In the Journals

Osteoporosis drugs improve bone health for patients with prostate cancer

Bisphosphonates and denosumab increased bone mineral density in men with nonmetastatic prostate cancer who received androgen deprivation therapy, according to findings published in Annals of Internal Medicine.

“Prostate cancer is the most common internal cancer in men and the third most common cause of cancer death in most industrialized countries,” Shabbir M.H. Alibhai, MD, MSc, from the University of Toronto, and colleagues wrote. “Among men with this disease, almost one in two receive androgen deprivation therapy (ADT) at some point after diagnosis. This therapy is associated with many potential adverse effects, including significant bone loss and increased risk for low trauma or fragility fractures similar to that in persons with primary osteoporosis. Although the greatest loss in bone mineral density (BMD) occurs within the first year of ADT use, continued use is associated with ongoing (albeit attenuated) loss in subsequent years along with increased risk for fractures.”

Alibhai and colleagues evaluated how effective drug, supplement and lifestyle interventions are at preventing fracture, improving BMD or preventing or delaying osteoporosis in men with nonmetastatic prostate cancer. They performed a meta-analysis of two systematic reviews and 28 reports of randomized trials that compared bone-targeted therapies with placebo, usual care or other active treatments in men with nonmetastatic prostate cancer who were initiating or continuing ADT.

Data showed that bisphosphonates and denosumab were effective at improving BMD. For change in BMD at the lumbar spine (mean difference = 6.3%; CI, 5.0% to 7.7%; P < .001; 14 trials), femoral neck (mean difference = 3.0%; CI, 2.4% to 3.7%; P < .001; 11 trials) and total hip (mean difference = 2.7%; CI, 1.8% to 3.5%; P < .001; 10 trials) from baseline to 12 months, there was a statistically significant difference favoring bisphosphonates over placebo. In one high-quality trial, denosumab also was more effective at reducing the incidence of new radiographic vertebral fractures than placebo at 12 months (0.3% vs. 1.9%; RR = 0.15; P = .004), 24 months (1.0% vs. 3.3%; RR = 0.31; P = .004) and 36 months (1.5% vs. 3.9%; RR = 0.38; P = .006); however, there were no trials that could accurately detect reduction in fractures for bisphosphonates. Furthermore, calcium or vitamin D were not compared against placebo in any of the trials. There was no statistically significant difference between exercise and usual care in change in BMD in three lifestyle intervention trials.

“Men with nonmetastatic prostate cancer who are receiving ADT are at risk for loss of BMD and fractures,” Alibhai and colleagues concluded. “Robust evidence showing fracture reduction is restricted to one approved drug (denosumab). Evidence from [randomized controlled trials] supporting improvements in BMD has been found for oral and IV bisphosphonates, but whether this is associated with reduced fractures remains unclear. Further trials powered to detect reduction in clinical fractures are needed.”

In an accompanying editorial, Azeez Farooki, MD, and Howard I. Scher, MD, both from the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, wrote that identifying and treating deadly tumors early is the main challenge in managing prostate cancer.

“Recently, a significant survival benefit was shown in two large-scale trials for the combination of ADT with the CYP17 inhibitor abiraterone, which produces testosterone levels 1 log lower than those achieved with traditional ADT vs. ADT alone,” they wrote. “Abiraterone further decreases estrogen levels and is coadministered with prednisone, which has itself been shown to increase fracture risk, even at the 5-mg dose studied. Use of this new regimen is likely to compound fracture risk and presents an important opportunity for comparative effectiveness studies of the available agents to better define the risk–reward ratio of specific interventions to maintain bone health.” – by Alaina Tedesco

Disclosure: Alibhai reports no relevant financial disclosures. Please see study for complete list of all other authors’ relevant financial disclosures.

Bisphosphonates and denosumab increased bone mineral density in men with nonmetastatic prostate cancer who received androgen deprivation therapy, according to findings published in Annals of Internal Medicine.

“Prostate cancer is the most common internal cancer in men and the third most common cause of cancer death in most industrialized countries,” Shabbir M.H. Alibhai, MD, MSc, from the University of Toronto, and colleagues wrote. “Among men with this disease, almost one in two receive androgen deprivation therapy (ADT) at some point after diagnosis. This therapy is associated with many potential adverse effects, including significant bone loss and increased risk for low trauma or fragility fractures similar to that in persons with primary osteoporosis. Although the greatest loss in bone mineral density (BMD) occurs within the first year of ADT use, continued use is associated with ongoing (albeit attenuated) loss in subsequent years along with increased risk for fractures.”

Alibhai and colleagues evaluated how effective drug, supplement and lifestyle interventions are at preventing fracture, improving BMD or preventing or delaying osteoporosis in men with nonmetastatic prostate cancer. They performed a meta-analysis of two systematic reviews and 28 reports of randomized trials that compared bone-targeted therapies with placebo, usual care or other active treatments in men with nonmetastatic prostate cancer who were initiating or continuing ADT.

Data showed that bisphosphonates and denosumab were effective at improving BMD. For change in BMD at the lumbar spine (mean difference = 6.3%; CI, 5.0% to 7.7%; P < .001; 14 trials), femoral neck (mean difference = 3.0%; CI, 2.4% to 3.7%; P < .001; 11 trials) and total hip (mean difference = 2.7%; CI, 1.8% to 3.5%; P < .001; 10 trials) from baseline to 12 months, there was a statistically significant difference favoring bisphosphonates over placebo. In one high-quality trial, denosumab also was more effective at reducing the incidence of new radiographic vertebral fractures than placebo at 12 months (0.3% vs. 1.9%; RR = 0.15; P = .004), 24 months (1.0% vs. 3.3%; RR = 0.31; P = .004) and 36 months (1.5% vs. 3.9%; RR = 0.38; P = .006); however, there were no trials that could accurately detect reduction in fractures for bisphosphonates. Furthermore, calcium or vitamin D were not compared against placebo in any of the trials. There was no statistically significant difference between exercise and usual care in change in BMD in three lifestyle intervention trials.

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“Men with nonmetastatic prostate cancer who are receiving ADT are at risk for loss of BMD and fractures,” Alibhai and colleagues concluded. “Robust evidence showing fracture reduction is restricted to one approved drug (denosumab). Evidence from [randomized controlled trials] supporting improvements in BMD has been found for oral and IV bisphosphonates, but whether this is associated with reduced fractures remains unclear. Further trials powered to detect reduction in clinical fractures are needed.”

In an accompanying editorial, Azeez Farooki, MD, and Howard I. Scher, MD, both from the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, wrote that identifying and treating deadly tumors early is the main challenge in managing prostate cancer.

“Recently, a significant survival benefit was shown in two large-scale trials for the combination of ADT with the CYP17 inhibitor abiraterone, which produces testosterone levels 1 log lower than those achieved with traditional ADT vs. ADT alone,” they wrote. “Abiraterone further decreases estrogen levels and is coadministered with prednisone, which has itself been shown to increase fracture risk, even at the 5-mg dose studied. Use of this new regimen is likely to compound fracture risk and presents an important opportunity for comparative effectiveness studies of the available agents to better define the risk–reward ratio of specific interventions to maintain bone health.” – by Alaina Tedesco

Disclosure: Alibhai reports no relevant financial disclosures. Please see study for complete list of all other authors’ relevant financial disclosures.