Drug May Help Women Rebuild Bones

Millions of women with advanced osteoporosis can take drugs to stop the crippling disease from getting worse, but they can’t regrow much lost bone--and thus they will always be frail.

Now scientists are studying a biologically engineered hormone that might one day help patients rebuild strong bones.

“We have the beginning of a whole area of research into how you rebuild a skeleton and cure the disease,” said Dr. Robert Lindsay, president of the National Osteoporosis Foundation and a lead investigator of the experimental drug, called recombinant parathyroid hormone.

It will take several more years of testing before scientists know if parathyroid hormone, or PTH, works well enough to prescribe, cautioned Dr. David Sartoris of UC San Diego. But “it is a therapy that has a lot of promise.”

Osteoporosis, or brittle-bone disease, afflicts 10 million Americans, mostly elderly women, and 18 million others have low bone mass. They’re at risk of severe injury, such as breaking a hip, along with chronic pain and a stooped posture as spinal vertebrae and other bones fracture. Osteoporosis causes 1.5 million fractures among Americans every year, and is estimated to cost $14 billion annually in medical bills and lost productivity.

Bone is living tissue: Cells called osteoclasts dissolve worn-out bone while other cells called osteoblasts replace it with new bone. During childhood, new bone builds faster than old bone dissolves. People hit their peak bone mass in their mid-20s.

Then the cycle changes and, as people age, bone removal exceeds new bone formation. When that happens too fast, or when people didn’t build up strong enough bones when young, osteoporosis occurs.

Various treatments, including estrogen and the popular non-hormonal drug Fosamax, can slow bone loss by targeting osteoclasts. If the patient’s bone loss isn’t too severe, they may slow it enough to let bone-building osteoblasts catch up and restore a little bone.

But “conventional treatments cannot build bone. So they can only hope to stabilize” the disease, explained Dr. Sherry Sherman, the National Institutes of Health’s clinical endocrinology director.

Small injections of parathyroid hormone, in contrast, appear to act on osteoblasts to stimulate new bone growth.

“If you’ve already lost a lot of bone--and certainly in elderly people it’s common--this offers a lot of promise,” Sherman said.

Lindsay studied 217 post-menopausal osteoporosis patients who injected PTH or a placebo for a year. The drug increased the density of the women’s spines by 7%, a significant boost. The hormone, a version made by Canada’s Allelix Biopharmaceuticals, also increased the size of the women’s spinal bones.

In another study, adding a different version of PTH to estrogen over three years produced “very dramatic increases in bone density in all parts of the skeleton,” Lindsay said. Combining the hormone with older drugs that slow bone loss may be key, he said.

The next step is making sure that the drug rebuilds quality bone that won’t easily break. Animal studies suggest it can restore bone to original strength, said Allelix Vice President John Dietrich. Now the company is looking for a U.S. partner to launch advanced trials this year to test that in women.

Drug giant Eli Lilly hopes to seek government permission to sell PTH in 2000, and is enrolling patients in an advanced study. But Lilly refused to release information about the study or how its version--a portion of the hormone instead of the entire molecule that Allelix uses--compares to other forms.

Several other companies are in earlier stages of study, and the National Institutes of Health is paying for additional work.

But even as scientists figure out how the hormone may rebuild bone, young people, especially women, must take steps now to prevent osteoporosis, Sartoris stressed. Women at risk--who include white or Asian women who are petite, thin or have relatives with osteoporosis--should get their first bone-density test between ages 21 and 35, he advised.

At that age, women whose bones are thinning have time to block further loss by exercising, consuming more calcium and vitamin D, stopping smoking or taking anti-osteoporosis medication.