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Relationship between Fetuin A, Vascular Calcification and Fracture Risk in Dialysis Patients
Hung Yuan Chen1,2, Yen Ling Chiu1,2, Shih Ping Hsu1,2
1Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Insights
Lower fetuin A levels and vascular calcification (VC) increase fracture risk in dialysis patients. Higher fetuin A levels are associated with fewer fractures, while VC independently predicts fracture occurrence.
Area of Science:
- Nephrology
- Bone Metabolism
- Vascular Biology
Background:
- Fractures are a significant complication in dialysis patients, worsening outcomes.
- Fetuin A plays a role in bone mineralization and inhibits vascular calcification (VC).
- The relationship between fetuin A, VC, and fracture risk in dialysis patients is not well understood.
Purpose of the Study:
- To investigate whether baseline fetuin A levels and the presence of VC predict incident major fractures in dialysis patients.
- To analyze the independent association of fetuin A and VC with fracture risk.
- To explore these associations using advanced statistical models.
Main Methods:
- Prospective observational cohort study of 685 dialysis patients.
- Median follow-up of 3.4 years.
- Assessment of baseline fetuin A levels, aortic arch calcification (VC), and major fracture incidence using Cox models and competing risk models.
Main Results:
- Higher baseline fetuin A levels were associated with a significantly lower incidence of major fractures.
- The presence of aortic arch calcification (VC) independently predicted an increased risk of fractures.
- These associations remained significant after accounting for competing risks, such as death.
Conclusions:
- Lower baseline fetuin A levels are linked to a higher risk of incident fractures in dialysis patients.
- Vascular calcification (VC) is an independent predictor of fractures in this population.
- These findings highlight potential therapeutic targets for fracture prevention 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.
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