Systemic bone loss following myocardial infarction in mice

Area of Science:

• Cardiovascular Science
• Bone Biology
• Endocrinology

Background:

• Myocardial infarction (MI) and osteoporotic fractures are significant causes of morbidity and mortality.
• Epidemiological data suggest a link between MI and bone loss, possibly due to shared underlying mechanisms.
• The sympathetic nervous system (SNS) and beta-3 adrenergic receptors (β3-AR) are implicated in atherosclerosis progression via monocyte release, a pathway potentially involved in bone metabolism.

Purpose of the Study:

• To investigate if the SNS-mediated pathway, involving β3-AR, contributes to systemic bone loss following MI.
• To determine the effect of MI on bone mineral density (BMD), bone mineral content (BMC), and monocyte levels in mice.
• To assess the therapeutic potential of a β3-AR antagonist in mitigating MI-induced bone loss.

Main Methods:

• Myocardial infarction was induced in male mice via left anterior descending artery ligation.
• Mice were randomized to receive a β3-AR antagonist (SR 59230A) or no treatment post-MI.
• Bone parameters (BMD, BMC, microarchitecture) and circulating monocyte counts were assessed using dual-energy x-ray absorptiometry and microcomputed tomography.

Main Results:

• MI induced significant decreases in femur and lumbar spine BMD and BMC compared to controls.
• Circulating monocyte levels were elevated in MI mice.
• β3-AR antagonist treatment showed a trend towards reducing bone loss, but results were inconsistent.

Conclusions:

• Myocardial infarction leads to systemic bone loss, potentially increasing fracture risk.
• The sympathetic nervous system, specifically the β3-AR pathway, may not be the primary driver of MI-induced bone loss.
• Bone loss is a significant comorbidity following MI that warrants further clinical investigation.