Twice-yearly intravenous infusion with denosumab, a new targeted therapy to stop bone loss, increased bone density and prevented spinal fractures in men receiving androgen-deprivation therapy for prostate cancer.

About one third of the two million prostate cancer survivors in the U.S. currently receive androgen-deprivation therapy, which blocks the release of testosterone. Testosterone is a molecular signal for prostate cancer cells to grow. Several medications used to treat osteoporosis, including drugs called bisphosphonates, have been shown to reduce androgen-deprivation-related bone loss in men in earlier small clinical studies, but none of those trials were adequate to demonstrate reduced fracture risk. Denosumab, a fully-human monoclonal antibody that blocks the action of osteoclasts?the cells that break down bone in the normal process of bone remodeling?is also being investigated to prevent fractures in women with osteoporosis.

Denosumab works by targeting rank ligand, a protein that acts as the primary signal to promote bone removal. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab mimicks the endogenous effects of osteoprotegerin, a cytokine, which can inhibit the production of osteoclasts.

In this latest study for denosumab, men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer were enrolled at 156 centers in North America and Europe and randomly assigned to receive injections of either denosumab or a placebo every six months for three years. Participants were also instructed to take daily calcium and vitamin D supplements during the study period. Among the participants who completed the study, denosumab significantly increased bone density at all the monitored sites ? including the lumbar spine, total hip and femoral neck ? and reduced new vertebral fractures by 62 percent. Bone density at the radius, one of the bones in the forearm, also increased in the treatment group, an improvement not seen with other osteoporosis drugs.

?Denosumab is an important new therapy to prevent painful fractures in prostate cancer survivors,? says Matthew Smith, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center, who led the study as part of the Denosumab HALT Prostate Cancer Study Group. ?An ongoing clinical trial will also evaluate whether denosumab prevents spread of prostate cancer to bone, the most common site of metastases in men with this disease.? Smith is also an associate professor of Medicine at Harvard Medical School.