Dr. Matthew Smith

About Dr. Matthew Smith

Bone loss and fractures can be a painful complication for men undergoing androgen deprivation therapy to treat prostate cancer. They are associated with loss of height, curvature of the spine, and decreased quality and length of life.

At the Massachusetts General Hospital Cancer Center, PCF-funded researcher Dr. Matthew Smith has worked to improve the health of prostate cancer survivors and helped lead the development of denosumab, a novel new drug that targets and inactivates osteoclasts – the cells responsible for bone loss.

“Fractures adversely impact the lives of men who have been treated for prostate cancer” said Dr. Smith, lead investigator of the Denosumab HALT Prostate Cancer Study Group. “But fractures are a a preventable problem. The results of this study may have an important impact on the care of many thousands of prostate cancer survivors.”

In the three-year trial study, twice-yearly injection of denosumab markedly increased bone mineral density at all monitored sites including the hip and spine. Importantly, denosumab also decreased spine fractures by 62 percent. The study, conducted at 156 institutions throughout the U.S. and Europe, included 1,468 men who were undergoing androgen deprivation therapy for prostate cancer.

Denosumab works by targeting the rank ligand (RANKL) pathway, a critical signaling protein that regulates bone remodeling. Androgen deprivation therapy results in excess RANKL activity leading to bone loss and fractures.

“What the PCF has done is to support, in a very timely way, high return yet potentially high risk research projects,” said. Dr. Smith. “When I proposed this original research in 1997 to look at this issue of fractures, there was really no other funding agencies interested due to the absence of preliminary data. The PCF helped to fund this innovative work and just a decade later, we’re looking at the completion of a trial that we believe may change the future of clinical practice.”