Physicians' Academy for Cardiovascular Education

The connections between vascular calcification and bone health

News - Dec. 30, 2011

The connections between vascular calcification and bone health

Jorge B. Cannata-Andia, Pablo Roman-Garcia and Keith Hruska
Nephrol Dial Transplant (2011) 26: 3429–3436

Vascular calcification, bone loss and increased fracture risk are age-associated disorders. Several epidemiological studies have suggested a relationship between vascular calcification, impaired bone metabolism and increased mortality. So far, this relationship had been under-estimated as osteoporosis and vascular calcification have been considered non-modifiable disorders of aging. Recent data suggest that this association is not simply an artefact of age, stressing that the co-incidence of vascular calcification with low bone activity and osteoporosis could be biologically linked.
During the development of vascular calcification, the transition of vascular smooth muscle cells towards an osteoblast-like phenotype promotes the release of the vesicular structures and mineralization within these structures is promoted by several players, including those related to mineral metabolism, like phosphorus, calcium or parathyroid hormone, which influence either the supersaturation within the structure or the expression of osteogenic factors. However, an intriguing question is whether the presence of vascular calcification impacts bone metabolism, thus demonstrating true crosstalk between these tissues. Evidence is now emerging, suggesting that some inhibitors of the Wnt pathway, such as secreted frizzled Proteins 2 and 4 and Dickkopf related protein-1 (DKK-1), may play a role linking vascular calcification and bone loss. An additional important question to answer, from the patient’s perspective, is whether or not progression of vascular calcification can be prevented or restricted and whether altering this progression we can efficiently impact patients’ outcomes. Much evidence suggests that the control of the chronic kidney disease–mineral and bone disorder components, particularly serum phosphorus, are the main targets to maintain normal bone turnover and protect against vascular calcification.

Promoters and inhibitors of vascular calcification. ALP, alkaline phosphatase; Ca, calcium; LDLox, oxidized low-density lipoprotein; MGP, matrix GLA protein; P, phosphorus; PTHrP, parathyroid hormone-related protein; TNF-a, tumour necrosis factor-alpha; Vit D3, calcitriol.

The active role of phosphorus in vascular calcification. Ca, calcium; Na, sodium; P, phosphorus;Pit-1, sodium-dependent phosphate co-transporter; SMC, smooth muscle cell

Authors summary

There is good evidence to suggest that impaired bone turnover, particularly low bone turnover, promotes the progression of vascular calcification. Several factors have been identified as possible links between bone and calcifying soft tissues, but a greater understanding of the key determinants of vascular calcification is still required. Maintenance of good bone health appears to be critical to maintaining good cardiovascular health in patients with CKD. Intriguingly, the original rationale for controlling serum phosphorus levels was to maintain bone health and it would appear that we have to focus again on this aspect of treatment to reduce cardiovascular mortality. Phosphate binders offer an effective approach to maintaining normal bone turnover and are likely to help to protect against vascular calcification.

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