Association Between Decreased Bone Mineral Density And Carotid Artery Calcification In The Elderly

Objective:Osteoporosis and cerebrovascular disease are common diseases of the elderly,often occur in the same individual,there are some common risk factors between them,and there may be the same pathological mechanism.Many studies have shown that bone mineral density（BMD）reduction can lead to increased incidence rate and mortality of cerebrovascular diseases.Arterial calcification is a serious manifestation of atherosclerosis and an important clinical index of cerebrovascular disease.It is worth noting that bithika Thompson published a special review on the bone vascular axis in Nature Reviews endocrinology in 2012,pointing out that some studies found that there were"osteoblast like cells"in the calcified vascular wall,suggesting that abnormal bone metabolism is related to the formation of calcified plaque in arteries.In 2017,Adrian covic published an important review on bone metabolism and arterial calcification in Lancet diabetes Endocrinol,suggesting that the disorder of bone and mineral metabolism is closely related to the occurrence of arterial calcified plaque.Therefore,the relationship between the occurrence of atherosclerotic plaques and the disorder of bone mineral metabolism is a hot issue.In the past,researches on osteoporosis and arterial calcification mainly focused on aorta,coronary artery and peripheral artery,but less on carotid artery calcification.Runt related transcription factor 2（Runx2）is a transcription factor of bone formation,which controls the physiological process of bone development and plays a key role in the differentiation and mineralization of osteoblasts.Fibroblast growth factor 23（FGF23）is a hormone derived from bone cells.It has been proved that the expression of FGF23 is increased in calcified coronary artery.The increase of serum FGF23 level can significantly increase the incidence of cardiovascular events.However,there are few studies on the relationship between Runx2 and FGF23 and carotid artery calcification.Objective to explore the relationship between the decrease of BMD and carotid artery calcification in the elderly,which is conducive to the prevention and treatment of carotid artery calcification and the reduction of stroke.Methods:（1）In the clinical study,228 elderly patients hospitalized in the Department of Neurology,the First Affiliated Hospital of Bengbu Medical College from January2019 to January 2021 were included.The clinical data and serological test indexes were collected,including the pathological data of 32 patients with carotid endarterectomy.The occurrence of carotid calcified plaques was detected by CT angiography（CTA）of the head and neck arteries.According to the results of CTA,the patients were divided into carotid non calcified plaque group and carotid calcified plaque group.BMD was measured by dual energy X-ray absorptiometry.Logistic multivariate regression risk model was used to analyze the risk factors of carotid artery calcification plaque.（2）Animal experiments,Thirty SPF grade Apo E^-/-mice were randomly selected.The carotid arteries were isolated and fixed with 4%paraformaldehyde.The carotid arteries were embedded in paraffin and sectioned.The expression of Runx2 and FGF23 was detected by immunohistochemistry.Colorimetry and enzyme linked immunosorbent assay（ELISA）was used to detect serum biomarkers of bone metabolism.Micro-CT scanning and three-dimensional reconstruction were performed on the intact femur of mice to detect the microstructure parameters of femur,including BMD,bone volume fraction（BV/TV）,trabecular number（TB.N）,structural model index（SMI）and trabecular separation（Tb.Sp）.Results:（1）Clinical studies showed that compared with the carotid non calcified plaque group,patients in the carotid calcified plaque group had older age,higher proportion of men,higher proportion of vascular risk factors,more osteoporosis and lower BMD（P<0.05 or P<0.01）.The levels of serum osteoprotegerin（OPG）,osteocalcin（OC）and C-terminal type I collagen terminal peptide（β-CTX）were higher in carotid artery calcified plaque group（P<0.05 or P<0.01）.Logistic regression analysis showed that age,male,current smoking,hypertension,diabetes and dyslipidemia,ischemic heart disease,osteoporosis and decreased BMD were closely related to the occurrence of carotid artery calcified plaque.The increase of serum OPG,OC andβ-CTX levels was closely related to the occurrence of carotid artery calcified plaque.The expression of Runx2 and FGF23 was increased in patients with carotid endarterectomy.（2）Animal experiments showed that the femoral BMD of mice with carotid artery calcification by Von Kossa staining was decreased by Micro-CT scanning.Immunohistochemistry showed that the expression levels of Runx2 and FGF23 were increased in carotid calcification mice.Conclusion:Clinical and experimental studies have proved that there is a significant correlation between the decrease of BMD and the occurrence of carotid artery calcification.The elevated levels of OPG,OC and CTX are closely related to the occurrence of carotid artery calcification.The expression of Runx2 and FGF23increased in the vascular tissues of patients with carotid artery calcification and mice with carotid artery calcification,suggesting that Runx2 and FGF23 are involved in the regulation of intravascular calcium deposition.