Snap, Crackle Mom

Thanks to thinning skeletons, half of all postmenopausal women and a quarter of men over 50 will fracture a bone. To prevent these breaks, health organizations are rethinking guidelines for identifying those at risk.

As anyone who has guided her frail grandmother into a chair recognizes, our bones weaken as we age. Delicate frames put people at a greater risk for fractures, which take longer to heal the older one gets. A broken finger won't destroy anyone's bridge game, but hip fractures can lead to constant pain, immobilization, and death.

To prevent these injuries, physicians need to identify those whose bones are most likely to snap. In 1994, doctors caught only one in 10 patients with osteoporosis--a bone-thinning disease that afflicts half of women over age 50, says epidemiologist Randall Stafford of Stanford University in Stanford, California: "Now we're up to [detection rates of] 40 to 50%." And he predicts that medical professionals will do better in the future: In late 2002, the Department of Health and Human Services recommended routine screening for osteoporosis in women over 65, a practice that will leave fewer sufferers unnoticed. Meanwhile, researchers are seeking better ways to detect people at risk of fracture. What they're learning about bone biology could lead to new treatments for keeping the skeleton strong.

Currently, efforts to identify people with osteoporosis rely on measurements of bone density. Doctors x-ray a hip, forearm, or other bit of skeletal swag and assign the bone a "T score" that reflects its thickness. A T score of –1 means that the bone is 10% less dense than it should be; a T score of –2.5 means the density is 25% lower than normal. According to the World Health Organization (WHO), people with a T score of –2.5 have osteoporosis and should be offered drugs or nutritional supplements that will prevent fractures.

However, these guidelines are somewhat arbitrary, says clinical researcher Ethel Siris of Columbia University in New York City. The worse a woman's T score, the more likely she is to suffer a break. But bone density doesn't foretell the whole story. For example, a 50-year-old woman with osteoporosis is less likely to break a bone than an 80-year-old with the same bone density. And women whose T scores fall between –1 and –2.5, a condition WHO defines as "osteopenia," fracture as well.

To address how well bone density measurements can finger those most likely to experience a break, Siris and colleagues looked at 149,000 women enrolled in the National Osteoporosis Risk Assessment study. Of the women who broke a bone within a year, only 18% had T scores lower than –2.5. "If doctors only treat by WHO guidelines, we're neglecting 82% of people [who] fracture," says Siris. But the answer isn't to simply treat everyone whose bones are a bit on the thin side, she says. No one knows, for example, whether current therapies will lower the chances of fracture in people with osteopenia, Siris says: "We need better strategies to identify those most at risk."

To that end, the National Osteoporosis Foundation has revised its guidelines, recommending that physicians take into account other factors, such as previous breaks. Siris and colleagues found that women who had already broken a bone after the age of 45 were most likely to break another, regardless of their T scores. Other risk factors included poor health and poor mobility. Based on such studies, WHO is developing an "absolute fracture probability score" that will churn out a probability that a person will break a bone within 10 years. "Nobody's bone density determines the quality of life," says geneticist Cliff Rosen of the Maine Center for Osteoporosis Research and Education in Bangor. "Their fractures do."

Other researchers are trying to identify ways to assess bone quality. "Aging is doing something to bone that we can't measure by bone density," says Rosen. Efforts are under way to address that problem. In 2001, the National Institutes of Health funded a handful of new research projects on measuring bone quality. Some investigators are pursuing compounds in blood that indicate that bone is falling apart. Others are trying to use computerized tomography and magnetic resonance imaging scans to visualize bone structure. Like a building, bones have struts and I-beams, and these deteriorate over time. Scanning looks promising, says Rosen, but no one yet knows how well quality measurements can predict risk of fracture. "We still have a ways to go," Rosen says.

Whether scientists are looking at density or quality, work in the past few years has revealed a delicate harmony between cells that build new bone, called osteoblasts, and those that chip away at old bone, called osteoclasts. These opposing forces maintain healthy bones, and the brittleness of elderly bones arises from an imbalance of the two. For example, estrogen stimulates new bone growth and dampens its destruction, but at menopause, quantities of that hormone plunge and the bone-breakers thrive unimpeded. Some scientists are targeting the various molecules or hormones that will calm these overzealous beasts; others are goading the lax builders to get back to work.

Different research reveals an as-yet-unexploited relation between fat and bone. For example, one recent study found a gene that controls whether cells grow into fat or bone-building cells, whereas another study found a gene that caused both weight gain and bone-thinning in mice. Although the work is in its early stages, drugs aimed at such genes might encourage the maintenance of healthy bones in older people.

In the meantime, Stafford says that physicians should keep up efforts at promoting disease prevention. In a recent study, he found that the diagnosis of osteoporosis and the use of fracture-preventive drugs rose dramatically between 1994 and 2003, whereas the percentage of doctors recommending calcium pills dropped by a third. The proper amount of calcium, vitamin D, and weight-bearing exercise help protect people's bones from thinning, he says.

The fight against deteriorating frames is hardly won, but researchers who study bone health might be further along than those who work on other systems that are ravaged by age. After all, "bone density is a better predictor of fracture risk than cholesterol is of a heart attack," says Siris. Perhaps with a better understanding of skeletal quality and basic biology, doctors can break bad bones' hold on old age.

Mary Beckman is a writer in southeast Idaho who makes sure her orange juice contains lots of calcium.

National Osteoporosis Foundation