Effects of orthodontic forces on bone turnover biomarkers in peri-miniscrew crevicular fluid: A systematic review.

Summary Objective Peri-miniscrew crevicular fluid (PMCF) analysis of biomarkers representing bone formation or resorption could provide a non-invasive way to monitor bone turnover around miniscrews and the response to force loading. Our objective was to systematically investigate the relevant available evidence. Materials and Methods Search without restrictions in eight databases and hand searching until March 2020 took place. We searched for prospective human studies measuring the levels of markers of bone formation and resorption in PMCF under the effect of orthodontic forces. Following study retrieval and selection, relevant data was extracted and the risk of bias was assessed following the Cochrane Collaboration guidelines. Results Four studies, two randomized and two non-randomized, were finally identified, following miniscrews for a period up to 90 days. Loading of miniscrews led to a transient increase in C-telopeptide of type I collagen amounts. Temporary increases were also observed for the enzymes: alkaline phosphatase and aspartate aminotransferase. Under the effect of orthodontic loading the total amount of Receptor Activator of Nuclear Factor-κB Ligand (RANKL) in the PMCF consistently increased compared to the unloaded group, at all sampling points. These changes led to a stable decrease in the osteoprotegerin (OPG)/RANKL ratio under force application throughout the study period, as OPG in this group, together with OPG and RANKL in the unloaded group, remained mostly unchanged. No differences were detected for the total OPG quantity between the two loading groups. The levels of bone specific alkaline phosphatase and chondroitin sulfate did not change significantly during observation. All studies presented some issues of concern regarding the risk of bias. Conclusion Biomarkers of bone turnover in PMCF showed variable responses following orthodontic loading. Overall, the findings were suggestive of adaptive bone alterations to physiologic force stimuli.