Researchers at the University of Granada (UGR), Spain have shown that sclerostin, a bone formation inhibitor protein, is also protective of the cardiovascular health of patients with type 2 diabetes.
The research was conducted by the MP20-Biomarkers of Metabolic and Bone Diseases research group at the Biohealth Research Institute in Granada (ibs.GRANADA). Led by Manuel Muñoz Torres, MD, PhD, a professor of medicine at UGR, the study of 260 people included 121 controls and 139 patients with type 2 diabetes. The study authors noted that this study was the first of its kind to examine whether sclerostin, a bone formation inhibitor protein, plays a detrimental or protective role in the development of atherosclerotic process in T2D population.
The study showed that patients with both type 2 diabetes who also had heart disease had significantly higher levels of sclerostin, pointing to a potential link between the protein and atherosclerosis. Sclerostin was also demonstrated to play a beneficial role in reducing arterial calcification, which is also associated with the development of atherosclerosis. They found that sclerostin overexpression reduced calcium deposits, decreased cell proliferation and inflammation, and promoted cell survival.
“Sclerostin could play a protective role in the development of atherosclerosis in T2D patients by reducing calcium deposits, decreasing proliferation and inflammation, and promoting cell survival in VSMCs under calcifying conditions,” the researchers wrote in their study which appears in the journal Cardiovascular Diabetology. “Therefore, considering the bone-vascular axis, treatment with anti-sclerostin for bone disease should be used with caution.”
The published results were a part of the doctoral thesis of researcher Sheila González Salvatierra and raise concerns about the use of anti-sclerostin antibody treatments in patients with type 2 diabetes as this may increase cardiovascular risk in this patient population. This class of drugs is often used in treating patients with osteoporosis and other bone diseases.
The investigators noted that a broad number of previous studies has described how the elevation of serum sclerostin levels associated with cardiovascular alterations. However, the function of this protein at the vascular level had not been studied in depth.
“Our biochemical results suggest a potential beneficial role of sclerostin on (cardiovascular diseases) in type 2 diabetes patients due to its inverse association with some cardiovascular risk factors such as LDL-c, calcium, and diastolic blood pressure, which are considered the main factors contributing to susceptibility to atherosclerosis,” the team noted.
The researchers noted that while sclerostin is clinically important in vascular calcification, the exact biochemical processes that regulate the protein are not yet well understood. This suggests the need for additional research to better understand the potential protective role it plays at the vascular level.
The investigators did note some limitation of the study, namely that the cross-sectional design did not allow for the establishment of a cause and effect relationship; the study cohort was comprised of only Caucasians; and the use of common antihypertensive, antihyperlipidemic and antidiabetic drugs in patients may have influenced the results.
Nevertheless, the team believes their findings have clinical significance.
“These findings, both basic and clinical, contribute to the current understanding of the shared mechanisms between systemic bone and vascular physiology and pathology,” the researchers concluded. “Thus, our results emphasize the importance of considering the bone-vascular axis when designing therapeutic approaches for the treatment of impaired bone metabolism or vascular diseases.”
