Key result
mRNA levels of TRAP and RANK ligand were significantly elevated in calcified parts of aortic valves (5.08-fold and 8.6-fold, respectively; P<0.001), correlating with stenosis severity.
Observational (n=46)
Effect estimate: TRAP 5.08-fold increase; RANK ligand 8.6-fold increase
p-value: p=<0.001
Bone turnover mediators, specifically TRAP and Runx2/Cbfa1, correlate with the severity of aortic stenosis, suggesting a critical role of osteoclast/osteoblast activity in disease progression.
May link systemic bone metabolism to stenosis severity; leaves open causal role and need for prospective trials before clinical consideration.
BACKGROUND: Bone remodeling in calcified aortic valves is thought to originate from microfractures at multiple sites of the valve, at which osteoclasts and osteoblasts are recruited. The aim of the present study was to assess circulating mediators of bone homeostasis, correlate them to the severity of stenosis and explore the spatio-temporal distribution of bone turnover in different parts of calcified aortic valve tissue. METHODS AND RESULTS: Plasma and explanted aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery. Plasma levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear-κB (RANK) ligand and Runt-related transcription factor 2 (Runx2/Cbfa1) exhibited a significant correlation to the severity of aortic stenosis. mRNA levels in normal, thickened and calcified parts of aortic valves assessed by quantitative real-time PCR were significantly elevated in calcified parts of valves for TRAP (5.08 ± 1.6-fold, P<0.001) RANK ligand (8.6 ± 4.2-fold, P<0.001) and RANK (1.98 ± 0.78-fold, P=0.015). In an age, gender and aortic valve anatomy-adjusted multivariable regression analysis the local transcript levels of TRAP correlated significantly with echocardiographic parameters quantifying stenosis severity in early stages, whereas the expression level of Runx2/Cbfa1 was a predictor of the stenosis severity in advanced stages. CONCLUSIONS: These findings suggest a critical role of bone turnover as a determinant of aortic stenosis severity.
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Nagy et al. (2013) conducted an observational in Aortic valve stenosis (n=46). Bone turnover mediators (TRAP, RANK ligand, Runx2/Cbfa1) vs. Normal and thickened parts of aortic valves was evaluated on mRNA levels of TRAP, RANK ligand, and RANK in calcified parts of valves (TRAP 5.08-fold increase; RANK ligand 8.6-fold increase, p=<0.001). mRNA levels of TRAP and RANK ligand were significantly elevated in calcified parts of aortic valves (5.08-fold and 8.6-fold, respectively; P<0.001), correlating with stenosis severity.