Association of cannabinoid receptor modulation with normal and abnormal skeletal remodelling: A systematic review and meta-analysis of in vitro, in vivo and human studies

Abstract To address the inconsistent findings from studies that used different models to explore the role of classical cannabinoid type 1 (CB1) and 2 (CB2) receptors in skeletal remodelling, we searched Medline, Web of Science and Embase for relevant studies from inception to June 23, 2020. We identified 38 in vitro, 34 in vivo and 9 human studies. A meta-analysis of in vitro studies showed that exposure to the inverse-agonists AM251 (mean difference [MD]:-26.75, 95% confidence interval [CI]:-45.36,-8.14, p=0.005), AM630 (standard[std.] MD:-3.11, CI:-5.26,-0.97, p=0.004; SR144528, std.MD:-4.88, CI -7.58,-2.18, p=0.0004) and CBD (std.MD:-1.39, CI -2.64,-0.14, p=0.03) is associated with reduced osteoclastogenesis, whereas the endocannabinoid 2-AG (std.MD:2.00, CI:0.11-3.89, p=0.04) and CB2-selective agonist HU308 (MD:19.38, CI:11.75-27.01, p Data availability The datasets used and analysed in the present study are available from the public sources described