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Surgery-first approach in orthognathic surgery: Psychological and biological aspects – A prospective cohort study
Accepted Manuscript Surgery-first approach in orthognathic surgery: psychological and biological aspects a prospective cohort study Sebastian Zingler, Priv.-Doz., Emad Hakim, Dominic Finke, Monika Brunner, Dr., Daniel Saure, Dr., Jürgen Hoffmann, Prof., Christopher J. Lux, Prof., Ralf Erber, Dr., Robin Seeberger, Priv.-Doz. PII:
S1010-5182(17)30197-X
DOI:
10.1016/j.jcms.2017.05.031
Reference:
YJCMS 2694
To appear in:
Journal of Cranio-Maxillo-Facial Surgery
Received Date: 21 December 2016 Revised Date:
31 May 2017
Accepted Date: 31 May 2017
Please cite this article as: Zingler S, Hakim E, Finke D, Brunner M, Saure D, Hoffmann J, Lux CJ, Erber R, Seeberger R, Surgery-first approach in orthognathic surgery: psychological and biological aspects - a prospective cohort study, Journal of Cranio-Maxillofacial Surgery (2017), doi: 10.1016/ j.jcms.2017.05.031. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title page Title:
Author names with highest academic degree(s) and affiliations Sebastian (given name) Zingler (family name) Priv.-Doz. a Emad (given name) Hakim (family name) a
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Dominic (given name) Finke (family name) a
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Surgery-first approach in orthognathic surgery: psychological and biological aspects - a prospective cohort study
Monika (given name) Brunner (family name) Dr. a
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Daniel (given name) Saure (family name) Dr. b Jürgen (given name) Hoffmann (family name) Prof.
c
Christopher (given name) J. Lux (family name) Prof. a Ralf (given name) Erber (family name) Dr. a
Affiliations a
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Robin (given name) Seeberger (family name) Priv.-Doz. c
Department of Orthodontics (Head: Prof. Dr. Christopher J. Lux), University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany b
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Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130.1, 69120 Heidelberg, Germany
c
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Department of Oral and Maxillofacial Surgery (Head: Prof. Dr. Dr. Jürgen Hoffmann), University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
To whom correspondence should be addressed and to whom requests for reprints should be sent Sebastian Zingler, Department of Orthodontics, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; Tel: +49 6221 566570, fax: +49 6221 565753, email: [email protected]
Sources of support This work was supported by a grant from the Dietmar-Hopp-Stiftung
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Summary
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Introduction: The aim of this pilot study was to investigate psychological and biological changes after application of a surgery-first orthognathic treatment approach.
Methods: A prospective cohort study of 9 patients (6 women and 3 men; mean age 26.7 years)
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suffering from skeletal Class II and III deformities was conducted. Skeletal changes from pre- to
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post-treatment were analyzed based on data acquired by use of cone-beam computed tomography (CBCT). Psychological changes were analyzed using the orthognathic quality of life (OQLQ) questionnaire, Sense of Coherence 29-item scale (SOC-29) and longitudinal day-to-day questionnaire. For biological evaluation, concentrations of IL-1β, IL-6, TGF β1-3, MMP-2 and VEGF were assessed in crevicular fluid by bead-based multiplex assays at one preoperative and
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various postoperative time points.
Results: A significant improvement (P=0.015) in quality of life, as measured with the OQLQ,
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was observed between baseline and 3 months post-surgery. The most affected dimensions were: facial aesthetics (p=0.022), oral function (p=0.051) and social aspects (p=0.057). Sense of
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coherence (SOC) significantly improved after treatment by 9 points (P= 0.029). Despite the significant improvement in OQLQ and SOC during the course of the study, the personal experience of appearance varied distinctly in course and intensity. In accordance with the temporal pattern of fracture healing, the analysis of crevicular fluid revealed an increase in proresorptive factors (IL-1 β, IL-6 and MMP-2) at early postoperative time points, while remodeling factors (members of the TGF-β superfamily) were detected at later postoperative time points.
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Conclusions: Orthognathic treatment using the surgery-first approach has a positive impact on patient’s psychosocial status. Accelerated tooth movement after surgery might, to a certain extent, be due to elevated levels of bone remodeling factors with overlapping functions during
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fracture healing and tooth movement.
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Keywords: orthognathic surgery, surgery-first approach, quality of life, sense of coherence,
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orthodontic tooth movement, regional acceleratory phenomenon
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Introduction Before the 1960s, presurgical orthodontic treatment was uncommon in patients requiring
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orthognathic surgery (Sharma et al., 2015). Back in those days, surgery was usually performed either before any orthodontic treatment or after completed orthodontic treatment, with no
appliances present in the mouth at the time of surgery (Huang et al., 2014). Thus, while not
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referred to as such, surgery-first approaches were conducted in these times.
Later, presurgical dental decompensation was recommended to increase surgical jaw movement
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and to maximize stable postoperative occlusion (Bell and Creekmore, 1973). In 1976, presurgical orthodontic treatment was first described by Worms et al. (Worms et al., 1976), and in the following years three-stage orthognathic treatment protocols and concepts were established which are still valid today (Proffit and Miguel, 1995). The disadvantage of having orthodontic
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interventions both before and after orthognathic surgery include long treatment times of 7-47 months, with an increased risk of enamel decalcification, gingival recession and root resorption, as well as aesthetic and functional drawbacks during the presurgical orthodontic treatment
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(Sharma et al., 2015).
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In 1991, Brachvogel et al. (Brachvogel et al., 1991) again proposed a surgery-first concept in order to reduce disadvantages associated with long presurgical orthodontic treatments. In Asia, Europe and the US a change in paradigm can currently be observed especially because of the long treatment times associated with presurgical orthodontic treatments (Huang et al., 2014). The major advantage of the surgery-first approach is the early correction of soft tissue problems (i.e lips, cheeks, tongue) and thus rapid improvements in facial aesthetics. Serious psychosocial difficulties can be encountered in patients with dentofacial abnormalities
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like skeletal dysgnathias (Rankin and Borah, 2003). These could encompass problems with social adaption, reduced self-esteem, impaired psychosocial development and negative effects on mental health (Alanko et al., 2010). Therefore, besides aesthetic and functional improvements,
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patients also seek advancement of their psychosocial situation. Presently, little information is available regarding the impact of the surgery-first approach on patients’ psychological status or quality of life outcomes (Park et al., 2015). Most previous studies on the psychological impact of
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orthognathic treatment addressed the conventional three-stage approach (Hunt et al., 2001, Soh and Narayanan, 2013). There is also little prospective systematic documentation of patient’s
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perception during postoperative recovery (Phillips and Blakey, 2008).
Shortening of the total treatment time and accelerated tooth movement after surgery due to altered bone remodeling are the most frequently reported advantages of the surgery-first approach (Sharma et al., 2015). Altered bone remodeling after periodontal surgery was first
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described decades ago (Bohannan, 1962). The phenomenon of altered bone remodeling is not restricted to the periodontium, but is also observed after orthognathic surgery in the operation field and adjacent regions. Frost described this local tissue reaction, accelerating the healing
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process, as the regional acceleratory phenomenon (RAP) (Frost, 1983). In orthodontics,
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corticotomies or interdental osteotomies to accelerate tooth movement are currently receiving increasing attention (Hoogeveen et al., 2014). The acceleratory phenomenon is not fully understood. In particular, molecular and cellular factors, as well as the regulatory processes, are unknown. However, RAP requires the coordinated, accelerated activity of both cell types involved in bone remodeling, osteoblasts and osteoclasts, and the spatial extension of the phenomenon requires soluble diffusible factors to control these activities. Bone healing after orthognathic surgery resembles fracture healing and is characterized by the
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orchestrated release of various factors which coordinate the activity of different cell types involved in initial inflammation and hematoma formation, followed by bone repair and finally remodeling. The individual stages during bone healing are controlled mainly by three groups of
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signaling molecules: (i.) pro-inflammatory cytokines (e.g. Interleukin- (IL) 1β) and proteolytic enzymes (e.g. matrix metalloproteinase- (MMP) 2), (ii.) members of the transforming growth factor- (TGF) β superfamily (e.g. TGF- β 1, TGF- β 2 and TGF- β 3) and (iii.) angiogenic factors
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(e.g. vascular endothelial growth factor (VEGF)). Orthodontic tooth movement also requires extensive bone remodeling (Meikle, 2006), which is likewise dependent on the coordinated
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release of pro-inflammatory cytokines, TGF- β family members and angiogenic factors. During tooth movement, IL-1 β and IL-6 were detectable in gingival crevicular fluid at compression sites where bone resorption will occur (Giannopoulou et al., 2006). In the further course of orthodontic therapy, TGF- β s become demonstrable in crevicular fluid (Kobayashi et al., 2000).
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In addition, a local hypoxia caused by compressed capillaries leads to the induction of VEGF during the early phases of tooth movement (Di Domenico et al., 2012). Thus, prominent similarities exist between the regulation of bone healing and orthodontic tooth movement. The
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abundance of factors orchestrating the bone healing process might be supportive for postoperative orthodontic tooth movement. We therefore evaluated, in a pilot experiment, the
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concentrations of IL-1 β, Il-6, MMP-2 and TGF β 1-3 in crevicular fluid by bead-based multiplex assays (Luminex) at one preoperative and various postoperative time points. As patient benefits seem to be mainly attributable to a shortened duration of therapy, it is important to understand the reason for reduced absolute therapy times in surgery-first patients. Thus, the overall aim of this pilot study was two-fold: first, to investigate psychological changes and, second, to evaluate biological changes after application of a surgery-first orthognathic treatment approach. In
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particular the study aimed: - To investigate patients' oral health-related quality of life before and 3 months after surgery.
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- To evaluate changes in sense of coherence (SOC), a psychosocial construct defined as a global orientation to life (Da Rosa et al., 2015), before and after completion of treatment.
of treatment, focusing on day-to-day changes.
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- To assess changes in patient’s self-perception of facial appearance during the first three months
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- To evaluate the concentrations of IL-1 β, IL-6, TGF β 1-3, MMP-2 and VEGF in crevicular fluid by bead-based multiplex assays at one preoperative and several postoperative time points.
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Materials and methods Patients and treatment modalities
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This prospective cohort study examined a consecutive series of patients who were treated with orthognathic and orthodontic treatment using the surgery-first approach. The study protocol was
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approved by the ethics committee of the medical faculty of the University of Heidelberg (approval no. S-633/2011). The study conformed to the Declaration of Helsinki and was performed according to the guidelines of Good Clinical Practice. Before participation, all participants received full oral and written information on the aims of the study and signed a written consent form. Within 18 months, 9 consecutive patients (6 women and 3 men) with a mean age of 26.7 (SD: 8.4) years suffering from skeletal class II (n=7) and class III (n=2) malocclusion had been included in the study. All patients underwent either monomaxillary (n=4)
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or bimaxillary (n=5) orthognathic surgery. The exclusion criteria were severe crowding requiring extractions, severe facial asymmetry, syndromal facial diseases, e.g. clefts, and
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temporomandibular joint disorder. The protocol for surgery-first treatment was developed at our departments for orthodontics and maxillofacial surgery. Plaster-cast model surgery was performed in the selected patient group. A
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stable 3-point occlusal support setup was an inclusion criterion, as well as the consideration of the final position of the upper and lower anterior teeth. A positive overbite and the fitting overjet
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were determined.
Brackets (0.022 slot preadjusted edgewise brackets, Synthesis™, Ormco Corp., West Collins, Orange, USA) were bonded 1 week before surgery. The molars were banded at the same time (Ormco Corp., West Collins, Orange, USA). The initial orthodontic wire was 016x022 stainless
inactive.
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steel (Remanium®, Dentaurum, Ispringen, Germany). The initial arch wire was annealed and
All patients received orthognathic surgery performed by the same surgeon. The surgical
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technique used for the maxilla was the classic Le-Fort I osteotomy described by Bell and Epker
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(Bell and Epker, 1976). For the mandible, the high oblique sagittal split osteotomy (HSSO) described by Seeberger et al. 2013 (Seeberger et al., 2013) and the bilateral sagittal split osteotomy (BSSO) described by Hunsuck 1968 (Hunsuck, 1968) and Epker 1977 (Epker, 1977) were used. The genioplasties were performed in the classic sliding way. Internal fixation was achieved by miniplates on all of the patients. Orthodontic elastics (Dentaurum, Inspringen, Germany) were used for temporary inter-maxillary fixation. The patient's final occlusion was supported by the final splint for the first weeks postoperatively. Supporting physiotherapy
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involving muscle and mouth opening exercises started 4-8 weeks postoperatively. After splint removal, active orthodontic treatment was resumed and continued until final settling of the
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occlusion was achieved. All patients underwent CBCT scans pre- and post-treatment, before the osteosynthesis removal and at the end of the orthodontic treatment. The scans were analysed by multiplanar
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reconstruction of the data using the IPlan 3.0 software (Brainlab®; Ispringen, Germany). The pre- and post-operative data were superimposed using the image fusion tool. Anatomic skeletal
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landmarks were then defined and the sagittal (pre- and post- treatment) changes evaluated. The measurement technique is depicted in Figure 1.
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Psychological parameters
The German version (Bock et al., 2009) of the Orthognathic Quality of Life Questionnaire (OQLQ) (Cunningham et al., 2002) was used to assess quality of life scores before and 3 months
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after surgery. The OQLQ consists of 22 questions, divided into 4 domains: facial aesthetics, oral function, social aspects and awareness of dentofacial deformity. The OQLQ is based on a four-
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point Likert scale, where 1 means “it bothers you little” and 4 means “it bothers you a lot”. An N/A (not applicable) option was also added. The total OQLQ score can range from 0 to 88. A lower score suggested improvements in quality of life, whereas a higher OQLQ score indicated a reduced quality of life.
Sense of coherence (SOC) is defined as a global orientation of the individual that determines the individual’s ability to use existing resources in order to overcome difficulties and cope with life
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stressors to perform healthy behaviors and stay well (Elyasi et al., 2015). People with stronger SOC cope better with existing stressors in life. In the present study, the German version of the 29-item sense of coherence scale (SOC-29) was answered on a seven-point Likert scale before
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and at the end of treatment (within 6-12 months after debonding). A sum of SOC-29 scale points was calculated. The minimum possible SOC score was 29 and the maximum possible score was
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203. Higher scores indicated stronger SOCs.
Additionally, a day-to-day survey was performed addressing patient perception regarding
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changes in their postoperative facial appearance. The question “Are you bothered by your appearance, e.g. your face in profile?” was graded on a 10-point Likert scale, with the endpoints ‘"0 = not at all"‘ and "10 = very much", and was completed by the patients at several time points: before surgery (baseline), then every 2-3 days after surgery for the following 2-4 weeks, and
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Biological parameters
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weekly beginning from week 5; in total 24 times within 12 weeks.
Sampling of gingival crevicular fluid (GCF) and multiplex assays: Sampling of GCF was
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performed preoperatively on the day before surgery and at three post-operative time-points: postOP1 (1 d), post-OP2 (7 d) and post-OP3 (14 d). For GCF sampling, sterile paper strips (Periopaper, Oraflow, New York, NY, USA) were inserted into labial pockets of each incisor until slight resistance was felt and left in situ for 30 s (Figure 2). The strips were transferred to Eppendorf tubes (1.5 mL Protein LoBind Tubes, Eppendorf, Hamburg, Germany) prefilled with 50 µl of sterile saline solution (0.9 % NaCl) and immediately frozen at – 80°C until further processing. Before bone remodeling, factor analysis tubes containing strips were vortexed (10 s)
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and briefly centrifuged. Total volumes of eluates were determined and, if necessary, brought to a final volume of 100 µL with the appropriate sample diluent. Analysis was performed using magnetic Luminex screening assays for IL-1 β, IL-6, MMP-2 (and VEGF) from R&D Systems
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(Wiesbaden, Germany) or Bio-Plex magnetic assays for TGF- β 1-3 (BioRad, München,
Germany). Analyses were performed in duplicate according to the manufacturers’ instructions. Measurements were performed with the Bio-Plex MAGPIX multiplex reader (Bio-Rad,
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München, Germany) using the xPonent for MAGPIX software (Ver. 4.2) from Luminex.
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Concentrations were normalized for eluted volumes of crevicular fluid.
Statistics
Data from all investigations were collected and descriptive statistics performed (mean, standard
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deviation, minimum and maximum). Due to the small sample size, non-parametric statistical tests were applied: several pairwise comparisons between different time points per group were performed using Mann-Whitney-U tests. Correlations between different variables were
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calculated by Spearman’s correlation coefficient. Boxplots were used for the graphical
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representations of the findings. Two-sided p-values <0.05 were considered statistically significant. Due to the exploratory nature of the study, no adjustment was made for multiple testing. The data were processed using R 3.2.2 (www.r-project.org).
Results Treatment time, dentoskeletal characteristics and dimensions of surgical jaw movement
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The mean total treatment time following our surgery-first protocol was 15.7 (SD 3.31) months. The mean time until final splint removal was 30 (SD 11.2) days.
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Seven patients suffered from class II malocclusion; two of them in combination with apertognathia and one with laterognathia. Two of them were treated by a monomaxillary
mandibular advancement, one by monomaxillary maxillary closure of the anterior open bite. The
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remaining patients were treated by bimaxillary surgery. In three of these patients, a sliding
genioplasty for advancement of the chin was performed. Two patients suffered from class III
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malocclusion. One was treated by maxillary advancement, the other by bimaxillary surgery. HSSO of the mandible was performed on seven patients and BSSO on two patients. The patients who received BSSO showed postoperative hypaesthesia of the lower lip for 4-6 weeks. The overall postoperative follow-up was uneventful in all nine patients. The findings are summarized
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in Table 1.
The post-treatment skeletal changes were measured and analyzed at first in the sagittal plane, due to the distinct effect on the patient profile after surgery. The pogonion advanced by 5.84 mm (SD
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6.88). The maximum advancement of the mandible after bimaxillary surgery and advancing genioplasties of the chin was 16 mm. The SNA prior to treatment was in mean 80.2° (SD 3.1°)
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and post-treatment 82.7° (SD 3.78). The pre-treatment mean SNB was 75.68° (SD 6.49) and post-treatment 78.23° (SD 5.08), indicating the maxilla-mandibular advancements in the patients. The maxillary advancement measured at the prosthion was in mean 2.96 mm (SD 2.93). The vertical change in the maxilla was in mean 1.16 mm (SD 4.51) measured at the nasal spine representing the actual bony change. The vertical change on the dental level was measured at the incisor tip. The vertical dental heights changed in mean by 2.03 mm (SD 3.41). We assume that this effect is caused by (i.) the closure of the open bite and (ii.) the occlusal settling. The results
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are summarized in Table 2 for the sagittal plane and in Table 3 for the vertical plane.
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Changes in quality of life (OQLQ)
The patient completion rate for the OQLQ was 100%. The baseline (preoperative) overall OQLQ score ranged from 8 to 77, with a mean of 36 (SD= 17.24). A significant reduction (P= 0.015) in
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the overall score of the OQLQ was observed between baseline and 3-month evaluation (mean 18,
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SD=12.69, range 0-45), thus indicating a significant improvement in quality of life during the first three months of treatment. Individual domain scores are shown in Figure 3. The most affected dimensions were: facial aesthetics (p=0.022), oral function (p=0.051) and social aspects (p=0.057).
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Changes in patients’ sense of coherence (SOC-29)
All patients completed the SOC-29 questionnaire both before and at the end of treatment. There were no missing items. The pre- and post-treatment SOC-29 scores are presented in Figure 4.
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The median pre-treatment SOC-29 score was 141.0 (range 107-173). A significant increase by 9 points (P= 0.029) in median SOC-29 scores was found between pre- and post-treatment
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evaluation.
Patient perception regarding changes in facial aesthetics Most patients (8 out of 9) reported favorable facial changes after surgery (Figure 5). One patient experienced only minor aesthetic changes. Most prominent changes were experienced during the
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first week of treatment. Despite the general improvement in OQLQ and SOC during the course of the study, the personal experience of appearance was distinctively variable in course and
Multiplex cytokine analysis in crevicular fluid
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intensity.
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To evaluate basic molecular markers of bone healing, we collected crevicular fluids
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postoperatively and at different postoperative time points (post-OP1 (1 d), post-OP2 (7 d) and post-OP3 (14 d)) from 9 patients who underwent orthognathic surgery. The concentrations of IL1 β, IL-6, MMP-2 and TGF- β 1-3 were evaluated and normalized for the total volume of sampled crevicular fluid. Absolute amounts of bone remodeling factors varied between the individual patients at the different time sampling times. However, during the course of samplings
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characteristics patterns were observed. The results are displayed as mean ± SEM determined from data of all 9 patients relative to the preoperative values in Fig. 6 (A – F). In line with an initial inflammatory response in the process of bone healing, marked increases in IL1 β, IL-6
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levels compared to preoperative levels were detected at the first postoperative time point (Fig. 6,
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A, C), which was followed by distinctly reduced levels at the following time points for all patients. The course of MMP-2 (Fig. 6, E) concentrations resembled that of IL-1 β and was also characterized by a marked peak at the first postoperative time point (Fig. 6, E) and subsequently decreasing concentrations. Matrix metalloproteinases appear in the early phase of bone healing, as well as in the later remodeling phase. MMP-2 in this study was found in a temporal pattern comparable to IL-1 β , which points to an involvement of MMP-2 in early resorptive events. TGF- β 1-3 appeared at later postoperative time points (Fig. 6, B, D, F) and remained at higher
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levels compared with preoperative levels during the course of the study. In addition, we analyzed VEGF, which was detectable at highest levels at the first postoperative time point, suggesting an
Discussion Psychological impact of the surgery-first approach
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early angiogenic response after surgery (Supplemental Fig.1 A).
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In this study we measured changes in oral health-related quality of life of surgery-first patients before and after surgery. Quality of life was significantly improved 3 months after surgery. We used the condition-specific orthognathic Quality of Life Questionnaire (OQLQ), which is considered one of the most valid and sensitive instruments for orthognathic patients (Soh and
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Narayanan, 2013, Murphy et al., 2011). Our results are consistent with those of previous OQLQ studies which demonstrated significant improvements in quality of life of patients as a result of conventional orthognathic surgical treatment (Hunt et al., 2001, Soh and Narayanan, 2013).
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However, in most previous studies improvements in patients' quality of life were not evident until 6 months to 1 year after surgery (Soh and Narayanan, 2013). In the study by Park et al.
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(Park et al., 2015), Class III patients treated either by conventional or surgery-first approaches were asked to estimate, retrospectively, their OQLQ scores just before and 3 months after surgery. Within this time span, the authors observed an improvement in the mean total OQLQ scores by more than 50%, which is consistent with our findings. In the present study, mean total OQLQ scores of the patients were lower than those of patients in the study by Park et al. (Park et al., 2015). These differences may partly be explained by differences in sample characteristics
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(i.e. type of malocclusion, ethnic and cultural differences) and study design. Regarding the dimensions of the OQLQ, we found the highest changes in facial aesthetics, followed by oral function, social aspects and awareness of dentofacial deformity. Similar findings were reported
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by Lee et al. (Lee et al., 2008), Choi et al. (Choi et al., 2010) and also Park et al. (Park et al., 2015).
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In addition to the OQLQ questionnaire, all patients completed the SOC-29 questionnaire before and after active orthodontic treatment. Antonovsky introduced the theory of salutogenesis and
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the terms sense of coherence and general resistance resources into psychology (Antonovsky, 1993). The theory of salutogenesis aimed to solve the question of why some people encountering major stress and severe adversity stay healthy and others do not. The answer was based on the sense of coherence (SOC) and the general resistance resources (GRRs). The SOC defines an enduring attitude facilitating quantification of how people view their lives and use GRRs under
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stress in order to maintain and improve their health. The SOC consists of at least three dimensions: comprehensibility, manageability and meaningfulness. GRRs are, for instance, wealth, intelligence, self-esteem, preventive health orientation and social support. Equipped with
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such resources, people will cope better with the challenges of life.
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To the best of our knowledge, this is the first study to assess sense of coherence levels in orthognathic patients. The surgery-first approach used in this study led to improved values after treatment. Thus, orthognathic patients experience more meaningfulness, intelligibility and selfefficacy. We used an adapted German version of the SOC-29 that proved to have high internal consistency with Cronbach’s alpha coefficients, ranging from .87 to .90 for the global scale and the subscales (Singer and Brähler, 2007). In the present study, the mean pre-treatment SOC-29 score of the patients was 138.36 (SD: 19.46). Compared to a German general population sample
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(mean 155.87, SD: 22.16) (Hannöver et al., 2004) the present sample scored significantly lower for SOC (p=0.0089), suggesting that there is potential for improving orthognathic patients' SOCs. An increase by 9 points in median SOCs was found between pre- and post-treatment
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evaluations. It should be pointed out that, post-therapy, no significant differences between SOC scores of orthognathic patients within this study and the general German population (Hannover et al., 2004) were evident (p=0.129). The present study also supports results from other studies
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showing that SOCs can be improved after intervention (Langeland et al., 2013).
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Patients reported favorable facial changes after surgery. However, despite the general improvement in OQLQ and SOC during the course of the study, the personal experience of appearance was distinctively variable in course and intensity. The results underline that postsurgical recovery varies from individual to individual, and emphasizes the need for careful monitoring, particularly during the first months after surgery. The results also demonstrate that
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individual patients may experience difficulties which are not detectable when analyzing mean scores only. Additional studies focusing on day-to-day changes are necessary to further
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investigate the psychological impact of the orthognathic treatment approach.
Bone healing and orthodontic tooth movement The beneficial effects of the surgery-first concept for orthognathic surgery are mainly due to accelerated orthodontic tooth movement. Thus, quality of life and overall satisfaction of patients might, to a notable extent, be dependent on the biological reason for the observed accelerated tooth movements after surgery. We hypothesized that various molecular factors which are massively elevated during bone healing after surgical procedures, and which are also involved in
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the regulation of bone remodeling during orthodontic tooth movement, are responsible for the acceleration of orthodontic tooth movement-dependent bone remodeling. Although the data gathered in this study is certainly not sufficient as reasonable proof for this theory, the courses of
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the levels of the bone remodeling factors compiled in this study support the hypothesis.
IL-1 β and IL-6, both pro-inflammatory markers associated with early inflammation after bone
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injury, were elevated in crevicular fluids shortly after surgery. MMP-2, as an example for collagenases and matrix-metalloproteinases involved in early resorptive as well as later
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remodeling events, showed a comparable temporal expression pattern. This was also the case for the paramount angiogenic factor VEGF, which is also known to be elevated early after bone injury. In contrast, TGF β 1-3, members of the TGF- β superfamily, were detectable at elevated levels at later time points than IL-1 β, IL-6 or MMP-2. These results are in agreement with the role of TGF β 1 in bone healing, where it induces osteoblast migration proliferation and
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differentiation (Tang et al., 2009). TGF- β s might act in synergy with overlapping functions during bone remodeling since TGF- β 2 and TGF- β 2 mimic TGF- β 1 function during the
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inhibition of osteoclastogenesis by inducing osteoprotegerin (Thirunavukkarasu et al., 2001). Bone remodeling initiated after the application of orthodontic forces is likewise dependent on the
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factors elevated during bone healing; the relative abundance of these factors after orthognathic surgical interventions might therefore contribute to the accelerated tooth movement in patients treated according to the surgery-first concept. Thus, we propose that patient satisfaction after surgery-first therapy is, to a relevant extent, attributable to accelerated tooth movement caused by the abundance of a variety of bone remodeling factors which function both in bone healing and in tooth movement. Clearly, further studies are needed to provide sufficient evidence for this concept.
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Conclusion
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The findings of this prospective clinical pilot study provide a new insight into psychological and biological aspects regarding orthognathic surgery using the surgery-first concept. Within the limitations of the study we conclude:
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(1) Total mean OQLQ scores significantly improved by more than 50 percent during the first
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three months of treatment, indicating that patients experienced a significant improvement in quality of life. The most affected OQLQ domains were facial aesthetics, oral function and social aspects.
(2) The sense of coherence (SOC) improved significantly after treatment. This suggests that
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surgical orthodontics improved patients' experience of meaningfulness and self-efficacy. (3) Changes in individual appearance were positively experienced by 90% of patients. Most prominent changes were experienced during the first week of treatment. Despite the general
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improvement in QLQ and SOC during the course of the study, the personal experience of appearance was distinctively variable in course and intensity. The results emphasize the need for
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careful monitoring of the psychological status in patients during the first three months of treatment.
(4) Biological aspects: From the data gathered within this study we propose that accelerated tooth movement after surgery is, to a relevant extent, due to elevated levels of bone remodeling factors required for fracture healing. Clearly, further studies are needed to provide sufficient evidence for this concept.
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Ethical approval
University of Heidelberg (approval no. S-633/2011).
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Sources of support
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The study protocol was approved by the ethics committee of the medical faculty of the
This work was supported by a grant from the Dietmar Hopp Stiftung.
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Competing interests
None of the authors claim a conflict of interest. Acknowledgements
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The authors wish to thank Ms. Edith Daum for supporting the MagPix Assays.
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List of references Alanko OM, Svedstrom-Oristo AL, Tuomisto MT: Patients' perceptions of orthognathic
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treatment, well-being, and psychological or psychiatric status: a systematic review. Acta Odontol Scand 68:249 260, 2010.
Antonovsky A: The structure and properties of the sense of coherence scale. Soc Sci Med 36:725
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733, 1993.
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Bell WH, Creekmore TD: Surgical-orthodontic correction of mandibular prognathism. Am J Orthod 63:256 270, 1973.
Bell WH, Epker BN: Surgical-orthodontic expansion of the maxilla. Am J Orthod 70:517 528, 1976.
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Bock JJ, Odemar F, Fuhrmann RA: Assessment of quality of life in patients undergoing orthognathic surgery. J Orofac Orthop 70:407 419, 2009.
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Bohannan HM: Studies in the alteration of vestibular depth I. Complete denudation. J Periodontol 33:354 359, 1962.
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Brachvogel P, Berten JL, Hausamen JE: [Surgery before orthodontic treatment: a concept for timing the combined therapy of skeletal dysgnathias]. Dtsch Zahn Mund Kieferheilkd Zentralbl 79:557 563, 1991.
Choi WS, Lee S, McGrath C, Samman N: Change in quality of life after combined orthodonticsurgical treatment of dentofacial deformities. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:46 51, 2010.
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Cunningham SJ, Garratt AM, Hunt NP: Development of a condition-specific quality of life measure for patients with dentofacial deformity: II. Validity and responsiveness testing.
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Community Dent Oral Epidemiol 30:81 90, 2002. da Rosa AR, Abegg C, Ely HC: Sense of Coherence and Toothache of Adolescents from Southern Brazil. J Oral Facial Pain Headache 29:250 256, 2015.
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Di Domenico M, D'Apuzzo F, Feola A, Cito L, Monsurro A, Pierantoni GM, Berrino L, De Rosa A, Polimeni A, Perillo L: Cytokines and VEGF induction in orthodontic movement in animal
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models. J Biomed Biotechnol 2012:Article ID 201689, 2012
Elyasi M, Abreu LG, Badri P, Saltaji H, Flores-Mir C, Amin M: Impact of Sense of Coherence on Oral Health Behaviors: A Systematic Review. PLoS One 10:e0133918, 2015.
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Epker BN: Modifications in the sagittal osteotomy of the mandible. J Oral Surg 35:157 159,
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Frost HM: The regional acceleratory phenomenon: a review. Henry Ford Hosp Med J 31:3 9,
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Giannopoulou C, Dudic A, Kiliaridis S: Pain discomfort and crevicular fluid changes induced by orthodontic elastic separators in children. J Pain 7:367 376, 2006. Hannöver W, Michael A, Meyer C, Rumpf HJ, Hapke U, John U: Antonovsky's sense of coherence scale and presentation of a psychiatric diagnosis. Psychother Psych Med 54:179 186, 2004. Hoogeveen EJ, Jansma J, Ren Y: Surgically facilitated orthodontic treatment: a systematic
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review. Am J Orthod Dentofacial Orthop 145:51 64, 2014. Huang CS, Hsu SS, Chen YR: Systematic review of the surgery-first approach in orthognathic
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surgery. Biomed J 37:184 190, 2014. Hunsuck EE: A modified intraoral sagittal splitting technic for correction of mandibular prognathism. J Oral Surg 26:250 253, 1968.
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Hunt OT, Johnston CD, Hepper PG, Burden DJ: The psychosocial impact of orthognathic
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surgery: a systematic review. Am J Orthod Dentofacial Orthop 120:490 497, 2001. Kobayashi Y, Hashimoto F, Miyamoto H, Kanaoka K, Miyazaki-Kawashita Y, Nakashima T, Shibata M, Kobayashi K, Kato Y, Sakai H: Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression. J
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Bone Miner Res 15:1924 1934, 2000.
Langeland E, Robinson HS, Moum T, Larsen MH, Krogstad AL, Wahl AK: Promoting sense of coherence: Salutogenesis among people with psoriasis undergoing patient education in climate
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therapy. BMC Psychol 1:11, 2013.
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Lee S, McGrath C, Samman N: Impact of orthognathic surgery on quality of life. J Oral Maxillofac Surg 66:1194 1199, 2008. Meikle MC: The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J Orthod 28:221 240, 2006. Murphy C, Kearns G, Sleeman D, Cronin M, Allen PF: The clinical relevance of orthognathic surgery on quality of life. Int J Oral Maxillofac Surg 40:926 930, 2011.
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Park JK, Choi JY, Yang IH, Baek SH: Patient's Satisfaction in Skeletal Class III Cases Treated With Two-Jaw Surgery Using Orthognathic Quality of Life Questionnaire: Conventional Three-
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Stage Method Versus Surgery-First Approach. J Craniofac Surg 26:2086 2093, 2015. Phillips C, Blakey G, 3rd: Short-term recovery after orthognathic surgery: a medical daily diary approach. Int J Oral Maxillofac Surg 37:892 896, 2008.
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Adult Orthodon Orthognath Surg 10:35, 1995.
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Proffit WR, Miguel JA: The duration and sequencing of surgical-orthodontic treatment. Int J
Rankin M, Borah GL: Perceived functional impact of abnormal facial appearance. Plast Reconstr Surg 111:2140 2146, 2003.
Seeberger R, Thiele OC, Mertens C, Hoffmann J, Engel M: Proximal segment positioning with
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high oblique sagittal split osteotomy: indications and limits of intraoperative mobile cone-beam computerized tomography. Oral Surg Oral Med Oral Pathol Oral Radiol 115:731 736, 2013. Sharma VK, Yadav K, Tandon P: An overview of surgery-first approach: Recent advances in
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orthognathic surgery. J Orthod Sci 4: 9 12, 2015.
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Singer S, Brähler E: Die „Sense ofo Coherence Scale“ Testhandbuch zur deutschen Version. Göttingen: Vandenhoek & Ruprecht, 2007. Soh CL, Narayanan V: Quality of life assessment in patients with dentofacial deformity undergoing orthognathic surgery--a systematic review. Int J Oral Maxillofac Surg 42:974 980, 2013. Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z, Zhao L, Nagy TR, Peng X, Hu J, Feng X, Van
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Hul W, Wan M, Cao X: TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med 15:757 765, 2009.
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Thirunavukkarasu K, Miles RR, Halladay DL, Yang X, Galvin RJ, Chandrasekhar S, Martin TJ, Onyia JE: Stimulation of osteoprotegerin (OPG) gene expression by transforming growth factor-
Chem 276:36241 36250, 2001.
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beta (TGF-beta). Mapping of the OPG promoter region that mediates TGF-beta effects. J Biol
Worms FW, Isaacson RJ, Speidel TM: Surgical orthodontic treatment planning: profile analysis
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and mandibular surgery. Angle Orthod 46:1 25, 1976.
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Captions to illustrations Table 1: Summary of patients and their malocclusions, together with the surgery performed and
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the technique applied
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Table 2: Pre- to post-treatment skeletal and dental changes in the sagittal plane.
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Table 3. Pre- to post-treatment skeletal and dental changes in the vertical plane.
Figure 1: Display of the measurement of anatomic landmarks for the pre- and postoperative evaluation of changes through orthognathic surgery. Blue is the preoperative situation and
data.
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magenta the postoperative result after image fusion and in the multiplanar reconstruction of the
Figure 2: For gingival crevicular fluid sampling sterile paper strips were inserted into labial
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pockets of each incisor
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Figure 3: Comparison of pre-treatment (T1, black) and post-treatment (T2, white) OQLQ scores by the four domains (medians and interquartile ranges and 3rd and 97th percentiles; crosses: mean values)
Figure 4: Comparison of pre-treatment (T1, left) and post-treatment (T2, right) SOC scores (medians and interquartile ranges and 3rd and 97th percentiles; crosses: mean values) Figure 5. Patient’s self perception of facial appearance during the first 93 days of treatment. The
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question “Are you bothered by your appearance, e.g. your face in profile?” was graded on a 10-
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point Likert scale with the endpoints "0 = not at all" and "10 = very much".
Figure 6. Bone remodelling factors in gingival crevicular fluid of surgery-first patients: Bone remodelling factors (IL-1 β (Interleukin-1 β); IL-6 (Interleukin-6), MMP-2 (Matrix
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metalloproteinase-2), TGF- β 1-3 (Transforming growth factor- β 1-3) were evaluated by
magnetic multiplex assays in crevicular fluid collected postoperatively (on the day before
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surgery) and at three postoperative time points post-OP1 (1 d), post-OP2 (7 d) and post-OP3. IL1 β (A), IL-6 (C) and MMP-2 (E) were detected before the members of the TGF-β superfamily TGF- β 1 (B) TGF- β 2 (D) and TGF- β 1 (F). The levels of bone remodelling factors are presented relative to preoperative levels (mean ± SEM, n=9). Factors were measured in
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duplicate.
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Supplemental Figure 1 VEGF (vascular endothelial growth factor levels in gingival crevicular fluid of surgery first patients. Gingival crevicular fluid was collected postoperatively (on the day before surgery) and at three postoperative time points post-OP1 (1 d), post-OP2 (7 d) and post-
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OP3.VEGF (A) was detectable at highest levels at the first postoperative time point, in
accordance with increased angiogenesis following vascular damage. VEGF levels are presented
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relative to preoperative levels (mean ± SEM, n=9). VEGF was measured in duplicate.
ACCEPTED MANUSCRIPT Tables Table 1: Summary of patients and their malocclusions, together with the surgery performed and the technique applied. Malocclusion
Surgery
Technique
Complications
Class II Class II Class II; Laterognathia Class II Class II; Apertognathia Class II
Monomaxillary mandible Monomaxillary mandible Bimaxillary Bimaxillary Bimaxillary Bimaxillary
HSSO HSSO HSSO HSSO; Genioplasty HSSO; Genioplasty BSSO
Class III
Bimaxillary
Class III Class II; Apertognathia
Monomaxillary maxilla Monomaxillary maxilla
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None None None None None Hypaesthesia of the lower lip for 6 weeks BSSO Hypaesthesia of the lower lip for 4 weeks LeFort I None 3-piece-maxilla; Genioplasty None
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Mean
Min
Max
SD
Value
5.14
- 3.0
15.4
6.96
mm
Pogonion
5.84
- 2.2
16.0
6.88
mm
Mental foramen left
4.27
- 3.6
11.9
5.59
mm
Mental foramen right
5.17
- 0.5
12.7
4.82
mm
Apex 13
2.18
- 0.4
4.6
Crown 13
2.37
- 0.9
7.4
Apex 23
2.68
- 0.9
7.0
Crown 23
2.42
- 0.9
7.3
Apex 33
5.02
- 2.3
14.6
Apex 43
5.04
- 1.6
13.2
Mandibular foramen left
1.58
- 3.0
Mandibular foramen right
2.82
0.0
A-point
2.52
0.0
B-point
4.73
Prosthion
2.96
Mesiobuccal apex 16
2.60
Mesiobuccal apex 26
2.62
SNA post
82.68
SNB pre
75.68
N-B-point pre N-B-point post N-Pogonion pre
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N-Pogonion post
mm
2.66
mm
2.89
mm
5.81
mm
5.39
mm
5.5
2.89
mm
8.0
2.94
mm
5.7
1.98
mm
- 2.7
12.8
5.17
mm
0.0
4.0
2.93
mm
0.0
6.0
2.13
mm
0.0
6.7
2.45
mm
76.1
84.3
3.10
degrees
77.8
87.7
3.78
degrees
64.4
87.7
6.49
degrees
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2.85
78.23
71.0
87.6
5.08
degrees
98.40
87.5
107.0
7.22
degrees
96.09
85.7
107.6
7.49
degrees
111.31
100.6
118.3
6.69
degrees
110.90
98.6
122.2
7.64
degrees
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SNB post
mm
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80.21
1.64
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SNA pre
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Menton
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Min
Max
SD
Value
Menton
- 0.62
- 4.3
2.1
2.22
mm
Pogonion
- 0.07
- 4.5
5.1
3.07
mm
Mental foramen left
1.34
- 0.7
4.4
1.87
mm
Mental foramen right
0.43
- 4.0
3.7
2.02
mm
Apex 13
0.57
- 3.4
5.8
2.98
mm
Crown 13
0.66
- 4.0
6.0
3.15
mm
Apex 23
0.44
- 3.5
4.4
2.62
mm
Crown 23
1.17
- 2.7
7.3
3.25
mm
Apex 33
2.28
- 1.4
7.2
2.74
mm
Apex 43
1.64
- 4.0
5.2
2.62
mm
Mandibular foramen left
- 0.32
- 2.7
1.4
1.24
mm
Mandibular foramen right
- 0.86
- 4.4
0.0
1.43
mm
A-point
0.82
- 6.7
8.0
4.54
mm
B-point
1.76
- 2.4
6.8
2.87
mm
Prosthion
0.81
- 4.3
8.6
4.33
mm
Nasal spine
1.16
- 3.3
9.0
4.51
mm
Mesiobuccal apex 16
0.10
- 6.3
3.0
2.79
mm
Mesiobuccal apex 26
1.16
- 1.6
4.8
2.10
mm
Incisor Tip
2.03
- 2.3
8.2
3.41
mm
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Variables
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Figures
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Figure 1: Display of the measurement of anatomic landmarks for the pre- and postoperative evaluation of changes through orthognathic surgery. Blue is the preoperative situation and magenta the postoperative result after image fusion and in the multiplanar reconstruction of the data.
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Figure 2: For gingival crevicular fluid sampling sterile paper strips were inserted into labial pockets of each incisor
EP
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Figure 3: Comparison of pre-treatment (T1, black) and post-treatment (T2, white) OQLQ
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scores by the four domains (medians and interquartile ranges and 3rd and 97th percentiles; crosses: mean values)
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Figure 4: Comparison of pre-treatment (T1, left) and post-treatment (T2, right) SOC scores (medians and interquartile ranges and 3rd and 97th percentiles; crosses: mean values)
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Figure 5. Patient’s self perception of facial appearance during the first 93 days of treatment. The question “Are you bothered by your appearance, e.g. your face in profile?” was graded on a 10-point Likert scale with the endpoints "0 = not at all" and "10 = very much".
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Figure 6. Bone remodelling factors in gingival crevicular fluid of surgery-first patients: Bone remodelling factors (IL-1β (Interleukin-1β); IL-6 (Interleukin-6), MMP-2 (Matrix metalloproteinase-2), TGF-β1-3 (Transforming growth factor-β1-3) were evaluated by magnetic multiplex assays in crevicular fluid collected postoperatively (on the day before surgery) and at three postoperative time points post-OP1 (1 d), post-OP2 (7 d) and postOP3. IL-1β (A), IL-6 (C) and MMP-2 (E) were detected before the members of the TGF-β superfamily TGF-β1 (B) TGF-β2 (D) and TGF-β1 (F). The levels of bone remodelling factors are presented relative to preoperative levels (mean ± SEM, n=9). Factors were measured in duplicate.
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A VEGF 20
15
10
5
0 pre-OP
post OP 1 post OP 2 post-OP 3
Sampling
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VEGF (fold of pre-OP level)
25
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Supplemental Figure 1 VEGF (vascular endothelial growth factor levels in gingival crevicular fluid of surgery first patients. Gingival crevicular fluid was collected postoperatively (on the day before surgery) and at three postoperative time points post-OP1 (1 d), post-OP2 (7 d) and post-OP3.VEGF (A) was detectable at highest levels at the first postoperative time point, in accordance with increased angiogenesis following vascular damage. VEGF levels are presented relative to preoperative levels (mean ± SEM, n=9). VEGF was measured in duplicate.
S1010-5182(17)30197-X
DOI:
10.1016/j.jcms.2017.05.031
Reference:
YJCMS 2694
To appear in:
Journal of Cranio-Maxillo-Facial Surgery
Received Date: 21 December 2016 Revised Date:
31 May 2017
Accepted Date: 31 May 2017
Please cite this article as: Zingler S, Hakim E, Finke D, Brunner M, Saure D, Hoffmann J, Lux CJ, Erber R, Seeberger R, Surgery-first approach in orthognathic surgery: psychological and biological aspects - a prospective cohort study, Journal of Cranio-Maxillofacial Surgery (2017), doi: 10.1016/ j.jcms.2017.05.031. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title page Title:
Author names with highest academic degree(s) and affiliations Sebastian (given name) Zingler (family name) Priv.-Doz. a Emad (given name) Hakim (family name) a
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Dominic (given name) Finke (family name) a
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Surgery-first approach in orthognathic surgery: psychological and biological aspects - a prospective cohort study
Monika (given name) Brunner (family name) Dr. a
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Daniel (given name) Saure (family name) Dr. b Jürgen (given name) Hoffmann (family name) Prof.
c
Christopher (given name) J. Lux (family name) Prof. a Ralf (given name) Erber (family name) Dr. a
Affiliations a
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Robin (given name) Seeberger (family name) Priv.-Doz. c
Department of Orthodontics (Head: Prof. Dr. Christopher J. Lux), University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany b
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Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130.1, 69120 Heidelberg, Germany
c
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Department of Oral and Maxillofacial Surgery (Head: Prof. Dr. Dr. Jürgen Hoffmann), University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
To whom correspondence should be addressed and to whom requests for reprints should be sent Sebastian Zingler, Department of Orthodontics, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; Tel: +49 6221 566570, fax: +49 6221 565753, email: [email protected]
Sources of support This work was supported by a grant from the Dietmar-Hopp-Stiftung
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Summary
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Introduction: The aim of this pilot study was to investigate psychological and biological changes after application of a surgery-first orthognathic treatment approach.
Methods: A prospective cohort study of 9 patients (6 women and 3 men; mean age 26.7 years)
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suffering from skeletal Class II and III deformities was conducted. Skeletal changes from pre- to
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post-treatment were analyzed based on data acquired by use of cone-beam computed tomography (CBCT). Psychological changes were analyzed using the orthognathic quality of life (OQLQ) questionnaire, Sense of Coherence 29-item scale (SOC-29) and longitudinal day-to-day questionnaire. For biological evaluation, concentrations of IL-1β, IL-6, TGF β1-3, MMP-2 and VEGF were assessed in crevicular fluid by bead-based multiplex assays at one preoperative and
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various postoperative time points.
Results: A significant improvement (P=0.015) in quality of life, as measured with the OQLQ,
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was observed between baseline and 3 months post-surgery. The most affected dimensions were: facial aesthetics (p=0.022), oral function (p=0.051) and social aspects (p=0.057). Sense of
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coherence (SOC) significantly improved after treatment by 9 points (P= 0.029). Despite the significant improvement in OQLQ and SOC during the course of the study, the personal experience of appearance varied distinctly in course and intensity. In accordance with the temporal pattern of fracture healing, the analysis of crevicular fluid revealed an increase in proresorptive factors (IL-1 β, IL-6 and MMP-2) at early postoperative time points, while remodeling factors (members of the TGF-β superfamily) were detected at later postoperative time points.
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Conclusions: Orthognathic treatment using the surgery-first approach has a positive impact on patient’s psychosocial status. Accelerated tooth movement after surgery might, to a certain extent, be due to elevated levels of bone remodeling factors with overlapping functions during
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fracture healing and tooth movement.
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Keywords: orthognathic surgery, surgery-first approach, quality of life, sense of coherence,
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orthodontic tooth movement, regional acceleratory phenomenon
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Introduction Before the 1960s, presurgical orthodontic treatment was uncommon in patients requiring
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orthognathic surgery (Sharma et al., 2015). Back in those days, surgery was usually performed either before any orthodontic treatment or after completed orthodontic treatment, with no
appliances present in the mouth at the time of surgery (Huang et al., 2014). Thus, while not
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referred to as such, surgery-first approaches were conducted in these times.
Later, presurgical dental decompensation was recommended to increase surgical jaw movement
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and to maximize stable postoperative occlusion (Bell and Creekmore, 1973). In 1976, presurgical orthodontic treatment was first described by Worms et al. (Worms et al., 1976), and in the following years three-stage orthognathic treatment protocols and concepts were established which are still valid today (Proffit and Miguel, 1995). The disadvantage of having orthodontic
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interventions both before and after orthognathic surgery include long treatment times of 7-47 months, with an increased risk of enamel decalcification, gingival recession and root resorption, as well as aesthetic and functional drawbacks during the presurgical orthodontic treatment
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(Sharma et al., 2015).
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In 1991, Brachvogel et al. (Brachvogel et al., 1991) again proposed a surgery-first concept in order to reduce disadvantages associated with long presurgical orthodontic treatments. In Asia, Europe and the US a change in paradigm can currently be observed especially because of the long treatment times associated with presurgical orthodontic treatments (Huang et al., 2014). The major advantage of the surgery-first approach is the early correction of soft tissue problems (i.e lips, cheeks, tongue) and thus rapid improvements in facial aesthetics. Serious psychosocial difficulties can be encountered in patients with dentofacial abnormalities
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like skeletal dysgnathias (Rankin and Borah, 2003). These could encompass problems with social adaption, reduced self-esteem, impaired psychosocial development and negative effects on mental health (Alanko et al., 2010). Therefore, besides aesthetic and functional improvements,
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patients also seek advancement of their psychosocial situation. Presently, little information is available regarding the impact of the surgery-first approach on patients’ psychological status or quality of life outcomes (Park et al., 2015). Most previous studies on the psychological impact of
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orthognathic treatment addressed the conventional three-stage approach (Hunt et al., 2001, Soh and Narayanan, 2013). There is also little prospective systematic documentation of patient’s
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perception during postoperative recovery (Phillips and Blakey, 2008).
Shortening of the total treatment time and accelerated tooth movement after surgery due to altered bone remodeling are the most frequently reported advantages of the surgery-first approach (Sharma et al., 2015). Altered bone remodeling after periodontal surgery was first
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described decades ago (Bohannan, 1962). The phenomenon of altered bone remodeling is not restricted to the periodontium, but is also observed after orthognathic surgery in the operation field and adjacent regions. Frost described this local tissue reaction, accelerating the healing
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process, as the regional acceleratory phenomenon (RAP) (Frost, 1983). In orthodontics,
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corticotomies or interdental osteotomies to accelerate tooth movement are currently receiving increasing attention (Hoogeveen et al., 2014). The acceleratory phenomenon is not fully understood. In particular, molecular and cellular factors, as well as the regulatory processes, are unknown. However, RAP requires the coordinated, accelerated activity of both cell types involved in bone remodeling, osteoblasts and osteoclasts, and the spatial extension of the phenomenon requires soluble diffusible factors to control these activities. Bone healing after orthognathic surgery resembles fracture healing and is characterized by the
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orchestrated release of various factors which coordinate the activity of different cell types involved in initial inflammation and hematoma formation, followed by bone repair and finally remodeling. The individual stages during bone healing are controlled mainly by three groups of
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signaling molecules: (i.) pro-inflammatory cytokines (e.g. Interleukin- (IL) 1β) and proteolytic enzymes (e.g. matrix metalloproteinase- (MMP) 2), (ii.) members of the transforming growth factor- (TGF) β superfamily (e.g. TGF- β 1, TGF- β 2 and TGF- β 3) and (iii.) angiogenic factors
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(e.g. vascular endothelial growth factor (VEGF)). Orthodontic tooth movement also requires extensive bone remodeling (Meikle, 2006), which is likewise dependent on the coordinated
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release of pro-inflammatory cytokines, TGF- β family members and angiogenic factors. During tooth movement, IL-1 β and IL-6 were detectable in gingival crevicular fluid at compression sites where bone resorption will occur (Giannopoulou et al., 2006). In the further course of orthodontic therapy, TGF- β s become demonstrable in crevicular fluid (Kobayashi et al., 2000).
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In addition, a local hypoxia caused by compressed capillaries leads to the induction of VEGF during the early phases of tooth movement (Di Domenico et al., 2012). Thus, prominent similarities exist between the regulation of bone healing and orthodontic tooth movement. The
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abundance of factors orchestrating the bone healing process might be supportive for postoperative orthodontic tooth movement. We therefore evaluated, in a pilot experiment, the
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concentrations of IL-1 β, Il-6, MMP-2 and TGF β 1-3 in crevicular fluid by bead-based multiplex assays (Luminex) at one preoperative and various postoperative time points. As patient benefits seem to be mainly attributable to a shortened duration of therapy, it is important to understand the reason for reduced absolute therapy times in surgery-first patients. Thus, the overall aim of this pilot study was two-fold: first, to investigate psychological changes and, second, to evaluate biological changes after application of a surgery-first orthognathic treatment approach. In
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particular the study aimed: - To investigate patients' oral health-related quality of life before and 3 months after surgery.
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- To evaluate changes in sense of coherence (SOC), a psychosocial construct defined as a global orientation to life (Da Rosa et al., 2015), before and after completion of treatment.
of treatment, focusing on day-to-day changes.
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- To assess changes in patient’s self-perception of facial appearance during the first three months
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- To evaluate the concentrations of IL-1 β, IL-6, TGF β 1-3, MMP-2 and VEGF in crevicular fluid by bead-based multiplex assays at one preoperative and several postoperative time points.
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Materials and methods Patients and treatment modalities
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This prospective cohort study examined a consecutive series of patients who were treated with orthognathic and orthodontic treatment using the surgery-first approach. The study protocol was
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approved by the ethics committee of the medical faculty of the University of Heidelberg (approval no. S-633/2011). The study conformed to the Declaration of Helsinki and was performed according to the guidelines of Good Clinical Practice. Before participation, all participants received full oral and written information on the aims of the study and signed a written consent form. Within 18 months, 9 consecutive patients (6 women and 3 men) with a mean age of 26.7 (SD: 8.4) years suffering from skeletal class II (n=7) and class III (n=2) malocclusion had been included in the study. All patients underwent either monomaxillary (n=4)
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or bimaxillary (n=5) orthognathic surgery. The exclusion criteria were severe crowding requiring extractions, severe facial asymmetry, syndromal facial diseases, e.g. clefts, and
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temporomandibular joint disorder. The protocol for surgery-first treatment was developed at our departments for orthodontics and maxillofacial surgery. Plaster-cast model surgery was performed in the selected patient group. A
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stable 3-point occlusal support setup was an inclusion criterion, as well as the consideration of the final position of the upper and lower anterior teeth. A positive overbite and the fitting overjet
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were determined.
Brackets (0.022 slot preadjusted edgewise brackets, Synthesis™, Ormco Corp., West Collins, Orange, USA) were bonded 1 week before surgery. The molars were banded at the same time (Ormco Corp., West Collins, Orange, USA). The initial orthodontic wire was 016x022 stainless
inactive.
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steel (Remanium®, Dentaurum, Ispringen, Germany). The initial arch wire was annealed and
All patients received orthognathic surgery performed by the same surgeon. The surgical
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technique used for the maxilla was the classic Le-Fort I osteotomy described by Bell and Epker
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(Bell and Epker, 1976). For the mandible, the high oblique sagittal split osteotomy (HSSO) described by Seeberger et al. 2013 (Seeberger et al., 2013) and the bilateral sagittal split osteotomy (BSSO) described by Hunsuck 1968 (Hunsuck, 1968) and Epker 1977 (Epker, 1977) were used. The genioplasties were performed in the classic sliding way. Internal fixation was achieved by miniplates on all of the patients. Orthodontic elastics (Dentaurum, Inspringen, Germany) were used for temporary inter-maxillary fixation. The patient's final occlusion was supported by the final splint for the first weeks postoperatively. Supporting physiotherapy
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involving muscle and mouth opening exercises started 4-8 weeks postoperatively. After splint removal, active orthodontic treatment was resumed and continued until final settling of the
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occlusion was achieved. All patients underwent CBCT scans pre- and post-treatment, before the osteosynthesis removal and at the end of the orthodontic treatment. The scans were analysed by multiplanar
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reconstruction of the data using the IPlan 3.0 software (Brainlab®; Ispringen, Germany). The pre- and post-operative data were superimposed using the image fusion tool. Anatomic skeletal
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landmarks were then defined and the sagittal (pre- and post- treatment) changes evaluated. The measurement technique is depicted in Figure 1.
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Psychological parameters
The German version (Bock et al., 2009) of the Orthognathic Quality of Life Questionnaire (OQLQ) (Cunningham et al., 2002) was used to assess quality of life scores before and 3 months
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after surgery. The OQLQ consists of 22 questions, divided into 4 domains: facial aesthetics, oral function, social aspects and awareness of dentofacial deformity. The OQLQ is based on a four-
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point Likert scale, where 1 means “it bothers you little” and 4 means “it bothers you a lot”. An N/A (not applicable) option was also added. The total OQLQ score can range from 0 to 88. A lower score suggested improvements in quality of life, whereas a higher OQLQ score indicated a reduced quality of life.
Sense of coherence (SOC) is defined as a global orientation of the individual that determines the individual’s ability to use existing resources in order to overcome difficulties and cope with life
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stressors to perform healthy behaviors and stay well (Elyasi et al., 2015). People with stronger SOC cope better with existing stressors in life. In the present study, the German version of the 29-item sense of coherence scale (SOC-29) was answered on a seven-point Likert scale before
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and at the end of treatment (within 6-12 months after debonding). A sum of SOC-29 scale points was calculated. The minimum possible SOC score was 29 and the maximum possible score was
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203. Higher scores indicated stronger SOCs.
Additionally, a day-to-day survey was performed addressing patient perception regarding
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changes in their postoperative facial appearance. The question “Are you bothered by your appearance, e.g. your face in profile?” was graded on a 10-point Likert scale, with the endpoints ‘"0 = not at all"‘ and "10 = very much", and was completed by the patients at several time points: before surgery (baseline), then every 2-3 days after surgery for the following 2-4 weeks, and
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Biological parameters
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weekly beginning from week 5; in total 24 times within 12 weeks.
Sampling of gingival crevicular fluid (GCF) and multiplex assays: Sampling of GCF was
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performed preoperatively on the day before surgery and at three post-operative time-points: postOP1 (1 d), post-OP2 (7 d) and post-OP3 (14 d). For GCF sampling, sterile paper strips (Periopaper, Oraflow, New York, NY, USA) were inserted into labial pockets of each incisor until slight resistance was felt and left in situ for 30 s (Figure 2). The strips were transferred to Eppendorf tubes (1.5 mL Protein LoBind Tubes, Eppendorf, Hamburg, Germany) prefilled with 50 µl of sterile saline solution (0.9 % NaCl) and immediately frozen at – 80°C until further processing. Before bone remodeling, factor analysis tubes containing strips were vortexed (10 s)
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and briefly centrifuged. Total volumes of eluates were determined and, if necessary, brought to a final volume of 100 µL with the appropriate sample diluent. Analysis was performed using magnetic Luminex screening assays for IL-1 β, IL-6, MMP-2 (and VEGF) from R&D Systems
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(Wiesbaden, Germany) or Bio-Plex magnetic assays for TGF- β 1-3 (BioRad, München,
Germany). Analyses were performed in duplicate according to the manufacturers’ instructions. Measurements were performed with the Bio-Plex MAGPIX multiplex reader (Bio-Rad,
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München, Germany) using the xPonent for MAGPIX software (Ver. 4.2) from Luminex.
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Concentrations were normalized for eluted volumes of crevicular fluid.
Statistics
Data from all investigations were collected and descriptive statistics performed (mean, standard
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deviation, minimum and maximum). Due to the small sample size, non-parametric statistical tests were applied: several pairwise comparisons between different time points per group were performed using Mann-Whitney-U tests. Correlations between different variables were
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calculated by Spearman’s correlation coefficient. Boxplots were used for the graphical
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representations of the findings. Two-sided p-values <0.05 were considered statistically significant. Due to the exploratory nature of the study, no adjustment was made for multiple testing. The data were processed using R 3.2.2 (www.r-project.org).
Results Treatment time, dentoskeletal characteristics and dimensions of surgical jaw movement
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The mean total treatment time following our surgery-first protocol was 15.7 (SD 3.31) months. The mean time until final splint removal was 30 (SD 11.2) days.
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Seven patients suffered from class II malocclusion; two of them in combination with apertognathia and one with laterognathia. Two of them were treated by a monomaxillary
mandibular advancement, one by monomaxillary maxillary closure of the anterior open bite. The
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remaining patients were treated by bimaxillary surgery. In three of these patients, a sliding
genioplasty for advancement of the chin was performed. Two patients suffered from class III
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malocclusion. One was treated by maxillary advancement, the other by bimaxillary surgery. HSSO of the mandible was performed on seven patients and BSSO on two patients. The patients who received BSSO showed postoperative hypaesthesia of the lower lip for 4-6 weeks. The overall postoperative follow-up was uneventful in all nine patients. The findings are summarized
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in Table 1.
The post-treatment skeletal changes were measured and analyzed at first in the sagittal plane, due to the distinct effect on the patient profile after surgery. The pogonion advanced by 5.84 mm (SD
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6.88). The maximum advancement of the mandible after bimaxillary surgery and advancing genioplasties of the chin was 16 mm. The SNA prior to treatment was in mean 80.2° (SD 3.1°)
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and post-treatment 82.7° (SD 3.78). The pre-treatment mean SNB was 75.68° (SD 6.49) and post-treatment 78.23° (SD 5.08), indicating the maxilla-mandibular advancements in the patients. The maxillary advancement measured at the prosthion was in mean 2.96 mm (SD 2.93). The vertical change in the maxilla was in mean 1.16 mm (SD 4.51) measured at the nasal spine representing the actual bony change. The vertical change on the dental level was measured at the incisor tip. The vertical dental heights changed in mean by 2.03 mm (SD 3.41). We assume that this effect is caused by (i.) the closure of the open bite and (ii.) the occlusal settling. The results
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are summarized in Table 2 for the sagittal plane and in Table 3 for the vertical plane.
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Changes in quality of life (OQLQ)
The patient completion rate for the OQLQ was 100%. The baseline (preoperative) overall OQLQ score ranged from 8 to 77, with a mean of 36 (SD= 17.24). A significant reduction (P= 0.015) in
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the overall score of the OQLQ was observed between baseline and 3-month evaluation (mean 18,
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SD=12.69, range 0-45), thus indicating a significant improvement in quality of life during the first three months of treatment. Individual domain scores are shown in Figure 3. The most affected dimensions were: facial aesthetics (p=0.022), oral function (p=0.051) and social aspects (p=0.057).
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Changes in patients’ sense of coherence (SOC-29)
All patients completed the SOC-29 questionnaire both before and at the end of treatment. There were no missing items. The pre- and post-treatment SOC-29 scores are presented in Figure 4.
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The median pre-treatment SOC-29 score was 141.0 (range 107-173). A significant increase by 9 points (P= 0.029) in median SOC-29 scores was found between pre- and post-treatment
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evaluation.
Patient perception regarding changes in facial aesthetics Most patients (8 out of 9) reported favorable facial changes after surgery (Figure 5). One patient experienced only minor aesthetic changes. Most prominent changes were experienced during the
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first week of treatment. Despite the general improvement in OQLQ and SOC during the course of the study, the personal experience of appearance was distinctively variable in course and
Multiplex cytokine analysis in crevicular fluid
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intensity.
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To evaluate basic molecular markers of bone healing, we collected crevicular fluids
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postoperatively and at different postoperative time points (post-OP1 (1 d), post-OP2 (7 d) and post-OP3 (14 d)) from 9 patients who underwent orthognathic surgery. The concentrations of IL1 β, IL-6, MMP-2 and TGF- β 1-3 were evaluated and normalized for the total volume of sampled crevicular fluid. Absolute amounts of bone remodeling factors varied between the individual patients at the different time sampling times. However, during the course of samplings
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characteristics patterns were observed. The results are displayed as mean ± SEM determined from data of all 9 patients relative to the preoperative values in Fig. 6 (A – F). In line with an initial inflammatory response in the process of bone healing, marked increases in IL1 β, IL-6
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levels compared to preoperative levels were detected at the first postoperative time point (Fig. 6,
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A, C), which was followed by distinctly reduced levels at the following time points for all patients. The course of MMP-2 (Fig. 6, E) concentrations resembled that of IL-1 β and was also characterized by a marked peak at the first postoperative time point (Fig. 6, E) and subsequently decreasing concentrations. Matrix metalloproteinases appear in the early phase of bone healing, as well as in the later remodeling phase. MMP-2 in this study was found in a temporal pattern comparable to IL-1 β , which points to an involvement of MMP-2 in early resorptive events. TGF- β 1-3 appeared at later postoperative time points (Fig. 6, B, D, F) and remained at higher
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levels compared with preoperative levels during the course of the study. In addition, we analyzed VEGF, which was detectable at highest levels at the first postoperative time point, suggesting an
Discussion Psychological impact of the surgery-first approach
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early angiogenic response after surgery (Supplemental Fig.1 A).
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In this study we measured changes in oral health-related quality of life of surgery-first patients before and after surgery. Quality of life was significantly improved 3 months after surgery. We used the condition-specific orthognathic Quality of Life Questionnaire (OQLQ), which is considered one of the most valid and sensitive instruments for orthognathic patients (Soh and
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Narayanan, 2013, Murphy et al., 2011). Our results are consistent with those of previous OQLQ studies which demonstrated significant improvements in quality of life of patients as a result of conventional orthognathic surgical treatment (Hunt et al., 2001, Soh and Narayanan, 2013).
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However, in most previous studies improvements in patients' quality of life were not evident until 6 months to 1 year after surgery (Soh and Narayanan, 2013). In the study by Park et al.
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(Park et al., 2015), Class III patients treated either by conventional or surgery-first approaches were asked to estimate, retrospectively, their OQLQ scores just before and 3 months after surgery. Within this time span, the authors observed an improvement in the mean total OQLQ scores by more than 50%, which is consistent with our findings. In the present study, mean total OQLQ scores of the patients were lower than those of patients in the study by Park et al. (Park et al., 2015). These differences may partly be explained by differences in sample characteristics
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(i.e. type of malocclusion, ethnic and cultural differences) and study design. Regarding the dimensions of the OQLQ, we found the highest changes in facial aesthetics, followed by oral function, social aspects and awareness of dentofacial deformity. Similar findings were reported
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by Lee et al. (Lee et al., 2008), Choi et al. (Choi et al., 2010) and also Park et al. (Park et al., 2015).
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In addition to the OQLQ questionnaire, all patients completed the SOC-29 questionnaire before and after active orthodontic treatment. Antonovsky introduced the theory of salutogenesis and
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the terms sense of coherence and general resistance resources into psychology (Antonovsky, 1993). The theory of salutogenesis aimed to solve the question of why some people encountering major stress and severe adversity stay healthy and others do not. The answer was based on the sense of coherence (SOC) and the general resistance resources (GRRs). The SOC defines an enduring attitude facilitating quantification of how people view their lives and use GRRs under
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stress in order to maintain and improve their health. The SOC consists of at least three dimensions: comprehensibility, manageability and meaningfulness. GRRs are, for instance, wealth, intelligence, self-esteem, preventive health orientation and social support. Equipped with
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such resources, people will cope better with the challenges of life.
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To the best of our knowledge, this is the first study to assess sense of coherence levels in orthognathic patients. The surgery-first approach used in this study led to improved values after treatment. Thus, orthognathic patients experience more meaningfulness, intelligibility and selfefficacy. We used an adapted German version of the SOC-29 that proved to have high internal consistency with Cronbach’s alpha coefficients, ranging from .87 to .90 for the global scale and the subscales (Singer and Brähler, 2007). In the present study, the mean pre-treatment SOC-29 score of the patients was 138.36 (SD: 19.46). Compared to a German general population sample
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(mean 155.87, SD: 22.16) (Hannöver et al., 2004) the present sample scored significantly lower for SOC (p=0.0089), suggesting that there is potential for improving orthognathic patients' SOCs. An increase by 9 points in median SOCs was found between pre- and post-treatment
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evaluations. It should be pointed out that, post-therapy, no significant differences between SOC scores of orthognathic patients within this study and the general German population (Hannover et al., 2004) were evident (p=0.129). The present study also supports results from other studies
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showing that SOCs can be improved after intervention (Langeland et al., 2013).
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Patients reported favorable facial changes after surgery. However, despite the general improvement in OQLQ and SOC during the course of the study, the personal experience of appearance was distinctively variable in course and intensity. The results underline that postsurgical recovery varies from individual to individual, and emphasizes the need for careful monitoring, particularly during the first months after surgery. The results also demonstrate that
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individual patients may experience difficulties which are not detectable when analyzing mean scores only. Additional studies focusing on day-to-day changes are necessary to further
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investigate the psychological impact of the orthognathic treatment approach.
Bone healing and orthodontic tooth movement The beneficial effects of the surgery-first concept for orthognathic surgery are mainly due to accelerated orthodontic tooth movement. Thus, quality of life and overall satisfaction of patients might, to a notable extent, be dependent on the biological reason for the observed accelerated tooth movements after surgery. We hypothesized that various molecular factors which are massively elevated during bone healing after surgical procedures, and which are also involved in
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the regulation of bone remodeling during orthodontic tooth movement, are responsible for the acceleration of orthodontic tooth movement-dependent bone remodeling. Although the data gathered in this study is certainly not sufficient as reasonable proof for this theory, the courses of
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the levels of the bone remodeling factors compiled in this study support the hypothesis.
IL-1 β and IL-6, both pro-inflammatory markers associated with early inflammation after bone
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injury, were elevated in crevicular fluids shortly after surgery. MMP-2, as an example for collagenases and matrix-metalloproteinases involved in early resorptive as well as later
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remodeling events, showed a comparable temporal expression pattern. This was also the case for the paramount angiogenic factor VEGF, which is also known to be elevated early after bone injury. In contrast, TGF β 1-3, members of the TGF- β superfamily, were detectable at elevated levels at later time points than IL-1 β, IL-6 or MMP-2. These results are in agreement with the role of TGF β 1 in bone healing, where it induces osteoblast migration proliferation and
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differentiation (Tang et al., 2009). TGF- β s might act in synergy with overlapping functions during bone remodeling since TGF- β 2 and TGF- β 2 mimic TGF- β 1 function during the
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inhibition of osteoclastogenesis by inducing osteoprotegerin (Thirunavukkarasu et al., 2001). Bone remodeling initiated after the application of orthodontic forces is likewise dependent on the
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factors elevated during bone healing; the relative abundance of these factors after orthognathic surgical interventions might therefore contribute to the accelerated tooth movement in patients treated according to the surgery-first concept. Thus, we propose that patient satisfaction after surgery-first therapy is, to a relevant extent, attributable to accelerated tooth movement caused by the abundance of a variety of bone remodeling factors which function both in bone healing and in tooth movement. Clearly, further studies are needed to provide sufficient evidence for this concept.
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Conclusion
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The findings of this prospective clinical pilot study provide a new insight into psychological and biological aspects regarding orthognathic surgery using the surgery-first concept. Within the limitations of the study we conclude:
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(1) Total mean OQLQ scores significantly improved by more than 50 percent during the first
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three months of treatment, indicating that patients experienced a significant improvement in quality of life. The most affected OQLQ domains were facial aesthetics, oral function and social aspects.
(2) The sense of coherence (SOC) improved significantly after treatment. This suggests that
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surgical orthodontics improved patients' experience of meaningfulness and self-efficacy. (3) Changes in individual appearance were positively experienced by 90% of patients. Most prominent changes were experienced during the first week of treatment. Despite the general
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improvement in QLQ and SOC during the course of the study, the personal experience of appearance was distinctively variable in course and intensity. The results emphasize the need for
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careful monitoring of the psychological status in patients during the first three months of treatment.
(4) Biological aspects: From the data gathered within this study we propose that accelerated tooth movement after surgery is, to a relevant extent, due to elevated levels of bone remodeling factors required for fracture healing. Clearly, further studies are needed to provide sufficient evidence for this concept.
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Ethical approval
University of Heidelberg (approval no. S-633/2011).
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Sources of support
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The study protocol was approved by the ethics committee of the medical faculty of the
This work was supported by a grant from the Dietmar Hopp Stiftung.
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Competing interests
None of the authors claim a conflict of interest. Acknowledgements
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The authors wish to thank Ms. Edith Daum for supporting the MagPix Assays.
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Captions to illustrations Table 1: Summary of patients and their malocclusions, together with the surgery performed and
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the technique applied
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Table 2: Pre- to post-treatment skeletal and dental changes in the sagittal plane.
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Table 3. Pre- to post-treatment skeletal and dental changes in the vertical plane.
Figure 1: Display of the measurement of anatomic landmarks for the pre- and postoperative evaluation of changes through orthognathic surgery. Blue is the preoperative situation and
data.
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magenta the postoperative result after image fusion and in the multiplanar reconstruction of the
Figure 2: For gingival crevicular fluid sampling sterile paper strips were inserted into labial
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pockets of each incisor
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Figure 3: Comparison of pre-treatment (T1, black) and post-treatment (T2, white) OQLQ scores by the four domains (medians and interquartile ranges and 3rd and 97th percentiles; crosses: mean values)
Figure 4: Comparison of pre-treatment (T1, left) and post-treatment (T2, right) SOC scores (medians and interquartile ranges and 3rd and 97th percentiles; crosses: mean values) Figure 5. Patient’s self perception of facial appearance during the first 93 days of treatment. The
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question “Are you bothered by your appearance, e.g. your face in profile?” was graded on a 10-
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point Likert scale with the endpoints "0 = not at all" and "10 = very much".
Figure 6. Bone remodelling factors in gingival crevicular fluid of surgery-first patients: Bone remodelling factors (IL-1 β (Interleukin-1 β); IL-6 (Interleukin-6), MMP-2 (Matrix
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metalloproteinase-2), TGF- β 1-3 (Transforming growth factor- β 1-3) were evaluated by
magnetic multiplex assays in crevicular fluid collected postoperatively (on the day before
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surgery) and at three postoperative time points post-OP1 (1 d), post-OP2 (7 d) and post-OP3. IL1 β (A), IL-6 (C) and MMP-2 (E) were detected before the members of the TGF-β superfamily TGF- β 1 (B) TGF- β 2 (D) and TGF- β 1 (F). The levels of bone remodelling factors are presented relative to preoperative levels (mean ± SEM, n=9). Factors were measured in
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Supplemental Figure 1 VEGF (vascular endothelial growth factor levels in gingival crevicular fluid of surgery first patients. Gingival crevicular fluid was collected postoperatively (on the day before surgery) and at three postoperative time points post-OP1 (1 d), post-OP2 (7 d) and post-
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OP3.VEGF (A) was detectable at highest levels at the first postoperative time point, in
accordance with increased angiogenesis following vascular damage. VEGF levels are presented
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relative to preoperative levels (mean ± SEM, n=9). VEGF was measured in duplicate.
ACCEPTED MANUSCRIPT Tables Table 1: Summary of patients and their malocclusions, together with the surgery performed and the technique applied. Malocclusion
Surgery
Technique
Complications
Class II Class II Class II; Laterognathia Class II Class II; Apertognathia Class II
Monomaxillary mandible Monomaxillary mandible Bimaxillary Bimaxillary Bimaxillary Bimaxillary
HSSO HSSO HSSO HSSO; Genioplasty HSSO; Genioplasty BSSO
Class III
Bimaxillary
Class III Class II; Apertognathia
Monomaxillary maxilla Monomaxillary maxilla
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None None None None None Hypaesthesia of the lower lip for 6 weeks BSSO Hypaesthesia of the lower lip for 4 weeks LeFort I None 3-piece-maxilla; Genioplasty None
ACCEPTED MANUSCRIPT Table 2: Pre- to post-treatment skeletal and dental changes in the sagittal plane. Variables
Mean
Min
Max
SD
Value
5.14
- 3.0
15.4
6.96
mm
Pogonion
5.84
- 2.2
16.0
6.88
mm
Mental foramen left
4.27
- 3.6
11.9
5.59
mm
Mental foramen right
5.17
- 0.5
12.7
4.82
mm
Apex 13
2.18
- 0.4
4.6
Crown 13
2.37
- 0.9
7.4
Apex 23
2.68
- 0.9
7.0
Crown 23
2.42
- 0.9
7.3
Apex 33
5.02
- 2.3
14.6
Apex 43
5.04
- 1.6
13.2
Mandibular foramen left
1.58
- 3.0
Mandibular foramen right
2.82
0.0
A-point
2.52
0.0
B-point
4.73
Prosthion
2.96
Mesiobuccal apex 16
2.60
Mesiobuccal apex 26
2.62
SNA post
82.68
SNB pre
75.68
N-B-point pre N-B-point post N-Pogonion pre
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N-Pogonion post
mm
2.66
mm
2.89
mm
5.81
mm
5.39
mm
5.5
2.89
mm
8.0
2.94
mm
5.7
1.98
mm
- 2.7
12.8
5.17
mm
0.0
4.0
2.93
mm
0.0
6.0
2.13
mm
0.0
6.7
2.45
mm
76.1
84.3
3.10
degrees
77.8
87.7
3.78
degrees
64.4
87.7
6.49
degrees
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2.85
78.23
71.0
87.6
5.08
degrees
98.40
87.5
107.0
7.22
degrees
96.09
85.7
107.6
7.49
degrees
111.31
100.6
118.3
6.69
degrees
110.90
98.6
122.2
7.64
degrees
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mm
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80.21
1.64
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SNA pre
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ACCEPTED MANUSCRIPT Table 3. Pre- to post-treatment skeletal and dental changes in the vertical plane. Mean
Min
Max
SD
Value
Menton
- 0.62
- 4.3
2.1
2.22
mm
Pogonion
- 0.07
- 4.5
5.1
3.07
mm
Mental foramen left
1.34
- 0.7
4.4
1.87
mm
Mental foramen right
0.43
- 4.0
3.7
2.02
mm
Apex 13
0.57
- 3.4
5.8
2.98
mm
Crown 13
0.66
- 4.0
6.0
3.15
mm
Apex 23
0.44
- 3.5
4.4
2.62
mm
Crown 23
1.17
- 2.7
7.3
3.25
mm
Apex 33
2.28
- 1.4
7.2
2.74
mm
Apex 43
1.64
- 4.0
5.2
2.62
mm
Mandibular foramen left
- 0.32
- 2.7
1.4
1.24
mm
Mandibular foramen right
- 0.86
- 4.4
0.0
1.43
mm
A-point
0.82
- 6.7
8.0
4.54
mm
B-point
1.76
- 2.4
6.8
2.87
mm
Prosthion
0.81
- 4.3
8.6
4.33
mm
Nasal spine
1.16
- 3.3
9.0
4.51
mm
Mesiobuccal apex 16
0.10
- 6.3
3.0
2.79
mm
Mesiobuccal apex 26
1.16
- 1.6
4.8
2.10
mm
Incisor Tip
2.03
- 2.3
8.2
3.41
mm
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Figures
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Figure 1: Display of the measurement of anatomic landmarks for the pre- and postoperative evaluation of changes through orthognathic surgery. Blue is the preoperative situation and magenta the postoperative result after image fusion and in the multiplanar reconstruction of the data.
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Figure 2: For gingival crevicular fluid sampling sterile paper strips were inserted into labial pockets of each incisor
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Figure 3: Comparison of pre-treatment (T1, black) and post-treatment (T2, white) OQLQ
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scores by the four domains (medians and interquartile ranges and 3rd and 97th percentiles; crosses: mean values)
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Figure 4: Comparison of pre-treatment (T1, left) and post-treatment (T2, right) SOC scores (medians and interquartile ranges and 3rd and 97th percentiles; crosses: mean values)
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Figure 5. Patient’s self perception of facial appearance during the first 93 days of treatment. The question “Are you bothered by your appearance, e.g. your face in profile?” was graded on a 10-point Likert scale with the endpoints "0 = not at all" and "10 = very much".
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Figure 6. Bone remodelling factors in gingival crevicular fluid of surgery-first patients: Bone remodelling factors (IL-1β (Interleukin-1β); IL-6 (Interleukin-6), MMP-2 (Matrix metalloproteinase-2), TGF-β1-3 (Transforming growth factor-β1-3) were evaluated by magnetic multiplex assays in crevicular fluid collected postoperatively (on the day before surgery) and at three postoperative time points post-OP1 (1 d), post-OP2 (7 d) and postOP3. IL-1β (A), IL-6 (C) and MMP-2 (E) were detected before the members of the TGF-β superfamily TGF-β1 (B) TGF-β2 (D) and TGF-β1 (F). The levels of bone remodelling factors are presented relative to preoperative levels (mean ± SEM, n=9). Factors were measured in duplicate.
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A VEGF 20
15
10
5
0 pre-OP
post OP 1 post OP 2 post-OP 3
Sampling
RI PT
VEGF (fold of pre-OP level)
25
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Supplemental Figure 1 VEGF (vascular endothelial growth factor levels in gingival crevicular fluid of surgery first patients. Gingival crevicular fluid was collected postoperatively (on the day before surgery) and at three postoperative time points post-OP1 (1 d), post-OP2 (7 d) and post-OP3.VEGF (A) was detectable at highest levels at the first postoperative time point, in accordance with increased angiogenesis following vascular damage. VEGF levels are presented relative to preoperative levels (mean ± SEM, n=9). VEGF was measured in duplicate.