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

Nature Reviews Endocrinology volume 8, pages 529–543 (2012)Cite this article

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Abstract

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

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Figure 1: Consequences of arterial stiffening and impaired Windkessel physiology.
Figure 2: Atherosclerotic versus medial arterial calcification.
Figure 3: Vascular osteogenic cell origins, functions and phenotypes in arterial calcification.
Figure 4: The biphasic relationship between cardiovascular disease and calciotropic hormones.
Figure 5: Age-dependent changes in cortical blood flow of long bones.
Figure 6: Clinical promises and pitfalls of the emerging bone–vascular axis.
Figure 7: Relationships between the metabolic milieu, genetics, arteriosclerosis and musculoskeletal disease.

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Acknowledgements

D. A. Towler was supported by NIH grants HL88651, HL69299, and HL81138, and the Barnes-Jewish Hospital Foundation.

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Thompson, B., Towler, D. Arterial calcification and bone physiology: role of the bone–vascular axis. Nat Rev Endocrinol 8, 529–543 (2012). https://doi.org/10.1038/nrendo.2012.36

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