neer (2001)
tistical analysis of failure time data
(1980)
bone therapy. N Engl J Med
The long and the short of 30 . bone therapy
MP Whyte (2006)
10.1097/00006254-199405000-00024
Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy.
S. Harris (1993)
10.1016/0920-9964(94)90250-X
Mechanisms of action
Christian Couture (1994)
10.1359/jbmr.0707onj
Bisphosphonate‐Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research
S. Khosla (2007)
10.1001/ARCHINTE.162.10.1140
Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis.
M. Maricic (2002)
10.1016/B978-012470862-4/50035-0
Outcomes of Osteoporotic Fractures
G. Greendale (2001)
Denosumab for Fr acture Prevention in Women with Osteoporosis n engl j med 361
(2009)
10.1038/361400A0
The long and the short of it
V. French (1993)
Copyright © 2009 Massachusetts Medical Society. All rights reserved. Denosumab for Fr acture Prevention in Women with Osteoporosis n engl j med 361
Downloaded From Www (2009)
The sta- 15
New York Kalbfleisch (2002)
RANKL inhibition for the management of postmenopausal osteoporosis and other metabolic bone diseases
(2008)
10.1007/s00198-006-0172-4
An estimate of the worldwide prevalence and disability associated with osteoporotic fractures
O. Johnell (2006)
The sta- 15. tistical analysis of failure time data New York
New York Kalbfleisch (1980)
10.1080/00401706.1982.10487769
The Statistical Analysis of Failure Time Data
J. D. Kalbfleisch (1980)
10.1097/01.ogx.0000219511.20627.d3
Denosumab in postmenopausal women with low bone mineral density.
M. Mcclung (2006)
10.1185/030079904X16768
Response to therapy with once-weekly alendronate 70 mg compared to once-weekly risedronate 35 mg in the treatment of postmenopausal osteoporosis
A. Sebba (2004)
10.1359/JBMR.040325
Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal Osteoporosis
C. Chesnut (2004)
10.1097/01.OGX.0000275406.83713.0F
Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.
D. Black (2007)
Response to therapy with onceweekly alendronate 70 mg compared to onceweekly risedronate 35 mg in the treatment of post - menopausal osteoporosis
AI Sebba (2009)
The long and the short of 30
Mp Whyte
J Bone Miner Res
(2004)
N Engl J Med
(2006)
Paracrine regulation of os- 29
Tj Martin
10.1007/s001980050010
Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis
J. Reginster (2000)
density and turnover in postmenopausal women with low bone mass after long - term continued , discontinued , and restarting of therapy : a randomized blinded phase 2 clinical trial
A Capron (2008)
10.1359/jbmr.2003.18.11.1947
BMD at Multiple Sites and Risk of Fracture of Multiple Types: Long‐Term Results From the Study of Osteoporotic Fractures
K. Stone (2003)
10.1007/s00223-003-0042-4
Risedronate Rapidly Reduces the Risk for Nonvertebral Fractures in Women with Postmenopausal Osteoporosis
J. T. Harrington (2003)
10.1056/NEJME068003
The long and the short of bone therapy.
M. Whyte (2006)
Paracrine regulation of osteoclast formation and activity: milestones in discovery.
T. Martin (2004)
10.1359/jbmr.070905
Recommendations for the Clinical Evaluation of Agents for Treatment of Osteoporosis: Consensus of an Expert Panel Representing the American Society for Bone and Mineral Research (ASBMR), the International Society for Clinical Densitometry (ISCD), and the National Osteoporosis Foundation (NOF)
S. Silverman (2008)
10.7326/0003-4819-146-12-200706190-00009
Ethical Issues in Stopping Randomized Trials Early Because of Apparent Benefit
P. Müller (2007)
10.4065/81.8.1013
Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases.
E. Siris (2006)
teoclast differentiation and activation
(2003)
10.1210/jc.2007-2814
Effects of denosumab on bone mineral density and bone turnover in postmenopausal women.
Henry G. Bone (2008)
10.1001/JAMA.282.14.1344
Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.
S. Harris (1999)
10.1016/S0140-6736(96)07088-2
Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures
D. Black (1996)
10.1016/j.jocd.2008.02.002
Clinical potential of RANKL inhibition for the management of postmenopausal osteoporosis and other metabolic bone diseases.
P. Delmas (2008)
10.1080/00401706.1991.10484817
Categorical Data Analysis
A. Agresti (1991)
10.1359/jbmr.0809010
Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial
Jacques P. Brown (2009)
10.1002/JBMR.5650080915
Vertebral fracture assessment using a semiquantitative technique
H. Genant (1993)
Effect of parathyroid hormone ( 1 - 34 ) on fractures and bone mineral density in postmenopausal women with osteoporo
RM Neer (2001)
10.1056/nejm200105313442214
The effect of risedronate on the risk of hip fracture in elderly women.
R. L. Goodman (2001)
Paracrine regulation of osteoclast formation and activity: milestones in discovery.
Martin Tj (2004)
10.1359/jbmr.070809
Two‐Year Treatment With Denosumab (AMG 162) in a Randomized Phase 2 Study of Postmenopausal Women With Low BMD
E. Lewiecki (2007)



This paper is referenced by
10.2169/internalmedicine.56.7797
Effects of Denosumab on Bone Metabolic Markers and Bone Mineral Density in Patients Treated with Glucocorticoids
M. Sawamura (2017)
10.1016/S0084-3741(10)79515-9
Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis
B. Clarke (2010)
10.1016/J.RHUM.2009.10.032
Nouvelles cibles thérapeutiques dans l’ostéoporose
Sophie Roux (2010)
10.1371/journal.pgen.1001217
Genome-Wide Association Meta-Analysis of Cortical Bone Mineral Density Unravels Allelic Heterogeneity at the RANKL Locus and Potential Pleiotropic Effects on Bone
L. Paternoster (2010)
10.1007/s11914-010-0045-9
Androgen Deprivation and Bone
J. Lattouf (2011)
10.1007/s11657-011-0060-1
Osteoporosis: burden, health care provision and opportunities in the EU
O. Ström (2011)
10.1016/S0003-4266(11)70005-1
Innovations thérapeutiques dans l’ostéoporose (anticorps antisclérostine et denosumab)
M.-A. Quemerais-Durieu (2011)
10.2217/AHE.11.86
The elderly inflammatory bowel disease patient and osteoporosis
Seymour Katz (2012)
10.1016/j.jcms.2012.10.014
Denosumab osteonecrosis of the mandible: a new entity? A case report.
Sarina E.C. Pichardo (2013)
Calcium intake and bone mineral density: systematic review
M. Bolland (2015)
10.1007/978-3-642-21892-7_8
Perspectives in the elderly patient: benefits and limits of bisphosphonates and denosumab.
Donatella Santini (2012)
10.1136/bmj.h4183
Calcium intake and bone mineral density: systematic review and meta-analysis
Vicky Tai (2015)
10.1371/journal.pone.0193846
The effects of denosumab and alendronate on glucocorticoid-induced osteoporosis in patients with glomerular disease: A randomized, controlled trial
Ken Iseri (2018)
10.14341/OSTEO9760
Long-term treatment options for postmenopausal osteoporosis: results of recent clinical studies of Denosumab
Z E Belaya (2018)
10.1016/J.RCREUE.2019.01.004
Second Colombian Consensus on the Management of Post-menopausal Osteoporosis: 2017 update
Adriana Medina Orjuela (2018)
10.1007/s00223-020-00673-8
Modulation of Transient Receptor Potential Channels 3 and 6 Regulates Osteoclast Function with Impact on Trabecular Bone Loss
Sebastián Martín Klein (2020)
10.1007/s00256-018-3118-y
Assessing the effects of long-term osteoporosis treatment by using conventional spine radiographs: results from a pilot study in a sub-cohort of a large randomized controlled trial
H. Dimai (2018)
10.1186/s11658-016-0013-1
Osteoporosis: the current status of mesenchymal stem cell-based therapy
J. Phetfong (2016)
10.1016/j.afos.2016.10.002
Thai Osteoporosis Foundation (TOPF) position statements on management of osteoporosis
T. Songpatanasilp (2016)
A Link Between Hot Flashes and Osteoporosis
(2010)
10.3389/fcell.2020.00325
Pros and Cons of Denosumab Treatment for Osteoporosis and Implication for RANKL Aptamer Therapy
Ning Zhang (2020)
10.20996/1819-6446-2019-15-3-359-367
Atherosclerosis and Osteoporosis. Common Targets for the Effects of Cardiovascular and Anti-Osteoporotic Drugs (Part II). The Effect of Antiosteoporotic Drugs on the Vascular Wall State
Irina A. Skripnikova (2019)
10.1080/00325481.2015.993278
Considerations regarding adherence of anti-osteoporosis therapy
Violet S. Lagari (2015)
10.1007/978-3-319-97952-6_32
Reconstructive Procedures in the Osteoporotic Patient
Jacob Januszewski (2019)
10.1371/journal.pcbi.1005372
Cheminformatics-aided discovery of small-molecule Protein-Protein Interaction (PPI) dual inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL)
G. Melagraki (2017)
10.1038/nrendo.2016.91
Physiological and pathophysiological bone turnover — role of the immune system
M. Weitzmann (2016)
Consecuencias clínicas de la persistencia de actividad inflamatoria en la arteritis de células gigantes. Estudio de factores implicados
A. G. Martínez (2010)
10.1155/2013/647189
Ethanol Extracts of Fresh Davallia formosana (WL1101) Inhibit Osteoclast Differentiation by Suppressing RANKL-Induced Nuclear Factor-κB Activation
Tzu-Hung Lin (2013)
10.1177/0896860819880095
Use of denosumab to treat refractory hypercalcemia in a peritoneal dialysis patient with immobilization and tertiary hyperparathyroidism
Ryan M Pratt (2020)
10.4414/SMF.2011.07411
Neue Wege in der Diagnostik und Therapie der Osteoporose
M. Kraenzlin (2011)
10.1111/cup.13070
Denosumab‐induced cutaneous hypersensitivity reaction with distinct clinical and histopathologic findings
Brian J King (2018)
10.1016/J.RCREU.2018.02.006
II Consenso Colombiano para el Manejo de la Osteoporosis Posmenopáusica
A. Orjuela (2018)
See more
Semantic Scholar Logo Some data provided by SemanticScholar