Injectable osteoporosis drug shows promise

A new drug for osteoporosis increases bone mineral density and decreases the rate of bone destruction in postmenopausal women.

The findings, which appear in the Feb. 23 issue of The New England Journal of Medicine, bode well for the chances that the drug, denosumab, will eventually reach the market.

The study centered on injections of denosumab, which made its administration different from almost every other treatment for osteoporosis. "They show that the drug is very potent," says Dr.

Michael Whyte, author of an accompanying editorial and a professor of medicine, pediatrics and genetics at Washington University in St. Louis. "When they administer the denosumab subcutaneously, the bone breakdown parameters plummet very rapidly."

An estimated 10 million Americans currently suffer from osteoporosis, and another 34 million are considered to be at risk for the disease. Women are four times more likely than men to develop the bone loss condition.

According to the study authors, one of the problems with current treatments for osteoporosis is lack of adherence. For whatever reason, great numbers of patients stop taking medications that are designed to add calcium and other strengthening substances to their bones. One group of researchers reported that fewer than 25 percent of women adhered over the course of one year.

By contrast, adherence rates for hypertension range from 50 percent to 75 percent. Denosumab, if approved, would be injected only once every several months.

People with osteoporosis experience a low bone mass and a weakening of the bone structure. This can eventually result in debilitating fractures, particularly of the hip, spine and wrist.

Denosumab is a humanized monoclonal antibody that tilts bone balance back toward an acceptable equilibrium. Phase 1 trials found that a single injection resulted in a decrease in bone destruction.

"It actually prevents the activation of the bone-busting cell osteoclasts," says Dr. Nieca Goldberg, chief of women's cardiac care at Lenox Hill Hospital in New York City and author of "The Women's Healthy Heart Program."

The current paper details the results of a phase 2 study evaluating the efficacy and safety of the agent. The study was designed and funded by the drug's maker, Amgen.

This relatively small study involved 412 postmenopausal women with low bone mineral density. Participants were randomly assigned to receive denosumab either every three months (at differing doses) or every six months (also at differing doses); or they took open-label oral alendronate (sold as Fosamax) once a week, or a placebo.

At the end of 12 months, women taking denosumab had an increase in bone mineral density at the lumbar spine (lower back) of 3 percent to 6.7 percent, versus 4.6 percent with Fosamax, and a loss of 0.8 percent with a placebo.

At the hip, women on denosumab experienced a gain of 1.9 percent to 3.6 percent, versus 2.1 percent with alendronate and a loss of 0.6 percent with a placebo.

At the distal radius or wrist, women taking denosumab experienced an increase of 0.4 percent to 1.3 percent, versus declines of 0.5 percent with Fosamax and 2 percent with placebo.

Researchers also noted reductions in blood levels of C-telopeptide three days after denosumab was administered: an indication of bone destruction.

In other words, denosumab given at three- or six-month intervals (30 and 60 milligrams, respectively) resulted in an increase in bone mineral density and a decrease in rates of bone destruction.

The increases in bone mineral density were similar or equal to those achieved with Fosamax.

Because the drug is injected under the skin, it likely would avoid the gastrointestinal upset which is a side effect of the currently prescribed osteoporosis medications known as bisphosphonates, Goldberg says. In addition, denosumab would only need to be administered a few times a year.

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c.2006 HealthDay News