Low bone turnover is associated with plain X-ray vascular calcification in predialysis patients

Abstract

Background Vascular calcification (VC) is a common finding in chronic kidney disease (CKD) patients and predicts subsequent cardiovascular morbidity and mortality in this population. Vascular calcification is linked to disordered mineral metabolism and has been associated with bone histomorphometry changes in CKD. However, data on predialysis patients is scarce. Methods A cross-sectional study was conducted on a cohort of 56 CKD patients not yet on dialysis, who underwent a transiliac bone biopsy for histomorphometric evaluation after double tetracycline labeling. Patients had no previous exposure to calcium salts, vitamin D agents, steroids or bisphosphonates. Vascular calcification was assessed at the time of biopsy, using Kauppila (plain X-ray of the lateral lumbar spine) and Adragão (plain X-ray of the pelvis and hands) scores. Results Vascular calcification was seen in two-thirds of the cohort. Subjects with VC were more likely to be male and have diabetes, and had significantly higher sclerostin and osteoprotegerin circulating levels than those without VC. The histomorphometric analysis showed that bone formation rate was significantly lower in VC compared to non-VC patients. In the multivariable logistic regression analysis, bone formation rate was independently associated with the presence of VC. Conclusions Vascular calcification is highly prevalent in predialysis patients, especially in those with diabetes. The independent association between bone formation rate and VC provides evidence of an important interaction between bone and vessel in CKD. Our results suggest that low bone turnover is a non-traditional risk factor for cardiovascular disease in predialysis patients.

Current and Emerging Markers and Tools Used in the Diagnosis and Management of Chronic Kidney Disease–Mineral and Bone Disorder in Non-Dialysis Adult Patients

“…This is supported by two recent studies in stage 3 and 4 CKD, which identified a link between high sclerostin levels and low rates of bone turnover with a corresponding increase in VC [90,150]. The independent association between VC and the rate of bone formation highlights evidence of a key interplay between bone and the cardiovascular system in patients with CKD [90].…”

“…The association with VC may be important, as outlined in a further study demonstrating that serum sclerostin levels correspond with an increased risk of both fatal and non-fatal cardiovascular events in a non-dialysis CKD population, even after multiple statistical adjustments [156]. This is supported by two recent studies in stage 3 and 4 CKD, which identified a link between high sclerostin levels and low rates of bone turnover with a corresponding increase in VC [90,150]. The independent association between VC and the rate of bone formation highlights evidence of a key interplay between bone and the cardiovascular system in patients with CKD [90].…”

“…Recently, a small study utilizing a plain X-ray of the lumbar spine, pelvis, and hands to assess VC reported that bone formation rate was significantly lower in patients with VC than patients without VC. This was the first study reporting a relationship between the histomorphometric qualities of bone and simple VC scores in non-dialysis patients [90].…”

Chronic Kidney Disease with Mineral Bone Disorder and Vascular Calcification: An Overview

“…Elevated sclerostin levels correlate with cardiovascular events, both fatal and non-fatal [ 144 ]. This association underscores the interplay between altered bone turnover and the development of vascular calcification [ 145 ].…”

Is Adynamic Bone Always a Disease? Lessons from Patients with Chronic Kidney Disease

“…The small sample size ( n = 41), the use of a semiquantitative method to evaluate VC (Kaupilla score), and the relatively low prevalence of VC (24.3%) may, at least partially, explain this unexpected result. In pre-dialysis patients, low bone-formation rate has been independently associated with VC, evaluated either by CT or by plain X-ray [ 4 , 87 ].…”