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Update From the Medical Journals: January 2007
January 30, 2007  By Mary Pickett, M.D.
Harvard Medical School What's the latest news in the medical journals this month? Find out what your doctor is reading. Anti-Acids and Antidepressants May Promote Bone Fractures The health of your bones is affected by a variety of hormones and by your nutrition. Researchers have suspected that subtle side effects from a few common medicines might gradually weaken your bones if you use them long-term. Two studies now validate these concerns. They reveal that bones are more likely to fracture in older adults who consistently use a certain type of strong anti-acid medicine or certain antidepressants. The first study was published December 27 in the Journal of the American Medical Association (JAMA). Stomach acid helps you absorb calcium from food so bones stay strong. Researchers from the University of Pennsylvania wanted to know whether bone fractures were more common in anti-acid users. Using a database of patient information from the United Kingdom, they identified a group of about 13,500 adults over age 50 who all had hip fractures between 1987 and 2003. They compared the medicines taken by these people to the medicines that were taken by a "control group," — a much larger group of patients who had similar ages and backgrounds but no history of fractures. Potent anti-acid medicines called proton pump inhibitors (PPIs) appeared more frequently on medicine lists for people in the fracture group than in the group without fractures. The researchers found that people who used PPI medicines for more than a year had 44% more fractures in their group compared with the group of non-users. The risk was highest for people who took higher doses of PPI drugs. The commonly used drugs in this class are omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), lansoprazole (Prevacid), and rabeprazole (Aciphex). The second study, published in the January 22 issue of the Archives of Internal Medicine, found a connection between the use of antidepressants called selective serotonin reuptake inhibitors (SSRIs) and fractures. The SSRI drug group includes fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro), among others. Researchers followed 5,008 adults over age 50 for five years. Out of this large group, 137 people used SSRI antidepressants on a daily basis. Among SSRI users, there were 13 fractures during the five years of study, which was twice the number of fractures among the non-users of antidepressants. At the end of the study, bone density for SSRI users was 2.4% lower in the spine and 4% lower in the hip, on average. It's not clear whether the fracture risk was increased as a result of taking the drug or because depression itself could lead to inactivity, which is harmful to bones. Still, it's troubling. The hormone serotonin is a key player in our brain chemistry. It also plays a role in bone build-up and bone breakdown, a process called remodeling. Increased serotonin in the body might cause bones to remodel in a way that makes them more prone to fracture. Falls were also more frequent among the SSRI users, and that may have added to the problem. These two studies raise concerns about long-term anti-acid use and long-term antidepressant use in adults over 50. Although these medicines are very useful, they should not be continued for more time than is necessary. Back to top Two Parkinson's Drugs Can Cause Heart Valve Damage Pergolide (Permax) and cabergoline (Dostinex) are drugs that are occasionally used to treat Parkinson’s disease or insomnia caused by restless legs syndrome. A study in the January 4 issue of the New England Journal of Medicine revealed that these drugs damage heart valves in roughly one out of four users, although other Parkinson’s drugs do not. Pharmacy experts worry that similar side effects might be seen with some related medicines which are used to treat migraine headaches. Damaged valves can contribute to heart failure or rhythm changes, and severely damaged valves may need surgical repair. You might not think about heart valves as vulnerable structures, but certain substances in your bloodstream can cause them to accumulate deposits that cause them to stiffen or deform. Researchers first became aware of this after seeing complications in people taking the combination weight-loss drug Phen-Fen (phentermine and fenfluramine). Fenfluramine was taken off the market when it was found to cause damage to heart valves. The two Parkinson's drugs that are now being linked to heart valve damage have a similar chemical effect to fenfluramine, and so do "ergot" migraine medicines (Cafergot, dihydroergotamine, Migranal, DHE). These medicines trigger a serotonin receptor that is found on the surface of heart valve cells, the serotonin "2B" receptor (also called 5-HT2B receptor). Researchers suspect that stimulation of this receptor is the root cause of the heart valve damage, but additional research will need to confirm this. In the meantime, cautious doctors will avoid these medicines if there are other acceptable treatment options for patients. It will be important to test all newly developed drugs with serotonin effect to see if they stimulate the "2B" receptor. ALERT on April 2, 2007: The FDA has urged manufacturers of pergolide drug products to voluntarily remove these drugs from the market. The manufacturers have complied. Patients currently taking the drug should NOT stop the drug until they have talked to their doctors. Alternative drugs that don't carry risk of heart valve damage and should work as well as pergolide are available. Back to top More News in Brief - Dense Breasts On Mammograms Mean Higher Risk For Breast Cancer. Mammograms find breast cancers. Now they can also help identify women who are at high risk for cancer, according to a study in the January 18 issue of the New England Journal of Medicine. This might allow high risk women to get more intensive screening tests. Researchers examined more than a thousand pairs of mammograms. In each pair, one mammogram was from a woman who had breast cancer and the other was from a woman who was matched by age, but did not have cancer. Cancer patients were more likely to have very dense breasts. This type of study, known as a "case-control" study, allows researchers to calculate breast cancer risk. The data showed that women with dense breast tissue across more than half of the area of their mammogram are about 17 times more likely to develop a cancer, compared with other women. This risk factor had not been previously known. Dense breasts may be responsible for as many as 26% of all breast cancers that occur. Women who have dense breasts seen on mammograms will benefit from extra screening tests, such as breast MRI, ultrasound, or digital mammography.
- Blood Test Can Identify Patients at Highest Risk for Heart Disease. In the January 10 issue of the Journal of the American Medical Association (JAMA), a study tracked the health of nearly 1,000 people with coronary artery disease. At the beginning of the study, a blood test was used to measure a specific protein named NT-proBNP. This protein appears in the blood when the heart muscle is uncomfortably pressured or stretched. After following the patients for an average tracking time of 3.7 years, the researchers could see that people who started with a high level of NT-proBNP were, as a group, more likely to develop a heart attack, stroke, or heart failure. This blood test is a new tool that will help doctors predict which patients with coronary artery disease need to be the most concerned about their heart disease and overall health. As this test becomes more widely available, people with a high NT-proBNP level might be advised to seek bypass surgery sooner or to take a more intensive combination of medications to protect the heart.
- Pregnant Women of Any Age Should Be Offered Down Syndrome Screening. In the January issue of Obstetrics & Gynecology, the American College of Obstetricians and Gynecologists published a revised recommendation for Down syndrome testing. Down syndrome is one of the most common genetic birth defects and can result in congenital heart defects, mental retardation, problems with vision and hearing, and other health problems. Now, instead of just offering testing to pregnant women over age 35 who have the highest risk for having a Down syndrome baby, the group is recommending that pregnant women of all ages be offered the tests. The main reason for this change is that testing has become easier. Previously, screening for the chromosome abnormality that causes Down syndrome was by amniocentesis, a procedure that removed a small amount of amniotic fluid by inserting a needle through the stomach into the uterus. Blood tests called the "triple screen" have been used in the second trimester of pregnancy as a pre-test for amniocentesis, to limit the number of women who need amniocentesis. For the past year, screening during the first trimester has been done with ultrasound and blood tests. These tests can identify at least 85% of Down syndrome babies. Amniocentesis is still used to verify true Down syndrome in pregnancy for women with suspicious test results, but most women can be comfortably reassured by the blood tests and ultrasound.
Back to top Mary Pickett, M.D., is a lecturer for Harvard Medical School and an assistant professor of medicine at Oregon Health & Science University. At OHSU, she is a director of student programs and she oversees teaching of students and medical residents. She practices general internal medicine in Portland, Ore.
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