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Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review
Samantha Louise Saunders1, Nathan Scott McOrist2, Kanika Chaudhri3,4
1Gosford Hospital, Gosford, New South Wales, Australia Samantha.Saunders@health.nsw.gov.au.
Introduction:
Whether bisphosphonates and RANKL inhibitors play a novel role in delaying cardiovascular calcification is unknown. Their action on regulatory enzymes in the mevalonic acid pathway, which is implicated in both bone and lipid metabolism, may be a novel therapeutic target to manage coronary artery disease (CAD). Such therapies may particularly be relevant in those for whom traditional cardiovascular therapies are no longer sufficient to control disease progression.
Methods And Analysis:
We will perform a systematic review which aims to synthesise evidence regarding whether use of bisphosphonates or use of the RANKL inhibitor denosumab delays coronary artery calcium (CAC) progression. Eligible studies will include longitudinal studies investigating CAC progression in patients aged >18 years taking either a bisphosphonate or denosumab compared with those who do not. Embase, MEDLINE and Cochrane will be searched using prespecified search terms. Studies will be screened by title and abstract independently and then in full to determine suitability for inclusion in the review. Extracted data will include that relating to study and participant characteristics. The primary outcome will be the CAC score. Secondary outcomes will include aortic and carotid artery calcification. Meta-analysis will be performed if sufficient data are available.
Ethics And Dissemination:
This study does not require ethics as it is a systematic review of the literature. The results of the review described within this protocol will be distributed via presentations at relevant conferences and publication within a peer-reviewed journal.
Prospero Registration Number:
The systematic review pertaining to this protocol is registered with PROSPERO (Registration ID: CRD42022312377).
Insights
This systematic review investigates if bisphosphonates and RANKL inhibitors can slow coronary artery calcium (CAC) progression. The findings will inform potential new treatments for coronary artery disease (CAD) when standard therapies are insufficient.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Bone Metabolism
Background:
- Cardiovascular calcification is a key indicator of coronary artery disease (CAD) progression.
- The mevalonic acid pathway influences both bone and lipid metabolism, suggesting a link to cardiovascular health.
- Existing cardiovascular therapies may not be sufficient for all patients, necessitating novel therapeutic targets.
Purpose of the Study:
- To systematically review evidence on whether bisphosphonates or denosumab (a RANKL inhibitor) delay coronary artery calcium (CAC) progression.
- To explore a potential novel therapeutic role for these agents in managing CAD.
- To identify if these therapies are particularly relevant for patients with advanced or refractory disease.
Main Methods:
- A systematic review of longitudinal studies involving patients over 18 years old.
- Searches of Embase, MEDLINE, and Cochrane databases using predefined terms.
- Independent screening of titles, abstracts, and full texts, followed by data extraction and potential meta-analysis.
Main Results:
- This section is to be populated upon completion of the systematic review and meta-analysis.
- The primary outcome measure is the change in coronary artery calcium (CAC) score.
- Secondary outcomes include calcification in the aorta and carotid arteries.
Conclusions:
- This systematic review will synthesize current evidence on bisphosphonates and RANKL inhibitors in cardiovascular calcification.
- Findings may highlight new therapeutic avenues for coronary artery disease (CAD) management.
- The study aims to provide evidence-based insights for clinicians treating patients with progressive cardiovascular calcification.
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