Three developments that could change how you treat osteoporosis
By Jason van Steenburgh
For physicians who treat osteoporosis, the news over the last six months could potentially change the way they practice.
The first announcement came last July, when the Women's Health Initiative released new data highlighting the risks of hormone replacement therapy. That bombshell frightened patients, leading some to question treatments that were helping stave off osteoporosis.
The issue of when and how to treat osteoporosis was further complicated last fall when the U.S. Preventive Services Task Force urged physicians to begin screening some women for the condition starting at age 60, rather than 65. While researchers say earlier screening will save lives, the guidelines raise questions about what drugs younger seniors should receive for osteoporosis. (The guidelines are online.)
Finally, in November 2002, the FDA gave its long-awaited approval to a new osteoporosis drug, teriparatide. Instead of merely slowing bone loss, experts say the new drug actually accelerates bone growth.
What do these developments mean for you, and should they change your approach to treating osteoporosis? To answer those questions, we talked to physicians who specialize in osteoporosis treatments and have followed these developments closely.
HRT's role in prevention
Here's the news that gave physicians the most headaches: Researchers presented new trial findings stating that women taking hormones face an increased risk of breast cancer, stroke and coronary events. The data were so alarming that researchers halted the trial and urged physicians to avoid using HRT in women who are at risk for or have family histories of those conditions.
Because the announcement generated so much controversy, experts say that many patient advocates and physicians may have overlooked vital information about HRT's role in preventing osteoporosis. According to data from the now-halted trial, hormones reduced hip fracture rates by 34%, a finding that supported previous data.
While some patients may want to stop hormone therapy, Robert R. Recker, MACP, director of the Osteoporosis Research Center at Creighton University in Omaha, Neb., said that menopausal patients who have risk factors for osteoporosis but not for coronary events or breast cancer remain ideal HRT candidates.
He recalled one recent patient who was conflicted about using HRT, but who nonetheless decided to begin using hormones. While the 52-year-old woman had a family history of osteoporosis and hot flashes, she had no family history or other risk factors for breast cancer or coronary events.
"We talked about the options," Dr. Recker said, "and she chose HRT. The plan is for her to stay on it to treat her menopausal symptoms and then to go to another drug like a bisphosphonate if the HRT doesn't prevent her from losing bone."
He added that he and the patient together decided that in the absence of severe bone loss, they would give HRT a chance to prevent the development of osteoporosis before moving to other therapies.
Dr. Recker said that HRT is a good option for women who are going through menopause and have low bone-density measures. (For more on testing for bone density, see "The role testing plays in osteoporosis treatment.") Patients with low bone density are especially good candidates for HRT if they have other risk factors for osteoporosis such as smoking or a family history of the condition, he said.
Dr. Recker said he doesn't push patients to stay on HRT if they have serious reservations about the drugs' side effects, but he encourages them to examine data from the Women's Health Initiative before forgoing hormone therapy. The study found that compared to a control group, 10,000 women taking hormone therapy for one year would experience seven more coronary heart disease events, eight more strokes, eight more pulmonary embolisms and eight more cases of invasive breast cancer each year.
When it came to colorectal cancer and hip fractures, however, the news was much better. Researchers found that for every 10,000 women taking HRT for a year, six fewer women developed colorectal cancers and five fewer developed hip fractures.
Perhaps even more importantly, Dr. Recker said, the study found HRT significantly reduced hip fracture rates in a population that had a low risk for hip fractures. He predicted that when HRT is studied in a population at high risk for fractures, researchers will find even stronger evidence for using hormones to prevent osteoporosis.
(For more on balancing the risks and benefits of HRT, see "Weighing the risks of hormone therapy" in the September ACP-ASIM Observer.)
If patients want to discontinue hormone therapy but tests indicate they have significant bone loss, switch them to a new treatment as soon as possible.
If hormone therapy had been preventing bone loss in these patients, that benefit will be lost rapidly, explained Robert L. Meckelnburg, FACP, a solo practitioner in Newark, Del., who specializes in osteoporosis. "After a year or two off estrogens, women drop back to where they were before they went on hormones," he said.
SERMs and bisphosphonates
Not everyone supports using HRT to prevent osteoporosis. Joel S. Finkelstein, MD, an endocrinologist at Massachusetts General Hospital in Boston who has researched osteoporosis treatments, said he uses HRT only to prevent osteoporosis in patients who have menopausal symptoms and can't tolerate bisphosphonates or selective estrogen receptor modulators (SERMs), the two main options for osteoporosis treatment.
"If their primary reason for being on HRT is osteoporosis, there are better and safer drugs," he explained. In addition, he said that no data associate either of these drugs with increased risks of coronary events or cancer.
As soon as HRT is failing to prevent bone loss, you should switch to an alternate treatment. Bisphosphonates and raloxifene (the only FDA-approved SERM) are the top choices to treat moderate to severe cases of osteoporosis.
Even if your patients with moderate to severe osteoporosis decide to stick with HRT, experts say you should consider an additional first-line treatment.
How do you choose between bisphosphonates and SERMs? Experts say that two factors-age and the location of bone loss-are critical in choosing a treatment strategy. Because different drugs decrease fracture rates in different parts of the skeleton, testing the hip and spine will probably determine which drug therapy to use.
Bisphosphonates. Most physicians turn to bisphosphonates as their first treatment choice because of the drugs' demonstrated ability to reduce hip fractures, a common fracture site in elderly women.
The drugs are recommended for a patient who has broken a limb, men and women in their late 60s or older, or anyone with severe bone loss. Often, women go on both bisphosphonates and HRT. (Studies show that this combination therapy is more effective than either treatment alone.)
A major downside of bisphosphonates is their tendency to cause gastrointestinal problems including heartburn and ulcers. Some of those effects can be minimized if a patient takes the medication with eight ounces of water, then sits upright for 30 minutes. For some patients, however, the adverse GI effects can be intolerable.
Although newer bisphosphonates have shown greater efficacy, Charlotte A. Harris, FACP, director of the Rush Osteoporosis Treatment Center in Chicago, said she sometimes uses etidronate, an older bisphosphonate that is not FDA-approved as an osteoporosis treatment. "A patient who has GI intolerance to the more modern ones can sometimes tolerate it," she said. "You go on it for two weeks, then take 10 weeks off."
Another note of caution about bisphosphonates: When patients discontinue the drugs, the bone-preserving effect is slowly lost. Some studies have suggested that the effect lasts in proportion to how long the patient used the drug.
A study published in the Dec. 3, 2002, Annals of Internal Medicine showed that patients who discontinued using the bisphosphonate alendronate had 11.2% lower bone mineral density after two years than those who continued with the treatment.
There is also a theoretical concern that long-term bisphosphonate use could be detrimental. Although there has been no evidence of long-term side effects, the drugs have been on the market for less than 10 years, and some researchers are concerned that evidence shows the drugs can accumulate in the bone.
"For a middle-aged patient on bisphosphonates who will live another three decades or more, we don't know what that will do," said Dr. Recker from Creighton. He also warned that there are concerns that bisphosphonates may inhibit bones' responsiveness to anabolic agents like teriparatide.
SERMs. For younger patients who are more likely to have brittle spines than brittle hips, raloxifene, which has been shown to increase spinal bone density, is the drug of choice. Raloxifene is also easier on patients' digestive systems than bisphosphonates.
Another reason to start patients on raloxifene? It can help prevent breast cancer and may reduce cholesterol.
Keep in mind, however, that women taking HRT for menopausal symptoms should avoid raloxifene if they suffer from hot flashes, as the drug actually exacerbates the condition.
New treatment for severe cases
If your patients have severe osteoporosis, you have a new option: teriparatide. Late last year, the FDA approved the drug, an injectable agent based on a parathyroid hormone that will be sold under the brand name Forteo.
The drug has shown remarkable efficacy in increasing bone density and reducing fractures. While other anti-resorptive agents stop bone from being lost, teriparatide actually stimulates new bone growth, said Massachusetts General's Dr. Finkelstein. He said he plans to use it in the most severe osteoporosis cases, especially patients who have had fractures.
Teriparatide can be taken for up to 24 months to help patients grow new bone. After that period, experts recommend reverting to standard anti-resorptive drugs like bisphosphonates and raloxifene to maintain those gains.
The major hurdle for physicians prescribing teriparatide will be convincing patients that their problem is severe enough to warrant daily injections. "It is a burdensome therapy in terms of expense and convenience," Dr. Harris said. "It will probably be used primarily in patients on bisphosphonates who are still breaking bones."
Because teriparatide has shown an anabolic effect in both sexes, Dr. Recker thinks he may eventually offer the drug to up to half of his osteoporosis patients. He predicted that many, however, will probably choose a medication that they can take orally.
Finally, there are some other drugs you have at your disposal.
Nasal calcitonin-salmon. One of the first approved treatments for osteoporosis is nasal calcitonin-salmon (Miacalcin). Dr. Meckelnburg said he occasionally uses it in combination with either bisphosphonates or raloxifene, mostly for its narcotic effect on acute fracture pain.
Dr. Finkelstein from Massachusetts General, however, said if the drug went before the FDA today for approval, it would probably be turned down. "It's extremely ineffective," he said. "I almost never use it, only when everything else has been tried."
Dr. Recker said he doesn't prescribe calcitonin-salmon because it can lead to problems with rhinitis. Because rhinitis causes patients to lose their sense of smell, it interferes with appetite, which can prevent osteoporotic patients from eating enough foods rich in calcium and vitamin D.
Intravenous zoledronic acid. Intravenous zoledronic acid, a bisphosphonate, has been shown to be effective, and many physicians use it as an off-label treatment for osteoporosis. It will be at least five years until it is FDA-approved as an osteoporosis treatment.
A study published in the Feb. 28, 2002, New England Journal of Medicine found that infusions of 0.25 mg, 0.5 mg or 1 mg every three months, 2 mg every six months, or 4 mg every 12 months had the same effect on bone density as oral bisphosphonates.
"It's a good option for people who can't handle oral bisphosphonates," said Felicia Cosman, MD, clinical director for the National Osteoporosis Foundation.
She said the perfect candidate for the drug has had wrist and spine fractures and cannot tolerate a once-a-week course of oral bisphosphonates, even with a proton pump inhibitor, because of severe ulcer disease and esophagitis.
The treatment's downside? "We have no fracture data yet," Dr. Cosman said.
Most physicians agree that the lack of studies concentrating on fracture efficacy as well as minimal information on dosage and regimen make this an option mainly for patients for whom other treatments have failed.
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP-ASIM.
Although the list of available drug therapies for osteoporosis is growing, modifying diet and lifestyle is still an important part of the equation. Here are some other strategies to improve bone strength:
Vitamins and minerals. Adequate vitamin D intake is especially important for individuals living in northern climates that have reduced sunlight several months a year and for elderly patients who rarely spend time outdoors.
"I use high-dose vitamin D injections, up to 800 mg daily," said Kendra Schwartz, MD, associate professor of family medicine at Wayne State University School of Medicine in Detroit. "Studies show it improves bone mineral density in patients from places without a lot of sunlight."
Proper calcium intake is also vital to the success of anti-resorptive agents. Experts point out that although physicians stress the importance of calcium intake, they don't make it clear to their patients that failure to take enough calcium while using bisphosphonates, SERMs or HRT will severely limit the drugs' effect on bone loss.
At the same time, taking supplements in the absence of drug therapies is also just a start. By themselves, calcium and vitamin D are only mildly effective in preventing bone loss.
Exercise. Patients who exercise regularly—even a little—avoid more falls (and fractures) because they have better endurance and balance.
A study in the Nov. 13, 2002, Journal of the American Medical Association showed that women who get four hours per week of even moderate exercise reduce their rate of hip fracture by 41% compared with women who are sedentary.
Hip protectors. Another proven way to avoid fractures? Pad vulnerable areas so that if a patient falls, the impact is spread out and doesn't cause a fracture.
The best way to accomplish this is through hip protectors. Studies have shown the devices drastically reduce hip fractures among compliant patients. The trick, of course, is getting patients to wear them.
"They are nearly 100% effective against hip fractures, inexpensive and very safe," said Robert R. Recker, MACP, director of the Osteoporosis Research Center at Creighton University in Omaha, Neb. "Patients argue against them because they think they will be big and bulky, but I have nurses wear them, then ask patients to tell me which nurse has one on. They can't. People get used to them very quickly."
"Most osteoporosis patients are thin to start with and the hip protector is very thin, similar to the shin guards that kids wear to play soccer," said Felicia Cosman, MD, clinical director for the National Osteoporosis Foundation. "The data are very good for the people who wear them."
You can use various imaging techniques to measure bone mineral density (BMD), a factor that is negatively correlated to fracture rates. Where patients fall on the T-scale—a measure of standard deviations below average BMD—should help guide your treatment strategy.
Robert L. Meckelnburg, FACP, a solo practitioner in Newark, Del., who specializes in osteoporosis, said that all women should have their BMD tested as soon as menopause begins, even if they are on HRT. He said that after the first test, he watches patients closely.
Because many women lose bone density even while taking hormones, Dr. Meckelnburg said, testing allows him to start women on more aggressive treatment as soon as they drop half of a standard deviation in the first few years after menopause. By testing patients early, he isn't seeing them for the first time when they are already two or three standard deviations below normal.
Felicia Cosman, MD, clinical director of the National Osteoporosis Foundation, however, argued that while testing all women's bone density at menopause would catch some cases of osteoporosis early, the cost of such widespread screening would not be worth the few cases that were caught.
Perhaps even more importantly, as you test younger women for bone loss, you identify more borderline cases, which raises questions about who to treat. Dr. Cosman said that T-scores below minus 2, for example, don't necessarily indicate the need for hormone therapy or other treatment.
"Advocating testing doesn't mean you advocate treatment," she said. "I'm not sure that patients with a BMD between minus 1 and minus 2.5 should be treated in the absence of fractures because the risk is rather low."
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