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Study provides evidence on genetic link between new osteoporosis drug and heart attack risk

Written By : Dr. Kamal Kant Kohli Published On 2023-05-10T09:30:49+05:30  |  Updated On 10 May 2023 3:00 PM IST
Study provides evidence on genetic link between new osteoporosis drug and heart attack risk
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UK: A new study published in Arthritis & Rheumatology has shed light on the potential safety concerns related to the intake of romosozumab, a new anti-osteoporosis drug.

The study, on analysing genetic data on nearly 34,000 people, revealed that lower levels of sclerostin (target of romosozumab) might raise the risk of type 2 diabetes mellitus (T2DM), hypertension, myocardial infarction (MI), and extent of coronary artery calcification (CAC), and lead to an atherogenic lipid profile.

Despite romosozumab being particularly effective at reducing the risk of fracture in women with severe osteoporosis, potential safety concerns following trial data suggest the drug may cause an increased risk of a heart attack. However, subsequent research has produced conflicting results.

An international team, led by Bristol Medical School researchers, sought to investigate whether having a genetic tendency towards lower circulating levels of sclerostin-a protein expressed from bone cells which inhibits bone formation, may increase the risk of a heart attack. They propose that this mimics the effect of giving the drug romosozumab, which stimulates bone formation and increases bone density by blocking sclerostin.

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, explained: “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 produced by bone cells and negatively impacts bone density. Administered as monthly injections, the drug helps to increase bone density and lower fracture risk.

“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 team applied a scientific technique called Mendelian randomisation. This approach, which uses genetic variants as proxies for a particular risk factor, established whether having a genetic tendency to lower levels of sclerostin in the circulation increases a person’s risk of 15 diseases and risk factors related to atherosclerosis (hardening of the arteries). These included, heart attack, stroke, type 2 diabetes and high blood pressure.

Using genetic data on 33,961 European individuals, the team identified several genetic variants associated with lower levels of sclerostin. Their analyses suggested that lowering sclerostin levels might lead to a 30 per cent increased risk of heart attack, as well as an increased risk of calcification of the arteries of the heart, hypertension and type 2 diabetes, whereas no effect was seen on stroke risk. A genetic predisposition to lower sclerostin also led to lipid profiles that were more likely to cause atherosclerosis.

Professor Jon Tobias added: “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 minimise 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.”

Reference:

Jie Zheng , Eleanor Wheeler, Maik Pietzner, Till F.M. Andlauer, Michelle S. Yau, April E. Hartley, Ben Michael Brumpton, Humaira Rasheed, John P Kemp Monika Frysz, Jamie Robinson, Sjur Reppe, Vid Prijatelj, Kaare M. Gautvik, Louise Falk, Winfried Maerz, Ingrid Gergei, Patricia A Peyser, Maryam Kavousi , Paul S. de Vries, Clint L. Miller, Maxime Bos, Sander W. van der Laan, Rajeev Malhotra, Markus Herrmann,First published: 25 April 2023 https://doi.org/10.1002/art.42538.

Arthritis & Rheumatologyromosozumabheart attackosteoporosissclerostin
Source : Arthritis & Rheumatology
Dr. Kamal Kant Kohli
Dr. Kamal Kant Kohli

Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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