Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review and meta-analysis protocol

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).