Men with non-metastatic prostate cancer who receive androgen deprivation therapy (ADT) risk loss of bone mineral density (BMD) and fractures, but both bisphosphonates and denosumab can improve their bone health, according to a new systematic review.
Results of randomized controlled trials support improvements in BMD for oral and intravenous bisphosphonates, but whether this reduces fractures remains unclear. “Robust evidence showing fracture reduction is restricted to one approved drug (denosumab),” wrote researchers led by Shabbir M. H. Alibhai, MD MSc, of the University Health Network in Toronto, Ontario in Canada.
The researchers published their results in Annals of Internal Medicine.
Nearly half of all men with non-metastatic prostate cancer receive ADT at some point. The therapy can lead to many potential adverse effects, including signiﬁcant bone loss and increased risk for low trauma or fragility fractures similar to those seen in patients with primary osteoporosis. Most of the loss in BMD occurs within the ﬁrst year of ADT use, however, continued use subsequently leads to more BMD loss, along with increased risk for fractures.
Following the lead of osteoporosis in women, experts now suggest systematic assessment of BMD with dual-energy x-ray absorptiometry at the time of initiation of ADT, periodic monitoring of BMD among men who continue ADT, fracture risk assessment using a validated fracture risk prediction algorithm, and counseling about lifestyle management and risk factor modiﬁcation to reduce risk for bone loss and falls, the researchers stated.
“However, studies have shown important gaps in the quality of bone health care for men with prostate cancer, including low rates of BMD testing before or during ADT, low rates of diet and lifestyle counseling, low rates of education about adverse effects of ADT, and low rates of pharmacologic therapy to reduce fracture risk,” they stated.
The researchers reviewed 30 studies, including two systematic reviews and 28 reports of 27 trials, evaluating the effectiveness of bone-targeted therapies aimed at preventing fracture and improving BMD in men with non-metastatic prostate cancer receiving ADT.
They found that bisphosphonates were effective in increasing BMD (intravenous were more effective than oral), but no trial was sufﬁciently powered to detect reduction in fractures.
In a high-quality trial, denosumab 60 mg given subcutaneously every 6 months improved BMD and reduced the incidence of new radiographic vertebral fractures at 1 year (0.3% vs 1.9%; P = .004), 2 years (1% vs 3.3%; P = .004), and 3 years (1.5% vs 3.9%; P = .006).
In a moderate-quality trial, toremifene at 2 years reduced any fractures (6.3% vs 10.1%; P = .036) and radiographic vertebral fractures (2.5% vs 4.9%; P < .05) compared with placebo, but it is not currently approved for this indication by the US Food and Drug Administration or Health Canada.
No trials compared calcium or vitamin D vs placebo. Three lifestyle intervention trials did not show a statistically signiﬁcant difference in change in BMD between exercise and usual care.
Further trials examining fracture outcomes in men receiving ADT are needed, the researchers stated.
One challenge is to identify men at highest risk for fracture. This would reduce the risk for overtreatment but ensure drug therapy for those most likely to beneﬁt. Risk assessment tools are recommended for men with prostate cancer receiving ADT, but have not been validated in the non-metastatic setting, the researchers noted.