Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study

Abstract

Background Sclerostin, an antagonist of the Wingless-type mouse mammary tumor virus integration site (Wnt) pathway that regulates bone metabolism, is a potential contributor of chronic kidney disease (CKD)–mineral and bone disorder (MBD), which has various forms of presentation, from osteoporosis to vascular calcification. The positive association of sclerostin with bone mineral density (BMD) has been demonstrated in CKD and hemodialysis (HD) patients but not in peritoneal dialysis (PD) patients. This study assessed the association between sclerostin and BMD in PD patients. Methods Eighty-nine PD patients were enrolled; their sera were collected for measurement of sclerostin and other CKD–MBD-related markers. BMD was also assessed simultaneously. We examined the relationship between sclerostin and each parameter through Spearman correlation analysis and by comparing group data between patients with above- and below-median sclerostin levels. Univariate and multiple logistic regression models were employed to define the most predictive of sclerostin levels in the above-median category. Results Bivariate analysis revealed that sclerostin was correlated with spine BMD ( r = 0.271, P = 0.011), spine BMD T-score ( r = 0.274, P = 0.010), spine BMD Z-score ( r = 0.237, P = 0.027), and intact parathyroid hormone (PTH; r = − 0.357, P < 0.001) after adjustments for age and sex. High BMD, old age, male sex, increased weight and height, diabetes, and high osteocalcin and uric acid levels were observed in patients with high serum sclerostin levels and an inverse relation was noticed between PTH and sclerostin. Univariate logistic regression analysis demonstrated that BMD is positively correlated with above-median sclerostin levels (odds ratio [OR] = 65.61, P = 0.002); the correlation was retained even after multivariate adjustment (OR = 121.5, P = 0.007). Conclusions For the first time, this study demonstrated a positive association between serum sclerostin levels and BMD in the PD population.

The relationship between sclerostin and carotid artery atherosclerosis in patients with stage 3–5 chronic kidney disease

“…Clinical studies have yielded inconclusive findings regarding the relationship between circulating sclerostin levels and iPTH in CKD patients. In dialysis patients, sclerostin was negatively correlated with iPTH [32,33], which may be related to the suppression of sclerostin production by osteocytes, or the decrease of bone mass in secondary hyperparathyroidism [32]. However, we did not observe a correlation between iPTH and sclerostin in CKD patients prior to dialysis, in agreement with previous reports [11,20].…”

Serum Sclerostin But Not DKK-1 Correlated with Central Arterial Stiffness in End Stage Renal Disease Patients

“…By binding to LRP5/6 or forming a tertiary complex with LRP5/6, sclerostin and DKK1, respectively, exerted their role in modulating the cross-talk of CKD-related bone disease and vasculatures with the results of vascular smooth muscle cells trans-differentiation and vascular calcification [7,11,15,31]. Thambiah et al and Kuo et al conducted studies in patients of advanced renal disease and PD and found a positive correlation between serum levels of sclerostin and bone mineral density (BMD) [31,32]. By intervention with an anti-resorptive agent, Miyaoka et al found denosumab had reno-protective effects with the reverse of the age-related decrease of eGFR by inhibiting bone resorption and suppressing seral phosphate load in non-CKD patients [33], which indicated a possible role of manipulating sclerostin toward renal or vascular protection.…”

New Insights to the Crosstalk between Vascular and Bone Tissue in Chronic Kidney Disease–Mineral and Bone Disorder

“…There is some controversy as to whether circulating Wnt inhibitors exert a direct effect on bone metabolism, partly due to the discrepancy between plasma levels of sclerostin and bone BMD. Even though sclerostin is a negative regulator of bone formation, a positive correlation between plasma levels of sclerostin and bone BMD has been reported in general population and CKD cohorts (CKD3 to CKD5 dialysis) [113][114][115][116][117][118][119][120]. These results question the role of circulating sclerostin in bone turnover and suggest that sclerostin may primarily exert paracrine signaling.…”