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Bone Drugs Less Helpful Together, 2 Studies Indicate

September 21, 2003|Thomas H. Maugh II | Times Staff Writer

Two drugs that are often used together to increase bone density in the elderly are actually less effective in combination than when used separately, researchers reported Saturday.

Many physicians had thought that the effects of the two drugs, parathyroid hormone and Fosamax, would be synergistic because they work by different mechanisms.

"But that turned out to be untrue," said Dr. Joel Finkelstein of Massachusetts General Hospital, who led one of the studies. In fact, in both men and women, Fosamax made the more powerful parathyroid hormone less effective.

"This is really going to cause us to have a rethink of the timing and indications for combination therapy," said Dr. Solomon Epstein of the Mount Sinai School of Medicine in New York City. "We are going to need a lot more work to find the optimum way to use these two therapies and the sequence in which they should be administered."

The surprising results represent the latest instance in which physicians' well-reasoned theories have been proven wrong by a clinical trial. In the best-known case, researchers believed that hormone-replacement therapy would prevent heart attacks and strokes in women, but that belief proved to be illusory.

"It's not until you really test these ideas that you can be sure about how well they work," Finkelstein said.

The two reports and an editorial about them are to be published in Thursday's New England Journal of Medicine. The findings were presented Saturday in Minneapolis at a meeting of the American Society for Bone and Mineral Research.

Bones in the human body are in a constant state of flux, continually being broken down into their primary constituents -- a process called resorption -- while simultaneously being rebuilt. As humans age, both processes speed up, but the rate of resorption increases, leading to a loss of bone density known as osteoporosis.

Osteoporosis affects more than 20 million Americans and is the cause of about 1.5 million bone fractures each year, 70% of them in women.

Most drugs for treating osteoporosis -- such as alendronate (trade-named Fosamax), risedronate, raloxifene and estrogen -- work by blocking resorption, which slows the breakdown of bones.

But last year, the Food and Drug Administration approved the sale of a form of the naturally occurring parathyroid hormone, or PTH, for treating osteoporosis. PTH promotes the formation of new bone and is a valuable addition to the treatment arsenal. Its primary drawback is that it costs about $7,000 a year and must be administered through daily injections. Putting the two types of therapy together seemed like an obvious strategy.

In the first trial, Dr. Dennis Black and his colleagues at UC San Francisco studied 238 post-menopausal women with low bone density. One group was given PTH, another group was given Fosamax and the third group was given both drugs. All were monitored for a year.

"We expected perhaps a 5% increase in bone density with each [drug], and maybe a 10% or even 15% increase with the combination," Black said. But he said the study showed that the two drugs together were less effective than either by itself.

Finkelstein and his colleagues performed a similar study of 83 elderly men, and their results were similar. Fosamax produced a small increase in bone density at four sites in the body and the combination produced a slightly greater increase, but PTH alone produced a significantly greater improvement.

The message of the two studies is clear, according to Dr. Sundeep Khosla of the Mayo Clinic: "If therapy with parathyroid hormone is contemplated, it should be used alone and not with alendronate or, by inference ... perhaps even any other anti-resorptive agent."

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