Arterial calcification and bone physiology: role of the bone–vascular axis

• Published in: Nature reviews. Endocrinology Vol. 8; no. 9; pp. 529 - 543
• Main Authors: Thompson, Bithika, Towler, Dwight A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2012; Nature Publishing Group
• Subjects: 631/443/63; 692/699/2743/316; 692/699/75/593/2193; 692/700/139/422; Atherosclerosis; Atherosclerosis - epidemiology; Atherosclerosis - etiology; Blood Vessels - metabolism; Blood Vessels - physiology; Bone and Bones - metabolism; Bone and Bones - physiology; Bone marrow; Calcification; Diabetes; Endocrinology; Fractures; Health; Hormones; Humans; Medicine; Medicine & Public Health; Metabolism; Mineralization; Models, Biological; Mortality; Osteoblasts; Peripheral Arterial Disease - epidemiology; Peripheral Arterial Disease - etiology; Physiological aspects; Physiology; review-article; Signal Transduction - physiology; Vascular Calcification - epidemiology; Vascular Calcification - etiology; United States
• ISSN: 1759-5029; 1759-5037
• DOI: 10.1038/nrendo.2012.36

Arterial calcification and metabolic bone disease increasingly afflict our aging, dysmetabolic population. Clinical and translational research efforts have converged to highlight that arterial calcification is actively regulated by osteotropic signals that control skeletal physiology and development. This Review discusses the emerging role of bone-vascular interactions in mineral metabolism and the endocrine regulation of arteriosclerotic disease. Bone never forms without vascular interactions. This simple statement of fact does not adequately reflect the physiological and pharmacological implications of the relationship. The vasculature is the conduit for nutrient exchange between bone and the rest of the body. The vasculature provides the sustentacular niche for development of osteoblast progenitors and is the conduit for egress of bone marrow cell products arising, in turn, from the osteoblast-dependent haematopoietic niche. Importantly, the second most calcified structure in humans after the skeleton is the vasculature. Once considered a passive process of dead and dying cells, vascular calcification has emerged as an actively regulated form of tissue biomineralization. Skeletal morphogens and osteochondrogenic transcription factors are expressed by cells within the vessel wall, which regulates the deposition of vascular calcium. Osteotropic hormones, including parathyroid hormone, regulate both vascular and skeletal mineralization. Cellular, endocrine and metabolic signals that flow bidirectionally between the vasculature and bone are necessary for both bone health and vascular health. Dysmetabolic states including diabetes mellitus, uraemia and hyperlipidaemia perturb the bone–vascular axis, giving rise to devastating vascular and skeletal disease. A detailed understanding of bone–vascular interactions is necessary to address the unmet clinical needs of an increasingly aged and dysmetabolic population. Key Points Clinically important and actively regulated processes control tissue mineralization in the skeleton and the arterial vasculature Bidirectional communication between the vasculature and bone—conveyed by cellular, endocrine and metabolic messengers—is critical to maintenance of bone health and vascular health Dysmetabolic states, such as diabetes mellitus, uraemia and hyperlipidaemia, perturb the bone–vascular axis and give rise to vascular and skeletal disease As understanding of the bone–vascular axis continues to improves, so too will our capacity to meet the clinical needs of patients with metabolic bone and cardiovascular disorders