BRISTOL, United Kingdom — Concerning new research is highlighting potential health hazards for women who take romosozumab, a new anti-osteoporosis drug. Researchers from the University of Bristol say using the medication to treat the bone disease could lead to a heart attack.
These findings come from an analysis of a genetic dataset encompassing close to 34,000 people. While romosozumab — which is available under the brand name Evenity — does appear to be effective at reducing the risk of fracture in women with severe osteoporosis, prior studies have suggested the drug could lead to an increased risk of myocardial infarction. However, follow-up studies have produced conflicting results.
So, an international team of scientists, led by Bristol Medical School researchers, set out to determine if possessing a genetic tendency towards lower circulating levels of sclerostin (a protein expressed from bone cells that inhibits bone formation) may increase heart attack risk. Study authors explain this condition essentially mimics the effect of romosozumab, which acts to stimulate bone formation and increase bone density through the blockage of sclerostin.
“Osteoporosis commonly affects older people, particularly women, where bones become weaker and more liable to fracture. Romosozumab is a new type of drug that is highly effective at treating this condition by blocking the protein sclerostin, which is produced by bone cells and negatively impacts bone density. Administered as monthly injections, the drug helps to increase bone density and lower fracture risk,” says Jon Tobias, Professor of Rheumatology at Bristol Medical School: Translational Health Sciences at the University of Bristol, and one of the study’s lead authors.
“We wanted to predict whether romosozumab’s action in blocking sclerostin might lead to an increased risk of heart attack, by examining effects of a genetic tendency to lower levels of sclerostin, on the basis that this might reproduce some of the effects of administering the drug,” the researcher continues in a university release.
Having less sclerostin connected to over a dozen diseases
During the study, researchers made use of a scientific technique called Mendelian randomization. This approach, which utilizes genetic variants as proxies for a particular risk factor, helped study authors successfully establish if exhibiting a genetic tendency towards lower levels of sclerostin increases an individual’s risk of 15 diseases and risk factors related to atherosclerosis (hardening of the arteries). These diseases included heart attack, stroke, Type 2 diabetes, and high blood pressure.
Next, the team analyzed genetic data encompassing 33,961 European individuals to identify several genetic variants associated with lower levels of sclerostin. These analyses indicated lowering sclerostin levels could lead to a 30-percent higher chance of heart attack, in addition to an increased risk of calcification of the arteries of the heart, hypertension, and Type 2 diabetes. No effect, however, was seen regarding stroke risk. Genetic predisposition to lower sclerostin also appeared to foster lipid profiles that were more likely to cause atherosclerosis.
“Our findings suggest that individuals genetically predisposed to lower circulating levels of sclerostin have an increased risk of cardiovascular events, reinforcing the need for strategies to minimize any potential impact of treatment with sclerostin inhibitors on heart attack risk, some of which are already in place, such as avoidance in patients with previous cardiovascular problems,” Prof. Tobias concludes.
Romosozumab (Evenity) has been approved for use by the U.S. Food and Drug Administration (FDA) and other regulatory agencies in several countries.
The study is published in the journal Arthritis & Rheumatology.
The study about Evenity does not prove anything. It is a study of association, not cause and effect.