Smoking and alcohol drinking and risk of non-union or delayed union after fractures: A protocol for systematic review and dose–response meta-analysis

INTRODUCTION: To the best of our knowledge, there is no consensus on dose–response between smoking, alcohol drinking, and bone healing. The aim of the present study is to conduct a comprehensive systematic review and dose–response meta-analysis of studies to estimate the influence of smoking and alcohol use on the success of non-pathologic bone fracture healing in adult patients. METHODS: A systematic search will be performed using MEDLINE, EMBASE and Cochrane CENTRAL, CINAHL, and AMED databases to identify randomized controlled trials and observational studies which have assessed the effect of smoking or alcohol drinking on fracture healing. Primary outcomes include delayed union or nonunion rate and time to union. Secondary outcomes are common complications which occur during bone healing including malunion and wound infection. Risk of bias will be evaluated using the Quality In Prognosis Studies (QUIPS) tool for quality assessment of each study. Dose–response meta-analysis will be performed between smoking, alcohol drinking, and bone healing. Evaluation of the quality of evidence will be conducted using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: The present study will assess the effects of smoking and alcohol drinking on non-pathologic bone fracture healing in adult patients. CONCLUSION: We hope that this systematic review and dose–response meta-analysis will provide high quality evidence on dose–response between smoking, alcohol drinking, and bone fracture healing. PROSPERO REGISTRATION NUMBER: CRD42019131454.