Is calcium a link between inflammatory bone resorption and heart disease?

eLife, 2022 · DOI: https://doi.org/10.7554/eLife.83841 · Published: December 29, 2022

Cardiovascular Science Endocrinology Genetics

Simple Explanation

Epidemiological studies suggest a link between conditions causing bone resorption, like osteoporosis and spinal cord injury, and increased risk of heart disease. These conditions are associated with inflammation. Children and adolescents possess a protective mechanism: their bodies respond to inflammation by upregulating a calcium-sensing receptor (CaSR), leading to lower blood calcium levels and increased calcium excretion. This may reduce cardiovascular risks. Adults with chronic inflammatory conditions lose this CaSR response, potentially causing calcium from resorbing bone to accumulate in the circulation. This excess calcium may contribute to coronary artery calcification and cardiovascular disease.

Study Duration

Not specified

Participants

Multiple studies with varying participant numbers

Evidence Level

Review Article

Key Findings

1
Chronic inflammatory conditions like post-menopausal osteoporosis, spinal cord injury, rheumatoid arthritis, and osteoarthritis are associated with an increased risk of cardiovascular disease.
2
Bisphosphonate use, which reduces bone resorption, is linked to reduced mortality, including cardiovascular-related mortality, in patients with post-menopausal osteoporosis, rheumatoid arthritis and critical illness.
3
Children and adolescents respond to inflammation by up-regulating the parathyroid calcium-sensing receptor, potentially protecting against cardiovascular morbidity, while adults lose this responsiveness.

Research Summary

This review explores the connection between inflammatory bone resorption and cardiovascular disease, highlighting epidemiological evidence linking conditions like osteoporosis and spinal cord injury to increased cardiovascular risk. It discusses the potential protective mechanism in children involving the upregulation of the calcium-sensing receptor (CaSR) in response to inflammation, leading to hypocalcemia and reduced cardiovascular risk. The review also examines the loss of CaSR responsiveness in adults with chronic inflammatory conditions, which may result in calcium accumulation and increased cardiovascular risk, suggesting potential preventive avenues.

Practical Implications

Cardiology Evaluation

Patients with chronic inflammatory conditions should be referred for cardiology evaluation to assess existing cardiovascular disease.

Calcimimetic Investigation

Investigate the use of calcimimetics to reactivate the adult parathyroid CaSR and restore calcium regulation.

Early Anti-Resorptive Use

Consider earlier use of anti-resorptive agents to lower the risk of atherogenesis in patients with chronic inflammatory conditions.

Study Limitations

1
The exact mechanism linking inflammation, bone resorption, and cardiovascular disease remains unclear.
2
The reasons for the age-related loss of parathyroid CaSR responsiveness are not known.
3
Longitudinal studies are needed to correlate blood calcium levels with vascular calcification in inflammatory conditions.

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