Osteoporosis Sufferers: This Time, It May Be a Breakthrough

Scientists who normally shy away from words such as “cure” and “breakthrough” say researchers are on the verge of what could be a revolution in the treatment of osteoporosis, the dangerous bone-thinning condition that is responsible for 1.5 million fractures in the United States each year.

Thanks to a vast improvement in scientific understanding of the process by which bone is created and destroyed, researchers have developed a new class of drugs that can actually trigger the formation of significant new bone to replace that lost to the disease. These drugs, based on human parathyroid hormone, reverse damage from osteoporosis far more effectively than any drugs currently on the market.

“Something that actually increases the formation of bone is the holy grail of osteoporosis research,” said Joan McGowan, a bone specialist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, which is part of the National Institutes of Health. “This is the first approach to having that kind of agent.”

Ten million Americans--most of them women over 50--have osteoporosis, and 18 million more are at risk because they have low bone mass. Of greatest concern are the 300,000 broken hips that result each year. One in every five people with a broken hip dies within a year from complications, such as blood clots induced by immobility. Half never walk again without assistance; more than a quarter need long-term care.

And though women are more likely than men to develop osteoporosis because they lose bone-building estrogen at menopause, 20% of those with osteoporosis are men. All together, hospitalization and nursing care for osteoporosis costs a staggering $13.8 billion a year, according to the National Osteoporosis Foundation.

Currently available medications such as estrogens and Evista (raloxifene) can help prevent the onset of osteoporosis, but they increase bone density only slightly. As a result, public health officials focus on preventing the disease through exercise and a diet rich in vitamin D and calcium.

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The first of the new parathyroid drugs, called Forteo, could reach the market as soon as the fall, and a major study showing its effectiveness in building new bone is scheduled for publication soon in a leading medical journal. Dr. Robert Neer, the lead author and director of the osteoporosis center at Massachusetts General Hospital, declines to give specifics, but the researchers have already shared some of the impressive results with other scientists. Based on a study of 1,637 postmenopausal women, Forteo (also called PTH 1-34) reduces the risk of spine fractures by 65% and of other fractures (including broken hips) by 54% when taken for one to two years.

This summer, the U.S. Food and Drug Administration is expected to convene an expert panel to review the drug for approval. Another still-unpublished study--by Dr. Claude Arnaud, professor of medicine emeritus at UC San Francisco--showed that when taken in combination with estrogen, PTH increases bone density in the spine by 27% and in the hip by 9%. Two other studies, presented at scientific meetings last year, support these findings.

“Most physicians don’t even want to breathe the word ‘cure’ because it makes them look like tonic salesmen,” Arnaud said. “But this is about as close to a cure as you can possibly get. We don’t know for sure that [bone] returns to normal, but bone is made, and it acts like normal bone in the sense that it’s strong.”

Skeptics point out that Eli Lilly, the maker of Forteo, had to stop the Neer study early because research in rats showed that PTH could cause bone cancers, although the rats got higher doses of PTH than humans would and rats are highly susceptible to bone tumors in general.

By the time the study was stopped in late 1998, though, Neer’s team had already collected much of its data. They also looked for signs of bone cancer in their human subjects and found none.

Other researchers agree that one of the most attractive features of the new PTH drugs is that they appear to be safe as well as effective.

“We are in a new era for osteoporosis treatment,” said Dr. Meryl LeBoff, director of skeletal health and osteoporosis at Brigham and Women’s Hospital, who is studying a different form of the drug called PTH 1-84.

What has made this new era possible is a more detailed understanding of the intricate biochemical processes that shape bones. Though many people imagine bone to be like cement--an inert substance that is simply there for structural support--it is actually a dynamic tissue that is always being turned over, or remodeled. The tearing down of bone tissue, done by cells called osteoclasts takes about two weeks; the rebuilding, by cells called osteoblasts, takes three months. At any given point, different bones are in different stages of the process.

If there were no tearing-down process, bones would get so big and heavy it would be impossible to walk. Scientists now know that osteoblasts, the bone builders, are the key to the entire process because they also tell the osteoclasts, through chemical signals, when to become activated and start destroying bone.

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Estrogen, in turn, regulates the osteoblasts, slipping into the bone-building cells through special receptors. Because estrogen is so crucial, it has long been the mainstay of osteoporosis prevention for women at menopause, when natural estrogen levels decline sharply. Estrogen therapy prevents further bone loss but does not significantly increase new bone formation.

Two other drugs--Fosamax (alendronate) and Actonel (risedronate)--work differently, said endocrinologist Dr. Michael F. Holick, director of the bone health care clinic at Boston University Medical Center.

Rather than boosting osteoblasts, as the hormonal therapies do, these so-called bisphosphonate drugs kill the bone-destroying osteoclasts. Some people get upset stomachs on Fosamax, but a new once-a-week version, approved last year, seems to reduce that problem. Still, the problem with all the drugs currently on the market is that they basically block the destruction of bone.

The bisphosphonates do yield a 2% to 3% increase in bone density per year, which over time produces as much as a 50% reduction in spinal and hip fractures. But parathyroid hormone increases bone density far more quickly--up to 5% a year.

Here’s how it works: When secreted normally by the parathyroid gland in the neck, PTH has one job--to keep blood calcium levels normal. When blood calcium drops, PTH signals osteoblasts to signal osteoclasts to destroy bone, thus releasing calcium to where it’s needed most--in the blood. The new PTH drugs “trick the system,” Holick said. By giving PTH in a single blast once a day, the osteoblasts become very active (thus building more bone) but don’t have time to stimulate the osteoclasts, which would tear bone down. The result is bone growth.

Despite its promise as a drug, PTH has its drawbacks. That it must be given by injection “will limit its appeal,” said Dr. Bess Dawson-Hughes, chief of the calcium and bone metabolism lab at the USDA Nutrition Center at Tufts University. Research is underway on variants of PTH that could be taken in pill form, as a nasal spray or as a cream.

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Judy Foreman writes a syndicated column on health issues. She is a fellow in medical ethics at Harvard Medical School. She can be reached by e-mail at foremanj@brandeis.edu. Her column will run occasionally in Health.