Abstract
Objective: Orthodontic force application releases multiple enzymes in gingival crevicular fluid (GCF) for activation, resorption, reversal, deposition of osseous elements and extracellular matrix degradation. The current systematic review critically evaluated all existing evidence on enzymes in orthodontic tooth movement. Methods: Literature was searched with predetermined search strategy on electronic databases (PubMed, Scopus, Embase), along with hand search. Results: Initial search identified 652 studies, shortlisted to 52 studies based on PRISMA. Quality assessment further led to final inclusion of 48 studies (13 moderately and 35 highly sensitive studies). Primary outcomes are significant upregulation in GCF levels of enzymes-aspartate aminotransferase (AST), alkaline phosphatase (ALP), matrix metalloproteinases (MMPs), lactate dehydrogenase (LDH), β-glucuronidase (βG), tartrate resistant acid phosphatase (TRAP), acid phosphatase (ACP) and down regulation in cathepsin B (Cb). Site specificity is shown by ALP, TRAP, AST, LDH, MMP9 with levels at compression site increasing earlier and in higher quantities compared with tension site. ALP levels are higher at tension site only in retention. A positive correlation of LDH, ALP and AST is also observed with increasing orthodontic force magnitude. Conclusions: A strong evidence of variation in enzymes (ALP, AST, ACP TRAP, LDH, MMPs, Cb) in GCF is found in association with different magnitude, stages and sites of orthodontic force application.
Highlights
Orthodontic forces cause an initial inflammatory response followed by alterations in the vascular and neural envelope and perpetual bone and tissue remodelling accompanied by paracrine release of bioactive mediators.[1,2,3] During orthodontic tooth movement (OTM), host-derived enzymes are released at various stages of activation, resorption, reversal and deposition of osseous elements and degradation of the extracellular matrix.[4]
Five studies were further excluded: three studies whose full texts were not retrieved despite contacting the authors repeatedly through mail and academic social networking sites; one was a review on matrix metalloproteinases (MMPs), and one had sample size smaller than inclusion criteria
MMP-9 increased in 4hr, peaked at 8hr using stainless steel ligatures for canine retraction in one study, while MMP9/NGAL ratio peaked in 72hr in another study.[13]
Summary
Orthodontic forces cause an initial inflammatory response followed by alterations in the vascular and neural envelope and perpetual bone and tissue remodelling accompanied by paracrine release of bioactive mediators.[1,2,3] During orthodontic tooth movement (OTM), host-derived enzymes are released at various stages of activation, resorption, reversal and deposition of osseous elements and degradation of the extracellular matrix.[4]. A systematic review (SR) by Kapoor et al[6] in 2014 studied variation in GCF level of cytokines with type and magnitude of orthodontic forces and growth status of patients. It established a positive correlation of GCF activity index IL1RA (interleukin receptor antagonist)/ IL-1β) with intensity of pain and velocity of OTM and a negative correlation with growth status of patients. Numerous other mediators alter GCF during OTM, comprehensively reviewed in SR by Alhadlaq[3] in 2015. The present SR aims to assess only a single family of mediators, enzymes, to establish their clinical correlations on sequential release in different phases of OTM and varying magnitude of orthodontic forces
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