You are prohibited from using or uploading content you accessed through this website into external applications, bots, software, or websites, including those using artificial intelligence technologies and infrastructure, including deep learning, machine learning and large language models and generative AI.
No AccessJournal of UrologyAdult Urology1 Dec 2009

Effects of Denosumab on Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

View All Author Information


In a recently completed 3-year, randomized, double-blind study, denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κB ligand, significantly increased bone mineral density and decreased new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. We conducted subgroup analyses to evaluate the relationships between subject characteristics and the effects of denosumab on bone mineral density at multiple skeletal sites.

Materials and Methods:

A total of 1,468 subjects were randomized 1:1 to receive 60 mg subcutaneous denosumab every 6 months or placebo for 36 months. In these analyses we evaluated the effects of denosumab on bone mineral density at the lumbar spine, total hip and distal 1/3 radius (substudy of 309 subjects) during 36 months in specific subgroups according to age, duration and type of prior androgen deprivation therapy, bone mineral density T score, weight, body mass index, bone turnover marker levels and prevalent vertebral fractures.


After 36 months denosumab significantly increased bone mineral density of the lumbar spine, total hip and distal 1/3 radius by 7.9%, 5.7% and 6.9%, respectively, compared with placebo (p <0.0001 for each comparison). Denosumab significantly increased bone mineral density to a degree similar to that observed in the overall analysis for every subgroup including older men as well as those with prevalent fractures, lower baseline bone mineral density, and higher serum C-telopeptide and tartrate-resistant alkaline phosphatase 5b. Mean increases in bone mineral density at each skeletal site were greatest for men with the highest levels of serum C-telopeptide and tartrate-resistant alkaline phosphatase 5b.


Denosumab significantly and consistently increased bone mineral density at all skeletal sites and in every subgroup, including men at greatest risk for bone loss and fractures.


  • 1 : Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol2007; 25: 1596. Google Scholar
  • 2 : EAU guidelines on prostate cancer. Eur Urol2008; 53: 68. Google Scholar
  • 3 : Androgen deprivation therapy for prostate cancer. JAMA2005; 294: 238. Google Scholar
  • 4 : Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet2002; 360: 103. Google Scholar
  • 5 : Adjuvant hormonal treatment with radiotherapy for locally advanced prostate cancer. Eur Urol1999; 35: 23. Google Scholar
  • 6 : Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med1999; 341: 1781. Crossref, MedlineGoogle Scholar
  • 7 : Contribution of androgen deprivation therapy to elevated osteoclast activity in men with metastatic prostate cancer. Clin Cancer Res2004; 10: 2705. Google Scholar
  • 8 : Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med2005; 352: 154. Google Scholar
  • 9 : Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med2001; 345: 948. Google Scholar
  • 10 : Natural history of bone complications in men with prostate carcinoma initiating androgen deprivation therapy. Cancer2004; 101: 541. Google Scholar
  • 11 : Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma. Cancer2005; 104: 1633. Google Scholar
  • 12 : Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol2002; 168: 1005. LinkGoogle Scholar
  • 13 : Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell1998; 93: 165. Google Scholar
  • 14 : Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol2008; 26: 4875. Google Scholar
  • 15 : Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med2009; 361: 745. Google Scholar
  • 16 : Diagnosis of osteoporosis and assessment of fracture risk. Lancet2002; 359: 1929. Google Scholar
  • 17 : Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol2005; 23: 7897. Google Scholar
  • 18 : Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab2005; 90: 6410. Google Scholar
  • 19 : Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med2007; 146: 416. Google Scholar
  • 20 : Prevention of bone loss with alendronate in postmenopausal women under 60 years of age: Early Postmenopausal Intervention Cohort Study Group. N Engl J Med1998; 338: 485. Google Scholar