Osteoporosis Drug Prompts Increase in Certain Bone Cells

By Amanda Gardner
HealthDay Reporter
Wednesday, December 31, 2008; 12:00 AM

WEDNESDAY, Dec. 31 (HealthDay News) -- Women who took the osteoporosis drug Fosamax for up to three years saw an increase in their number of osteoclasts, or cells that remove old, brittle bone, a new study says.

These women also had "giant" osteoclasts -- single cells fused together -- with as many as 40 nuclei. Normally, one would see only seven or eight nuclei in one grouping, the study authors said.

At this point, it's unclear what these findings mean in the "real world."

"Seven or eight cells fused together are more efficient at dissolving calcium from the bone and remodeling," said Dr. James Liu, chairman of the department of obstetrics and gynecology at MacDonald Women's Hospital at Case Medical Center, University Hospitals in Cleveland. "[The study authors] don't know what this means beyond that. Right now, we're just learning these nuances."

Whether these findings will signal future problems is an open question, agreed study lead author Dr. Robert S. Weinstein, a staff physician at Central Arkansas Veterans Healthcare System and a professor of medicine at University of Arkansas for Medical Sciences, both in Little Rock.

"These drugs were used for two to three years in the trial, but clinicians today use them for five and 10 years, and we know these cells accumulate and are there even before the drug is stopped," he said. "It's conceivable there could be a problem at some point. Works need to be done on what is the fate of these drugs."

The findings were published in the Jan. 1 issue of the New England Journal of Medicine.

A second paper in the journal -- a letter to the editor from U.S. Food and Drug Administration epidemiologist Diane K. Wysowski -- noted an increase in the number of reports of esophageal cancer among people taking Fosamax (alendronate).

"Bone is a dynamic tissue -- it continually remodels and repairs itself," Weinstein explained. "Just like an aircraft wing after many flights gets fatigue damage and needs to be repaired, bone also bears the weight of individuals and undergoes damage and needs repair. There's a system [in which] cells remove the old pockets that are no longer at full capacity and replaces them with new bone.

"This is accomplished by two kinds of cells: armies of osteoclasts that erode cavities in the bone, then teams of osteoblasts which replace old bone with new, strong bone," he continued.

Postmenopausal osteoporosis results from an imbalance in that remodeling process. Fosamax, part of a class of drugs known as bisphosphonates, is thought to prevent that imbalance by decreasing the number of bone-eroding cells.

But, after examining 51 bone biopsy specimens from healthy postmenopausal women (40 to 59 years of age) who had participated in a three-year trial and who took different doses of Fosamax versus a placebo, the study authors found the opposite was actually true.


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