INTRODUCTION

Orthodontic movement results from applying a force vector to a tooth for some time.^1,2 The establishment of pressure and tension zones along the periodontal ligament is one of the theories that explain orthodontic movement.^1,2 On the pressure side, the periodontal ligament undergoes disorganization and decreased production of fibers, in addition to a decrease in blood flow and cell replication.^2,3 Simultaneously, on the tension side, the stimuli produced by stretching of the fiber bundles increase the cell replication rate and, consequently, enhance periodontal fiber production.^2,4

The orthodontic force triggers a sequence of biological responses, which is a consequence of interferences in the physiological balance of the dental complex.^1,2 Tooth-supporting structures and dental pulp may undergo extensive microscopic changes when exposed to different degrees of mechanical loading.^2,5 There is still controversy regarding the optimal force level during orthodontic movement. However, it is commonly accepted that the application of inadequate or excessive forces results in unnecessary tissue damage.^2,5 Several factors can influence pulpal changes while orthodontic treatment occurs, such as the type or direction of movement, distribution, intensity, and force duration.^2,5,6

Several previous studies have reported changes in the dental pulp tissue after orthodontic force. Adequate knowledge related to pulp integrity preservation during orthodontic treatment is key for clinicians when applying orthodontic mechanics. Thus, this systematic review aimed to answer the following question: In permanent teeth, does orthodontic force promote changes in the histomorphology or the expression of tissue factors in dental pulp?

MATERIALS AND METHODS

RESULTS

Study Selection and Characteristics

The initial search resulted in 3584 references, from which 97 studies were included for full-text assessment. Then, 66 studies were excluded, resulting in 31 included studies (Figure 1). Of these, 26 were observational studies, and five were RCTs.

View Figure

• Download as Powerpoint
• Download Figure

Eighteen studies evaluated the occurrence of histomorphological changes in the pulp after different forces: intrusion;^4,11–14 extrusion;^13,15–18 tipping movement;¹⁹ conventional orthodontic movement;^3,20–23 or rapid maxillary expansion (RME).^24–26 Fourteen studies evaluated the expression of tissue factors after orthodontic force application, including methionine-enkephalin (ME),^27–29 calcitonin gene-related peptide (CGRP),^27,30 substance P (SP),^27,28 matrix metalloproteinase (MMP) 2 and 9,^6,31 beta-Endorphin,²⁷ c-Fos,⁶ caspases 3 and 9,²⁰ proliferating cell nuclear antigen (PCNA),²⁰ heat shock protein-60 (HSP60),²⁰ macrophageal nitric oxide synthase (iNOS),^31,32 neural nitric oxide synthase (nNOS),³² aspartate aminotransferase (AST),^33–37 and alkaline phosphatase (AP).³⁴

Risk of Bias Within Studies and Quality of Evidence

Among the observational studies, six were classified as low RoB,^{3,11,12,21,29,33} nineteen as moderate RoB,^{4,15,17–20,22–25,28,30–32,34–38} and one as high RoB.²⁶ All RCTs^{6,13,14,16,27} were classified as some concerns (Figure 2).

View Figure

• Download as Powerpoint
• Download Figure

GRADE analysis of the quality of the evidence was classified as very low for all outcomes (Table 1). Very low-quality evidence indicates that the real effect probably differed from the estimated effect.³⁹ Therefore, there was very little confidence that the articles' effect was due to the application of orthodontic force. The high number of observational studies classified as moderate RoB and the fact that all RCTs were classified as some concerns, contributed to the RoB parameter being classified as serious or very serious. Inconsistency was classified as very serious for all outcomes due to the methodological heterogeneity existing among the included studies. Imprecision was classified as serious in observational studies due to the absence of presentation or the broad confidence interval for some results.

Table 1. Analysis of the Quality of Evidence: GRADE* Assessment

View Fullscreen

Results of Individual Studies and Data Synthesis

Table 2 shows detailed information on the results of the included studies. Histomorphological changes were observed in the dental pulp of teeth moved orthodontically, such as odontoblastic aspiration,¹¹ vacuolization, and odontoblastic layer disruption,^13–16,20 disruption of the cell-free zone and predentin layer,^14,15 adipose degeneration,¹⁴ fibrous tissue formation,^12,13,16,24 cementum and dentin resorption,^{4,11,14,15,26} pulp stone formation,^12,14,15,26 morphological changes of myelinated axons,¹⁸ respiration rate depression,²³ and necrosis areas.¹³ Among the vascular alterations, blood vessel congestion and dilatation,^{12,14,16,19,25} vascular degeneration,⁴ hemorrhagic foci,^16,25 growth and increase in the area of microvessels,^{3,15,19,21,24} reduction in the number of microvessels,²² and infiltration of chronic inflammatory cells^11,25 were observed. Changes in the levels of 14 tissue factors expressed by the dental pulp were observed after orthodontic force: increased levels of AST,^34,37 CGRP,³⁰ SP,²⁷ c-Fos,⁶ MMP-9,⁶ HSP60,²⁰ caspases-3 and -9,²⁰ PCNA,²⁰ ME,²⁸ nNOS and iNOS³², and decreased levels of MMP-2 and -9,³¹ ME,^28,29 and AP.³⁸

Table 2. Characteristics of the Included Studies

View Fullscreen

Table 2. Extended

View Fullscreen

DISCUSSION

It is widely accepted that orthodontic force often results in undesirable effects on the dentoalveolar complex; the dental pulp is one of the affected tissues. This systematic review included 31 articles describing dental pulp changes after orthodontic mechanotherapy. Maintaining pulp vitality increases the mechanical resistance of the teeth and long-term survival.⁴⁰ Therefore, the clinician must be aware of the histomorphological aspects that the pulp may undergo due to orthodontic therapy to use adequate force and minimize damage to the tissue.

The phenomenon of movement of odontoblasts or their nuclei, known as “odontoblast aspiration”, was observed after intrusion.¹¹ Several procedures can induce this alteration, characterized as a defense mechanism of the dentin-pulp complex against an applied external force.⁴¹ Disruption of the odontoblastic layer,^13–16,20 cell-free zone, and predentin layer^14,15 were also observed. These changes were commonly observed in studies that assessed dental material biocompatibility, in which the rupture of these tissue zones' integrity characterized an adverse event to their use.^42,43 Based on this information, these changes in the pulp architecture could be explained as a non-physiological reaction of the tissue to orthodontic force.

Atrophic changes in tissues, such as fibrosis, are usually asymptomatic⁴⁴ and were observed in the pulp of teeth subjected to RME,²⁴ intrusion,¹² and extrusion.^13,16 Fibrosis is usually the result of a chronic condition resulting from a low-intensity stimulus that persists for a prolonged time, as seen in teeth affected by occlusal trauma or functioning as an abutment.^44,45 Such results are controversial since pulp fibrosis was observed after orthodontic force for a short period (one week). Like other connective tissues, the pulp creates an inflammatory reaction as a defense mechanism when an external agent acts in a harmful way.^46,47 The severity of inflammation is decisive in maintaining pulp vitality.⁴⁸ In teeth subjected to orthodontic force, vascular events were mild and did not promote pulp degeneration. Congestion and dilation of blood vessels,^{12,14,16,19,25} small hemorrhagic foci,^16,25 and infiltration of chronic inflammatory cells^11,25 were observed, however, not affecting pulp integrity.

Angiogenesis refers to the formation of new blood vessels from pre-existing capillaries, which is of great importance in pulp regeneration.⁴⁹ It is responsible for most blood vessels formed in the pulp under pathological conditions.⁴⁹ Angiogenesis is initiated by a drop in the oxygen rate and decreased supply of nutrients for tissues.⁴⁹ A drop in blood flow may occur due to orthodontic movement, especially in the first hours of force application.^2,50 Angiogenesis was observed by an increased number of microvessels and their area in the pulp in teeth after orthodontic movement.^{3,15,19,21,24}

Increased levels of some tissue factors have been observed in response to orthodontic force. SP and CGRP are neuropeptides released by pulp neurons due to various types of noxious stimuli.⁵¹ Increases in the levels of these neuropeptides have been observed after orthodontic force, suggesting that it can be harmful to the pulp if not controlled, as the elevation of the rates of these factors can trigger vasodilation, edema, activation of the immune system, and recruitment of inflammatory cells to the pulp.^30,51 C-Fos is a transcription factor involved in the proliferation and differentiation of pulp cells⁵² and MMP-9 is an enzyme that degrades substances in the extracellular matrix during pathological processes. Therefore, increased levels of these biomarkers indicate damage to the pulp tissue due to orthodontic force.⁵² AST is an intracellular enzyme released extracellularly after cell death; its increased levels can be considered a marker of tissue damage.⁵² The AST levels reported by the included studies^34,37 were comparable with levels in teeth with reversible pulpitis.⁵³ Although a threshold AST level associated with pulp inflammation has not been defined, a significant increase in its levels in response to orthodontic force indicated that certain reactive mechanisms were occurring in the pulp.

The included studies showed a moderate RoB and in no case did the study's quality checklists meet all the parameters evaluated. Most studies showed moderate RoB mainly due to bias in the selection of the size and characteristics of the sample and heterogeneity between the exposed and non-exposed subjects. The method of assessment outcomes, the insufficient follow-up time for the results to occur, and the bias in measuring and interpreting the outcome contributed to these results. Quality of evidence was assessed using the GRADE-tool and demonstrated very-low strength overall performance. The imprecision of the results was mainly due to the broader confidence interval presented by the studies or the lack of presentation of these data. The included studies showed high heterogeneity; therefore, the inconsistency was assessed as very serious.

This systematic review had limitations that need to be discussed. The methodological heterogeneity of the studies due to the lack of standardization of the orthodontic force and assessment method of the results, and the limited number of studies, made it difficult to compare the results. Therefore, a combined quantitative synthesis was not considered adequate.⁵⁴ Many studies had small sample sizes and samples with heterogeneous characteristics. Therefore, the results may have less statistical power and should be interpreted with caution by the clinician. Although limited by the very low quality of the studies, this SR had important strengths to highlight. The wide data collection approach, through multiple databases, allowed the inclusion of a large number of articles related to the review topic. The inclusion of studies of all languages and the use of no filter also reinforced the search process. These characteristics allowed a wide scope in the selection of articles, which increased the possibility of making a qualitative analysis of the data available in the literature within this field of research to synthesize the evidence and to set the baseline for future studies that, hopefully, will benefit from the critical analysis of the current published data.

The main objective of this review was to assess whether teeth moved orthodontically displayed pulp histomorphological changes to contribute to the diagnosis of dental pulp status during orthodontic movement. Based on the very low strength of evidence of the included articles, it was not possible to infer that regulary used orthodontic force was able to promote meaningful dental pulp changes. However, the studies seemed to suggest that the application of orthodontic force could promote, in an unidentified group of patients, several morphological changes as well as the expression of pulp tissue factors. Future research that investigates the effects of orthodontic force on pulp tissue requires RCTs, with larger samples and appropriate length of follow-up, along with standardized evaluation methods to obtain results with greater power of scientific evidence.

CONCLUSIONS

• Although the included articles suggest that orthodontic forces may promote changes in pulp histomorphology and in the expression of tissue factors, the very low level evidence produced by the included articles does not support any categorical conclusion that these changes are consistently generated by orthodontic movement.