PTH and Alendronate: Combining Treatments Shows No Bone Density Advantage

Combining the bone-building treatment parathyroid hormone (PTH) with alendronate, a drug that slows bone loss, produces no significant improvement in bone mineral density (BMD) beyond that produced by the individual drugs, according to two new studies involving postmenopausal women and men with low BMD.

The two studies, reported in the September 25 issue of the New England Journal of Medicine and supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), one of the National Institutes of Health, both tested BMD in the spine and hip. BMD, a common indicator of bone health, is used to diagnose the bone-weakening disease osteoporosis, detect low bone mass before the disease develops and help predict the risk of future fractures.

Although clinicians had hoped to optimize osteoporosis treatment and increase BMD by combining the two potent medications, the two trials show that PTH alone increases BMD at least as well as or better than combination therapy. Further studies, say some scientists, are needed to see if the optimal effects of these drugs might be achieved by sequential or cyclic therapy. A comparative study of fracture rates would also be needed to assess drug effectiveness.

"Both patients and physicians benefit from knowing how the combination compares to single drug treatment," said NIAMS Director Stephen I. Katz, M.D., Ph.D. "These findings could offer important clinical guidance to those at high risk for fractures and those who treat them."

One study, a randomized, blinded clinical trial involving 238 postmenopausal women with low hip or spine BMD, was carried out at four centers and coordinated at the University of California San Francisco by Dennis Black, M.D., and his colleagues. In the study, featured at the recent meeting of the American Society for Bone and Mineral Research in Minneapolis, the women were given a daily regimen of PTH, alendronate, or a combination of the two. After 12 months, results showed no significant benefit to combining treatments.

A second 30-month trial, carried out by Joel Finkelstein, M.D., and his colleagues at the NIAMS-funded Specialized Center of Research in Osteoporosis at Massachusetts General Hospital, involved 83 men aged 46 to 85 years with low BMD who were treated with PTH, alendronate, and a combination of both. The Massachusetts researchers also found that the combination treatment did not produce any additive effects on BMD scores. Spine and hip BMD in the men's study actually increased less with combination therapy than with PTH alone, as did spine BMD in the women's study. Both women's and men's studies suggested that alendronate reduces the bone-building effects of PTH.

PTH, a medication used to treat osteoporosis, is taken by injection and has been shown to stimulate new bone formation. Alendronate is one of a group of drugs known as bisphosphonates, which reduce the activity of cells that cause bone loss. Combining the two, scientists thought, might logically increase BMD more than either drug alone. However, these studies demonstrate that there is no advantage to giving the two drugs together. Moreover, the therapeutic effect of PTH is somewhat diminished when the two agents are combined.

Osteoporosis is a skeletal disorder marked by reduced bone strength that predisposes a person to an increased risk of fractures. This skeletal disorder is a major health risk for 28 million Americans. In the United States today, 10 million individuals already have osteoporosis and 18 million more have low bone mass, placing them at increased risk for the disease.

Additional support for the men's study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Research Resources, which along with NIAMS are part of the Department of Health and Human Services' National Institutes of Health.

To contact Dr. Black, call Eve Harris at the University of California San Francisco, at (415) 885-7277. To contact Dr. Finkelstein, call Sue McGreevey at Massachusetts General Hospital, at (617) 724-2764.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

References: Black D, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. NEJM 2003;349(13):1207-1215.

Finkelstein J, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. NEJM 2003;349(13):1216-1226.