Heart Failure but Not Myocardial Infarction Is Causing Bone Loss in Rodent Models in an FGF23-Independent Manner

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 3 different experimental models of cardiac injury. Firstly, terminal myocardial in-farction was induced in adult wild-type mice by coronary ligation, followed by periph-eral quantitative computed tomography (pQCT), 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) mu-tants and VDR-deficient mice to investigate bone changes in a HF model caused by af-terload-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 es-pecially 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.