Adverse effects of orthodontic forces on dental pulp. Appearance and character. A systematic review

Figures & data

Figure 1. PRISMA flow diagram presenting the identification and screening of eligible articles for this systematic review. Edited from: Page et al., 2021 [16].

Table 1. Criteria for assessment of the methodological quality of the studies.

Criteria	Category A* High quality	Category B* Moderate quality	Category C Low quality
Blinded outcome measures	Yes	No	Yes/no
Study design
Randomised, controlled	Yes	Yes/no	Yes/no
Prospective	Yes	Yes/no	Yes/no
Cohort	No	Yes	Yes/no
Retrospective	No	Yes	Yes/no
Control or reference group	Yes	Yes**	Yes/no**
Well-defined diagnosis and end points	Yes	Yes	Unclear
Described tests of reliability and reproducibility	Yes	Yes	Unclear
Purely defined material or large attrition	No	No	Yes

Modified from Bondemark et al., 2007 [17] and Reddy et al., 2017 [18].

*Lack of any of the requirements lowers the category.

**Baseline values accepted as controls.

Table 2. Studies related to the changes in pulpal blood flow (PBF), tooth sensibility, expression of inflammation-related proteins and histological and morphological changes as a consequence of orthodontic force.

Tooth movement Test	Authors (year)[Ref]	Appliance/force/grouping	Methods^a/studied proteins^b	Target teeth	Follow-ups	Results
Alignment and levelling
Blood flow	Salles et al. (2013) [20]	Fixed appliance −0.014ʺ NiTi wire –force 70–100 g (n = 12)	LDF/	Maxillary left central incisors	20 min, 48 h, 72 h, 1 m	Significant reduction in PBF, observable after 20 min and reaching its peak after 72 h. Recovery back to baseline by 1 m.
	Ersahan & Sabuncuoglu (2018) [21]	Fixed appliance −0.014ʺ NiTi wire –force 70–100 g Group 1 (n = 14): 18–25-year-olds Group 2 (n = 14): 42–55-year-olds	LDF/	Maxillary incisors	24 h, 3d, 7d, 3wk, 1 m	Significant decrease in PBF in both groups after 24 h. Group 1: recovery back to baseline by 3wk. Group 2: some recovery but still significantly reduced at 1 m. PBF values of group 2 were significantly lower compared to group 1 at all time points, including baseline.
	Abu Alhaija et al. (2019) [22]	Group 1 (n = 25): fixed appliance, −0.014” NiTi wire Group 2 (n = 20): clear aligners	LDF/	Maxillary right quadrant (dd. 11–16) and mandibular left quadrant (dd. 31–36).	20 min, 48 h, 72 h, 1 m	Significant reduction in PBF in both treatment groups. The reduction was already observable after 20 min and reached its peak after 72 h in both groups, recovering back towards baseline afterwards. No significant differences between the two treatment groups.
	Abu Alhaija et al. (2021) [23]	Group 1 (n = 20): fixed appliance (a split mouth design) –combined 0.014ʺ–0.018ʺ NiTi wire Group 2 (n = 20): Fixed appliance –combined 0.016ʺ–0.018ʺ NiTi wire	LDF/	Mandibular dentition 1st molar to 1st molar	20 min, 24 h, 72 h, 1 w and 1 m after placement of the wires	Significant reduction in PBF in both treatment groups. The reduction was already observable after 20 min. Significant reduction occurred within 24 h and it continued reaching the maximum decrease at 72 h. Thereafter, the PBF gradually recovered reaching baseline values within 1 m. No significant differences between the two treatment groups.
	Abu Alhaija & Taha (2021) [24]	Fixed appliance, conventional/self-ligating brackets (a split mouth design) −0.016” NiTi wire levelling −0.016ʺ × 0.022ʺ NiTi wire alignment (n = 22)	LDF/	Mandibular dentition 1st molar to 1st molar	20 min, 24 h, 72 h, 1w and 1 m after the placement of each arch wire	With both brackets, PBF started to decrease after 20 min of the arch wire insertion. The lowest values were reached at 72 h. The values started to increase after 1w and reached the baseline values after 1 m.
Tooth sensibility	Modaresi et al. (2015) [25]	Fixed appliance: −0.016ʺ NiTi wire ligated to all permanent teeth (n = 39)	EPT/	Maxillary and mandibular incisors and canines	0, 5 min (immediately after bonding), 4 wk after the placement of the arch wire	Upon initiation, the mean value of EPT for each tooth increased and one month later, the mean EPT values dropped. At this time point, 16% of the experimental teeth failed to respond.
Inflammation related proteins	Veberiene et al. (2015) [26]	Group 1 (n = 20 teeth): fixed appliance 1) 0.016ʺ Sentalloy (alignment) 2) 016ʺ × 0.022ʺ Sentalloy −150 g 3) 0.018ʺ × 0.025ʺ Sentalloy −200 g Group 2 (n = 11 teeth): no treatment	/AST	Maxillary second premolars	6 m	No statistical difference in the AST^a levels between the experimental group (27.54 × 10^-5 U/mg) and the untreated control group (25.29 × 10^-5 U/mg).
Space closure (retraction)
Blood flow	Sabuncuoglu & Ersahan (2016) [27]	Group 1 (n = 12: fixed appliance −0.016ʺ × 0.022ʺ SS wire -Mini implants + closed coil -Force 100 g Group 2 (n = 12): controls	LDF/	Maxillary canines	24h, 3d, 7d, 4wk. approx. 4 m	A very small initial increase in PBF (24 h) followed by a significant decrease after 3d and 7d. Recovery back to baseline after 4wk, 4 m.
Histological and morphological changes	Hatrom et al. (2021) [28]	Fixed appliance –modified bracket system (0.018ʺ/0.022ʺ) in incisors − 0.018ʺ × 0.025ʺ SS wire –NiTi coil spring –Force 250 g Group 1 (n = 12): piezocision assisted en-masse retraction Group 2 (n = 11): traditional en-masse retraction		Maxillary incisors and canines	Mean 122.7 d	Significant reduction in all six measured pulp volumes after treatment when compared to pulp volume before treatment. No difference between traditional and piezocision-assisted treatment.
Intrusion
Blood flow	Sabuncuoglu & Ersahan (2014) [29]	Fixed appliance −0.016ʺ × 0.022ʺ SS segmental arch –Mini implants + NiTi closed coil Group 1 (n = 10): force 40 g Group 2 (n = 10): force 120 g	LDF/	Maxillary incisors Contralateral teeth as controls	3d, 3wk	Significant reduction in PBF after 3d in both force groups. Recovery almost back to baseline by 3wk. No significant differences between the two force groups.
	Sabuncuoglu & Ersahan (2015) [30]	Fixed appliance Group 1 (n = 10): −0.016ʺ × 0.016ʺ conventional utility arches –Force 25 g per one incisor, 100 g in total Group 2 (n = 10): −0.016ʺ × 0.022ʺ segmental SS wire dd 12–22 –Mini implants + NiTi closed coil –Force 100 g Group 3 (n = 10): controls	LDF/	Maxillary incisors	24 h, 3d, 7d, 3wk	Significant reduction in PBF after 24 h and 3d for groups 1 and 2. Recovery back to baseline by 3wk.
	Sabuncuoglu & Ersahan (2014) [31]	Group 1 (n = 10): fixed appliance −0.016ʺ × 0.022ʺ SS wire –Mini implants + elastics –Force 100 g Group 2 (n = 6): controls	LDF/	Maxillary 1st molars	3 d, 3 wk, 3  m, 6 m	Significant reduction in PBF after 3d and 3wk. Recovered back to baseline after 3 m and 6 m.
	Ersahan & Sabuncuoglu (2015) [32]	Fixed appliance −0.016ʺ × 0.022ʺ SS wire -Mini implants + elastics Group 1(n = 10): force 125 g Group 2 (n = 10): force 250 g	LDF/	Maxillary 1st molars Contralateral molars as controls	24 h, 3 d, 7 d, 3 wk, 4 wk, 3 m, 6 m	Significant reduction in PBF for both groups after 3d. PBF stayed constantly lowered between 3d–3wk, increased slightly after 4wk and reached the baseline values after 3 m. The drop in PBF was more significant in the heavy force group.
Tooth sensibility Inflammation related proteins	Veberiene et al. (2009) [19]	Group 1(n = 21): fixed appliance –A rigid unit connecting 1st molars −0.016ʺ × 0.022ʺ SS spring for intrusion from the 1st molar –Avg. force 61 g (range 34–106g) Group 2(n = 21): controls	EPT/ /AST	Maxillary or mandibular premolars. Contralateral teeth as controls	7d	Significantly elevated EPT readings in the experimental teeth (26.95 μA) compared to the control teeth (7.76 μA). Significantly higher AST^a activity after 7d in the test teeth (0.57 U/mg) compared to the control teeth (0.35 U/mg). Significantly higher AST^a activity after 7d in the test teeth (0.57 U/mg) compared to the control teeth (0.35 U/mg).
	Chavarría-Bolaños et al. (2014) [33]	Group 1 (n = 8 teeth): a looped SS wire from the 1st molar to the 1st premolar –Force 150–200 g Group 2 (n = 8 teeth): control teeth	/CGRP, SP, β-endorphin, met-enkephalin	Premolars Contralateral premolars as controls	24h	SP^c expression was significantly higher in the experimental group (131.91 pg/mg) compared to the control group (83.51 pg/mg). For CGRP^b, β-endorphin and met-enkephalin, the changes were not statistically significant, but all of them had slightly higher levels in the experimental group.
	Chavarría-Bolaños et al. (2015) [34]	Group 1 (n = 8 teeth): a looped, 0.018ʺ × 0.025ʺ SS wire from the 1st molar to the + premolar –Force 150–200 g Group 2 (n = 8 teeth): control teeth	/CGRP,SP,β-endorphin, met-enkephalin	Premolars, Contralateral premolars as controls	7d	The expression levels of SP^c and CGRP^b were significantly higher in the experimental group (SP 145.93, CGRP 22.46) compared to the control group (SP 83.51, CGRP 13.73). β-endorphin and met-enkephalin had slightly elevated expression in the experimental group, but the changes were not statistically significant.
Histological and morphological changes	Ramazanzadeh et al. (2009) [35]	Removable appliance Group 1(n = 20): –An open NiTi coil –Force approx. 25 g ± 5 g Group 2 (n = 12 teeth): control teeth		Maxillary 1st premolars Contralateral premolars as intra-patient controls for the first 6 premolars extracted at 3 days	3d 3wk	Significant vacuolisation and disruption of the odontoblastic layer, both after 3d and 3wk. In the extrusion group, fibrous tissue formation was significantly higher at 3wk compared to 3d or controls. There were no statistical differences between the groups in the degrees of inflammation, pulp vessel dilation or pulp stone formation.
	Lazzaretti et al. (2014) [36]	Group 1 (n = 17): fixed appliance, a split mouth design –A transpalatal bar of 1.0 mm SS wire + 0.019 × 0.025ʺ partial SS arch from the 1st molar to the 1st premolar –Force 60 g Group 2 (n = 17): control teeth		Maxillary 1st premolars Contralateral premolars as controls	21d	The experimental group had a higher prevalence of fibrotic tissue, odontoblastic aspiration and pulpal nodules compared to the control group, and had more vasodilation and large congested blood vessels. Inflammatory cell infiltration was not observed in any tooth.
Extrusion
Histological and morphological changes	Ramazanzadeh et al. (2009) [35]	Removable appliance –Extrusion with ¼ʺ light elastics -Group 1 (n = 20 teeth): force approx. 75 g -Group 2 (n = 12 teeth): control teeth		Maxillary 1st premolars Contralateral premolars as intra-patient controls for the first 6 premolars extracted at 3 days	3d 3wk	Significant vacuolisation and disruption of the odontoblastic layer, both after 3d and 3wk. In the extrusion group, fibrous tissue formation was significantly higher at 3wk compared to 3d or controls. There were no statistical differences between the groups in the degrees of inflammation, pulp vessel dilation or pulp stone formation.
Inflammation related proteins	Caviedes-Buchelli et al. (2021) [37]	Group 1 (n = 10 teeth): Fixed appliance −0.017ʺ × 0.025ʺ segmented TMA wire from the 1st molar to the 1st premolar –Force appr. 56 g Group 2 (n = 10 teeth): control teeth	/CGRP, SP, VEGF	Maxillary/mandibular premolars	24h	The expression levels of SP^c, CGRP^b and VEGF^d were significantly higher in treatment group (SP 1.0163, CGRP 0.0749, VEGF 0.0014 pmol/mg) than in control group (SP 0.3665, CGRP 0.0367, VEGF 0.0004 pmol/mg).
Tipping and torque
Tooth sensibility	Alomari et al. (2011) [38]	Group 1 (n = 47): a non-extraction treatment with upper and lower fixed appliances. Retention with a removable appliance. Group 2 (n = 23): controls	EPT, CT with Endo-Ice/	Maxillary incisors and canines	2h, 3d, 60d, 120d, 180d, 240d, 300d, 360d, after debonding, 1, 3, 6, 9 and 12 m of retention	Increase in the number of negative responses to EPT and CT, highest in both after 60d. Increase in EPT readings, also highest after 60d. Gradual recovery (decline) in EPT readings and number of negatives thereafter.

A summary of applied materials, methods and main results.

^aTesting methods: laser Doppler flowmetry (LDF), electric pulp testing (EPT), cold testing (CT).

^bStudied proteins: aspartate aminotransferase (AST), calcitonin gene-related peptide (CGRP), substance P (SP), vascular endothelial growth factor (VEGF).

^cStainless steel (SS).

Figure 2. Progression of mean pulpal blood flow (PBF) values relative to the baseline value of each study or group (PBF at timepoint X/Baseline PBF of the same group). *Average between tooth types, **average between tooth types and treatment methods, ***baseline value not presented in numerical form in the source study, interpreted from a graph to be 13.0 AU (arbitrary units).

Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

 PubMed Web of Science ®Google Scholar

Bondemark L, Holm AK, Hansen K, et al. Long-term stability of orthodontic treatment and patient satisfaction. A systematic review. Angle Orthod. 2007;77(1):181–191.

 PubMed Web of Science ®Google Scholar

Reddy RR, Gosla Reddy S, Vaidhyanathan A, et al. Maxillofacial growth and speech outcome after one-stage or two-stage palatoplasty in unilateral cleft lip and palate. A systematic review. J Craniomaxillofac Surg. 2017;45(6):995–1003.

 PubMed Web of Science ®Google Scholar

Salles AWR, Salles AMC, Nogueira GEC. Laser Doppler blood-flow signals from human teeth during an alignment and leveling movement using a superelastic archwire. ISRN Dent. 2013;2013:102816.

 PubMedGoogle Scholar

Ersahan S, Sabuncuoglu FA. Effect of age on pulpal blood flow in human teeth during orthodontic movement. J Oral Sci. 2018;60(3):446–452.

 PubMed Web of Science ®Google Scholar

Abu Alhaija ESJ, Al-Abdallah SY, Taha NA. A comparative study of initial changes in pulpal blood flow between clear aligners and fixed orthodontic appliances. Am J Orthod Dentofacial Orthop. 2019;156(5):603–610.

 PubMed Web of Science ®Google Scholar

Abu Alhaija ESA, Shahin AY, Badran SA, et al. Pulpal blood flow changes and pain scores related to using superelastic 0.018-inch nickel titanium as the first orthodontic alignment archwire: a prospective clinical trial. J Appl Oral Sci. 2021;29:e20210089.

 PubMed Web of Science ®Google Scholar

Abu Alhaija ES, Taha NA. A comparative study of initial changes in pulpal blood flow between conventional and self-ligating fixed orthodontic brackets during leveling and alignment stage. Clin Oral Investig. 2021;25(3):971–981.

 PubMed Web of Science ®Google Scholar

Modaresi J, Aghili H, Dianat O, et al. The effect of orthodontic forces on tooth response to electric pulp test. Iran Endod J. 2015;10(4):244–247.

 PubMedGoogle Scholar

Veberiene R, Latkauskiene D, Racinskaite V, et al. Aspartate aminotransferase activity in the pulp of teeth treated for 6 months with fixed orthodontic appliances. Korean J Orthod. 2015;45(5):261–267.

 PubMed Web of Science ®Google Scholar

Sabuncuoglu FA, Ersahan S. Changes in human pulp blood flow during canine retraction. Acta Odontol Scand. 2016;74(6):436–442.

 PubMed Web of Science ®Google Scholar

Hatrom AA, Howait MS, Zawawi KH, et al. Pulp volume changes after piezocision-assisted tooth movement: a randomized clinical trial. BMC Oral Health. 2021;21(1):28.

 PubMed Web of Science ®Google Scholar

Sabuncuoglu FA, Ersahan S. Changes in maxillary incisor dental pulp blood flow during intrusion by mini-implants. Acta Odontol Scand. 2014;72(7):489–496.

 PubMed Web of Science ®Google Scholar

Sabuncuoglu FA, Ersahan S. Comparative evaluation of pulpal blood flow during incisor intrusion. Aust Orthod J. 2015;31(2):171–177.

 PubMed Web of Science ®Google Scholar

Sabuncuoglu FA, Ersahan S. Changes in maxillary molar pulp blood flow during orthodontic intrusion. Aust Orthod J. 2014;30(2):152–160.

 PubMed Web of Science ®Google Scholar

Ersahan S, Sabuncuoglu FA. Effects of magnitude of intrusive force on pulpal blood flow in maxillary molars. Am J Orthod Dentofacial Orthop. 2015;148(1):83–89.

 PubMed Web of Science ®Google Scholar

Veberiene R, Smailiene D, Danielyte J, et al. Effects of intrusive force on selected determinants of pulp vitality. Angle Orthod. 2009;79(6):1114–1118.

 PubMed Web of Science ®Google Scholar

Chavarría-Bolaños D, Martinez-Zumaran A, Lombana N, et al. Expression of substance P, calcitonin gene-related peptide, β-endorphin and methionine-enkephalin in human dental pulp tissue after orthodontic intrusion: a pilot study. Angle Orthod. 2014;84(3):521–526.

 PubMed Web of Science ®Google Scholar

Chavarria-Bolaños D, Flores-Reyes H, Lombana-Sanchez N, et al. Sensory neuropeptides and endogenous opioids expression in human dental pulp with asymptomatic inflammation: In vivo study. Mediators Inflamm. 2015;2015:879126.

 PubMed Web of Science ®Google Scholar

Ramazanzadeh BA, Sahhafian AA, Mohtasham N, et al. Histological changes in human dental pulp following application of intrusive and extrusive orthodontic forces. J Oral Sci. 2009;51(1):109–115.

 PubMedGoogle Scholar

Lazzaretti DN, Bortoluzzi GS, Torres Fernandes LF, et al. Histologic evaluation of human pulp tissue after orthodontic intrusion. J Endod. 2014;40(10):1537–1540.

 PubMed Web of Science ®Google Scholar

Caviedes-Bucheli J, Lopez-Moncayo LF, Muñoz-Alvear HD, et al. Expression of substance P, calcitonin gene-related peptide and vascular endothelial growth factor in human dental pulp under different clinical stimuli. BMC Oral Health. 2021;21(1):152.

 Web of Science ®Google Scholar

Alomari FA, Al-Habahbeh R, Alsakarna BK. Responses of pulp sensibility tests during orthodontic treatment and retention. Int Endod J. 2011;44(7):635–643.

 PubMed Web of Science ®Google Scholar

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.