Kapoor, Priyanka; Monga, Nitika; Kharbanda, Om Prakash; Kapila, Sunil; Miglani, Ragini; Moganty, Rajeswari

doi:10.1590/2177-6709.24.2.40.e1-22.onl

Resumo

Objetivo:

a aplicação da força ortodôntica libera múltiplas enzimas no fluído crevicular gengival (FCG), desencadeando a ativação, reabsorção, reversão, deposição de elementos ósseos e degradação da matriz extracelular. A presente revisão sistemática avaliou criticamente toda a evidência disponível sobre os níveis de enzimas durante a movimentação ortodôntica.

Métodos:

utilizando-se estratégias predeterminadas, foram realizadas buscas em bases de dados eletrônicas (PubMed, Scopus, Embase), sendo também feitas buscas manuais.

Resultados:

a busca inicial identificou 652 estudos e, com base nas diretrizes do PRISMA, foram selecionados 52 estudos. A avaliação qualitativa resultou na inclusão final de 48 estudos (13 estudos com moderada sensibilidade e 35 com alto nível de sensibilidade). Os desfechos primários foram o aumento significativo dos níveis no FCG das enzimas aspartato aminotransferase (AST), fosfatase alcalina (FA), metaloproteinases de matriz (MMPs), lactato desidrogenase (LDH), β-glucuronidase (βG), fosfatase ácido-resistente ao tartarato (TRAP), fosfatase ácida (FAC) e baixa regulação de catepsina B (Cb). Especificidade quanto ao local foi mostrada para FA, TRAP, AST, LDH e MMP9 com os níveis no lado de compressão aumentando mais rápido e em maiores quantidades, quando comparado ao lado de tensão. Os níveis de FA foram maiores no lado de tensão somente no período de contenção. Uma correlação positiva de LDH, FA e AST também foi observada à medida que a magnitude de força ortodôntica aumentou.

Conclusões:

há fortes evidências indicando que as variações nas enzimas (FA, AST, FAC, TRAP, LDH, MMPs, Cb) presentes no FCG estão associadas a diferentes magnitudes, estágios e locais de aplicação da força ortodôntica.

Palavras-chave:
Movimento dentário; Fluído crevicular gengival (FCG); Enzimas; Revisão sistemática

[1] Contact address:
Priyanka Kapoor E-mail: pkapoor@jmi.ac.in - drkapoorpriya@gmail.com

Criteria	Sub criteria	Inclusion	Exclusion
Participants/population	Type of sample	Human studies	Animal studies, in vitro studies
	Age groups	if specified	Not mentioned
	Male to female ratio	if specified	Not mentioned
	Controls	present (either internal /external)	No controls
	Sample size (sample size, not number of teeth studied)	≥5	<5
Intervention(s), exposure(s)	Mediators studied	enzymes [AST, MPO, ALP,βG, LDH, CatB, Cs, cAMP RII, MMPs]	Other than enzymes (cytokines/ hormones/PGs)
	Exposure	Orthodontic force application in healthy patients	Studied in periodontal inflammation/ root resorption/ not related
	Orthodontic mechanics	Specified	Not specified
	Oral hygiene regimen	Mentioned	Not mentioned
	Use of antibiotic/anti-inflammatory drugs	Not used	Not mentioned/ used
	Medium of study	GCF	Other than GCF/ peri-implant fluid/saliva
	GCF sample collection instrument	Periopaper/micropipette/ endodontic paper	Not mentioned

S. No.	Criteria (29)		Response
	Yes	No	Unclear
I. Study design
1.	Objective: objective clearly formulated
2.	Sample size: considered adequate
3.	Spectrum of patients representative of patients receiving the test in practice
4.	Ethical clearance mentioned
5.	Selection criteria: clearly described
6.	Randomization: stated
7.	Baseline characteristics: clearly defined
8.	Control: clearly defined
9.	Orthodontic mechanics explained in sufficient detail to permit replication of experiment
10.	Orthodontic force: clearly specified
11.	Description of execution of index test: sufficient to permit replication of test
12	Absence of time difference between index test & control: mentioned
13.	Index test executed at specified time and environmental conditions
14.	Use of proper indices for assessment of gingival & periodontal status (pre-treatment)
15.	Use of proper indices for assessment of gingival & periodontal status (at each observation time)
16.	Oral hygiene regime: mentioned
17.	Prophylaxis done (pre-treatment)
18.	Prophylaxis done (at each observation time)
II. Study measurements
1.	GCF handling characteristics: explained
2.	Measurement method: appropriate to the objective
3.	Reliability: adequate level of agreement
III. Statistical analysis
1.	Dropouts: dropouts included in data analysis
2.	Statistical analysis: appropriate for data
3.	Confounders: confounders included in analysis
4.	Statistical significance level: P value stated
5.	Confidence intervals provided
IV. Study results and conclusions (3)
1.	Index test compared to baseline
2.	Index test compared to control
3.	Conclusions: specific

Ref No.	Oral px (Pre t/t)	Oral px (Every ob po)	Oral hy instr/motiv	Mw	fq/o mw/d	asm for gv & pd in (pre t/t )	At every ob po
7	Y	NM	Y	Cx glu	2	Y	Y
8	Y	NM	NM	NM	NM	Y	NM
9	NM	NM	Y	0.15% Benz HCL/d	1 /d	NM	NM
10	Y	NM	Y	0.5 oz of 0.2% cx glu	2/d	NM	NM
11	Y	NM	NM	NM	NM	Y	NM
12	NM	NM	NM	NM	NM	NM	NM
13	Y	Y	Y	NM	NM	NM	NM
14	Y	NM	Y	NM	NM	Y	Y
15	Y	NM	NM	NM	NM	Y	NM
16	Y	Y	Y	NM	NM	Y	Y
17	Y	Y	Y	0.5 oz of 0.2% cx glu	2/d	Y	Y
18	NM	NM	NM	NM	NM	Y	Y
19	Y	Y	Y	0.5 oz of 0.2% cx glu	Y	Y	Y
20	Y	Y	Y	0.12% cx glu	2 /d for 4 wk	NM	NM
21	NM	NM	Y	NM	NM	Y	NM
22	NM	NM	Y	NM	NM	NM	NM
23	Y	Y	NM	NM	NM	Y	Y
24	Y	Y	Y	cx glu	2/d	Y	NM
25	NM	NM	NM	Benz HCL	NM	NM	NM
26	Y	NM	Y	NM	NM	Y	Y
27	NM	NM	NM	NM	NM	Y	NM
28	Y	NM	Y	NM	NM	Y	Y
29	NM	NM	NM	NM	NM	Y	NM
30	NM	NM	Y	NM	NM	Y	Y
31	Y	NM	Y	cx glu	NM	Y	Y
32	NM	NM	NM	NM	NM	Y	Y
33	Y	NM	Y	NM	NM	Y	Y
34	NM	NM	Y	NM	NM	NM	NM
35	Y	NM	Y	NM	NM	NM	NM
36	Y	NM	NM	NM	NM	NM	NM
37	Y	Y	Y	N	N	Y	Y
38	Y	Y	Y	N	N	Y	Y
39	Y	Y	Y	N	N	Y	Y
40	Y	Y	Y	N	N	Y	T
41	Y	Y	Y	N	N	Y	Y
42	NM	NM	Y	cx glu	2 /d	Y	Y
43	Y	NM	Y	N(against it)	N	Y	NM
44	Y	Y	Y	0.012% cx glu	2/d	Y	Y
45	Y	Y	Y	Cx glu	NM	Y	Y
46	Y	Y	Y	NM	NM	Y	Y
47	Y	NM	Y	NM	NM	Y	NM
48	Y	NM	Y	NM	NM	Y	Y
49	NM	NM	NM	NM	NM	NM	NM
50	NM	NM	NM	NM	NM	Y	Y
51	Y	Y	NM	NM	NM	Y	NM
52	Y	NM	Y	NM	NM	Y	NM
53	Y	NM	Y	NM	NM	Y	NM
54	Y	NM	NM	NM	NM	Y	NM

Ref No.	sts al ap	cf	Drop outs	Up / down rg	Pk	sd oc	cr	sts sn rd
7	1-tailed paired Student t	Y	NM	βG: inc	M-010 PM-07 CI-08	IL-1β sign inc for Mo- O5 to O10 for PM-O6 to 010 For CI-04, 06, 07, 09, 010 & dec at O2 for Mo, PM, CI	stronger F cause higher levels of IL-1β & βG	βG inc for Mo- 07 to 010 PM-07, 08, 010 CI-06, 07, 010 & dec at O2 for Mo, PM, CI
8	ANOVA, paired t test	Y	NaM	Inc at 2h, bas in 7d	2h	Inc MPO in saliva at 2h, B in 7d	+ve cr of lvl in GCF & saliva	Inc at 2h
9	(ANOVA) Kolmogorov-Smirnov test, Paired-samples test	Y	N	Inc	2wk	NM	NM	In cns F: Lvl pk at 2wk In gradually inc F: Lvl pk at 3wk
10	Kolmogorov and Smirnov (ANOVA) & Tukey’s post-hoc test	Y	N	Inc	14d	GCF vol inc from 0 - 21d Sn inc at 14d	Exp si; lvl inc on 14d cr with pk in GCF vol	Exp si; pk at 14d
11	Paired t test Pearson’s cr	Y	N	LDH inc at 2, 3& 4 wk(100 g) & 1, 2 & 3wk (150 g). AST inc at 4 & 5wk (100 g) & 3 & 4wk (150 g). TRAP inc at 5wk (100 g)	AST: 1wk TRAP: 2wk ALP: 5wk	In saliva:AST inc at 5wk, TRAP at 2wk, ALP at 1 to 5wk	Weak cr b/w enz quantity & activity	LDH inc at 2, 3 & 4 wk (100 g) & 1, 2 & 3wk (150 g). AST inc at 4 & 5wk (100 g) & 3 & 4wk (150 g) TRAP inc at 5wk (100 g)
12	Friedman test for intergp & intragp, Wilcoxon test for related samples, Kruskal-Wallis test for independent samples in both gps	Y	N	inc	2h	minm & severe crw: inc from 0 at 2h, 7d, 14d in saliva	No cr of crw with change in MPO	At 2h, 7d sn inc from B & 14d
13	Intra gp: Friedman’s test, Wilcoxon test Inter gp: Mann-Whitney U test, Pearson’s test	Y	N	inc	MMP9: 8h MMP9/NGAL: 72h	TSP1: inc from B at 8h to 72h, dec at 1wk	Strong & sn cr b/w MMP9/NGAL & TSP1 in IxT	MMP9: inc from B at 4h, 8h, 1wk, 2wk. MMP9/NGAL: inc from B at 8h,24h, 72h
14	Intergp: Mann Whitney U test. Intra gp: Students unpaired t-test	Y	N	Inc	ACP: 3d ALP, AST: 15d	NM	NM	Inter gp; ACP: pk at 3d ALP, AST: pk at 15d Intra gp: ACP, ALP, AST higher in Mx I than Mo
15	SAS version 9.2 proc mixed subroutine	Y	N	No sts sn change	NM	Exp si: in Ad, IL-1/1L-1RA dec in 3wk aftr 1st wi lig ado, RANKL/OPG pk at 6wk aftr 1st rect wi lig	NM	b/w Exp & cT; no sts sn change B/w Ad & adol: no sts sn diff
16	MedCalc software Intergp: Student’s t-test, ANOVA.	Y	N	SL+ NiTi wi: inc SL+ thrm wi: dec	No sts sn change	Visual pl scr dec sts sn	NM	No sts sn change b/w Exp & cT or within each gp
17	Luminex analysis	Y	N	MMP1,3:inc, pk at 24h MMP8: pk at 14d	24h	NM	NM	No sts sg diff b/w comp & tn, MMP1, 3: inc, pk at 24h MMP8: pk at 14d
18	Paired non-parametric Kruskall-Wallis. Spearman Rank Sum anal	Y	NM	Inc	Exp-TIMP, MMP-9:4h cmp: TIMP-1, MMP-9:4h, TIMP-2: 7d	+ve cr of GCF vol & PI at 0 at tn, cmp +ve cr of TNF-α, IL-1β, IL-8, GM-CSF to speed of OTM at 4h in Exp cr of IL-1β, IL-8, TNF-α inc to if at 0 at cmp	+ve cr of MMP-9 & TIMP to speed of OTM at 4h in Exp	TIMP1 & 2, MMP-9 inc at 4h in Exp
19	GraphPad®Instat, ANOVA, Friedman	Y	NM	Inc	14d, 21d	NM	NM	Inc at 7, 14, 21d
20	Friedman, Mann-Whitney	Y	NM	Inc	1h	GCF vol higher in cmp than tn at 21d	NM	MMPs inc at 1h, dec at 24h
21	ANOVA		NM	Cp: dec Cys:inc	1d	GCF vol inc in 1d, dec at 1m	-ve cr in Cp & Cys Lvl	Cp;dec at 1d, inc to B in 1m Cys;inc in 1d, dec to B in 1
22	ANOVA	Y	NM	Inc	MMP1-1h MMP2-1h,8h	NM	NM	Inc in MMP1 (tn) -1h-3h, (cmp) -1h Inc in MMP2 (tn) - 1h, (comp)-8h
23	Mann-Whitney U-tests	N	NM	Inc at 24h at Ix t >cT	24h	GCF vol no sn diff at 24h	NM	Inc at 24h
24	ANOVA &LSD	Y	NM	Inc	14d	NM	NM	Inc in ALP -7, 14 at Ms & D
25	Friedman test	Y	NM	Dec	I d	Dpd, osteocalcin dec	NM	Dec from 0 to 28 d, inc on 7d
26	Friedman and Bonferroni-corrected, Wilcoxon paired signed rank tests	Y	NM	Inc	14d	NM	NM	ct gp greater than Ag gp on 14 d & 21d
27	NM	Y	NM	Lvl of MMP-8 inc in Ix t>c	NM	NM	NM	Lvl of MMP-8 inc 12 times in Ix t>c
28	Friedman & Bonferroni-corrected, Wilcoxon paired signed rank tests	Y	NM	Inc	28d	Aa colonization inc sn on 28d in ExpT & ct gp	NM	Inc at 28d in Ix T as compd to Ct T & Ag T
29	Friedman & Bonferroni-corrected, Wilcoxon paired signed rank tests	Y	NM	Inc	tn:7d cmp:7&14d	NM	NM	AST: inc in Ix T & ct T as compd to Ag T, inc in IxT as compd to ctT on tn si on 14d & on cmp on 7d & 14d, inc in IxT on cmp than tn on 7d
30	Mann Whitney U-test	Y	N	Inc	24h		NM	CpB higher at 24h at IxT
31	Bonferroni-corrected, 1-way repeated measures ANOVA, paired Student t test	Y	NM	Inc	14d	NM	NM	Sign inc on both M & D at 1,2,3,4 wks
32	One-tailed paired Student t test	Y	N	Inc	βG -25d IL-1β-	sn inc in IL-1β level at 4d &19d to 60d AL	NM	inc in βG at 25d to 60d AL
33	Student’s t test	Y	N	IL-1β, IL-6, TNF-α, EGF, β2-µG	inc	24h	Intra-grp in Exp: IL-1β inc at 24h > BS,IL-6 inc at 24h > BS or 168h,TNF-α inc at 24h > BS or 168h, EGF inc at 24h>BS Intergrp btw cont & Exp: IL-1β inc in Exp>cont at 24h, Mean IL-6 in Exp >ant cont, TNF-αin Exp at 24h> ant cont, EGF in Exp at 24hr> ant cont	NM
Ref No.	sts al ap	cf	Drop outs	Up / down rg	Pk	sd oc	cr	sts sn rd
34	ANOVA	Y	NM	Inc	7d	TNF-α in D & Ms sites of TT sn higher than both sites of c, also >.B, inc sn at 1 h & 24h. IL-10 dec during Exp period at c & TT	NM	TRAP5b Level in D & Ms sites of TT were sn higher than that at both sites of cT compd with B values, inc was sn at 1 h & 24h.
35	Shapiro-Wilk test	Y	NM	inc	100g gp-TRAP-3wk 150g gp-ALP & TRAP -5wk	NM	NM	In 100 g gp, TRAP sn inc in 3-5 wk compd to TRAPB. ALP & AST slightly inc. In 150 g gp, ALP & TRAP slightly inc compd with their B. AST sn inc in 5 wk.
36	Student’s paired t test	Y	NM	Inc	M:4wk D:1.5N-2wk	NM	NM	LDH at Ms site in 1.0 N &1.5 N gp, inc sn on 4th wk. At D site, LDH with 1.5 N was higher than 1.0 N throughout 5 wk of TM. LDH with 1.5 NF inc at both Ms (wk 2) & D site (wk 3) with sn diff to 1.0 N F
37	Kruskal Walis test.	Y	NM	TRAP inc in 150g F: Ms site peak 3wk, D site Pk 4wk den dec 100g F: Ms site 2wk Pk den dec, D site 5wk 4wk: Lvl in 150g> 100g F (D site) 5wk: Lvl in 100g>150g F (Dsite)	150g: D site -4wk, Ms site-3wk 100g:D site-5wk. Ms site-2wk	Rate of OTM at 150g>100g	150g F at 3 & 4wk>100g f, +ve cr of Lvl of TRAP & rate of OTM	150g gp, Ms si: inc at 3wk>BS At D si: inc at 4k>BS TRAP at 150 gm>100gm F at 4wk (D site)
38	Paired sample t-test	Y	NM	inc, pk at 2wk, at D >Ms- 1wk	Ms, D Si: 2wk	NM	NM	Inc at 1wk, 2wk from Bas
39	Paired sample t-test	Y	NM	Dec: 1wk,4wk on Ms, D si	4wk	NM	-ve cr of amt of OTM & Lvl of ALP	Dec at 4wk
40	Wilcoxon signed rank test	Y	NM	Inc: at 1wk,4wk, stabilised	4wk	NM	NM	Inc at 1wk, 4wk, At D si>Ms si
41	Wilcoxon signed rank test	Y	NM	Inc at 1wk, dec in next 3wk	1wk	N	NM	Pk at 1wk at Ix T>cT
42	unpaired and paired t-test	Y	NM	Inc at archwi >self lig site, inc at 1wk	1wk	Bac count in archwi>self lig	+ve cr in self lig & AST Lvl	Inc at archwi >self lig
43	ANOVA, paired t-test using SPSS	Y	NM	ALP, ACP inc at 14d, 28d, ALP at Ms>D, ACP inc in Ms &D	ALP, ACP : 14d	NM	NM	ALP, ACP inc, ALP inc more on M si
44	ANOVA, Student's t-test	Y	NM	ALP dec, D of C > Ms of 2nd PM on 1, 7, 14, 21, 28d	Dec	NM	NM	Dec at D of C > Ms of 2nd PM on 1, 7, 14, 21, 28d
45	Friedman test followed by a Bonferroni-corrected Wilcoxon paired signed rank test	Y	Y	ALP inc in 3m, 6m	Inc	PD with ALP actv	+ve corr of ALP lvl with time at tn si	ALP at 3m, 6m > cT
46	ANOVA,Tukey’s HSD Post-Hoc test, Mann-Whitney U-test	Y	NM	ALP inc 14d, 28d	28d	NM	NM	ALP at Ms si of TT>CT at 14d, 28d At Ms si>Dsi at 14d, 28d
47	ANOVA, Independent Samples t-test, Mann- Whitney U-test	Y	NM	ACP inc both Ms & D si D si>M si at 7d, 21d	21d	NM	NM	D si>M si at 7d, 21d TT>cT at 7d, 21 d at Dsi
48	ANOVA,Tukey HSD	Y	NM	LDH inc at TT>cT 7d, 14d,21d	28d	NM	NM	LDH inc frm 7d-14d at TT, TT>cT at 7, 14, 21d
49	Friedman & Bonferroni-corrected Wilcoxon paired signed rank tests	Y	N	AST inc from BS in T/t gp from BS to 2wk followed by dec Inc in CC gp from BS to 1wk followed by dec AST level in comp >tn on 1wk	14d	GCF flow in T/t=CC>AC gp	+ve correl of mechanical stress to AST levels, T/t>CC	sn inc in T/t &CC vs AC gp: 1, 2, 3, 4w sn inc in T/t vs CC gp: 1, 2wk AST level in comp >tn on 1wk
50	One-way ANOVA was used for multiple group and Student t test for group-wise comparisons	Y	N	inc in ALP b/w 21d & 28d :of 200% in active TB gp, of 260% in Rt screw gp	TB: 21d Rt screw:28d	Space closure rate, root resorption, Rt, anchorage loss with Hycon screw were assessed	+ve correl of ALP in Hycon screw gp with actvn of screw	Sign diff in ALP on 21d & 28d b/w TB & Rt screw gp
51	independent t tests, _2 tests, or Mann-Whitney, intraexaminer reliability - concordance correlation coefficient (CCC) & Bland-Altman method	N	Y	MMP8,9, MMP8/TIMP1, MMP9/TIMP1, resistin at BS>1h>1wk>compl of Aln CRP, MPO, TIMP, RANKL inc from BS to compl of Aln Adiponectin BS<1h<1wk>compl of Aln Leptin dec from BS to compl of Aln	NM	resistin at BS>1h>1wk>compl of Aln CRP, RANKL inc from BS to compl of Aln Adiponectin BS<1h<1wk>compl of Aln Leptin dec from BS to compl of Aln	Mediators correl with Aln rate- MPO, RANKL, Leptin, Resistin	MPO at BS<1h<1d<compl of Aln
52	Fisher’s PLSD followed by post hoc, Bonferroni- Dunn	Y	N	ALP on cmp site: 0>2wk>4wk<1y tn site: 0<2wk<4wk<1y	tn site: 1y cmp site: before actvn	NM	+ve correl of intermolar distance with ALP level in tn site	tn site:0 (before actvn) < 4wk, 0<1y cmp site: 0>4wk, 0<1y, 2wk>4wk
53	paired & unpaired ‘t’ test and ANOVA.	Y	N	MPO inc from BS to 2h in HANT, SE, MSSS gp	2h	NM	MPO in HANT>SE>MSSS	sn diff in MPO b/w SE & MSSS :2h, 2wk, b/w HANT & MSSS:2h, b/w SE & MSSS:1wk
54	Chi-square Student’s t-test, and one-way analysis of variance	Y	N	MPO inc from BS to 2h in HANT, SE, MSNiTi gp, HANT>SE & MS NiTi:2h	2h	NM	NM	sn diff b/w SE & MSNiTi: 2h, 1, 2wk, b/w HANT & MSNiTi:2h
55	Independent & paired sample t- test	Y	N	AST inc from BS to 1wk, then dec in Exp gp	1wk	NM	NM	Levels greater in Exp than Cn gp at 1, 2, 3, 4wk

S. No.	Criteria (29)	Response
S. No.	Criteria (29)	Yes	No	Unclear
I. Study design (18)
1.	Objective: objective clearly formulated	48	-	-
2.	Sample size: considered adequate	2	-	46
3.	Spectrum of patients representative of patients receiving the test in practice	48	-	-
4.	Ethical clearance mentioned	40	8	-
5.	Selection criteria: clearly described	48	-	-
6.	Randomization: stated	21	27	-
7.	Baseline characteristics: clearly defined	47	1	-
8.	Control: clearly defined	46	-	2
9.	Orthodontic mechanics explained in sufficient detail to permit replication of experiment	45	1	2
10.	Orthodontic force: clearly specified	35	12	1
11.	Description of execution of index test: sufficient to permit replication of test	45	-	3
12	Absence of time difference between index test & control: mentioned	36	12	-
13.	Index test executed at specified time and environmental conditions	4	44	-
14.	Use of proper indices for assessment of gingival & periodontal status (Pre-treatment)	40	8	-
15.	Use of proper indices for assessment of gingival & periodontal status (at each observation time)	17	29	2
16.	Oral hygiene regime-mentioned	32	3	13
17.	Prophylaxis done (Pre-treatment)	34	14	-
18.	Prophylaxis done(at each observation time)	11	37	-
II. Study measurements (3)
1.	GCF handling characteristics: explained	47	-	1
2.	Measurement method: appropriate to the objective	48	-	-
3.	Reliability-adequate level of agreement	48	-
III. Statistical analysis (5)
1.	Dropouts: dropouts included in data analysis	1	47	-
2.	Statistical analysis: appropriate for data	48		-
3.	Confounders: confounders included in analysis	-	48	-
4.	Statistical significance level: P value stated	48	-	-
5.	Confidence intervals provided	48	-	-
IV. Study results and conclusions (3)
1.	Index test compared to baseline	48
2.	Index test compared to control	48
3.	Conclusions: specific	40		8