The study disproved a previously untested but widespread belief among bone researchers that combining the two types of drugs -- bone-building parathyroid hormone (PTH) and bone resorption inhibiting bisphosphonates -- should interact in a beneficial way for patients. The combination is no better than either drug alone and may even reduce the bone-building benefit, according to study results.
Black presented the findings at the American Society for Bone and Mineral Research in Minneapolis on September 20. The study results are also reported in the September 25 issue of the New England Journal of Medicine.
The randomized, double-blind trial measured the bone density of 238 postmenopausal women for one year as they took one of three daily treatments. Participants in the multi-site study took either parathyroid hormone (PTH 1-84); the bisphosphonate alendronate, marketed as Fosamax; or both. All the women began the trial with low bone mineral density.
Parathyroid hormone in the form of PTH 1-34 has been available for treatment of severe osteoporosis since its FDA approval in 2002. This trial evaluated the full-length molecule PTH 1-84 that contains 50 additional amino acids. Despite a wide-spread belief among bone researchers that bisphosphonates and parathyroid hormone would interact in a synergistic way to compound the benefit for patients, no benefit was demonstrated. Rather, the findings suggest that the concurrent use of alendronate may reduce the bone-building, or anabolic, effects of parathyroid hormone.
"We're in the early stages of use for a whole new class of bone-building medications for osteoporosis," said UCSF Professor Dennis Black, PhD, principal investigator. "These anabolic agents offer an alternative, and, with decreased reliance on estrogen, new approaches to the treatment of osteoporosis are even more important," he added.
Black said that although bisphosphonates are currently used effectively by millions of women, physicians and patients alike would welcome alternatives, particularly for women with severe disease. Estrogen, once used as a first choice treatment for osteoporosis, has been shown to increase risk of breast cancer and, in women with heart disease, to increase the risk of stroke.
The cooperative, multi-site trial by the National Institute of Arthritis and Musculoskeletal and Skin Disorders, part of the National Institutes of Health, involved women in Minneapolis, Pittsburgh, Maine and New York.
Healthy bones exhibit a continual cycle of growth and resorption into the body. Parathyroid acts to both promote bone growth and accelerate its resorption and is initially more active in promoting bone growth, the researchers said. Thus they hypothesized that, as compared with parathyroid hormone therapy alone, the combination of parathyroid hormone with alendronate would induce larger increases in bone mineral density, preserve the increase in bone formation and minimize any increase in bone resorption. The study, however, found no evidence to support the hypothesis.
Black said parathyroid hormone deserves greater study, although its use may be limited by two factors: its current cost is about $7-8000 per year, and it is currently available only as an injectable medication. While this study suggested that the simultaneous combination of these two drugs is not more beneficial than either alone, the serial combination, particularly the use of bisphosphonates following PTH, has not been studied, Black said.
Osteoporosis is a condition resulting from bones that have lost calcium and thickness. Because of this thinning of the bones, a person with osteoporosis is at increased risk for fracture. It is responsible for 1.5 million fractures annually, according to the National Osteoporosis Foundation.
Additional authors are Susan Greenspan, MD, University of Pittsburgh; Kristine Ensrud, MD, MPH,University of Minnesota; Lisa Palermo, MA, UCSF; Joan McGowan, PhD, National Institute of Arthritis and Musculoskeletal and Skin Diseases; Thomas F. Lang, PhD, UCSF; Patrick Garnero, PhD, Synarc; Mary Bouxsein, PhD, Beth Israel Deaconess Medical Center; John Bilezikian, MD, Columbia University; Clifford Rosen, MD, Maine Center for Osteoporosis Research and Jackson Laboratory.
The study was funded by the NIH. Alendronate for the trial was provided by Merck. Parathyroid hormone (PTH 1-84) was provided by NPS Pharmaceuticals.