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Heart Failure but Not Myocardial Infarction Is Causing Bone Loss in Rodent Models in an FGF23-Independent Manner
Svetlana Slavic1,2,3,4,5, Nejla Latic2, Norbert Hassler1
1Ludwig Boltzmann Institute of Osteology, Heinrich-Collin-Strasse 30, 1140 Vienna, Austria.
Insights
Myocardial infarction (MI) and heart failure (HF) cause bone loss, but only HF induced by transverse aortic constriction (TAC) led to reduced bone mineral density (BMD) in mice, independently of FGF23.
Area of Science:
- Cardiovascular Biology
- Bone Metabolism
- Translational Medicine
Background:
- Myocardial infarction (MI) and heart failure (HF) are linked to decreased bone mineral density (BMD).
- The direct causal relationship between cardiac injury and bone loss remains unclear.
- Investigating specific cardiac conditions and their impact on bone is crucial for understanding comorbidities.
Purpose of the Study:
- To determine if MI and HF directly induce bone loss.
- To differentiate the skeletal effects of MI versus pressure-overload HF.
- To explore the role of FGF23 in cardiac injury-induced bone changes.
Main Methods:
- Induction of terminal MI in mice via coronary ligation.
- Myocardial ischemia-reperfusion (I/R) injury in young and aged rats.
- Transverse aortic constriction (TAC) in wild-type, Fgf23/VDR double mutant, and VDR-deficient mice.
- Bone phenotyping using pQCT, histomorphometry, and biochemical analyses.
Main Results:
- MI, in both terminal ischemia and I/R models, did not alter BMD in mice or rats.
- TAC significantly reduced femoral cortical BMD in mice.
- FGF23 deficiency did not prevent TAC-induced bone loss, indicating an FGF23-independent mechanism.
Conclusions:
- Pressure-overload heart failure (HF) induced by TAC causes significant bone loss, particularly affecting cortical bone.
- Myocardial infarction (MI) does not appear to directly cause bone loss in these models.
- The bone loss associated with TAC-induced HF is independent of FGF23 signaling.
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.
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