Systemic bone loss following myocardial infarction in mice

Priscilla M. Tjandra, Manali P. Paralkar, Benjamin Osipov, Yi Je Chen, Fengdong Zhao, Crystal M Ripplinger, Blaine A. Christiansen

Research output: Contribution to journalArticlepeer-review

Abstract

Myocardial infarction (MI) and osteoporotic fracture are leading causes of morbidity and mortality, and epidemiological evidence linking their incidence suggests possible crosstalk. MI can exacerbate atherosclerosis through the sympathetic nervous system (SNS) activation and β3 adrenoreceptor-mediated release of hematopoietic stem cells, leading to monocytosis. We hypothesized that this same pathway initiates systemic bone loss following MI, since osteoclasts differentiate from monocytes. In this study, MI was created with left anterior descending artery ligation in 12-week-old male mice (n = 24) randomized to β3-adrenergic receptor (AR) antagonist (SR 59230A) treatment or no treatment for 10 days postoperatively. Additional mice (n = 21, treated and untreated) served as unoperated controls. Bone mineral density (BMD), bone mineral content (BMC), and body composition were quantified at baseline and 10 days post-MI using dual-energy x-ray absorptiometry; circulating monocyte levels were quantified and the L5 vertebral body and femur were analyzed with microcomputed tomography 10 days post-MI. We found that MI led to circulating monocyte levels increases, BMD and BMC decreases at the femur and lumbar spine in MI mice (−6.9% femur BMD, −3.5% lumbar BMD), and trabecular bone volume decreases in MI mice compared with control mice. β3-AR antagonist treatment appeared to diminish the bone loss response (−5.3% femur BMD, −1.2% lumbar BMD), though these results were somewhat inconsistent. Clinical significance: These results suggest that MI leads to systemic bone loss, but that the SNS may not be a primary modulator of this response; bone loss and increased fracture risk may be important clinical comorbidities following MI or other ischemic injuries.

Original languageEnglish (US)
JournalJournal of Orthopaedic Research
DOIs
StateAccepted/In press - 2020

Keywords

  • bone loss
  • DXA
  • myocardial infarction
  • β-adrenergic receptor
  • μCT

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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