Bone–Vascular Axis in Chronic Kidney Disease

Abstract

C hronic 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 bonevascular 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)(16)(17).In the present issue of the Journal, Adragao et al. (18) provide new evidence linking altered bone metabolism to coronary calcifications in patients with stage-5 CKD on hemodialysis. In their cross-sectional study performed on 38 hemodialyzed patients, they analyzed the relationships between bone biopsy parameters (bone volume/total volume, bone formation rate/ bone surface, and activation frequency) and coronary calcifications determined by multislide computer tomography. Their principal conclusion was that low bone volume is associated with more coronary calcifications, whereas histomorphometric parameters of bone turnover were independent of coronary calcifications.Their results complete those of Barreto et al. (12), who found a negative correlation between coronary calcifications and trabecular bone volume or its thickness. The absence of correlations between histomorphometric indexes of bone turnover and coronary calcifications dif...

MICS, an easily ignored contributor to arterial calcification in CKD patients

“…Both of these conditions will cause bone loss and increase the possibility of AC (60). The evidence suggests the existence of a bone-vascular axis, and vascular mineralization coexists paradoxically with bone demineralization (21,58). MICS is found to play a key role in activating this axis and inducing AC.…”

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

“…Thus, the old well known relationship between kidney disease and bone ("renal osteodystrophy") is now extended to a new bone-vascular axis (23,26), and bone has even been recently considered as a new endocrine organ at the heart of CKD-MBD (27).…”

Osteoporosis in mineral and bone disorders of chronic kidney disease

“…26 It has been long recognized that CKD-MBD (formerly referred to as renal osteodystrophy) has a significant impact on vascular calcification. London et al 27 demonstrated that arterial pulse wave velocity and aortic calcification are increased in CKD patients with decreased bone turnover, namely, in those who do not easily incorporate minerals into the bone, but also do not release them from the skeleton (clinical entity known as adynamic bone disease, usually characterized by low or low-normal PTH levels). 27 The search for correlations between such parameters of mineral metabolism as alkaline phosphatase, bone-specific alkaline phosphatase, PTH, calcium and phosphate, BMD, and vascular calcification in CKD has provided no firm conclusions so far.…”

“…London et al 27 demonstrated that arterial pulse wave velocity and aortic calcification are increased in CKD patients with decreased bone turnover, namely, in those who do not easily incorporate minerals into the bone, but also do not release them from the skeleton (clinical entity known as adynamic bone disease, usually characterized by low or low-normal PTH levels). 27 The search for correlations between such parameters of mineral metabolism as alkaline phosphatase, bone-specific alkaline phosphatase, PTH, calcium and phosphate, BMD, and vascular calcification in CKD has provided no firm conclusions so far. It is generally acknowledged, however, that low PTH levels, low alkaline phosphatase activity, and low BMD (indices of low bone turnover) are associated with more extensive vascular calcification.…”

“…It is generally acknowledged, however, that low PTH levels, low alkaline phosphatase activity, and low BMD (indices of low bone turnover) are associated with more extensive vascular calcification. [27][28][29][30][31][32][33] Osteoporosis or other clinical conditions with increased calcium and phosphate mobilization from the skeleton result in hypercalciuria and phosphaturia in patients with healthy kidneys (and may eventually contribute to the formation of renal stones). In subjects with CKD, the kidneys are no longer a "safety valve" for increased amounts of calcium and phosphate.…”