Bone–Vascular Axis in Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is characterized by changes in mineral metabolism associated with alterations of its hormonal regulation and various forms of bone disease. In the past, these associations focused attention on the kidney–bone axis. The last decade has seen renewed interest on interactions among mineral metabolism disorders and extraosseous and cardiovascular calcifications observed in CKD or end-stage renal disease (ESRD). Vascular calcification is an active process similar to bone formation that implicates a variety of proteins involved in bone and mineral metabolism (1,2) and is considered part of a systemic dysfunction defined as CKD–mineral and bone disorder (3). Growing evidence linking bone with different functional and structural characteristics of the arterial tree has contributed to developing the concept of the bone–vascular axis (4). The first observations suggesting the existence of the bone–vascular axis were the frequent associations of osteoporosis and atherosclerotic vascular calcifications observed in postmenopausal women (5–7). Longitudinal population-based studies revealed a relationship between the progression of vascular calcifications and bone demineralization, and others were identified between bone mineral density (BMD) and aortic or central artery calcifications (6), or coronary arteries in type 2 diabetes (8). The osteopenia–osteoporosis association was also linked with arterial functional indexes, such as aortic stiffness and interactions independent of calcifications, suggesting broader biologic interplay (9,10). Relationships between bone and vascular modifications were also observed in CKD and ESRD patients. In dialysis patients, coronary artery calcification score was found to be inversely correlated with vertebral bone mass (11,12). In addition, a high systemic arterial calcification score combined with bone histomorphometry suggestive of low bone activity was observed in hemodialysis patients (13,14). Arterial stiffening and low spine BMD or calcaneal osteopenia were significantly associated in CKD and hemodialysis patients (15–17). …