Denosumab in men receiving androgen-deprivation therapy for prostate cancer
Open accessAbstract
BACKGROUND: Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. METHODS: In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures. RESULTS: At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups. CONCLUSIONS: Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.)
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In 1468 men with nonmetastatic prostate cancer receiving androgen deprivation therapy, who have castrate levels of sex steroids, denosumab reduced vertebral fracture risk by 62%.
“In 1468 men with nonmetastatic prostate cancer receiving androgen deprivation therapy, who have castrate levels of sex steroids, denosumab reduced vertebral fracture risk by 62% (49).”
From A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management (2017) · cites this paper as [49]
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- Authors
- Smith, M. R., Egerdie, B., Toriz, N. H., Feldman, R., Tammela, T. L. J., Saad, F., Heracek, J., Szwedowski, M., Ke, C., Kupic, A., Leder, B. Z., & Goessl, C.
- Affiliations
- Massachusetts General Hospital (US)
- Centro Medico Nacional Siglo XXI (MX)
- Tampere University Hospital (FI)
- Amgen (United States) (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2009-08-20
- Volume
- 361
- Issue
- 8
- Pages
- 745-755
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3038121
- OpenAlex
- W1992053982
- Cited by
- 1,140
- References
- 37
- Citations by year
- 2026: 28 · 2025: 34 · 2024: 34 · 2023: 34 · 2022: 45 · 2021: 48 · 2020: 52 · 2019: 43 · 2018: 77 · 2017: 54 · 2016: 56 · 2015: 65 · 2014: 82 · 2013: 100 · 2012: 134
- FWCI
- 63.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- Funders
- Prostate Cancer Foundation
- Amgen
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- New England Research Institutes
- Astellas Pharma
- National Institutes of Health (5k24ca121990-02)
- National Cancer Institute (K24-CA121990, 5K24 CA121990-02)
- Topics
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- denosumab, androgen deprivation therapy, prostate cancer, bone mineral density, vertebral fractures, bone loss, RANKL inhibition, non-metastatic prostate cancer, lumbar spine, femoral neck, total hip
- MeSH terms
- Denosumab, Aged, Aged, 80 and over, Androgen Antagonists, Antibodies, Monoclonal, Double-Blind Method, Humans, Injections, Subcutaneous, Gonadotropin-Releasing Hormone, Lumbar Vertebrae, Male, Middle Aged, Orchiectomy, Osteoporosis, Prostatic Neoplasms, Bone Density, Incidence, Spinal Fractures, Bone Remodeling, Bone Density Conservation Agents, Fractures, Bone, RANK Ligand, Antibodies, Monoclonal, Humanized
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