Editors' ChoiceHEART ATTACK

Getting to the heart of bone loss

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Science Translational Medicine  14 Oct 2020:
Vol. 12, Issue 565, eabe8125
DOI: 10.1126/scitranslmed.abe8125

Abstract

Heart attack leads to systemic bone loss in mice, indicating fracture risk as a clinical comorbidity of heart attack.

After a heart attack (myocardial infarction), changes occur throughout the body that perpetuate the development of other comorbidities. Many of these changes are coordinated by the immune system’s response to the original injury. Comorbidities include, for example, the development of insulin resistance and the exacerbation of preexisting atherosclerosis. Epidemiological evidence suggests there is a strong link between heart attack and later bone fracture; yet, it remains unknown whether the correlation is the result of a single pathology underlying both events or whether heart attack can initiate bone loss and thereby increase the risk of fracture.

Here, Tjandra et al. sought to determine whether myocardial infarction (MI) leads to acute systemic bone loss and further investigated a potential mechanistic role of monocytosis (an increase in the number of circulating monocytes that results from tissue injury). Nine days after surgically induced MI in mice, measures of bone mineral density (BMD) and bone mineral content (BMC) across the whole body revealed only moderate reductions relative to uninfarcted controls. Closer scrutiny of the femur and lumbar spine, however, was more conclusive: both regions demonstrated a significant reduction in BMD and BMC. Further analysis of the bone structure revealed a tendency for MI to reduce the trabecular bone fraction, trabecular thickness, and overall bone area. However, these trends were not significant, and minimal differences in the mechanical properties of the bone were identified by mechanical analysis. Bone resorption is controlled by osteoclasts, which are both derived from and potentially activated by cells of the monocyte lineage. The authors therefore investigated the potential for an established β3-adrenergic receptor antagonist to mitigate bone loss, by blocking the sympathetic nervous system signaling responsible for monocytosis. The drug tended to mitigate losses in BMD and BMC, but results were not corroborated by structural analysis and increased circulating neutrophil and monocyte counts were observed. Given these inconsistencies, a conclusive role for sympathetic nervous system-initiated monocytosis could not be determined, and the underlying mechanism of bone loss therefore remains unclear.

Systems biology approaches continue to reveal interesting and clinically impactful connections that further our understanding of disease progression. Although the investigations in this paper were limited to mouse models, they provide the first direct evidence that acute cardiac injury can precipitate systemic skeletal remodeling. Further understanding of the mechanisms that underlie ischemic injury comorbidities, including bone loss and insulin resistance, is a critical step in the development of prophylactic therapies that can interrupt the progression of these secondary conditions.

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