The article summarizes the results of the phase 2, multi-center trial evaluating the effect of denosumab in postmenopausal women with low BMD. Denosumab is a RANK Ligand inhibitor under development by Amgen, Inc. of Thousand Oaks, Calif. The investigational therapy is designed to target RANK Ligand, a protein that is the primary mediator of osteoclast formation, function and survival. Osteoclasts are the cells responsible for bone removal.
"We are very encouraged by the study's results," said Michael McClung, MD, FACP, principal investigator of the denosumab study and director of Oregon Osteoporosis Center at Providence Portland Medical Center in Portland, Ore. "These data document that targeting the RANK Ligand pathway may provide a new treatment option for bone loss diseases including osteoporosis."
The phase 2 data indicated that denosumab provides rapid and sustained responses of bone metabolism in patients with low BMD. Denosumab, when administered twice yearly, increased total hip, spine, distal 1/3 radius and total body BMD similar to current therapy in the one-year trial. Researchers reported that subcutaneous injections of denosumab significantly increased BMD at the lumbar spine from 3.0 to 6.7 percent after 12 months as compared with a decrease of 0.8 percent with placebo (p<0.001). Researchers also observed significant increases in BMD in the total hip from 1.9 to 3.6 percent in women who received denosumab compared with a decrease of 0.6 percent in the placebo group (p<0.001).
Across all doses and dosing intervals, distal 1/3 radius BMD increased from 0.4 to 1.3 percent with denosumab while BMD decreased by 2.0 percent in the placebo group (p<0.001), and total body BMD increased from 0.6 to 2.8 percent as compared with a decrease of 0.2 percent with placebo (p<0.01). Results also indicated that denosumab had a rapid onset of action, inhibiting the action of osteoclasts within 72 hours. According to Dr. McClung, "The ability to control bone metabolism and increase BMD so effectively with such a convenient dosing regimen shows a potential advantage of this therapeutic strategy over current therapies."
The incidence of adverse events was similar among the denosumab, placebo, and Fosamax groups.
Study Design
Investigators at 29 centers in the United States randomized 412 postmenopausal women, average age 63, with low BMD to receive denosumab, placebo or Fosamax. The purpose of the study was to determine the safety and efficacy of denosumab on lumbar spine BMD compared with placebo at 12 months. The doses of denosumab evaluated included 6, 14 or 30 mg every three months or 14, 60, 100 or 210 mg every six months. Denosumab was administered by subcutaneous injection. Patients receiving Fosamax followed the approved indication and oral dosing instructions of 70 mg once weekly.
About Osteoporosis
In the United States, 10 million individuals are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis. Of the 10 million Americans estimated to have osteoporosis, eight million are women and two million are men. In addition, one in two women and one in four men over age 50 will have an osteoporosis-related fracture in their remaining lifetime.
About Providence Portland Medical Center
Providence Portland Medical Center is part of Providence Health System, the state's largest health system and second-largest private employer. Providence Portland is recognized for excellence in patient care and research in such areas as cancer, heart, orthopedics, women's health, rehabilitation services and behavioral health. Providence Health System in Oregon, ranked as the fourth most integrated health care system in the nation, offers a comprehensive array of health and education services through its seven hospitals, medical clinics, health plans, long-term care facilities and home health services. Visit www.providence.org/oregon.
Journal
New England Journal of Medicine