Statins Associated With a Higher — or Lower — Risk of Osteoporosis, Depending on the Dose Everyday Health MenuNewslettersSearch Osteoporosis News Statins Are Associated With a Higher — or Lower — Risk of Osteoporosis Depending on the DoseA new study finds that low daily doses of these cholesterol-lowering medications are associated with lower osteoporosis risk, while higher doses are associated with higher risk. By Don RaufOctober 4, 2019Everyday Health ArchiveFact-CheckedThe effect of statins on bone health may depend on the dose.iStockThe observation that statins can stimulate bone formation was first made at least 20 years ago. In 1999, for example, researchers reported in Science that two statins increased bone formation and bone volume in mice and rats. Later studies confirmed the effect in humans, including a systematic review and meta-analysis published in January 2017 in Osteoporosis International, which found the use of statins is associated with increased bone mineral density in the hip area and lumbar spine. Now a study published September 26 in the Annals of the Rheumatic Diseases suggests that while lower doses of statins may help prevent osteoporosis — a condition in which bones become less dense and, consequently, more likely to break — taking too much may actually impair bone health. An analysis of health records from about 8 million Austrian adults revealed fewer cases of osteoporosis among those taking up to 10 milligrams daily of the statins lovastatin, pravastatin, simvastatin, or rosuvastatin compared with those not taking statins. But scientists found that the trend reversed for those taking statins in daily doses of 20 milligrams or more, and the higher the dosage, the stronger this effect. “We were able to demonstrate a high risk of being diagnosed with osteoporosis under high-dose statin treatment, whereas low dosages of statins were associated with a lower risk of osteoporosis,” says the lead investigator, Michael Leutner, MD, a doctoral student in the clinical department of endocrinology and metabolism at the Medical University of Vienna in Austria. More specifically, people who were taking 0 to 10 milligrams of simvastatin daily had a 30 percent lower risk of being diagnosed with osteoporosis when compared with people not taking statins. On the other hand, people taking 40 to 60 milligrams of simvastatin a day had a 64 percent higher risk of being diagnosed with osteoporosis when compared with non-statin users, and those taking 60 to 80 milligrams a day had a 230 percent higher risk. Results were similar for the other statins. Cholesterol s Effect on Sex Hormones May Play a Role Exactly how statins exert their effects on bones is not completely known. “In mouse models and in vitro studies [lab studies using human cells], statins have been shown to enhance bone formation, for example by increasing the expression of bone morphogenic protein (BMP2), which is an osteoprotective protein,” says one of the study's coauthors, Alexandra Kautzky-Willer, MD, the head of the gender medicine unit and the university course of gender medicine at the Medical University of Vienna. The researchers speculate that statins — by lowering the body’s cholesterol production — could affect levels of sexual hormones and therefore impact osteoporosis. Cholesterol is a basic building block for the production of estrogen hormones and testosterone. “In higher dosages, the possible inhibiting effect of statins on sex hormones could overrule the osteoprotective effect,” says Dr. Kautzky-Willer. The study authors point out that the risk of osteoporosis, including a higher risk of bone fractures, is especially high in post-menopausal women. Indeed, according to the Centers for Disease Control and Prevention, 1 in 4 American women over age 65 has osteoporosis, while 1 in 20 American men over 65 has the condition. “Due to the osteoprotective effect of estrogens, the decline in sex hormones in post-menopausal women is an important and major risk factor for osteoporosis,” says Dr. Leutner. Lower levels of testosterone in men have also been associated with lower bone mineral density. Study authors point out that women taking 0 to 10 milligrams of simvastatin had a 26 percent lower risk of being diagnosed with osteoporosis when compared with nonusers. Those taking a higher amount, of 60 to 80 milligrams, had a 272 percent higher risk. For men, those taking 0 to 10 milligrams of simvastatin had a 42 percent lower risk of being diagnosed with osteoporosis when compared with nonusers, but a 254 percent higher risk when taking 60 to 80 milligrams of the medication. What if You Currently Take Statins Statins have a proven track record in reducing the risk of heart attacks, stroke and other cardiovascular events by lowering high cholesterol levels, according to the American Heart Association. When blood levels of “bad” cholesterol (low-density lipoprotein, or LDL) increase, fatty deposits can build up in the arteries, which can reduce or block blood flow to the heart. Connie Newman, MD, an adjunct professor of medicine in the division of endocrinology, diabetes, and metabolism at New York University School of Medicine in New York City, and the president of the American Medical Women's Association, cautions that this study should not discourage people from taking the potentially lifesaving medications. “Patients should continue statin therapy to lower cholesterol and reduce their risk of cardiovascular disease,” says Dr. Newman, who was not involved in this research. “This applies to all patients, including those with osteoporosis and those at increased risk of osteoporosis.” Newman notes that the study was observational rather than a randomized controlled trial. That’s to say, the scientists based their results on a statistical analysis of health data of more than 7.9 million adults from 2006 and 2007 to measure the rate of the diagnosis of osteoporosis in statin users compared with a control group consisting of non–statin users. “Observational studies are subject to numerous biases that could confound the results, and cannot make valid conclusions about cause and effect,” says Newman. “In short, the proper interpretation of these data is critical to avoid misleading doctors and the public. My advice to all patients is to reassure them that statins — at low or high doses — have not been shown to cause osteoporosis.” More Studies Needed to Clarify the Relationship Between Statins and Osteoporosis The Medical University of Vienna research team plans further prospective studies to explore the relationship between statins and osteoporosis. “We propose that monitoring high-risk patients, that is, post-menopausal female patients under high-dosage statin therapy, might be useful to offer an individual therapy to prevent or treat osteoporosis,” the study authors wrote. “Thus, larger and prospective studies with a focus on dosages of statins should be conducted to clarify the relationship with osteoporosis.” NEWSLETTERS Sign up for our Chronic Pain Newsletter SubscribeBy subscribing you agree to the Terms of Use and Privacy Policy. 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