Association between bone mineral metabolism and vascular calcification in end-stage renal disease

Abstract

Background Development of vascular calcification is accelerated in patients with end-stage renal disease. In addition to traditional risk factors of cardiovascular disease (CVD) abnormal bone and mineral metabolism together with many other factors contribute to the excess cardiovascular burden in patients on dialysis. Aortic calcification score and coronary calcification score are predictive of CVD and mortality. The aim of this study was to evaluate the possible relationship between arterial calcification and bone metabolism. Methods Thirty two patients on dialysis were included. All patients underwent a bone biopsy to assess bone histomorphometry and a 18F-NaF PET scan. Fluoride activity was measured in the lumbar spine (L1 – L4) and at the anterior iliac crest. Arterial calcification scores were assessed by computerized tomography for quantification of coronary artery calcification score and lateral lumbar radiography for aortic calcification score. Results This study group showed high prevalence of arterial calcification and 59% had verified CVD. Both CAC and AAC were significantly higher in patients with verified CVD. Only 22% had low turnover bone disease. There was a weak association between fluoride activity, which reflects bone turnover, measured in the lumbar spine, and CAC and between PTH and CAC. There was also a weak association between erosion surfaces and AAC. No significant association was found between calcification score and any other parameter measured. Conclusions The results in this study highlight the complexity, when evaluating the link between bone remodeling and vascular calcification in patients with multiple comorbidities and extensive atherosclerosis. Several studies suggest an impact of bone turnover on development of arterial calcification and there is some evidence of reduced progression of vascular calcification with improvement in bone status. The present study indicates an association between vascular calcification and bone turnover, even though many parameters of bone turnover failed to show significance. In the presence of multiple other factors contributing to the development of calcification, the impact of bone remodeling might be diminished. Trial registration The study is registered in ClinicalTrials.gov protocol registration and result system, ID is NCT02967042. Date of registration is 17/11/2016.

Management of fracture risk in CKD—traditional and novel approaches

“…Moreover, 18 F-NaF uptake in the arterial wall correlates with risk factors for atherosclerosis [ 56 ]. A recent study demonstrated independent positive associations between 18 F-NaF uptake in bone, histomorphometric parameters of bone turnover in bone biopsies and arterial calcification in end-stage renal disease patients [ 57 ], in line with a previous study of bone biopsy-based histomorphometric parameters of bone turnover and coronary calcification in dialysis patients [ 58 ].…”

NaF-PET Imaging of Atherosclerosis Burden

“…Forty-five articles were included in this review [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] ( Figure 1 ), to which were added selected articles on methodological and other aspects. Findings in the articles are summarized in the following sections and in Tables S1–S6 in the Supplementary Material .…”

“…Several studies dealt with one arterial bed only, i.e., coronary arteries [ 16 , 17 , 18 , 20 , 29 , 30 , 31 , 38 , 39 , 44 ], global heart [ 22 , 23 , 24 , 25 , 27 , 34 ], pulmonary arteries [ 11 ], left carotid artery [ 28 ], aorta [ 26 , 32 , 41 , 42 , 48 , 49 ], abdominal aorta [ 13 , 33 , 45 ], or several arterial beds [ 5 , 6 , 7 , 8 , 9 , 10 , 12 , 14 , 15 , 21 , 35 , 36 , 37 , 40 , 41 , 43 , 46 , 47 ]. Eight reports were experimental animal studies [ 5 , 6 , 32 , 42 , 43 , 45 , 48 , 49 ], and one was an image case report [ 44 <...…”

“…FDG and NaF uptake did not correlate in any arterial segment. Lastly, in dialysis patients with co-morbidities and many co-factors, Aaltonen et al [ 8 ] observed a weak association between lumbar spine turnover mirrored by NaF activity and coronary calcification and between parathyroid hormone and coronary calcification. However, arterial wall calcification in PXE and dialysis patients is typically medical calcinosis, which may not follow the same NaF uptake mechanism as endothelial microcalcification.…”

Serum OPG and RANKL Levels as Risk Factors for the Development of Cardiovascular Calcifications in End-Stage Renal Disease Patients in Hemodialysis

“…Several studies suggest an association between bone mineral metabolism and vascular calcifications in CKD patients and an impact of bone turnover on their development [ 34 ]. There is also evidence of the reduced progression of VCs after the improvement in bone status [ 35 ].…”