Bone Health and Bone-Targeted Therapies for Nonmetastatic Prostate Cancer: A Systematic Review and Meta-analysis



Bone health is a significant concern in men with prostate cancer.


To evaluate the effectiveness of drug, supplement, and lifestyle interventions aimed at preventing fracture, improving bone mineral density (BMD), or preventing or delaying osteoporosis in men with nonmetastatic prostate cancer.


Ovid MEDLINE (1946 to 19 January 2017), EMBASE (1980 to 18 January 2017), and the Cochrane Database of Systematic Reviews (19 January 2017).


Randomized trials and systematic reviews of trials that were published in English; involved men with nonmetastatic prostate cancer; and compared bone-targeted therapies with placebo, usual care, or other active treatments.


Two reviewers independently extracted study characteristics and assessed study risk of bias for each outcome.


Two systematic reviews and 28 reports of 27 trials met inclusion criteria. All trials focused on men with nonmetastatic prostate cancer who were initiating or continuing androgen deprivation therapy (ADT). Bisphosphonates were effective in increasing BMD, but no trial was sufficiently powered to detect reduction in fractures. Denosumab improved BMD and reduced the incidence of new radiographic vertebral fractures in 1 high-quality trial. No trials compared calcium or vitamin D versus placebo. Three lifestyle intervention trials did not show a statistically significant difference in change in BMD between exercise and usual care.


Most trials were of moderate quality. Only 2 randomized controlled trials were designed to examine fracture outcomes. Potential harms of treatments were not evaluated.


Both bisphosphonates and denosumab improve BMD in men with nonmetastatic prostate cancer who are receiving ADT. Denosumab also reduces risk for radiographic vertebral fractures, based on 1 trial. More trials studying fracture outcomes are needed in this population.

Ann Intern Med. 2017 Aug 8. doi: 10.7326/M16-2577. [Epub ahead of print]

Alibhai SMH1, Zukotynski K1, Walker-Dilks C1, Emmenegger U1, Finelli A1, Morgan SC1, Hotte SJ1, Tomlinson GA1, Winquist E1.

Author information

1 From University of Toronto, University Health Network, Odette Cancer Centre, and Princess Margaret Hospital, Toronto; McMaster University and Juravinski Cancer Centre, Hamilton; University of Ottawa and The Ottawa Hospital Cancer Centre, Ottawa; and Western University and London Health Sciences Centre, London, Ontario, Canada.