FRI0486 NO IMPACT OF ANTI-RANK LIGAND AND PTH ANALOGUES ON CARDIOVASCULAR RISK IN IDIOPATHIC AND POSTMENOPAUSAL OSTEOPOROSIS: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS
Authors: Laurence Ferrieres, Yannick Degboe, Michel Laroche, Arnaud Constantin, Adeline Ruyssen-Witrand
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Emerging evidence suggests a possible association between osteoporosis and cardiovascular disease<sup>1,2</sup>. The mutual effects of drugs used in these two diseases are now a point of interest. Two meta-analyses have been conducted to explore the cardiovascular effects of bisphosphonates<sup>3,4</sup>. There is no review for other osteoporosis treatments, such as anti-rank ligand antibody and parathyroid hormone analogues. <h3>Objectives</h3> A literature review and meta-analysis of randomized controlled trials was conducted to address the impact of PTH analogues and anti-Rank Ligand on cardiovascular events and overall mortality in individuals with idiopathic osteoporosis. <h3>Methods</h3> A systematic literature review was conducted in December 2017 in the PubMed, Embase, Cochrane databases, and updated on PubMed in December 2018, by selecting trials including a treatment (anti-Rank Ligand or PTH analogue) and a control group. We also conducted a search for abstracts of the French Rheumatology Society, American College of Rheumatology and European League Against Rheumatisms annual meetings over the past 3 years. Relative risks and 95% confidence intervals for each event were estimated using the Inverse Variance fixed effects method. The main endpoints were the occurrence of cardiovascular events and all-cause of mortality. <h3>Results</h3> Of the 2782 reports initially found (503 articles via PubMed, 1309 via Embase, 474 via the Cochrane Library and 15 abstracts from annual meetings, 16 articles were used for the meta-analysis. All studies were randomized; no exploitable prospective cohort study was found. The number of adverse events of interest was available for 6 studies for the anti-Rank Ligand corresponding to 26 864 patient-years. After meta-analysis, there was no significant difference between the placebo group and the anti-Rank Ligand group for overall mortality (RR 0.79, 95% CI (0.60-1.04)), the combined cardiovascular endpoint (overall mortality, coronary artery disease and stroke: RR 0.95, 95% CI (0.78-1.16)), and the individual risk of coronary artery disease (RR 1.14, 95% CI (0.76-1.73)), arrhythmia (RR 1.03, 95% CI (0.63-1.68)) and ischemic or hemorrhagic stroke (RR 1.03, 95% CI (0.72-1.47)). The number of adverse events of interest was available for 10 studies for the PTH analogue group, corresponding to 6 220 patient-years. After meta-analysis, there was no significant difference between the placebo group and the PTH analogue group for overall mortality (RR 0.89, 95% CI (0.35-2.29)), the combined endpoint (overall mortality, coronary artery disease and stroke: RR 0.71, 95% CI (0.37-1.36)), and the individual risk of coronary artery disease (RR 0.65, 95% CI (0.19-2.27)), arrhythmia disorders (RR 1.43, 95% CI (0.73-2.80)) and ischemic or hemorrhagic stroke (RR 0.60, 95% CI (0.19-1.96)). <h3>Conclusion</h3> The anti-Rank Ligand and the PTH analogues have no short-term impact on the cardiovascular risk and the overall mortality in postmenopausal osteoporosis. To better answer the question whether these treatments are able to reduce the long-term cardiovascular risk, further comparative studies with longer duration are required. <h3>References</h3> [1] von der Recke P, et al. The association between low bone mass at the menopause and cardiovascular mortality. Am J Med. 1999;106(3):273-278. [2] Veronese N, et al. Relationship Between Low Bone Mineral Density and Fractures With Incident Cardiovascular Disease: A Systematic Review and Meta-Analysis. J Bone Miner Res Off J Am Soc Bone Miner Res. 2017;32(5):1126-1135. [3] Kim DH, et al. Bisphosphonates and Risk of Cardiovascular Events: A Meta-Analysis. Pizzi C, ed. PLOS ONE. 2015;10(4):e0122646. [4] Kranenburg G, et al. Bisphosphonates for cardiovascular risk reduction: A systematic review and meta-analysis. Atherosclerosis. 2016;252:106-115. <h3>Disclosure of Interests</h3> None declared