Sclerostin quo vadis? - is this a useful long-term mortality parameter in prevalent hemodialysis patients?

BACKGROUND/AIMS: Cardiovascular calcification contributes to the increased mortality in hemodialysis patients. Sclerostin was identified as an antianabolic bone factor causing soft tissue calcification. Data on prospective large-scale studies associating sclerostin with mortality in hemodialysis patients are so far inconsistent.

METHODS

In our multicenter prospective longitudinal study following hemodialysis patients, we assessed the associations of sclerostin and bone remodeling markers with long-term mortality. We evaluated the relationship between circulating sclerostin, Fibroblast growth factor 23 (FGF23) and traditional bone remodeling markers. Sclerostin levels in hemodialysis patients were compared with healthy controls.

RESULTS

We enrolled 239 hemodialysis patients with a median follow up of 1461 days. In Cox regression analysis, FGF23 (HR 1.40;95%CI 1.11-1.76), parathyroid hormone (PTH) (HR 1.80;95%CI 1.44-2.26) and alkaline phosphatase (AP) (HR 1.50;95%CI 1.10-2.04) per SD, 25(OH)vitamin D (HR 0.42;95%CI 0.23-0.76) per natural log but not sclerostin (HR 1.02;95%CI 0.75-1.38) per SD increase were associated with mortality. FGF23, PTH and AP were negatively associated with sclerostin. Among control and hemodialysis females, sclerostin levels were lower than in men.

CONCLUSION

Higher FGF23, PTH, AP and lower 25(OH)vitamin D but not sclerostin predict long-term mortality. Sclerostin was negatively associated with FGF23, PTH and AP and lower in females than in males.