Relationship between Fetuin A, Vascular Calcification and Fracture Risk in Dialysis Patients

BACKGROUND: Fractures are a common morbidity that lead to worse outcomes in dialysis patients. Fetuin A inhibits vascular calcification (VC), potentially promotes bone mineralization and its level positively correlates with bone mineral density in the general population. On the other hand, the presence of VC is associated with low bone volume in dialysis patients. Whether the fetuin A level and VC can predict the occurrence of fractures in dialysis patients remains unknown. METHODS: We performed this prospective, observational cohort study including 685 dialysis patients (629 hemodialysis and 56 peritoneal dialysis) from a single center in Taiwan for a median follow-up period of 3.4 years. The baseline fetuin A level and status of presence of aortic arch calcification (VC) and incidence of major fractures (hip, pelvis, humerus, proximal forearm, lower leg or vertebrae) were assessed using adjusted Cox proportional hazards models, recursive partitioning analysis and competing risk models. RESULTS: Overall, 177 of the patients had major fractures. The incidence rate of major fractures was 3.29 per 100 person-years. In adjusted analyses, the patients with higher baseline fetuin A levels had a lower incidence of fractures (adjusted hazard ratio (HR), 0.3; 95% CI, 0.18‒0.5, fetuin A tertile 3 vs. tertile 1 and HR, 0.52; 95% CI, 0.34‒0.78, tertile 2 vs. tertile 1). The presence of aortic arch calcification (VC) independently predicted the occurrence of fractures (adjusted HR, 1.95; 95% CI, 1.34‒2.84) as well. When accounting for death as an event in competing risk models, the patients with higher baseline fetuin A levels remained to have a lower incidence of fractures (SHR, 0.31; 95% CI, 0.17‒0.56, fetuin A tertile 3 vs. tertile 1 and 0.51; 95% CI, 0.32‒0.81, tertile 2 vs. tertile 1). INTERPRETATIONS: Lower baseline fetuin A levels and the presence of VC were independently linked to higher risk of incident fractures in prevalent dialysis patients.