A UC San Francisco researcher will lead one of the first large trials in the country to study a combination drug therapy for osteoporosis, much in the same way physicians prescribe two or more drugs to treat other diseases such as HIV, high blood pressure and cancer. The study is being funded by the National Institute for Arthritis, Musculoskeletal and Skin Diseases (NIAMS), which is part of the National Institutes of Health. The trial is a collaborative study including UCSF and the Universities of Maine, Minnesota, Pittsburgh and Columbia University.
The trial will treat women with osteoporosis who will take varying combinations of two drugs: recombinant human parathyroid hormone (1-84) and alendronate. These two agents work in different ways. Bone is constantly being formed (formation) and broken down (resorption). Recombinant human parathyroid hormone 1-84 speeds up both bone formation and resorption with a net increase in bone formation. Alendronate is an anti-resorptive, a drug that inhibits bone resorption, and is FDA-approved for the treatment of osteoporosis.
In a young, healthy person, the rate of bone formation and resorption is balanced, said Dennis Black, PhD, principal investigator of the study and UCSF professor of epidemiology and biostatistics. But in older women, resorption often happens at a much faster pace than formation, resulting in osteoporosis. Anti-resorptive therapies, such as alendronate, are the only FDA-approved agents to treat osteoporosis.
"The idea of the trial is to combine something that speeds up formation and resorption with something that slows down resorption, resulting in a net gain of bone strength," Black said. "We want to test combinations of two agents that have different ways of acting."
NPS Pharmaceuticals, Inc. (Nasdaq:NPSP) is providing the recombinant human parathyroid hormone (1-84). Based on a Phase II trial of the hormone, study investigators are confident about its efficacy and safety, Black said. Merck and Company (NYSE:MRK) is supplying the alendronate for the trial. Preliminary studies have provided enough evidence to suggest that greater increases in bone mass can be realized by administering the two agents together.
"The combination of the PTH hormone with estrogen, another anti-resorptive drug, has been shown to be very promising in a preliminary study, which included very large gains in bone mass by as much as 25 percent over two years," Black said. "The hope is that this particular combination will be effective in treating women with severe disease and actually build new bone." The National Health and Nutrition Examination Survey recently estimated 10 million people in the U.S. have osteoporosis. The disease is characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility and increased risk of debilitating fractures to the hip, spine and wrist. According to the National Osteoporosis Foundation, 80 percent of those with osteoporosis are women.
This two year study will enroll 240 women in a multi-center, randomized trial. The participating centers are: Columbia University in New York City, University of Pittsburgh, University of Minnesota and Maine Center for Osteoporosis Research and Education. Enrollment begins in June.
For more information on the clinical trial, please contact one of the following: The UCSF Coordinating Center project director Annie Woodhouse, (415) 597-9282; the Columbia University study coordinator Kristen Lee, (212) 305-2903; the University of Minnesota study coordinator Paula Bowman, (612) 725-2000, ext. 5841; the University of Pittsburgh study coordinator Jodi Ribich, (412) 692-2479; and the Maine Center for Osteoporosis study coordinator Lori Fowler, (207) 262-1177.