Dynamics of Bone Turnover Markers in Patients with Heart Failure and Following Haemodynamic Improvement Through Ventricular Assist Device Implantation

AIMS: Abnormal bone metabolism and progressive demineralization have been described in patients with heart failure (HF). We hypothesized that mechanical unloading through implantation of a ventricular assist device (VAD) with subsequent haemodynamic improvement would correct abnormal bone metabolism in patients with advanced HF. METHODS AND RESULTS: Serum was collected from 14 controls, 20 patients with moderate HF, 34 patients with advanced HF undergoing VAD implantation, and 34 patients at the time of VAD explantation (mean duration: 169 ± 125 days). Bone metabolism markers were measured using enzyme-linked immunosorption assay (ELISA) or chemiluminescence immunoassay (CLIA). Compared with controls, HF patients showed increased parathyroid hormone (PTH: 42 ± 19 vs. 117 ± 117 pg/mL in HF; P < 0.02) with decreased 25-hydroxyvitamin D [25(OH)D: 29 ± 14 vs. 21 ± 11 ng/mL in HF; P = 0.05]. While procollagen-1 N-terminal peptide (P1NP) and osteocalcin were similar, cross-linked C- and N-telopeptides of type I collagen (CTX and NTX) were both higher in HF (NTX: 14 ± 6 vs. 20 ± 11 ng/mL; P < 0.05; CTX: 0.35 ± 0.13 vs. 1.05 ± 0.78 ng/mL; P < 0.01 for controls and HF, respectively). P1NP increased markedly after VAD implantation (49 ± 37 vs. 121 ± 62 ng/mL; P < 0.0001), with a mild decrease in CTX and NTX levels indicating a shift towards anabolic bone formation. Serum PTH correlated with estimated glomerular filtration rate (r = -0.245, P < 0.05). CONCLUSION: Patients with advanced HF are characterized by increased levels of biochemical markers of bone resorption potentially as a result of secondary hyperparathyroidism and uncoupling of bone remodelling. Haemodynamic improvement and mechanical unloading after VAD implantation lead to correction of bone metabolism and increased levels of anabolic bone formation markers.