Good News : New drug can create bone

Bones often get compared to banks. People who don’t build up a healthy savings of bone density when they’re young, so the analogy goes, may find themselves in debt come retirement.

Researchers are working on drugs that can offer last-minute deposits. In 2002, physicians welcomed the first new osteoporosis drug in five years, and tests of more are in the pipeline. Meanwhile, manufacturers are making existing drugs easier to take, and researchers are making discoveries in bone metabolism that may lead to more choices.

Still, challenges remain. Hormone-replacement therapy was once popular but lost favor with the discovery that it may increase the risk of heart attacks and cancer. Research published in July in the New England Journal of Medicine found mixed results for Evista, which has been a bone-strengthening alternative to hormone therapy. While use of the drug for five years reduced the risk of fractures and breast cancer by about one woman per thousand, it also increased the odds of blood clots and strokes.

Nothing offers a cure.

“We have a few good choices, but we certainly need better in several areas,” says Dr. Gordon Strewler, an osteoporosis expert from Beth Israel Deaconess Medical Center in Boston.

The need is expected to increase as the population ages. Federal health authorities estimate some 10 million Americans already have bones brittle to the point of full-fledged osteoporosis, and another 34 million may be on the brink of developing the condition. Women run a greater risk than men; thin people a greater risk than heavier people.

Basically, though, osteoporosis is a disease of aging. About a third of women older than 80 will suffer a broken hip. As many as 20 percent will die from the complications.

Bones may seem solid as rocks, but they are more like rigid pipes with honeycombs inside. Their airy internal latticework constantly resculpts itself, drawing on calcium, vitamin D and exercise. Some cells remove bone from the matrix while others replace what’s lost. Osteoporosis occurs when the cells on teardown duty outperform cells doing construction.

“People think of bone as kind of a dead tissue, but it’s actually very alive tissue,” says Dr. Dennis Black of the University of California, San Francisco.

Medicines usually work by slowing the natural turnover of bone. The bone-removing cells are called osteoclasts; their counterparts are osteoblasts. They are the yin and yang of bone strength. Almost all osteoporosis medications hamper the work of osteoclasts.

The newest drug on the market, however, is the first to boost osteoblasts, the cells that create bone. Called Forteo, the drug comes in a daily injection. The most painful side effect so far appears to be on the wallet. It can cost about $7,000 a year.

Writing in June in the journal Archives of Internal Medicine, researchers from Stanford University School of Medicine tried to analyze whether the advantages of the drug justified its cost, considering an analysis of a hypothetical group of 200,000 women - a study population far larger than would be feasible in the real world. Based on what’s known about each drug’s effectiveness and price, the researchers had a computer compare the costs and benefits of Forteo with other treatments, evening out the fact that some women would benefit greatly from the treatment while others would pay for medicine that didn’t make much difference.

In the overall population, the new drug wasn’t a bargain, says researcher Hau Liu. In most scenarios, “Forteo is not cost-effective, primarily because of its high price,” he says. “You can get a lot of benefit from existing therapy already.”

The numbers in the analysis worked out this way: Fosamax alone provided an extra year of perfect health for about $11,600. Forteo would cost more than $172,000.

And although Forteo appears better able to improve bone density, so far that hasn’t translated to striking differences in fracture rates, Liu says. This is perhaps because improved fracture rates depend on more than just better bone density. The strength of any material rests on its entire internal structure - a china plate is heavier than a plastic one, but only one will break when it hits the floor.

All of which does not mean that Forteo isn’t a useful drug.

“It’s not the first thing you reach for,” agrees Dr. William Fears, chief of endocrinology at Methodist Dallas Medical Center. However, he does prescribe it to people at highest risk of fracture, or for whom standard drugs won’t work.

The most common drugs are known as bisphosphonates, which have been used for more than a decade. Seen the commercials with women raving about their osteoporosis pill? It’s probably a bisphosphonate such as Fosamax or Boniva.

In 2004, physicians reported that women who took Fosamax for 10 years (with a 10-milligram dose) saw an increase in lower-spine density of about 14 percent. While the drugs appear safe, scientists can’t say whether the suppression of bone turnover might cause long-term side effects.

Still, bisphosphonates remain the drugs of choice for most patients, Black says. The drawback is that they can cause gastrointestinal side effects and must be taken with a strict ritual: first thing in the morning, before breakfast, with a glass of water, while remaining upright. Since the pills don’t make people feel different, even with all this trouble, patients often abandon them.

That’s why drug makers increasingly offer drugs that can be taken once a week or once a month and through injections. The modifications are aimed at convenience, not effectiveness.

Researchers also are trying to find the best combinations of Forteo and bisphosphonates. Because animal studies raised the possibility of a risk of bone cancer, Forteo is approved for any person to use for only up to two years. Last year, Dr. Black from San Francisco reported in the New England Journal of Medicine that a year after stopping Forteo, the buildup of bone eroded unless Forteo was followed with Fosamax. This back-to-back use of the drugs produced a greater improvement in bone mass, the study found.

Doctors hope to have more choices soon. A drug called denosumab has looked promising. It is administered by injection, and works by interfering with the body’s ability to make osteoclasts. It is unlikely to work better than a bisphosphonate but, at just two doses a year, would be easy to take.

In addition, it has a quicker, reversible effect, says Dr. Michael McClung, director of the Oregon Osteoporosis Center.

By the time denosumab could make it on the market, physicians should be better able to target medications to the patients who would most benefit. Current assessments are based largely on bone-density scans. A bone scan is a useful predictor of fracture risk, but it doesn’t speak to bone quality, McClung says.

“Bone density doesn’t tell us about things like bone turnover and bone architecture,” he says. Experts are about to release better measures for predicting fractures, guidelines that will measure age, medical history and family risk. In other words, people who are on the verge of finding their bones overdrawn.