Building Up The Arsenal Against Bone Disease

With boomers hitting 50, osteoporosis is on the rise--but so are promising treatments

It has been called the "silent disease," because victims often don't know they have it until their bones start breaking. Lately, though, there's been nothing quiet about osteoporosis. With more baby boomers turning 50, this chronic bone ailment, which afflicts half of all women over 65, is a pressing public health concern. To stem potentially huge medical costs, researchers are racing to develop drug treatments that attack the disease in novel ways.

The cost to the nation of weak bones is clear: In a recent study, the Mayo Clinic, in Rochester, Minn., estimated that 28 million Americans--two-thirds of them women--suffer from osteoporosis. That's more than the victims of breast, uterine, and ovarian cancers combined. Treatment costs totaled $14 billion in 1995. By 2015, the Mayo Clinic study projected, 41 million Americans could be afflicted.

In July, the picture got bleaker. A study published in the New England Journal of Medicine revealed that a group of children with a genetic marker for osteoporosis showed signs of low bone mass by age 7. "Some scientists have suggested that, at heart, this is a pediatric disease," says Dr. L. Joseph Melton, a Mayo researcher.

Ironically, it is also avoidable. If people spent their lives eating calcium-rich foods, exercising, and avoiding cigarettes, their bones would remain strong through old age, say experts, even if they carry the osteoporosis gene. With that fracture-free goal in mind, the National Academy of Sciences in August raised the recommended daily intake of calcium from 1,000 milligrams to 1,300 for males and females, starting at age 9.

HOLY GRAIL. Once the disease sets in, though, guzzling milk won't cure it. But new drugs may help. In the past two years, several treatments have been approved by the Food & Drug Administration or entered clinical trials (table). And biotech companies are zeroing in on the genetic triggers that preserve bone mass.

For drug companies, the Holy Grail is a medicine that would prevent fractures by maintaining peak bone mass. The skeleton exists in a state of constant change, with cells called osteoclasts breaking down old bone as countervailing osteoblasts build it up anew. Most people reach peak bone mass by the time they hit 30. After that, the balance of power shifts to the osteoclasts, and healthy adults lose 3% to 5% of their bone mass per decade. For women, though, the loss rises to 1% to 5% a year for the first 10 years after menopause, when estrogen that keeps osteoclasts in check declines markedly. Osteoporosis occurs when the rate of bone loss greatly outbalances bone creation.

Today, doctors recommend that all women start preventive treatment in the first five years after menopause, through estrogen-replacement therapy. But estrogen has a serious drawback: It may trigger breast or uterine cancer. "Designer estrogens"--the technical term is selective estrogen receptor modulators (SERMs)--may offer a safer alternative. These chemically synthesized variants of the estrogen molecule ape the hormones that bolster bone, while not affecting breast and uterine tissue. The first SERM to reach the FDA, Eli Lilly & Co's raloxifene, was granted priority-review status by the agency in June, and could hit the market next year. Studies show that raloxifene can increase bone density by 2% to 3% over two years. In August, Glaxo Wellcome reported the discovery of a SERM that they claim may prevent both osteoporosis and breast cancer.

PURSUIT OF PRECISION. For women who shun estrogen, there is an alternative hormone called calcitonin. Sold by Sandoz Pharmaceuticals Corp., it may increase bone density slightly. Merck & Co.'s Fosamax, meanwhile, is the first of a newer class of drugs called bisphosphonates to reach the market. It binds to the bone matrix and deflects osteoclasts, building bone mass by 5% to 10% over three years.

The trouble with these and other remedies--bone-builders such as fluoride and parathyroid hormone--is that they target the endrocrine system, which controls a host of body functions beyond bone formation that could be negatively affected. So researchers are seeking more precise agents that control just osteoclasts and osteoblasts. Once identified, such compounds could be taken early in life to increase bone mass. For example, Dr. Steven L. Teitelbaum, a bone specialist at Washington University School of Medicine in St. Louis, recently cloned a compound that interferes with the receptor that allows osteoclasts to attach to bone. "It would make no sense to give estrogen pre-menopause," says Teitelbaum. "It does make sense to emphasize the factors that strengthen bone."

Ideally, researchers would like to figure out how to actually create bone. Researchers at Genome Therapeutics Corp., a biotechnology outfit in Waltham, Mass., and Nebraska's Creighton University School of Medicine, are studying a large family in the Midwest with extremely strong bones. Their goal is to identify and then clone the gene responsible for the family's osteoblasts. That process may take years. But it could ultimately lead to drugs that would be a lot better at building strong bones than a glass of milk.

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