Help Is on the Way
For Your Skeleton

Doctors and researchers are trying a new approach to the crippling and painful loss of bone that people, particularly women, experience as they age: rebuilding bones instead of merely trying to slow their deterioration.

The new techniques for treating osteoporosis and low bone density involve everything from vibrating-motion therapy -- an idea being tested by the Army -- to powerful new drugs that can stimulate new bone formation. The goal is to manipulate the natural cycle by which bones destroy and rebuild themselves over a lifetime.

One of these bone-building drugs is on the market, and a second will be available soon. Drug companies are developing therapies based on newly discovered genes that aid in bone formation, as well as creating more powerful and effective versions of existing drugs. All told, six new osteoporosis drugs will be on the market in the next four years, and many more are in the pipeline; there are nearly 600 osteoporosis trials listed on recruitment and government Web sites.

At a recent meeting of the American Society for Bone and Mineral Research, researchers presented a slew of new evidence on bone-building therapies they say will revolutionize the treatment of osteoporosis and eventually could eliminate it. "For the last 20 years, we've been trying to hold on to whatever bone people have," says Clifford Rosen, director of the Maine Center for Osteoporosis Research and Education. "Now the paradigm has shifted totally to say we can rebuild the skeleton and make it like new again."

The new discoveries come at a time when low bone density is an increasing problem. The National Osteoporosis Foundation estimates that by 2010, more than 52 million women and men will be affected by osteoporosis and low bone mass. Though women account for 80% of osteoporosis cases, two million men have the disease. Meanwhile, a once-popular approach to protecting bones, standard estrogen-replacement therapy, has fallen out of favor, amid studies showing an increased risk of breast cancer, heart attack and stroke.

"Paying attention to your skeleton is something no one thinks about until they are over 60 and get their first fracture, but both men and women reach peak bone mass at about 30, and that's when they should be thinking about how fast they are losing bone," says Andrew Stewart, chief of endocrinology at the University of Pittsburgh School of Medicine who discovered one of the bone-building agents now in clinical trials.

Many of the older drugs on the market -- so-called antiresorptives such as Merck's Fosomax and Procter & Gamble's Actonel -- work mainly to slow or stop bone loss by attacking bone-removing cells called osteoclasts. By contrast, a new class of drugs stimulate bone-forming cells known as osteoblasts. A number of studies are under way to test combinations of the two types of drugs.

The first bone-building agent, Eli Lilly's injectable drug Forteo, approved in 2002, is a synthetic form of parathyroid hormone, or PTH. Although the body's own PTH actually causes bone loss when elevated, intermittent injections of PTH have the opposite effect. Lilly's trials showed that Forteo reduced the risk of moderate or severe spinal fracture as much as 90% when compared with a placebo. More than 70% of patients treated with the drug achieved at least a 5% rise in bone mineral density in the spine, and 44% gained 10% or more. Lilly says that more than 50,000 people are taking the drug, and it is in the early stages of developing an oral version.

Joyce Barmak, a social worker in her 50s, began taking Forteo 18 months ago, after treatment with Fosomax failed to stem a worsening case of osteoporosis. Ms. Barmak's own mother had suffered such a severe case of osteoporosis that "I knew it could be a death sentence for me," she says. Though she has yet to receive a follow-up bone scan, she sustained only an incomplete fracture after a bad fall at work last year and has since healed.

More bone-building drugs, known as skeletal anabolic agents, are likely to hit the market in the next few years. NPS Pharmaceuticals recently completed clinical trials on a second type of PTH known as Preos and is expected to file for Food and Drug Administration marketing approval this year. Dr. Stewart and others are conducting trials on a related hormone, known as PTHrP. Early studies show it might be even more effective than PTH because it stimulates bone formation but not bone loss. NPS and GlaxoSmithKline are developing calcilytics, small molecules that help release the body's own stores of parathyroid hormone.

Of course, the new anabolic agents are costlier; Forteo, which must be injected under the skin by patients using a pen-like device, costs about $560 for a one-month supply, compared with about $70 a month for drugs such as Fosomax. Forteo showed a slight risk of bone cancer in animal studies and at present, Forteo can be taken only for two years.

People who want to participate in research can visit ClinicalTrials.gov for government-funded studies. Drug-company trials are listed on recruitment sites such as Acurian.com and Centerwatch.com, but it's important to consult your doctor before considering a trial. Other useful Web sites include University of Washington professor Susan Ott's site, (http://courses.washington.edu/bonephys/), the National Osteoporosis Foundation (www.nof.org) and the new Powerful Bones/PowerfulGirls (http://www.cdc.gov/powerfulbones).

Researchers also are pursuing the idea that new exercise regimens and physical interventions, without drugs, could stimulate bone growth. Bone gets stronger or weaker depending on functional demands -- the reason that a professional tennis player has 35% more bone in the playing arm than the nonplaying arm.

The Soldier Systems Center in Natick, Mass., is testing aerobic training, strength training and a combination of the two to see which works best to build bone and prevent stress fractures. "The goal is to find the right balance between just enough exercise and too much, and to determine where bone strengthening ends and where weakening begins," says Maj. Rachel Evans, director of the Army's bone-research program.

Army recruits also are testing a less rigorous workout: standing on a vibrating metal plate for 15 minutes daily to test how well high-frequency, low-magnitude vibrations boost bone mass in the legs. Tests on animals showed significant increases in muscle mass, and two recently published studies on postmenopausal women and on children with cerebral palsy also showed improvement. NASA is testing the device on astronauts.

Juvent Inc., a medical-device company, will market the motion-therapy device in Europe this year and is preparing a clinical study in the U.S. The idea is for doctors to be able to prescribe the device, which is expected to cost about $2,000, says the developer, Clinton Rubin, chairman of the biomedical-engineering department at the State University of New York at Stony Brook. (Some commercially available machines offer to vibrate the body for strength, but they may be dangerous if they vibrate fast enough to damage bone, muscle and cartilage.)

"This provides some control for a devastating disease without worrying about the long-term effects of medication," he says.

© 2003 Wayne Hollopeter, M.D. All Rights Reserved
This website hosted by Wild Web West. Contact: Webmaster