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    Osteoporosis Drugs Work, but How?

    Study Shows Fosamax Is Effective but May Not Work the Way Experts Believed
    WebMD Health News

    Dec. 31, 2008 -- Millions of people with osteoporosis take bisphosphonates like the drug Fosamax to make their bones stronger. The drugs work well, but a new study shows that they probably don't work in the way experts have thought.

    It has been widely believed that bisphosphonates work by targeting and impairing the action of cells known as osteoclasts -- and reducing their number. These cells break down bone in a process known as bone resorption.

    But in the new study, many postmenopausal women who took Fosamax showed increases in osteoclast numbers compared to women who took a placebo.

    The longer the women were on the drug, the more osteoclasts they tended to have. And many also showed evidence of giant and detached osteoclasts, which have not been previously recognized, researcher Robert Weinstein, MD, of the University of Arkansas for Medical Sciences, tells WebMD.

    The study appears in the Jan. 1, 2009, issue of the New England Journal of Medicine.

    "The bisphosphonates do work. They are a mainstay of osteoporosis treatment," he says. "But it is clear that they don't work the way we thought they did."

    Fosamax vs. Placebo

    Weinstein and colleagues from the University of Arkansas and the Central Arkansas Veterans Healthcare System examined 51 bone biopsy specimens obtained following a three-year trial designed to determine the effectiveness of Fosamax for improving bone health.

    Some of the women in the study took Fosamax and others took placebo.

    The bone biopsies revealed a 260% increase in osteoclasts among women who took 10 milligrams of the bisphosphonate daily for three years, compared to women in the placebo group.

    Roughly a third of the osteoclasts were giant and detached, and these giant cells were still present a year after the women stopped taking the drug.

    While the cells appeared dysfunctional, Weinstein points out that this may not be the case in women who take osteoporosis drugs for many years.

    "We don't really know the long-term consequences of building up a large army of these giant cells," he says. "It appears that they do no direct damage, but we can't say this for sure."

    And since most clinicians aren't aware of the link between bisphosphonate use and the giant cells, they may mistake them for some other bone disorder, leading to unnecessary testing and even treatment, he adds.

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