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Serum sclerostin: the missing link in the bone-vessel cross-talk in hemodialysis patients?
S Pelletier1, C B Confavreux, J Haesebaert
1Département de Néphrologie - Bâtiment 3C, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, France, Solenne.pelletier@chu-lyon.fr.
Insights
Higher sclerostin levels and poorer bone structure are linked to severe abdominal aortic calcification (AAC) in maintenance hemodialysis (MHD) patients. Sclerostin may connect bone disease and vascular calcification in MHD.
Area of Science:
- Nephrology
- Endocrinology
- Cardiovascular Medicine
- Bone Biology
Background:
- Severe abdominal aortic calcification (AAC) is a predictor of cardiovascular mortality in maintenance hemodialysis (MHD) patients.
- In end-stage renal disease, high aortic calcification is linked to reduced bone turnover.
- Sclerostin, an inhibitor of the Wnt pathway, is implicated in bone formation and may relate to vascular calcification in MHD.
Purpose of the Study:
- To investigate the association between serum sclerostin levels and abdominal aortic calcification (AAC) in MHD patients.
- To explore the relationship between bone microarchitecture, assessed by HR-pQCT, and severe AAC in MHD patients.
- To determine if sclerostin is involved in the link between mineral and bone disorders and vascular calcification in MHD.
Main Methods:
- Fifty-three MHD patients were included in the study.
- Serum sclerostin levels were measured before dialysis sessions.
- Abdominal aortic calcification (AAC) scores were assessed using DEXA, and tibia bone status was evaluated by HR-pQCT.
- Patients were categorized into mild/no AAC (score < 6) and severe AAC (score ≥ 6) groups.
Main Results:
- Elevated serum sclerostin levels were independently associated with severe AAC (OR = 1.43 per 0.1 ng/mL increase, p=0.006).
- Poorer tibia cortical thickness was also independently associated with severe AAC (OR = 0.16 per 1 SD increase, p=0.018).
- These associations remained significant after adjusting for cardiovascular risk factors and dialysis-related confounders.
Conclusions:
- Higher serum sclerostin levels and diminished tibia cortical bone structure are positively and independently associated with severe AAC in MHD patients.
- Serum sclerostin may serve as a potential biomarker for both mineral and bone disorders and vascular risk in MHD patients.
- These findings highlight the intricate relationship between bone metabolism and vascular health in patients undergoing maintenance hemodialysis.
Unlabelled:
We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients.
Introduction:
Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients.
Methods:
Fifty-three MHD patients, aged 53 years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above).
Results:
In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1 ng/mL increase [95 % confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results.
Conclusions:
Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients.
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