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Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review
Samantha Louise Saunders1, Kanika Chaudhri2, Nathan Scott McOrist3
1School of Medicine, The University of Notre Dame Australia, Darlinghurst, New South Wales, Australia Samantha.Saunders@health.nsw.gov.au.
Insights
This systematic review found insufficient evidence that bisphosphonates or RANKL inhibitors delay coronary artery calcification (CAC) progression. More research is needed to confirm any potential link between these drugs and CAC.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Medical Research
Background:
- Coronary artery calcification (CAC) is a marker of atherosclerosis.
- Bisphosphonates and Receptor Activator of Nuclear Factor-kappa B Ligand (RANKL) inhibitors are medications with potential effects on vascular calcification.
Purpose of the Study:
- To systematically review and determine if bisphosphonates and RANKL inhibitors can delay the progression of coronary artery calcification (CAC).
Main Methods:
- A systematic review of longitudinal studies was conducted using MEDLINE, EMBASE, and CENTRAL databases.
- Studies included adults (>18 years) taking bisphosphonates or denosumab (a RANKL inhibitor) compared to controls.
- Risk of bias was assessed using ROBINS-I and RoB2 tools.
Main Results:
- Four observational studies and one RCT (n=377) were included. Some studies showed potential CAC reduction with bisphosphonates or RANKL inhibitors, but results were inconsistent.
- One study reported a significant CAC reduction with bisphosphonates (p<0.01), while another showed a significant reduction with RANKL inhibition (p=0.03).
- Other studies found no statistically significant difference, and meta-analysis was not feasible due to study heterogeneity.
Conclusions:
- Current evidence is insufficient to support a correlation between bisphosphonate or RANKL inhibitor use and the progression of coronary artery calcification.
- Further research is warranted to clarify the role of these medications in managing CAC.
Objectives:
To determine whether bisphosphonates and NF-κB ligand (RANKL) inhibitors delay coronary artery calcification (CAC).
Design:
A systematic review was conducted.
Data Sources:
MEDLINE, EMBASE and CENTRAL.
Eligibility Criteria:
Longitudinal studies investigating CAC progression in adults (>18 years) taking either a bisphosphonate or denosumab compared with those who did not.
Data Extraction And Synthesis:
Study and participant characteristics, and primary outcome ( ∆ CAC from baseline to follow-up) were extracted. The Risk Of Bias In Non-Randomised Studies-of Interventions (ROBINS-I) and Risk-of-Bias Tool for Randomised Trials (RoB2) tools were used to assess the risk of bias for observational and randomised controlled trials (RCTs), respectively. Outcome measures were reported.
Results:
Four observational studies and one RCT (n=377) were included. Three studies solely reported the effect of bisphosphonates on ∆ CAC; one study (n=56) demonstrated a statistically significant CAC reduction in the intervention group (-372 mm3/year) compared with control (+159 mm3/year) (p<0.01). One study (n=14) demonstrated a difference in ∆ CAC between intervention (+880 mm3/year) versus control (+2220 mm3/year), however, no p value comparing groups was reported. One study (n=115) found no statistically significant difference between intervention and control.One study (n=42) exclusively investigated the effect of RANKL on ∆ CAC; there was a statistically significant reduction in CAC at 6-month follow-up between intervention (-133±124 modified Agatston unit (AU)) and control (+188±72 modified AU), p=0.03.One study (n=150) compared both bisphosphonates and denosumab to control and found no statistically significant difference between either intervention group and control over 24 months. Meta-analysis was not performed due to limited, heterogeneous studies.
Conclusions:
There is insufficient evidence supporting the correlation between bisphosphonate or RANKL inhibitor use and CAC progression. Further research is warranted.
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