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Cited by 3,489Bone health and osteoporosis researchBone Metabolism and DiseasesBone health and treatments

Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis

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Cummings, Steven R., Martin, Javier San, McClung, Michael R., Siris, Ethel S., Eastell, Richard, Reid, Ian R., Delmas, Pierre, Zoog, Holly B. +8 more·2009·New England Journal of Medicine
DOI 10.1056/nejmoa0809493
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Abstract

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.)

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  • The reduced fracture risk with pharmacologic therapy in patients with spine and hip fractures is true for fracture patients with BMD in both the low bone mass and osteoporosis range.

    “This is true for fracture patients with BMD in both the low bone mass and osteoporosis range [49–58].”

    From Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014) · cites this paper as [56]

    The Subjects section says participants needed an osteoporosis-range T score at the lumbar spine or total hip; the baseline-characteristics table also shows that some had a prior vertebral fracture. The fracture-results section reports reduced fracture risk with denosumab overall, but our copy does not report that reduction separately for patients with prior spine or hip fractures in both the low-bone-mass and osteoporosis BMD ranges. (LLM, conf=0.86)

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  • There are abundant data that patients with spine and hip fractures will have reduced fracture risk if treated with pharmacologic therapy.

    “There are abundant data that patients with spine and hip fractures will have reduced fracture risk if treated with pharmacologic therapy.”

    From Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014) · cites this paper as [56]

    The Discussion reports that denosumab reduced vertebral, nonvertebral, and hip fracture risk in postmenopausal women with osteoporosis. But the trial does not establish that patients who already had spine or hip fractures benefit: baseline characteristics identify some women with prevalent vertebral fractures, while the reported treatment effects are for the study groups overall. It also tests one pharmacologic therapy, not pharmacologic therapy generally. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Denosumab reduces the incidence of hip fractures by about 40% over 3 years.

    “Denosumab reduces the incidence of vertebral fractures by about 68 %, hip fractures by about 40 %, and nonvertebral fractures by about 20 % over 3 years [56].”

    From Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014) · cites this paper as [56]

  • Denosumab reduces the incidence of vertebral fractures by about 68% over 3 years.

    “Denosumab reduces the incidence of vertebral fractures by about 68 %, hip fractures by about 40 %, and nonvertebral fractures by about 20 % over 3 years [56].”

    From Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014) · cites this paper as [56]

  • Denosumab reduces the incidence of nonvertebral fractures by about 20% over 3 years.

    “Denosumab reduces the incidence of vertebral fractures by about 68 %, hip fractures by about 40 %, and nonvertebral fractures by about 20 % over 3 years [56].”

    From Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014) · cites this paper as [56]

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Cites

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Research works printed but not linked: 3

  1. [1]1. ogy and outcomes of osteoporotic frac- tures. Lancet 2002;359:1761-7.
  2. [15]15. Russell RG, Watts NB, Ebetino FH, 16. Rogers MJ. Mechanisms of action of bis- phosphonates: similarities and differen- ces and their potential influences of clini- cal efficacy. Osteoporos Int 2008;19:733-59.
  3. [20]20. Harris ST, Watts NB, Genant HK, et al. 22. Effects of risedronate treatment on verte- bral and nonvertebral fractures in women with postmenopausal osteoporosis: a ran- domized controlled trial. JAMA 1999;282: 1344-52.

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Authors
Cummings, S. R., Martin, J. S., McClung, M. R., Siris, E. S., Eastell, R., Reid, I. R., Delmas, P., Zoog, H. B., Austin, M., Wang, A., Kutilek, S., Adami, S., Zanchetta, J., Libanati, C., Siddhanti, S., & Christiansen, C.
Affiliations
  • University of California, San Francisco (US)
  • Columbia University Irving Medical Center (US)
  • University of Sheffield (GB)
  • University of Auckland (NZ)
  • Inserm (FR)
  • Amgen (United States) (US)
  • University of Verona (IT)
  • Center for Clinical & Basic Research (DK)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2009-08-20
Volume
361
Issue
8
Pages
756-765
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa0809493
OpenAlex
W2160005424
Cited by
3,489
References
39
Citations by year
2026: 187 · 2025: 220 · 2024: 203 · 2023: 164 · 2022: 226 · 2021: 210 · 2020: 223 · 2019: 200 · 2018: 208 · 2017: 195 · 2016: 180 · 2015: 238 · 2014: 168 · 2013: 222 · 2012: 197
FWCI
223.08
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • BORIS (University Library Bern) (submittedVersion)
  • Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • IRIS (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • Lithuanian University of Health Sciences (submittedVersion)
  • ResearchSpace (University of Auckland) (submittedVersion, cc-by)
  • SERVAL (Université de Lausanne) (submittedVersion)
  • Use Siena air (University of Siena) (submittedVersion)
Funders
  • Amgen
  • Eli Lilly and Company
  • Pfizer
  • AstraZeneca
  • GlaxoSmithKline
  • Servier
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords
denosumab, osteoporosis, postmenopausal women, fracture prevention, RANKL inhibition, vertebral fractures, hip fracture, non-vertebral fractures, bone mineral density, monoclonal antibodies, osteoclasts, bone resorption, adverse events, osteonecrosis of the jaw, hypocalcemia, cancer risk, cardiovascular risk
MeSH terms
Denosumab, Aged, Aged, 80 and over, Antibodies, Monoclonal, Female, Hip Fractures, Humans, Middle Aged, Risk, Bone Density, Osteoporosis, Postmenopausal, Incidence, Spinal Fractures, Bone Remodeling, Bone Density Conservation Agents, Fractures, Bone, RANK Ligand, Antibodies, Monoclonal, Humanized

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