1. Bisphosphonates and denosumab increased bone mineral density (BMD) in men receiving androgen deprivation therapy (ADT) for nonmetastatic prostate cancer, with denosumab also showing some evidence of vertebral fracture reduction.
2. Three trials for lifestyle intervention showed no statistically significant difference in BMD compared to exercise and standard care.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Nearly half of men with prostate cancer receive ADT sometime after diagnosis. Some of the risks of ADT include bone loss and higher risk of low trauma fractures. Considering that most men with prostate cancer are elderly and already at risk of osteoporosis, the risks of ADT therapy are even more important. This systematic review sought to evaluate drug, supplement, and lifestyle interventions for their effectiveness in improving BMD, preventing fracture, or preventing or delaying osteoporosis in males with nonmetastic prostate cancer. Bisphosphonates improved BMD, but there were no trials with sufficient power to detect fracture reduction. Denosumab increased BMD, and one high-quality trial showed that denosumab decreased the incidence of vertebral fractures. Three trials for lifestyle intervention showed no statistically significant difference in BMD compared to exercise and standard care. For men receiving ADT for nonmetastatic prostate cancer, bisphosphonates or denosumab may improve BMD. Additional trials evaluating fracture outcomes in this population are needed.
A strength of the study is that rigorous methodologies were used to assess both pharmacologic and nonpharmacologic treatment trials. In addition, updated meta-analysis and sensitivity analyses were used for evidence summary. Limitations of the study include the lack of randomized controlled trials (RCTs) examining fracture outcomes, trials being mainly of moderate quality, and the lack of evaluation of potential treatment harms.
In-Depth [systematic review and meta-analysis]: Using data from Ovid MEDLINE (1946 to 19 January 2017), EMBASE (1980 to 18 January 2017), and Cochrane Database of Systematic Reviews (19 January 2017), researchers from McMaster University evaluated two systematic reviews and 28 reports (of 27 trials) that focused on males receiving ADT for nonmetastatic prostate cancer. RCTs or systematic reviews pertaining to therapies aimed at bone health improvement were analyzed. Bisphosphonates improved BMD, with evidence suggesting that intravenous forms of the drug may have higher effectiveness than oral forms. Denosumab (60 mg administered subcutaneously every 6 months) also improved BMD and reduced the occurrence of new vertebral fractures detected on radiographs. Toremifene also reduced fracture incidence, but it is not approved by the U.S. Food and Drug Administration for this purpose.
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