Abstract
Myocardial infarction (MI) and heart failure (HF) are associated with low bone mineral density (BMD). We aimed to investigate whether MI and HF directly cause bone loss using three different experimental models of cardiac injury. Firstly, terminal myocardial infarction was induced in adult wild-type mice by coronary ligation, followed by peripheral quantitative computed tomography (pQCT) and histomorphometric and biochemical analyses at 4 and 9 weeks post-infarction. Secondly, myocardial ischemia-reperfusion injury (I/R) was performed in 4- and 9-month-old rats, followed by bone phenotyping 4 weeks after injury. Finally, transverse aortic constriction (TAC) was performed in adult wild-type mice, double Fgf23/VDR (fibroblast growth factor-23/vitamin D receptor) mutants, and VDR-deficient mice to investigate bone changes in an HF model caused by afterload-induced cardiac hypertrophy, 4 and 6 weeks after TAC. We found unchanged BMD after MI, in both the terminal ischemia model in mice and in the myocardial I/R injury model in young and aged rats. On the other hand, TAC significantly reduced especially cortical BMD in femora. Global knockout of Fgf23 in Fgf23/VDR compound mutants did not rescue the TAC-induced skeletal phenotype. Collectively, our data demonstrate that TAC-induced HF, but not MI, is causing bone loss in mice in an FGF23-independent manner.