Immune Changes Induced by Orthodontic Forces: A Critical Review.

Orthodontic tooth movement (OTM) is generated by a mechanical force that induces an aseptic inflammatory response in the periodontal tissues and a subsequent coordinated process of bone resorption and apposition. In this review, we critically summarize the current knowledge on the immune processes involved in OTM inflammation and provide a novel insight into the relationship between classical inflammation and clinical OTM phases. We found that most studies focused on the acute inflammatory process, which ignites the initial alveolar bone resorption. However, the exact mechanisms and the immune reactions involved in the following OTM phases remain obscure. Recent studies highlight the existence of a typical innate response of resident and extravasated immune cells, including granulocytes and natural killer (NK), dendritic, and γδT cells. Based on few available studies, we shed light on an active, albeit incomplete, process of resolution in the lag phase, supported by continuously elevated ratios of M1/M2 macrophage and receptor activator of nuclear factor κB ligand/osteoprotegerin ratio. This partial resolution enables tissue formation and creates the appropriate environment for a transition between the innate and adaptive arms of the immune system, essential for the tissue's return to homeostasis. Nevertheless, as the mechanical trigger persists, the resolution turns into a low-grade chronic inflammation, which underlies the next, acceleration/linear OTM phase. In this stage, the acute inflammation dampens, and a simultaneous process of bone resorption and formation occurs, driven by B and T cells of the adaptive immune arm. Excessive orthodontic forces or tooth movement in periodontally affected inflamed tissues may hamper resolution, leading to "maladaptive homeostasis" and tissue loss due to uncoupled bone resorption and formation. The review ends with a brief description of the translational studies on OTM immunomodulation. Future studies are necessary for further uncovering cellular and molecular immune targets and developing novel strategies for controlling OTM by local and sustained tuning of the inflammatory process.

γδT Cells Are Essential for Orthodontic Tooth Movement.

Sustained mechanical forces applied to tissue are known to shape local immunity. In the oral mucosa, mechanical stress, either naturally induced by masticatory forces or externally via mechanical loading during orthodontic tooth movement (OTM), is translated, in part, by T cells to alveolar bone resorption. Nevertheless, despite being considered critical for OTM, depletion of CD4+ and CD8+ T cells is reported to have no impact on tooth movement, thus questioning the function of αßT cells in OTM-associated bone resorption. To further address the role of T cells in OTM, we first characterized the leukocytes residing in the periodontal ligament (PDL), the tissue of interest during OTM, and compared it to the neighboring gingiva. Unlike the gingiva, monocytes and neutrophils represent the major leukocytes of the PDL. These myeloid cells were also the main leukocytes in the PDL of germ-free mice, although at lower levels than SPF mice. T lymphocytes were more enriched in the gingiva than the PDL, yet in both tissues, the relative fraction of the γδT cells was higher than the αß T cells. We thus sought to examine the role of γδT cells in OTM. γδT cells residing in the PDL were mainly Vγ6+ and produced interleukin (IL)-17A but not interferon-γ. Using Tcrd-GDL mice allowing conditional ablation of γδT cells in vivo, we demonstrate that OTM was greatly diminished in the absence of γδT cells. Further analysis revealed that ablation of γδT cells decreased early IL-17A expression, monocyte and neutrophil recruitment, and the expression of the osteoclastogenic molecule receptor activator of nuclear factor-κß ligand. This, eventually, resulted in reduced numbers of osteoclasts in the pressure site during OTM. Collectively, our data suggest that γδT cells are essential in OTM for translating orthodontic mechanical forces to bone resorption, required for relocating the tooth in the alveolar bone.

Bovine Bone Promotes Osseous Protection via Osteoclast Activation.

The current study aimed at investigating the long-term biological mechanisms governing bone regeneration in osseous defects filled with bovine bone (BB). Tooth extraction sockets were filled with BB or left unfilled for natural healing in a C57BL/6 mouse alveolar regeneration bone model (n = 12). Seven weeks later, the alveolar bone samples were analyzed histologically with hematoxylin/eosin and tartrate-resistant acid phosphatase staining. A separate group (n = 10) was used for RNA sequencing. Osteoclast inhibition was induced by zoledronic acid (ZA) administration at 2 wk postextraction in a third group (n = 28) for examination of osseous changes and cellular functions with micro-computed tomography and quantitative reverse transcription polymerase chain reaction, respectively. Histological and radiological osseous healing was observed in both BB-filled and normal-healing sockets. However, BB regenerated bone showed significant robust expression of genes associated with bone homeostasis and osteoclasts' function. Osteoclasts' inhibition in BB-filled sockets led to decreased bone resorption markers and reduced bone formation to a greater extent than that observed in osteoclasts' inhibition with natural healing. BB displays long-term biologically active properties, despite a naive osseous histological appearance. These include activation of osteoclasts, which in turn promotes osseous remodeling and maturation of ossified bone.

[Failure in the orthodontic treatment of impacted maxillary canines].

Maxillary canine impaction occurs in 1-3% of most Western populations and its orthodontic treatment is often difficult. Failure to resolve the impaction is not uncommon and may lead to malpractice lawsuits. The information in the literature about the reasons for non-resolution of this condition is sparse and unsubstantiated. This encourages the dispensing of inappropriate treatment that may result in severe tooth, soft and hard tissue damage as well as a prolonged treatment period. This review describes the epidemiology, pathogenesis and the wide range of reasons that may lead to failure to resolve the canine impaction. It shows that a lack of appreciation of anchorage demands and inaccurate positional diagnosis of the 3-D location and orientation of impacted teeth are the major reasons for failure. In addition, the review shows that invasive cervical root resorption (ICRR) is a frequently undiagnosed or unrecognized cause of failure of orthodontic resolution of impacted canines, and should be distinguished from replacement resorption (ankylosis). Corrective measures which may lead to successful treatment are further recommended. Special emphasis is placed on the crucial role of cone beam computerized tomography in the accurate radiographic diagnosis and early detection of pathology of impacted tooth and damage to adjacent anchor teeth. The importance of teamwork in achieving the best treatment outcome is stressed.

Conventional wisdom and the surgical exposure of impacted teeth.

OBJECTIVES: To provide evidence against the notion that direct contact between the crown of an impacted tooth and alveolar bone is an impediment to orthodontically assisted eruption of teeth. SETTING AND SAMPLE POPULATION: The Department of Orthodontics at the Hebrew University-Hadassah School of Dental Medicine, in Jerusalem, Israel, and the private practices of the authors. MATERIALS AND METHODS: Patients reported were those affected by impacted teeth, including individuals who were normal healthy patients, with and without resorption of the adjacent incisor roots, as well as individuals suffering from Cleidocranial dysplasia and increased bone density, and individuals with autogenous and synthetic bone grafts. A closed eruption surgical technique was used in which only a small window was opened into the dental follicle of the impacted tooth, leaving a maximum amount of bone covering much of the crown surface. Orthodontic extrusion forces were then applied. RESULTS: For all teeth, enamel-to-bone contact did not prevent a rapid response to the extrusive forces. CONCLUSION: Radical removal of bone during the exposure of an impacted tooth is unnecessary and potentially may be harmful in terms of the periodontal prognosis of an otherwise successfully treated outcome.

Assessing the levels of immunoglobulins in the saliva of diabetic individuals with periodontitis using checkerboard immunodetection.

BACKGROUND: Current methods for determining salivary antibodies are cumbersome for large-scale screenings. OBJECTIVES: To test checkerboard immunodetection for monitoring salivary antibodies and to profile them in diabetic individuals with periodontitis. METHODS: Salivary anti-Porphyromonas gingivalis, anti-Actinobacillus actinomycetemcomitans and total IgA levels of 10 individuals were compared using checkerboard immunoblotting and enzyme-linked immunosorbent assay (ELISA). RESULTS: Close correlation between both methods was found in anti-P. gingivalis IgA and total IgA, but not in anti-A. actinomycetemcomitans IgA, because of high background levels in ELISA. Thereafter, checkerboard immunodetection was used to compare salivary antibodies of 20 adult type II diabetic with 32 non-diabetic individuals with (n=22) or without (n=10) periodontitis. Patients with periodontitis (regardless of their diabetic condition) expressed increased levels of total IgA in both whole and parotid saliva, but reduced levels of anti-A. actinomycetemcomitans IgA in whole saliva. Consequently, the proportion of anti-A. actinomycetemcomitans IgA in the total IgA was lower in saliva of patients with periodontitis compared with healthy controls. CONCLUSIONS: Checkerboard immunodetection was reliable and economical for screening saliva samples for multiple antibody reactions. Our results support previous reports which suggested that patients with periodontitis are able to secrete high levels of salivary Ig, but are hampered in targeting their salivary response toward A. actinomycetemcomitans.

Age-dependent deficiency in saliva and salivary antibodies secretion in Down's syndrome.

OBJECTIVE: Down's syndrome (DS) individuals suffer from an increased susceptibility to infections. Here, we assessed age-related changes in the salivary-specific humoral immunity of DS subjects. DESIGN: Parotid and whole saliva were collected from a young group of DS (YDS, n=30, 23.3+/-4 years), an older group of DS individuals (ODS, n=10, 51.9+/-8 years) and compared to two age-matched groups of healthy volunteers--a young group (YC, n=29, 22.8+/-5 years) and an older group (OC, n=10, 48.4+/-9 years). The levels of total IgA, and specific antibodies to three common oral pathogens (Porphyromonas gingivalis, Actinobacillus (Aggregatibacter) actinomycetemcomitans and Streptococcus mutans) were analysed. RESULTS: The limited increases in IgA concentrations could not compensate the dramatic reduction in the salivary flow rate observed in DS individuals. Therefore, the median secretion rates of the specific antibodies in whole and parotid saliva were 70-77% and 34-60% (respectively) lower in YDS individuals as compared to YC and farther 77-100% and 75-88% (respectively) lower in ODS compared to YDS. In contrast, the antibody secretion rates were similar for parotid saliva, or even increased for whole saliva of OC, compared with YC. Consequently, a dramatic cumulative extreme reduction (>92%) in the bacterial specific salivary antibodies differentiated the adult DS individuals from to their age-matched controls. CONCLUSIONS: Our results indicate a severe immunodeficiency in the secretion rate of the specific salivary IgA response of in DS individuals which intensifies with age.

[Orthodontic anchorage in the era of osseointegration].

The introduction of the concept of osseointegration had a profound impact on dentistry of the 20th century. The idea of using this concept in orthodontics already started in the late 70th. There demand for achieving optimal esthetic results in a minimal treatment time, and the significant increase in the number of adult orthodontic patients, made osseointegration an essential adjunct to orthodontic therapy. The use of osseintegrated anchorage devices helps the clinician to overcome one of the most limiting aspects of orthodontic therapy--inadequate anchorage. In the last years a large variety of osseointegrated anchorage devices have been developed and introduced in orthodontics. The purpose of the present article is to present several cases that illustrate how to solve anchorage problems by the using the principles of osseointegration and mechanical retention. The selection of the most appropriate anchorage device for each specific case will be emphasized.

Salivary LL-37 secretion in individuals with Down syndrome is normal.

Antimicrobial peptides play an important role in the innate immune response. Deficiency in salivary LL-37 antimicrobial peptide has been implicated in periodontitis in patients with morbus Kostman syndrome. Down syndrome is associated with periodontitis, diminished salivary flow, and salivary immunoglobulin deficiency. In the present study, levels of LL-37 and its hCAP18 precursor were measured in saliva samples from young individuals with Down syndrome and compared with levels in those from age-matched healthy controls. LL-37 and human cathelicidin antimicrobial protein (hCAP18) were detected in whole but not in parotid saliva. hCAP18 was more abundant than LL-37. The concentrations of salivary hCAP18 and LL-37 were found to be higher in individuals with Down syndrome than in healthy controls, but their secretion rates were similar. We concluded that, while the adaptive immunity of individuals with Down syndrome is impaired at the oral mucosa, the secretion rate of the LL-37 component of the innate immune system is normal.

The outcome of a preventive dental care programme on the prevalence of localized aggressive periodontitis in Down's syndrome individuals.

BACKGROUND: Periodontal disease in Down's syndrome (DS) individuals develops earlier and is more rapid and extensive than in age-matched normal individuals. The present study evaluated a group of DS patients, who had been participating in a 10-year preventive dental programme, for the impact of the programme on their periodontal status. METHODS: Thirty DS patients (mean age 23.3 +/- 4 years) were compared with 28 age-matched healthy controls (mean age 22.8 +/- 5 years). The hygiene level, gingival condition and periodontal status (periodontal probing depth, clinical attachment level and radiographic alveolar bone loss) were determined. RESULTS: In spite of similar oral hygiene and gingival measures, DS patients, as opposed to the control ones, had a severe periodontal disease. The prevalence, extent and severity of periodontitis in the DS group were significantly greater than in the control group. The teeth most commonly and severely affected were the lower central incisors and the upper first molars. DS patients lost significantly more teeth due to periodontitis. CONCLUSIONS: The clinical and radiographic picture found in the present DS group is characteristic of localized aggressive periodontitis. Within the limitations of this study, it seems that the preventive dental programme had no effect on periodontal destruction progression of localized aggressive periodontitis in DS individuals and that impaired oral hygiene plays a relatively minor role in the pathogenesis of this disease. Future controlled studies are needed to assess the effectiveness of different preventive dental programmes in preventing the progression of periodontitis in DS patients.

Patients' perceptions of recovery after surgical exposure of impacted maxillary teeth treated with an open-eruption surgical-orthodontic technique.

This study assessed patient perceptions of immediate post-operative recovery after the surgical exposure of impacted maxillary teeth with an open-eruption technique. Thirty patients (24 females and six males) underwent surgical exposure of 39 impacted maxillary teeth using this technique. After surgery the patients were contacted by telephone daily for 7 days, to complete a health-related quality of life (HRQOL) questionnaire, which assessed their perception of recovery in four main areas: pain, oral function, general activity, and other symptoms. Severe pain was reported by 30 per cent of the patients in the first post-operative day (POD 1), which declined to 6.7 per cent by POD 6. Consumption of analgesics declined gradually over the post-operative days (POD 1: 80 per cent, POD 7: 20 per cent). Difficulty in eating required 5 days to reach minimal levels; enjoying everyday food, 2.5 days; school attendance, limitations in daily routine, swallowing, and speech, 2 days each; swelling, bad taste/smell, 1.5 days each; within 1 day all other measures attained minimal levels. The need for bone removal during the exposure resulted in delayed recovery with regard to the ability to eat. In general, females reported delayed recovery for pain. The present data may serve as basic guidelines against which future studies which assess post-operative management of patients after surgical exposure of impacted teeth by an open-eruption technique may be compared.

Parotid salivary immunoglobulins, recurrent respiratory tract infections and gingival health in institutionalized and non-institutionalized subjects with Down's syndrome.

BACKGROUND: The purpose of the present study was to evaluate the possible correlation between recurrent respiratory infections (RRIs), gingival health and the secretion rates of salivary immunoglobulins (Igs) in institutionalized (I) and non-institutionalized (NI) individuals with Down's syndrome (DS). METHODS: Stimulated parotid saliva was collected from nine I and 14 NI subjects with DS. Salivary flow rate, secretion rates of total salivary IgM, IgG and IgA, and the incidence of RRIs were determined. Gingival health was recorded by using the plaque index, the gingival index and the percentage of bleeding surfaces (BS). RESULTS: The mean salivary flow rate and parotid Ig secretion rates in the I group were 25% of those of the NI group. The prevalence of RRIs in the I group was more than twice that in the NI group. Oral hygiene and gingival health were significantly better in the NI group. CONCLUSIONS: The lower parotid Ig secretion rates in I individuals with DS might be a possible factor involved in their susceptibility to recurrent infections compared to NI subjects with DS.

Periodontal status following surgical-orthodontic alignment of impacted central incisors with an open-eruption technique.

Several factors may affect the outcome of the orthodontic/surgical modality for the resolution of impacted central incisors, but particularly the manner in which the impacted tooth is exposed. The present study aimed to evaluate the post-retention clinical appearance and periodontal status of impacted maxillary central incisors which were exposed and aligned with an open-eruption surgical-orthodontic technique. Twelve subjects (four males, eight females), aged 22 years (range 15-38 years), previously treated for a unilateral impacted central incisor (ICI), were examined 10 years (range 3-25 years) post-retention. A split-mouth method was used for the comparison with the unaffected side. One treated central incisor exfoliated 10 years post-retention, thus the results were based on the remaining 11 patients. Statistically significant differences were found between the affected and control incisors in most of the periodontal parameters measured, although some were small and of minimal clinical importance. The increase in the mesio-labial pocket depth was associated with a highly significant 10 per cent reduction in bone level at this site (P = 0.007). A highly statistically significant increase in crown length (P < 0.001) and a reduction in the width of the attached gingiva (P = 0.005) were seen in these previously impacted teeth. An abnormal gingival contour was present in eight treated incisors and positional relapse in five cases. It is concluded that the convenience of the open-eruption technique must be weighed against the long-term negative aesthetic and periodontal effects on the treated tooth, although the findings of this study should be viewed with caution due to the limited sample size.

Severe impairment of secretory Ig production in parotid saliva of Down Syndrome individuals.

Infections associated with Down Syndrome (DS) are prevalent in the mucosal-gastrointestinal and respiratory systems, for reasons that are uncertain. The purpose of the present study was to assess the levels of parotid salivary immunoglobulins (Ig) in a group of DS individuals as a possible factor in the susceptibility of mucosal surfaces to infections. Twenty-nine DS and 10 age- and sex-matched healthy individuals were included. Salivary flow rate and IgA, IgG, and IgM concentrations were recorded. The secretion rates of IgA and IgG were diminished by 83% (p < 0.001) and 75% (p = 0.05), respectively, whereas the secretion rate of IgM was not statistically significantly lower. Analysis of the data suggests that DS individuals are immunodeficient in the humoral mucosal immune response. This may explain, in part, the high incidence of recurrent infections in target organs of the secretory immune system in DS subjects.

A link between parotid salivary Ig level and recurrent respiratory infections in young Down's syndrome patients.

The purpose of the present investigation was to assess the correlation between recurrent respiratory infections and the levels of salivary Ig in a group of young Down's syndrome (DS) individuals. Twenty-three DS and 10 age- and sex-matched healthy individuals were included. DS individuals who had experienced three or more upper respiratory tract infections (n = 10) in the previous 12 months were compared to DS individuals who had not experienced recurrent respiratory infections (n = 13) and to healthy controls (n = 10). A statistically significant reduction in the Ig salivary secretion rate was recorded in the subgroup with recurrent respiratory infections. No significant differences were seen between the subgroup without recurrent respiratory infections and controls. It is suggested that the secretory immune system provides local immune protection against pathogens in the respiratory tract. Detection of salivary Ig levels may serve as a predictor of the susceptibility of DS individuals to recurrent respiratory tract infections.

The use of orthodontic treatment and immediate implant loading to restore the traumatic loss of a maxillary central incisor.

This clinical case describes a new orthodontic/surgical concept for immediate loading of hydroxyapatite-coated cylindric implants, placed at the end of orthodontic treatment, to restore a traumatically lost maxillary central incisor. Further clinical and histologic studies are necessary to promote routine clinical application of this technique.

[The orthodontic treatment of children with disabilities].

Due to the medical progress in the past decades, the life expectancy and quality of the physically and/or mentally disabled children have been much improved. While this has facilitated their entry into society, it has also created greater demands on our profession, from those who care for them. A displeasing dental appearance may have a significant emotional impact on an individual's well being and can bias judgments of social acceptability, ability and personality. Gross misplacement of the teeth occurs more often and with much greater severity in the disabled child than in the general population. The increased concern for facial appearance and oral functions has generated an increased demand for orthodontic treatment, but the difficulties imposed by the handicapping conditions have made many practitioners believe that these patients are not amenable to treatment. At the Center for the Treatment of Craniofacial Anomalies in the Orthodontic Department of the Hadassah School of Dental Medicine, Jerusalem we have been treating children with disabilities for several years. An investigation of the referral patterns of our patients has revealed ignorance of dentists, physicians and social workers of what can and may be done to improve the dental and facial appearance of these children. This finding was the principle reason for this article, in which we will show how successful delivery of treatment is possible for many of the disabled.

Immediate loading of single-tooth implants: immediate versus non-immediate implantation. A clinical report.

The hypothesis of the present study was that immediate loading of implant-supported restorations replacing single missing teeth could be a successful procedure. The present study compared the clinical success of immediately loaded single-tooth implants placed in fresh extraction sites to that of immediately loaded single-tooth implants placed in healed sites. From the years 1997 to 1998, 26 patients, ranging in age from 18 to 70 years, presented for the placement of 28 immediately loaded implants intended to support single-tooth ceramometal restorations. Nineteen implants were placed into fresh extraction sites, and 9 implants were placed into healed sites. Temporary prefabricated acrylic resin crowns were prepared and adjusted. At the time of traditional second-stage surgery (3 to 6 months after implantation), the implants were restored with single-tooth ceramometal prostheses. The survival rates were 82.4% and 100% for immediate and non-immediate implants, respectively. Follow-up ranged from 6 to 24 months from the day of implant placement, with a mean of 13 months for the immediate implants and 16.4 months for the non-immediate implants. Radiographic marginal bone loss after 3 to 6 months did not extend beyond the abutment-implant junction. Within the limits of the present investigation, immediate loading of single-tooth implants placed in healed sites is a possible treatment alternative. Immediate loading of single-tooth implants placed in fresh extraction sites carried a risk of failure approximating 20% in this patient population.

The effect of precise reattachment of the mentalis muscle on the soft tissue response to genioplasty.

PURPOSE: This study compares vertical and horizontal profile changes of the lower lip and chin after genioplasty with or without precise reattachment of the mentalis muscle. PATIENTS AND METHODS: Ten patients in whom the mentalis muscle was isolated, identified, marked, and precisely reapproximated comprised the study group. Eleven patients treated without precise reattachment of the mentalis comprised the control group. Preoperative (3 to 6 days before the surgery) and postoperative (6 months after surgery) lateral cephalograms were analyzed to assess the horizontal and vertical soft tissue changes of the lower lip and chin area. RESULTS: All the significant changes in the present study were noted in the vertical parameters. In most of the study group, the length of the lower lip was either maintained or increased. In the control group, the lower lip length was either preserved or decreased. The mean vertical difference between the 2 groups was nearly 6 mm. Consequently, the study group displayed the same or less of the lower incisors postsurgery compared with the original presurgery exposure in the rest position. The opposite was true for the control group, in which the exposure of the lower incisor crowns at rest increased. Similar changes were noticed in the distance from the vermilion to the reference plane. The vertical position of the soft tissue supramentale remained unchanged in the study group, whereas in the control group the soft tissue supramentale was located in an inferior position (mean = 2.14 mm). The clinical expression of this phenomena is chin ptosis. CONCLUSIONS: Precise reattachment of the mentalis muscle during an intraoral surgical approach produces a superior result.

Prosthetic considerations in the restoration of orthodontically treated maxillary lateral incisors to replace missing central incisors: a clinical report.

The treatment of young patients with missing maxillary incisors poses a challenge to prosthodontists and orthodontists. The 2 principal treatment options are (1) the reopening or maintenance of space for future autotransplantation and/or prosthodontic restoration of the missing teeth, or (2) total orthodontic space closure, followed by prosthodontic modification of the lateral incisors to simulate the central incisors. This article discusses only the second option and describes 2 alternative methods for the modification of crown anatomy. These procedures facilitate the orthodontic closure of missing central incisor spaces to ensure satisfactory, esthetic results.