Osteoporosis Drugs Prevent Fractures, but Patients Worry About Side Effects; Weighing the Risks
MELINDA BECK WSJ Sept 15, 2009
Osteoporosis has haunted my family for generations, as it has many other families.
My great-grandmother was bent nearly horizontal from collapsed vertebrae. My grandmother lost a foot in height as her spine deteriorated, and broke her hip just pushing a grocery cart. I made her a new backbone out of papier-mâché when I was 4.
My mother did everything she could to avoid the family curse, but she also suffered painful collapsed vertebrae. All three women died, directly or indirectly, as a result of osteoporosis.
Osteoporosis has expanded the gaps in the spongy tissue within a spinal vertebra, increasing the bone’s brittleness and probability of fracture.
That was before the bone-building drugs called bisphosphonates became widely available in the mid-1990s. Thanks in part to them, the number of hip fractures has dropped significantly in the U.S. and Canada in recent years.
Osteoporosis remains a serious health problem for the 10 million Americans who have it and the 34 million who are at risk due to low bone mass; 80% of sufferers are women. It's estimated that one half of women and one-quarter of men over age 50 will suffer an osteoporosis-related fracture.
But reports of scary side effects from bisphosphonates including Fosamax, Actonel and Boniva are circulating on the Internet and in medical journals. Hundreds of lawsuits allege that the drugs cause a rare condition in which part of the jaw bone dies. The first case to be tried against Merck & Co.'s Fosamax ended in a hung jury last week in federal court in New York City. And some critics say the drugs with sales of $8.3 billion a year in the U.S. are being oversold to women who may never need them.
All that leaves women facing a difficult dilemma: Powerful osteoporosis drugs known to prevent future debilitating injuries are also suspected of increasing the risk for other terrible conditions. Balancing the risks and benefits is different for every woman, and depends on factors such as genetic history, diet and lifestyle. Figuring out how to proceed also requires having a very careful discussion with a qualified physician.
A good place to start is with your family tree. Having a parent with osteoporosis raises your own risk significantly. Caucasians, Asians and Hispanics also have higher rates of osteoporosis than African-Americans. So far, scientists have identified 15 related genes but there isn't likely to be a predictive genetic test anytime soon.
That's because environmental factors also play a big role. The more bone you build up during the peak building years before age 30, the more reserves you'll have when net bone loss sets in. For women, that happens very rapidly after menopause when estrogen levels decline. Men lose bone far more slowly, although hormone-deprivation drugs for prostate cancer can also set them up for osteoporosis, as can a very strong hereditary load.
A diet rich in calcium (from dairy products and vegetables), plenty of exposure to vitamin D and weight-bearing exercise all help to build strong bones. Too little of those can weaken them, as can smoking, drinking alcohol, and a taking a variety of medications, including corticosteroids, anticonvulsants and antidepressants. Excessive dieting and exercising and being very thin with a body-mass index of less than 20 can also leave your bones with little reserve. Being obese actually lowers your risk, though it can overstress your joints.
But some people can do everything right and still develop osteoporosis if they have a strong genetic predisposition.
A bone-mineral-density test can give you one indication of how strong your bones are. Women with several risk factors should have one at menopause; or at least at age 65. The most common such test, called a DEXA (for dual-energy X-ray absorptiometry) is quick and painless and measures the amount of bone in your hip, spine or wrist. Results, called T-scores, compare that density with an average peak at age 30.
A T-score of minus 2.5 or below indicates osteoporosis. A T-score between minus 1 and minus 2.4 is considered osteopenia meaning low bone density but not full-blown osteoporosis.
You and your doctor can also assess your risk by using an online tool developed by the World Health Organization called FRAX, for Fracture Assessment Risk Tool. (See www.shef.ac.uk/FRAX.) It asks your sex, age, weight, height, hip-bone density and factors such as smoking, drinking, and parental hip fractures. It computes your chances of suffering a major bone fracture in the next 10 years.
What to do with that information is still somewhat controversial. "If you already have severe osteoporosis, you don't need a FRAX score to tell you you need treatment," says Bess Dawson-Hughes, director of the Bone Metabolism Lab at Tufts University, who has advised many of the drug makers. "Where we have struggled is what to do with that large group of healthy people who have low bone mass."
The National Osteoporosis Foundation's latest guidelines say that women who have a 3% risk of developing a hip fracture or 20% risk of other major fracture in the next 10 years are candidates for treatment, on cost-effectiveness grounds. In studies of older women with osteoporosis, Fosamax has been found to reduce the chance of hip and spine fractures as much as 50% . But it's less clear to what extent such drugs can prevent osteopenia from becoming osteoporosis.
Experts say that individual patients should never be treated based on T-scores or FRAX probabilities alone. Many other considerations apply.
Are You at Risk?
The more "yes" answers, the greater your risk for developing osteoporosis:
- Do you have a small, thin frame and/or are you Caucasian or Asian?
- Have you or a member of your immediate family broken a bone as an adult?
- Are you a postmenopausal woman?
- Have you had an early or surgically-induced menopause?
- Have you taken high doses of thyroid medication or used glucocorticoids 5 mg a day (for example, prednisone) for three or more months?
- Have you taken, or are you taking, immunosuppressive medications or chemotherapy to treat cancer?
- Is your diet low in dairy products and other sources of calcium?
- Are you physically inactive?
- Do you smoke cigarettes or drink alcohol in excess?
"You need to consider the unique characteristics of this lady in front of you," says Ethel Siris, director of the Toni Stabile Osteoporosis Center at Columbia Presbyterian Medical Center, who has also consulted for the drug makers. For example, a 50-year-old woman with osteopenia may not be a candidate for treatment based on her FRAX alone. But if she falls a lot and her mother suffered spinal fractures, which the FRAX doesn't ask about, it may make sense to treat her for a few years and see how her bone density does, Dr. Siris says. Meanwhile, a 70-year-old who has the same T-score probably started out with better bone density, but she has had 20 more years for her bone architecture to erode, so her bones are more fragile, even though they weigh the same.
The official guidelines also don't take into account potential side effects of the bisphosphonates, which are also highly individual. Gastrointestinal upsets are the most common; the oral medications aren't recommended for patients who can't sit upright for at least a half-hour because these drugs can irritate the esophagus. Gastro-esophageal reflux disease (GERD) can make such discomfort worse. A woman with severe GERD might fare better on Reclast, a once-a-year injection of bisphosphonate.
Some patients have also reported severe bone and muscle pain while taking bisphosphonates. The Food and Drug Administration alerted doctors last year that they might see this and consider discontinuing the drugs at least temporarily. Who is most affected and how long it lasts seems unpredictable. "I treat a gazillion patients and I see this rarely," says Dr. Siris. "When I do, we stop and re-evaluate."
Cases of osteonecrosis of the jaw (ONJ) in which parts of bone become exposed during dental work and don't heal are more serious but very rare. No one knows the exact incidence. Estimates range from 1 in 1,000 to 1 in 100,000 patients taking bisphosphonates for osteoporosis. (It's far more common in cancer patients on much higher doses.) Merck and other manufacturers say there is no evidence that the drugs cause ONJ at doses used for osteoporosis, but some dentists have become wary of doing invasive dental work on women taking bisphosphonates.
"We often advise patients who need extensive, invasive dental work to get that done first, then start the drugs and the issue disappears," says Ian Reid, a professor at the University of Auckland in New Zealand who has written on biosphosphonate safety.
A few doctors have reported unusual fractures of the thigh bone in women taking bisphosphonates for many years. One theory is that because the drugs inhibit the breakdown of old bone, they may be maintaining bone that is unusually brittle. Here too, the incidence seems extremely rare and the link remains unproven. But experts agree that it warrants further study and that patients and doctors should investigate any unusual thigh pain which has preceded several of the fractures.
On balance, most experts say that women with confirmed osteoporosis face a much higher risk of fractures if they don't treat their condition than if they do. "These horrible cases are incredibly rare, whereas hip fractures are not rare in the aging population and they can kill you," says Dr. Siris. She notes that there are still many unknowns about drugs, including how long it is safe for women to stay on them. Many doctors are using them with patients only about five years at a time and then re-evaluating.
Other osteoporosis drugs on the market work differently and carry different risks. Evista (raloxifene) acts on estrogen receptors and can cut the risk of breast cancer as well as spinal fractures in some women, although it doesn't prevent hip fractures. Forteo (teriparatide) is a daily injection for women with severe osteoporosis, but has been linked with bone malignancies in rats. Last month an advisory panel recommended that the FDA approve denosumab, a biological agent that blocks the production of osteoclasts that break down bone. It would be a twice-yearly injection.
Estrogen-replacement therapy can also help women postpone the rapid loss of bone mass that occurs after menopause. It's no longer recommended for bone protection alone in part because of the added risk of heart disease and breast cancer found in older women in the Women's Health Initiative studies. But the risk-benefit profile seems more favorable for younger women who want relief from menopausal symptoms like hot flashes. "If you hate your life without estrogen, you can go back on it and that's your bone-loss drug as well," says Dr. Siris.
Some clinics urge women to fight osteoporosis with lifestyle changes rather than pharmaceuticals. Many experts agree that sufficient calcium (at least 1,200 mg per day from food or supplements) and vitamin D (800 to 1,000 IUs per day) and weight-bearing exercise (at least 30 minutes, three times a week) are critical for building and maintaining strong bones, but they may not be sufficient for reversing serious bone loss once it's set in.
All camps agree that the very best way to strong bones is to build them well to begin with. Nearly 90% of bone mass in females is built by age 18, yet few adolescent girls are getting the recommended amounts of calcium and vitamin D.
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