Peritoneal dialysis per se is a risk factor for sclerostin-associated adynamic bone disease

Abstract

Chronic kidney disease--mineral bone disorder (CKD-MBD) is a complex syndrome influenced by various factors, such as age, CKD etiology, uremic toxins, and dialysis modality. Although extensively studied in hemodialysis (HD) patients, only a few studies exist for peritoneal dialysis (PD) patients. Since most of these older studies contain no bone biopsy data, we studied the pattern of renal osteodystrophy in 41 prevalent PD patients. The most common presentation was adynamic bone disease (49%). There was a significant inverse association between serum sclerostin (a Wnt/β-catenin pathway inhibitor that decreases osteoblast action and bone formation) and the bone formation rate. Bone alkaline phosphatase had the best sensitivity and specificity to detect both high- and low-turnover diseases. The comparison between nondiabetic PD and HD patients, matched by age, gender, parathyroid hormone level, and length of dialysis, revealed low 25-hydroxyvitamin D levels, worse bone mineralization, and low bone turnover in the nondiabetic PD group. Thus, adynamic bone disease was the most frequent type of renal osteodystrophy in PD patients. Sclerostin seems to participate in the pathophysiology of adynamic bone disease and bone alkaline phosphatase was the best serum marker of bone turnover in these patients.

Sclerostin and DKK1: new players in renal bone and vascular disease

“…16,31 Both serum and bone sclerostin correlate negatively with the histomorphometric parameters of bone turnover and osteoblastic number in dialysis patients. 13,28 In line with this observation, circulating sclerostin levels were found to correlate negatively with biomarkers of bone formation 31,39 and resorption. 31 High sclerostin levels may explain why persistently elevated sclerostin levels in CKD patients with mild hyperparathyroidism could eventually overcome osteitis fibrosa and lead to adynamic bone disease.…”

“…[10][11][12] Circulating Wnt signaling inhibitors may be modulated by glucocorticosteroids, but their impact is not unequivocal. 5 DKK1 and sclerostin are upregulated in diabetes 13 and by mediators of inflammation. 14 DKK1 and sclerostin expression in osteocytes are decreased during skeletal mechanical loading.…”

Biomarkers Predicting Bone Turnover in the Setting of CKD

“…Clinical data show increasing circulating sclerostin levels with progression of CKD to levels that are twofold to fourfold higher in dialysis patients compared to healthy controls [29]. Circulating sclerostin levels correlate negatively with histomorphometric parameters of bone turnover in dialysis patients [17,19]. A low circulating sclerostin was superior to a high iPTH for the negative prediction of high bone turnover; a high sclerostin level is a better predictor of non-high turnover bone than a low PTH level.…”

TGF-Beta Signaling in Bone with Chronic Kidney Disease

“…High sclerostin levels may reflect increased osteocyte numbers and skeletal mass [122,123]. Both serum and bone sclerostin levels correlate negatively with the histomorphometric parameters of bone turnover and osteoblastic number in dialysis patients [124,125]. In line with this observation, circulating sclerostin levels have been found to correlate negatively with biomarkers of bone formation [123,126] and resorption [123].…”