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Interaction of vascular and bone disease in patients with normal renal function and patients undergoing dialysis

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 26–33 (2007)Cite this article

Abstract

The cardiovascular risk of patients undergoing dialysis is 20–30 times higher than that of individuals of the same age, without abnormal renal function, from the general population. Observational studies of patients with normal and abnormal renal function have shown that there is an association between bone disease, vascular calcification and cardiovascular outcome and that worsening of these conditions happens in parallel. Basic science studies are elucidating several mechanisms that could explain the interaction between bone disease, vascular calcification and cardiovascular outcome. For example, the expression of osteoprotegerin—a protein that regulates bone resorption by binding receptor activator of nuclear factor κB (RANK) ligand (RANKL), thus preventing interaction with the receptor RANK and the stimulation of osteoclast maturation—is regulated by several cytokines. Additionally, osteoprotegerin seems involved in the genesis of atherosclerosis. Imbalances of bone mineral metabolism, bone matrix secretion and vascular smooth-muscle-cell apoptosis seem involved in the ossification of the arterial wall in chronic kidney disease, and could explain some of the complex interactions between bone and vascular disease in renal failure. In this article we present a brief review of some of the basic mechanisms involved in vascular calcification and the clinical evidence of an association of vascular and bone disease.

Key Points

  • Clinical, epidemiological and basic science studies indicate that arterial and bone disease are closely interconnected

  • Vascular calcification is a well established marker of arteriopathy and is associated with poor outcome in the general population as well as in dialysis patients

  • Vascular calcification, probably secondary to an active process resembling bone formation, often accompanies worsening bone density

  • An association between bone loss and increased cardiovascular risk has been documented in postmenopausal women and elderly men, and seems particularly relevant in patients with chronic kidney disease

  • In patients with chronic kidney disease, abnormalities of calcium and phosphorus metabolism, as well as use of calcium containing phosphate binders have been associated with severity and progression of arterial calcification and adverse long-term outcome

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Figure 1: The osteoprotegerin/RANK/RANKL axis of bone formation regulation.

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Authors and Affiliations

  1. and A Bellasi is a research scholar in the Division of Cardiology, P Raggi is Professor of Medicine–Cardiology and Professor of Radiology, both at Emory University School of Medicine, Atlanta, GA, USA.,

    Paolo Raggi & Antonio Bellasi

  2. C Giachelli is a professor in the Department of Bioengineering at the University of Washington, Seattle, WA.,

    Cecilia Giachelli

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  1. Paolo Raggi
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  2. Cecilia Giachelli
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  3. Antonio Bellasi
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Correspondence to Paolo Raggi.

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Competing interests

P Raggi has received honoraria and research grants from and is part of a medical advisory board for Genzyme Therapeutics, Cambridge, MA, USA.

C Giachelli is part of a medical advisory board for Genzyme Therapeutics, Cambridge, MA, USA.

A Bellasi declared he has no competing interests.

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Raggi, P., Giachelli, C. & Bellasi, A. Interaction of vascular and bone disease in patients with normal renal function and patients undergoing dialysis. Nat Rev Cardiol 4, 26–33 (2007). https://doi.org/10.1038/ncpcardio0725

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