Journal de l'ostéoporose et de l'activité physique
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Bone Metabolism in Chronic Heart Failure

Panagiotis Zotos, Elisabet Kaldara, Christos Kapelios, Vasilios Sousonis, Emmeleia Nana, Varvara Agapitou, Stavros Dimopoulos, Christos D Kontogiannis, Athanasios Chalazonitis, Zafiria Margari, Eleni Karga, John V. Terrovitis and John N. Nanas

Purpose: Chronic Heart Failure (HF) is complicated by bone loss and osteoporosis, which have been linked to hyperparathyroidism. We studied the bone metabolism and possible role of cytokines in patients suffering from HF.

Methods and results: We measured bone alkaline phosphatase (BALP), C-telopeptides of type I collagen (β-CTx) and Interleukin-(IL) 6 in 60 men, 56 ± 11 years of age, suffering from chronic HF, and in 13 age-matched men free from HF. We also measured total body and femoral bone densitometry and parathyroid hormone (PTH). The β-CTx concentrations were significantly higher in men with than in men without HF. The concentrations of BALP (12.4 ± 4.9 vs. 9.9 ± 3 μg/l; P=0.03) and β-CTx (0.67 ± 0.35 vs. 0.33 ± 0.21 ng/ml; P<0.001) were significantly higher in patients in New York Heart Association (NYHA) functional classes III or IV than in patients in classes I or II. Moderately strong correlations were observed between β-CTx, BALP, PTH and bone densitometry measurements. Positive correlations were observed between NYHA functional classes and a) mean PTH (r2=0.19; P<0.001) and b) mean β-CTx (r2=0.30; P<0.001) concentrations. Moreover, increasing serum β-CTx and BALP concentrations were correlated with measurements consistent with decreasing bone mass and increasing severity of HF. IL-6 was also correlated with β-CTx, BALP and PTH, though not with measurements of bone density. Increased serum concentrations of IL-6 were correlated with the severity of HF. β-CTx was a strong predictor of adverse clinical events (hazard ratio 6.32; 95% confidence interval 1.8-22.5; P=0.005), including after controlling for other prognostic markers of chronic HF severity and measurements of bone densitometry.

Conclusion: Chronic HF, particularly at advanced stages, was associated with an acceleration of bone turnover and uncoupling of bone formation and resorption. These changes in bone metabolism, among others, could be due to secondary hyperparathyroidism and the chronic inflammatory state associated with chronic HF. The increased osteoclastic activity observed in chronic HF was associated with a poor prognosis.