January 16, 2009

UAMS Osteoporosis Drug Research in New England Journal of Medicine

 Robert Weinstein, M.D., displays a tool used to determine a woman’s risk for osteoporosis.
Robert Weinstein, M.D., displays a tool used to determine a woman’s risk for osteoporosis.

Jan. 16, 2009 | Researchers at the University of Arkansas for Medical Sciences (UAMS) have found that a common drug treatment for osteoporosis raises new questions about how the drug affects certain bone cells.

In a study published Jan. 1 by the New England Journal of Medicine, UAMS researchers found that postmenopausal women who took the drug bisphosphonate alendronate (Fosamax) for up to three years had an increase in their number of osteoclasts, the cells responsible for removing bone.

Postmenopausal osteoporosis results from an imbalance in the cells responsible for removing old bone (osteoclasts) and replacing it with new, stronger bone (osteoblasts).

Fosamax, part of a class of drugs known as bisphosphonates, is thought to prevent the imbalance by decreasing the number of bone-eroding cells (osteoclasts).

But UAMS and Central Arkansas Veterans Healthcare System researchers, led by Robert S. Weinstein, M.D., found that the alendronate bisphosphonate treatment significantly increases the number of osteoclasts.

And although the alendronate bisphosphonate drugs are still considered effective in the prevention of osteoporosis, the large increase in osteoclasts raises questions.

The drug decreases the ability of the osteoclasts to remove bone, but it significantly increases the number of these osteoclasts, Weinstein said.

In the study, 51 bone biopsy specimens were taken from healthy postmenopausal women (age 40 to 59). Some were given the Fosamax and others received a placebo.

Those who received the typical daily dose of the drug (10 milligrams) had 2.6 times the number of osteoclasts compared with women in the placebo group. Also, the number of osteoclasts increased with increasing amounts of the drug.

Weinstein, the study’s lead author, is a professor of medicine and director of the Bone Morphometry Laboratory in the UAMS Center for Osteoporosis and Metabolic Bone Disease. Co-authors of the study are Paula Roberson, Ph.D., and Stavros Manolagas, M.D., Ph.D. Roberson is professor and chair of UAMS BioStatistics, while Manolagas founded the UAMS Center for Osteoporosis and Metabolic Bone Diseases. Manolagas is the Thomas A. Andreoli, M.D., M.A.C.P., Clinical Scholar Chair in Internal Medicine, and he is a professor and vice chair for research in the department.

About a third of the osteoclasts were giant and detached, and they were still present a year after the women stopped taking the drug.

The cells appeared to be dysfunctional, but Weinstein said it’s unknown whether that would hold true for someone taking a bisphosphonate for many years.

“Although these cells may well be dysfunctional and of no direct pathophysiologic consequence to the patient, awareness of the phenomenon is crucial,” Weinstein said, “because the giant osteoclasts could lead to a mistaken diagnosis of another bone disorder in addition to osteoporosis such as Paget’s disease, fibrous dysplasia, giant cell tumor, or hyperparathyroidism, and cause unnecessary additional lab tests or referrals.”

The UAMS Center for Osteoporosis and Metabolic Bone Diseases pools the expertise of researchers from across the UAMS campus. It is one of the largest osteoporosis research centers in the world, having brought in about $50 million, including continuous program funding for more than a decade from the National Institutes of Health.