Boning up on building better bones

Major strides have been made in the treatment of osteoporosis. A recent study showed that more and more patients have been seeing their doctors for the treatment of this brittle bone disease, thanks to increased awareness and the availability of effective therapies to stem bone loss.

Bone is a living tissue that is constantly being formed and broken down by bone-building cells called osteoblasts and bone-eating cells called osteoclasts. Osteoporosis results when more bone is lost than is replaced.

Treatment for the condition involves exercise and medication. Until recently, three osteoporosis medications – alendronate (Fosamax), risedronate (Actonel), and raloxifene (Evista) – were available. All work the same way: They slow down bone loss by reducing the rate at which bone breaks down.

Now, a new class of drugs offers hope to women with advanced osteoporosis, those most likely to break bones that had become porous, fragile, and brittle. The new class of drugs, called skeletal anabolics, is different from antiresorptive agents because they can stimulate new bone formation and increase bone mineral density, rather than prevent further bone loss.

Used in combination with other osteoporosis treatments, these new drugs could help women avoid fractures altogether. "This is a very exciting time," remarks Clifford J. Rosen, MD, past president of the American Society for Bone and Mineral research (ASBMR).

One Shot A Day

The first of these drugs on the market, teriparatide (Forteo) – a genetically engineered form of parathyroid hormone (PTH) – inhibits the growth of osteoclasts, thus preventing too much bone from being absorbed. It also increases the number of osteoblasts, replacing lost bone and improving its density. A study published in 2001 in the New England Journal of Medicine of 1,600 postmenopausal women with osteoporosis found that the use of PTH for 21 months increased bone density and reduced vertebral fractures of the spine by 65 percent and fractures at other sites by 53 percent.

According to a January 2003 study in the Journal of Bone and Mineral Research, teriparatide is also effective in improving bone mineral density in men with osteoporosis. However, the effect of teriparatide on fracture risk in men has not been studied.

Only one study has directly compared teriparatide with other treatments for osteoporosis. In that study, published in 2002 in The Journal of Clinical Endocrinology and Metabolism, 146 postmenopausal women with osteoporosis were randomized to receive teriparatide or alendronate. After a year, participants taking teriparatide had an increase in spine bone density that was eight percent greater than that of the alendronate group. In addition, a smaller percentage of teriparatide patients had non-vertebral fractures than did alendronate patients (four percent vs. 14 percent).

Currently approved for postmenopausal women at high risk of fracture (or who have had a previous fracture), teriparatide is self-administered as a daily injection. It should not be used for the prevention of osteoporosis. People who should not take it include children, women who are pregnant or breast-feeding, those with cancer that has spread to the bone, and those with high blood calcium levels. The daily dose of teriparatide is 20 mcg. You can take it any time of the day with or without food or drink.

A recombinant PTH (Preos) is currently under study. Like teriparatide, Preos is injected daily. An initial study reported at the ASBMR meeting last year showed Preos produced an average of eight percent increase in bone mineral density over a year. Scientists are now trying to determine the maximum tolerable dose of recombinant PTH.

Animal studies suggest using PTH for longer than two years may raise the risk of a form of bone cancer called osteosarcoma. Since its safety has not been evaluated beyond two years in human beings, the drug should not be used for longer periods. Teriparetide’s effects last after it is stopped, and experts say women can maintain improved bone density by taking antiresorptive agents, such as Fosamax and Actonel, or drugs called selective estrogen receptor modulators (SERMs), such as Evista. SERMs act like estrogen to prevent excess resorption of bone but without the risk of breast or uterine cancer. Now under active study is whether PTH is more effective when used alone or in combination with SERMs.

Another promising drug is zoledronic acid (Zometa), already approved in the US for treating patients whose cancer has spread to the bone. In cancer patients, Zometa can reduce fractures and compression of the spinal cord. Preliminary results from clinical trials in women with osteoporosis show that annual, semiannual, or quarterly injections of Zometa can increase bone mineral density. Zometa is a kind of "super biophosphonate" that can be injected once a year, says Kenneth W. Lyles, MD, professor of medicine at the Duke University Medical Center in Durham, North Carolina. Dr. Lyles is conducting a fracture prevention trial with Zometa. If larger clinical trials confirm its effectiveness, the manufacturer may file for FDA approval as early as this year.

What To Do Now

Women most at risk for osteoporosis include those with a family history of the disease, who have had a previous fracture of any kind, women who are thin and small-boned, and those who are on prolonged corticosteroid therapy.

But all women are potentially at risk. Data reported in the May 24, 2004 Archives of Internal Medicine from among 149,524 women enrolled in the National Osteoporosis Risk Assessment (NORA) study showed that 82 percent of those who developed fractures a year after a bone mineral density (BMD) test did not qualify for a diagnosis of osteoporosis.

"One of the shortcomings of BMD testing is that we can only see how much mineral is there, not the quality of bone," Dr. Lyles told a recent briefing sponsored by the American Federation for Aging Research. "We are now developing imaging devices that will allow us to see the architecture of the bone, not just the thickness." For now, women over age 50 should consider BMD testing to see where they stand; all women over 65 need the test. The US National Osteoporosis Foundation also recommends testing for younger postmenopausal women who smoke, who are thin, or who have a parent or sibling who had a fracture as an adult. Every woman over the age of 35 to 40 who suffers a fracture should also be tested, and those with confirmed osteoporosis should be treated with one of the approved medications. A bone density test before treatment helps in assessing treatment progress.

If your BMD test shows your bone density is normal, you need not be retested for at least two years. If testing reveals osteoporosis, your doctor should prescribe treatment, no matter what your age. Enough treatment options exist that you should be able to find one that works well for you.

Women should also get 1,200-1,500 mg of calcium a day, 600-800 IU of vitamin D, and do regular weight-bearing exercise, such as walking. A German study in the Archives of Internal Medicine involving 50 early postmenopausal women with osteoporosis who were not taking medication found that those who exercised four times a week had stable BMD, while those who did not exercise lost bone. Says Dr. Lyles: "Bone is like a bank account. Your body makes lots of deposits and withdrawals. You want to slow the number of transactions."