Orthodontic tooth movement in relation to angular bony defects

220 © Australian Society of Orthodontists Inc. 2017 Objectives: This review provides a comprehensive assessment of the benefits of adjunctive orthodontic treatment with or without periodontal regenerative surgery in the treatment of angular bony defects, defect volume, and periodontal tissue conditions in adult patients. Methods: An electronic keyword search was conducted in the literature database PubMed as well as in Google Scholar. Originally, studies describing all types of orthodontic tooth movement (tipping, bodily movement, intrusion, extrusion) in relation to bone defects such as periodontal, furcation and extraction site defects were reviewed. Only those articles depicting tooth movement after periodontal therapy and the control of inflammation were included. Results: Evidence indicates that orthodontic tooth movement can result in the reduction or elimination of periodontal bony defect dimensions, a reduction in probing pocket depth and a gain in clinical attachment level. Furthermore, the published data show that orthodontic tooth movement before or after regenerative surgery can provide therapeutic benefits in the recovery of angular bony defects. Conclusions: This review supports the premise that adjunctive orthodontic treatment in adults with reduced but healthy periodontal tissues is a solution for the modification of bony defect contours with or without periodontal regenerative therapy. (Aust Orthod J 2017; 33: 220-235)


Introduction
Worldwide studies have shown that the prevalence of gingival inflammation in adults is high (50 to 90%), with 30% of the population advancing to periodontal disease. 1,2 The most visible clinical sign of advanced periodontitis is pathological tooth migration as a result of the destruction of tooth supporting structures. This presents a major aesthetic and functional concern for patients. The frequency of periodontal disease increases with age, 3 and so an increasing number of adults who suffer from periodontal disease and subsequent tooth migration are seeking orthodontic treatment. Adult orthodontic therapy requires a different approach to address the reduction or elimination of angular bony defects, solve occlusal and aesthetic problems and facilitate the management of several restorative challenges associated with tipped abutment teeth, excess spacing, inadequate pontic space, hyper-erupted incisors and diastema. 4,5 Orthodontics is a requirement in the interdisciplinary approach to help adult individuals suffering from periodontal disease to maintain a natural dentition with a stable occlusion, acceptable masticatory function and pleasant aesthetics. The aim of this paper is to present a comprehensive literature review to highlight the benefits of adjunctive orthodontic treatment alone or in combination with periodontal regenerative therapy, and to provide evidence that an interdisciplinary approach offers alternative options in the management of angular bony defects, as a result of periodontal, furcation and extraction events.

Considerations of orthodontic treatment in adult patients
There are a number of factors to consider during orthodontic treatment in adults. Conditions that are natural outcomes of aging are reduced vascularity of the periodontal ligament (PDL), a decrease in the number of fibroblasts and an insufficient source of pre-osteoblasts. Together, these conditions reduce bone reactivity to mechanical forces. 6 As a result, the duration of orthodontic treatment in adults may be longer compared with young individuals; 6,7 moreover, retention should be prolonged in order to allow desired bone remodelling. 6,8 An additional factor of importance in adults is that cortical bone becomes denser while the cancellous bone reduces, which, in combination with a reduced capacity of the PDL to respond, may increase the risk of root resorption during orthodontic tooth movement (OTM). 6,8 Furthermore, patients suffering from periodontal tissue breakdown have a reduced tissue surface and an alteration in the applied biological and biomechanical conditions. Tissue hyalinisation occurs more easily in adults 9 and the centre of resistance (CR) of periodontallycompromised teeth is often displaced more apically. 10,11 This increases the likelihood of tipping movements leading to the creation of greater moments during force application. 6,9 Although bodily tooth movement is frequently a clinical aim, small elements of tipping, rotation, torque, intrusion or extrusion can also be produced. 12 Nevertheless, the literature recommends the application of light forces in adults, in order to avoid tissue overloading and hyalinization, which may lead to adverse effects and further tissue breakdown. [13][14][15] A longitudinal study, 16 comparing tissue alterations during orthodontic treatment in adults with reduced or normal periodontal tissues to those of adolescents, showed that there is no significant difference in loss of connective tissue attachment between the two groups. Therefore, with proper biomechanical design, adults with normal periodontal tissues as well as those with reduced but healthy periodontal support can undergo orthodontic therapy without experiencing an increased risk of periodontal tissue breakdown or tooth loss.

Experimental studies
Animal studies have shown that in the absence of inflammation, even in cases in which periodontal support is reduced, orthodontic bodily forces are not capable of inducing gingivitis. 17,18 Moreover, in the presence of inflammation, applied forces will not convert gingivitis into destructive periodontitis. However, bodily movement of teeth in relation to inflamed infrabony defects may increase pocket depth and lead to a loss of connective tissue attachment, especially when the tooth is moved into the defect. 19 Infrabony defects are common in adults and may form as a result of destructive periodontal disease. 34 Intruding and tipping movements of teeth harbouring plaque were also found capable of creating infrabony pockets, 21 although the loss of clinical attachment level (CAL) might have been overestimated due to deeper probe penetration in the presence of inflammation. 35 Alternatively, studies in monkeys have concluded that the intrusion of teeth with a normal periodontium does not lead to a loss of connective tissue attachment, 23 or to a decrease of marginal bone level. 24 The same has been reported for extrusive movements. 22

Clinical studies and systematic reviews
Clinical and systematic review studies have shown that, if periodontal health and proper oral hygiene standards are maintained during active orthodontic therapy, there is minimal risk of clinically significant injury occurring to the supporting tissue, 9,25,27,29 even in cases in which periodontal support is severely reduced. 16,29 Moreover, in a long-term study that evaluated the periodontal status after orthodontic therapy, it was apparent that orthodontic treatment during adolescence had no noticeable effect on periodontal health in later life. 32 However, if oral hygiene is neglected during orthodontic treatment, there is an increased risk of adverse periodontal effects. 25 Contrary clinical studies have shown that orthodontic treatment may result in a small but statistically significant worsening of the periodontal status after treatment. 26,28,30,33 However, the reported differences might have been due to biased results, host-specific factors (alteration of oral hygiene habits during orthodontic therapy), or site-specific changes (such as molar bands or extractions) rather than as a direct adverse consequence of orthodontic forces. 33 The results from the above studies indicate the importance of periodontal therapy prior to the commencement of and during orthodontic treatment. In the absence of inflammation, OTM may take place without clinically significant injuries to the periodontium. It has been reported that the new periodontal architecture after tooth realignment may facilitate better oral hygiene as well as provide support to reduced, but otherwise healthy, tissues. 36,37

Material and methods
In order to examine the effect of OTM in relation to angular bony defects on the periodontal tissues and its impact on defect volume, an electronic keyword search in the literature database PubMed was conducted using the phrases: 'orthodontic tooth movement (bodily movement/intrusion/extrusion/ tipping) in relation to or of teeth with angular bony defects (periodontal/infrabony/intrabony or alveolar defects)', 'orthodontic resolve of periodontal defects' and 'orthodontics-periodontal regeneration/healing'.
The search revealed 276 articles, from which 33 were included for critical review. Moreover, from an electronic keyword search in Google Scholar ('orthodontic tooth movement in relation to infrabony defects') nine additional papers were included from 412 identified. The reference lists of the identified papers related to the topic were also reviewed for completeness and this process resulted in the inclusion of six additional studies. Articles containing all types of OTM in relation to angular, furcation as well as extraction defects were included. Studies with a title or abstract irrelevant to the subject were excluded. Furthermore, since the deleterious effect of force application on inflamed tissues is widely recognised, only studies in which OTM occurred after appropriate periodontal therapy and a control of inflammation were selected. As a result, two additional studies 19,38 were excluded. Therefore, from the search, 48 articles were included in the present study ( Figure 1) and were divided into two major topics: OTM in relation to angular bony defects treated with non-regenerative periodontal therapy (Table I) and OTM in relation to angular bony defects treated with regenerative surgery (Table II). Each group was subsequently subdivided into animal, clinical and systematic reviews.   Orthodontic movement of teeth with underlying periodontal problems, such as, soft tissue and hard tissue problems (osseous craters, 3-wall infrabony defects, hemiseptal defects and furcation defects).
Osseous craters will not improve with orthodontic therapy therefore preorthodontic osseous surgery might be indicated in order to maintain these areas during appliance wear.
3-wall defects are best treated with regenerative surgery prior to OTM.
Hemiseptal defects can often be eliminated with appropriate orthodontic treatment. Radiologic bone fill of defects. Extrusion and bodily tooth movement.
Clinically positive results.
Radiologic positive results concerning the correction of periodontal defects.  Therefore, healing occurred with long junctional epithelium (LJE). 45 However, one experimental study reported that defect fill occurred with new attachment formation on a root surface previously bordered by an inflammatory lesion. 40 Studies also indicated that OTM is a stimulating factor for bone apposition 42 and that this process is significantly greater in periodontal defects in which PDL and root damage are involved than in alveolar bone defects with no PDL involvement (representing defects in extraction sites). 44 Tipping movement towards infrabony defects was reported to have no negative effects on diminished non-inflamed periodontal tissues. 45 The intrusion of teeth with Class III furcation defects following open flap debridement (OFD) led to their clinical reduction to Class II or I. 46 An alternative study, 41 in which extrusion occurred without repeated fiberotomies in a defect area, concluded that the periodontium followed the extrusive movement of the tooth with no increase in probing pocket depth (PPD), but with some (0.5 mm) gingival margin recession.

OTM in relation to angular bony defects treated with non-regenerative periodontal therapy
Based on the data from the clinical studies shown in Table Ib, it was concluded that orthodontic intrusion, with or without previous periodontal surgery directed at infrabony defects, may lead to PPD reduction and CAL gain. 36,[54][55][56]60 Extrusion and uprighting of tipped teeth did not to lead to CAL loss. 49 A PPD reduction was reported in one study after extrusion 48 but a contrary study described a mean 1 mm reduction in bone height. 47 Extrusive, 47 52 it was noted that extrusive movements could be used for the management of extraction site defects and for increasing the dimensions of the alveolus, thus facilitating subsequent implant placement. In two clinical reviews 53,61 it was suggested that OTM alone is more efficient in resolving one-and twowall infrabony defects. However, the treatment of interproximal craters and three-wall infrabony defects required pre-orthodontic osseous or regenerative surgery. It was also reported that furcation lesions were the most difficult to maintain and may worsen during OTM. The systematic review studies shown in Table Ic also support the concept that bodily tooth movement with intrusion after periodontal surgery, 9 or with extrusion 62 of teeth in defect areas, leads to positive clinical results and radiographic bone fill of the defects.  (Table IIa), clinical 4,68-83 (Table IIb) and systematic review 9 (Table IIc) studies focusing on defects treated with a combined orthodontic-regenerative approach. Most animal [63][64][65][66][67] and clinical studies 4,68-74,76-82 indicated that OTM after periodontal regenerative surgery is beneficial and leads to successful treatment of infrabony or extraction defects without damaging the augmentation biomaterials. However, one reviewed study reported a reduction of bone regeneration on the pressure side after OTM, 64 whereas in two experimental studies 63,66 and one clinical re-entry case report 70  Intrusion and bodily tooth movement into the defect (pressure side) and away from the defect (tension side) 1 month after GTR b (Emdogain at tension side and membrane at the pressure side).

OTM in relation to angular bony defects treated with regenerative periodontal surgery
Periodontal regenerative procedures appear to enhance conditions for subsequent OTM of teeth with attachment loss.
Bone regeneration was high in control, intrusion and tension side groups but reduced on the pressure side. Group III: GTR associated to bone autograft (BA).
Group IV: GTR/BA and I.
Intrusion 1 month after the regenerative periodontal treatment with membrane and BA did not improve bone formation in the defect area, suggesting that interaction between orthodontic movement and biomaterial degradation must be analyzed in future research.
Bony defects were created in the alveolar process midway between the central incisor and mandibular first molar.
Treatment of the defects with bioactive glass particles and collagen membrane in combination with OTM immediately after surgery (Group I), 2 weeks after surgery (Group II) and no OTM (Group III).
Combined therapy enhanced bone formation. The defects treated with immediate application of OTM showed a statistically significant increase in trabecular count and total area of newly formed bone compared to the other groups.  67 and controlled clinical trial, 81 indicated that combined ortho-regenerative treatment might offer additional benefits in bone formation and in clinical periodontal parameters, such as PPD reduction and CAL gain, compared with regenerative treatment alone.
Reports have also shown that regenerative procedures prior to OTM may improve the topography and volume of bone, as well as the supporting tissues, thereby providing a favourable environment for subsequent tooth movement into bone deficient areas. 64,71,80 Additional clinical studies 71,80 reported that in the case of orthodontic space closure in extraction sites, previous treatment with regenerative techniques offers favourable conditions for successful tooth movement (no resulting inflammation or root resorption), while at the same time preventing gingival invaginations. In addition, OTM prior to regenerative procedures may increase the success rate of subsequent regenerative therapy. 75,83 For example, in a case report 75 it was shown that the deepening of a periodontal defect around the mandibular central incisor, due to the reduction of its horizontal width caused by OTM, increased blood circulation and improved the success rate of the subsequent GTR.
There has been a discussion initiated by experimental and clinical studies, related to the timing of OTM after tissue regenerative procedures. An experimental 67 study performed in animals and a human clinical study 81 reported beneficial results if OTM was applied immediately after regenerative surgery compared with a delayed application (two weeks in the animal study, or two months later in the clinical study) or no OTM. In turn, a clinical study 82 reported that early orthodontic movement, even if it took place in immature bone during the healing time, did not affect the maturation process of the periodontal apparatus. However, a systematic review 9 indicated that there was no clear sign of the timing of GTR in patients requiring orthodontic intrusion.

Discussion
Periodontal defects are commonly encountered in adults presenting for orthodontic therapy. Accepted methods of treatment of the defects include osseous resection, grafting procedures or even extraction when the defect jeopardises adjacent teeth, but these methods pose limitations. 48 The present review is the first to thoroughly evaluate the benefits and concerns of adjunctive orthodontic treatment with or without regenerative therapy in the reduction or the elimination of angular bony defects (infrabony, furcation and alveolar defects).

Adjunctive orthodontic treatment in periodontal defects treated without regenerative surgery One-, two-, three-wall infrabony defects and interproximal craters
Infrabony pockets are angular defects with inflamed connective tissue and with the gingival epithelium located apical to the crest of the alveolar bone. 34 Their classification is schematically illustrated in Figure 2. 84 From a review of the limited clinical studies, the present paper concludes that OTM can be successfully utilised as an alternative adjunctive procedure in the management of one-and two-walled periodontal defects. This is of paramount importance in cases in which excessive osseous resection is contraindicated. Specifically, conventional periodontal therapy or curettage followed by orthodontic forced eruption with occlusal equilibration has been shown as capable of levelling periodontal defects and leading to the reduction or elimination of their volume. 48,58 It could be hypothesised that bone formation is stimulated by the tension created within the PDL. Nonetheless, this approach might require subsequent endodontic and prosthodontic therapy. In addition, in periodontally compromised patients, orthodontic uprighting of mesially tipped molars, with periodontal defects on their mesial aspect, may produce favourable effects in PPD reduction after proper inflammation control. 47  Case report 17-year-old girl with localized juvenile periodontitis.
Combined perio-ortho therapy: initial non-invasive periodontal surgery followed by levelling, aligning and intruding of incisors and subsequent regenerative surgery (EDTA g , autogenous bone graft, emdogain, GTR).
Following OTM a decreased pocket depth in the maxillary incisors was observed. In addition, a deepening with reduction of the horizontal width of the defect in the mandibular central incisor caused by OTM increased the success rate of the subsequent GTR.

Maeda et al. 2008 76
Case report 55-year-old male with a missing maxillary first molar and mesially inclined neighbouring second molar with a severe circumferential bone defect.
Combined ortho-regenerative treatment with bone grafting and subsequent second molar uprighting with extrusion.
These procedures minimized the bone defect and at the same time offered a suitable site for implant placement in the first molar area.

Ghezzi et al. 2008 77
Descriptive case series 14 patients with severe infrabony defects and pathologic tooth migration.
GTR and subsequent bodily movement and intrusion of teeth into 1-,2-and 3-wall infrabony defects.
OTM 1 year after GTR did not improve the healing of infrabony defects treated with GTR but did not damage the regenerated tissues. OTM in, and tooth eruption through non-autogenous bone graft (used in experimental setups, periodontal defects, cystic lesions and alveolar clefts).
OTM in bone graft as well as tooth eruption through bone graft are not only possible but might provide positive results. The articles presented a low level of evidence and diversity in question therefore more research is warranted in order to avoid risks of orthodontic treatment in such cases. Both treatment modalities were effective in managing 2-or 3-wall infrabony defects but limited orthodontics provided additional benefit to EMD/DFDBA in 2-wall defects (statistically significant open probing attachment level gain in ortho group in 2-wall defects).

Reichert et al. 2011 80
Clinical trial 3 patients where analogous premolars were extracted for orthodontic reasons.
One extraction socket was filled with a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute (NanoBone) with the contralateral serving as a control (split-mouth design).
Orthodontic space closure was initiated 6 weeks later.
OTM was possible through NanoBone, space closure succeeded without complications (root resorption, inflammation). Gingival invaginations were also prevented in the test group.
Group I: immediate application of OTM (test group).
Group II: delayed (2 months later) application of OTM (test group).
Group III: regenerative therapy alone (control group).
Immediate application of OTM had a statistically significant positive difference in clinical and radiographic parameters (PPD reduction, CAL gain, increase in bone density and bone fill).

Pinho et al. 2012 4
Case report 43-year-old woman with multiple missing teeth, mild chronic periodontitis, and a malocclusion with a cant of the occlusal plane.
Periodontal regenerative therapy (Emdogain/Bio-Oss) in 2-wall infrabony defects in the anterior maxillary region and mesially of the mandibular right canine followed by intrusion 3 months later.

Ghezzi et al. 2013 82
Prospective case series 10 patients with infrabony defects (PPD greater or equal to 6 mm) and pathologic tooth migration contributing one defect each.
Treatment with EMD/collagen bovine mineral bone in combination with OTM initiating 1 month after surgery.
Early orthodontic movement, even if it took place in immature bone during the healing time, did not adversely affect the maturation process of the periodontal apparatus.  Moreover, intrusion seven to ten days after OFD of migrated maxillary incisors with infrabony defects has been shown to result in CAL gain, PPD reduction and an elimination or decrease in defect volume. 36,[54][55][56] Therefore, in the management of pathologically migrated teeth, adjunctive orthodontic treatment may be the best clinical practice due to the additional aesthetic benefits offered by resolving the commonly encountered midline diastema and elongated teeth in the aesthetic zone. Interestingly, it was suggested that early OTM might be effective in assisting the coronal shift of the soft tissues with considerable aesthetic gain. 36 The best results were obtained when tooth intrusion was performed with light forces (5-15 g per tooth) and with the line of action of the force passing close to the CR. 4 It is important to note that the periodontal surgical treatment preceding orthodontic intrusion is essential for the large decrease in PPD observed. The systematic review studies agree with the above conclusions but the lack of sound scientific evidence is stressed. 9,62 Histologically, in all but one of the experimental studies, it was shown that an infrabony defect was filled without the formation of a new attachment but with LJE healing. 39,41,[43][44][45] Similarly, Geraci et al. 40 observed new connective tissue attachment formation in twoand three-wall infrabony defects. It is possible that the different methodologies used for the creation of the defects might account for the reported results. It seems that two-and three-wall pockets have an increased potential for regeneration due to greater possibilities for in-growth of connective tissue from the lateral walls. 12 Although in the animal study, 40 three-wall infrabony defects were successfully treated with OTM, reviews 53,61 of clinical studies argue that orthodontic movement alone cannot reproducibly improve threewall pockets. A similar conclusion was indicated for interproximal craters. Therefore, it is important to appreciate that, after proper inflammation control, OTM alone may be successfully used to resolve oneand two-wall defects, whereas in cases of three-wall lesions and interproximal craters, pre-orthodontic regenerative or osseous surgery, respectively, may be necessary. The need for surgery should be based on the patient's response to initial treatment, the patient's periodontal resistance, the location of the defect and the predictability of maintaining defects nonsurgically while the patient is wearing orthodontic appliances. 53

Furcation defects (Class I, Class II and Class III)
It has been shown that it is hard to manage furcation defects during orthodontic treatment. 53,61 A retrospective study 38 showed that if tipped molars with furcation involvement are orthodontically uprighted, simultaneous extrusion might increase the severity of the furcation defects, especially in the presence of inflammation. Excessive force application and poor inflammation control, rather than OTM, may have been the main reasons for periodontal deterioration. Nonetheless, pre-orthodontic osseous (for Class I) or regenerative therapy (for Class II) and other treatment modalities such as OFD, hemisection and root amputation (for Class III) might be indicated depending on the type of furcation lesion. 53,61 Indeed, an experimental study 46 performed in animals reported that intrusion after OFD in Class III furcation defects may improve bone in-fill and reduce the clinical size of these defects.

Alveolar bone defects
Alveolar bone defects, such as extraction sites, may also be successfully treated with adjunctive OTM, 42,44,52 but bone apposition was found to be less compared with infrabony defects. 44 An interesting approach when managing extraction site defects of teeth with a poor prognosis for subsequent implant placement is the use of orthodontic extrusion of the 'hopeless' teeth in order to enhance the soft and hard tissue topography of potential implant recipient sites, prior to tooth extraction. 52

Adjunctive orthodontic treatment in periodontal defects treated with regenerative surgery
It has been indicated that OTM might be a stimulating factor for bone apposition. 42,44 This could be due to an increase in the number of mitotic cells in the PDL 14 enhancing connective tissue healing, as well as restricting JE apical down-growth. 45 Therefore, it is suggested that, even if OTM itself does not guide new connective tissue attachment formation, it could be used to enhance the results of regenerative therapy. 45,74 In turn, regenerative periodontal procedures, with the use of bone synthetic materials, 80 could be implemented prior to OTM in order to create favourable pre-orthodontic conditions in complex cases. 9 Although clinical studies have shown it is possible to treat deep infrabony defects with OFD and subsequent OTM by inducing osteogenesis, 55 only periodontal regeneration procedures have been proven capable of providing new connective tissue attachment in humans. 82

Feasibility of OTM in regenerated areas
Animal studies indicate that teeth can be moved into defective bone areas previously filled with a xenograft with no adverse effect on the regenerative healing process or root resorption. 63,66 It has been observed that, after OTM, the biomaterial was replaced by new bone. However, the success of OTM when using synthetic bone replacement material is strongly linked to the choice of material, according to the likelihood of its resorption, or its participation in the remodelling processes. 80 Similar findings were shown in a case report, 70 in a descriptive case series 73 and a clinical review study. 78 Specifically, in the review study, 78 it was concluded that OTM in, and tooth eruption through, certain non-autogenous bone graft materials is possible and might provide positive results. However, when reviewing different regenerative materials, the report supported that hydroxyapatite (HA) ceramic cannot be recommended prior to OTM due to possible adverse effects related to dental malformations, root resorption or stagnation of tooth movement. However, tricalcium phosphate (TCP) was reported to be promising. In addition, it was mentioned that bioglasses used in conjunction with OTM may show positive results but their use is questioned. The low level of currently available evidence was stressed, as was the impossibility of providing recommendations or guidelines related to material use. 78 An RCT has also reported the successful outcome of OTM in two-and three-wall defects treated with allografts (EMD/DFDBA). 79 Moreover, a clinical case series has shown that OTM could be successfully undertaken after GTR with no damage to the regenerated tissues. 69,77 An extensive review on the different types and indications of regenerative materials is beyond the scope of the present study. However, additional research is considered necessary to avoid risks and possible adverse effects when moving teeth into allografts.

Time of initiation of OTM after regenerative surgery
Several clinical studies indicated that OTM was initiated only 10 to 14 days after bone grafting procedures with a xenograft. 70,73 A clinical trial even concluded that immediate application of OTM with regenerative therapy had the best clinical and radiographic outcome compared with delayed treatment (two months later) and with no adjunctive OTM. 81 The early initiation of OTM after bone grafting with bovine bone was also supported in a prospective case series. 82 In contrast, orthodonticregenerative therapy with resorbable and nonresorbable membranes required a longer healing time prior to the initiation of OTM (two to six months, up to one year) to facilitate adequate tissue healing. 69,72,74,77 A systematic review concluded that there is no clear indication concerning the timing of GTR in cases of teeth that require orthodontic intrusion. 9 The benefit of OTM on the regenerative process Most of the reviewed studies reported that OTM, although feasible, has no or minor additional benefits for the regenerated tissues when performed after regenerative therapy. 46,64,65,77 In contrast, studies that included control groups 67,79,81 determined that subsequent OTM enhanced the regenerative potential of surgical techniques. The variability in the timing of OTM after regenerative therapy and the heterogeneity in defect morphology observed in the reviewed studies could possibly account for the differences. It might be suggested that, if OTM starts well after regenerative surgery, there might not be significant changes in the clinical parameters since tooth movement occurs in mature bone. 79 Moreover, the additional benefit of OTM on eliminating three-wall defects treated with EMD/DFDBA was shown to be inconsequential, since this defect morphology is conducive for periodontal regeneration. Adjunctive OTM might be more beneficial after regenerative treatment in the case of two-wall infrabony pockets. 79 In addition, OTM performed prior to regenerative surgery was reported capable of increasing the success rate of future GTR, but this evidence is limited to a case report study. 75 It seems that additional research is needed to further explore the possible benefit of OTM on regenerative therapy as well as identify the best timing of initiation of OTM after or prior to regenerative procedures.

Level of scientific evidence
The reviewed studies present a low level of evidence and are mostly limited to experimental animal research and case reports or case series with limited sample sizes. When evaluating the results of the current search, it was considered that in animal studies the repair of the bony defects could be attributed to specific metabolic characteristics of bone tissue of each species, which may significantly differ from the bone metabolism in humans. 9 However, it is essential to study and/or review the animal study outcomes, as this is mostly the only in-depth histological evidence available. In addition, since the resulting articles showed great diversity in methodology, it was not possible to perform a quantifying review. Perhaps standardisation of future studies will permit comparability between the different clinical protocols. Nonetheless, an effort was made to critically evaluate the best evidence currently available and draw useful clinical recommendations.

Clinical recommendations
The present results in general support the concept that adjunctive orthodontic treatment should be performed in adults to modify the tissue topography, reduce or eliminate angular bony defects and therefore obviate the need for excessive bone removal. 59 Treatment can also be successfully applied in conjunction with regenerative surgery in cases in which healing with formation of new connective tissue attachment is desirable. Furthermore, treatment may create a periodontal architecture that facilitates oral hygiene and helps in the prevention of further tissue breakdown. 36,37 The most common types of adjunctive OTM presented in this review are bodily tooth movement and intrusion of pathologically migrated incisors into infrabony defects, extrusion and uprighting of mesially tipped molars and extrusion of teeth away from infrabony lesions. Since the recommended interdisciplinary clinical protocol differs based on the type of angular bony defect present, a proper diagnosis is essential. A pretreatment threedimensional assessment of the defect morphology with cone-beam computed tomography (CBCT), in addition to the traditional clinical and radiographic evaluation of the patient, is helpful in identifying the type of periodontal procedure and adjunctive tooth movement warranted in each defect site. Nevertheless, the importance of proper inflammation control, regular periodontal maintenance (in a two-to threemonth recall basis) and communication between the orthodontist and the periodontist is stressed during this interdisciplinary treatment approach.

Conclusions
The literature indicates that adjunctive orthodontic treatment in adult patients with advanced periodontal disease could be a reliable therapeutic option for realigning migrated teeth, improving the occlusion, aesthetics, function and bone architecture in complex clinical cases. Future studies should employ welldesigned RCTs in large cohorts of adult populations to provide statistical evidence of the efficacy and effectiveness of OTM alone or in combination with periodontal regenerative surgery. Such studies will also address the few controversies noted in the present review.