Wednesday, January 16, 2013

Bite-Jumping Appliance

The mechanism of Class II correction in Herbst appliance treatment. A cephalometric investigation.

"Sagittal skeletal and dental changes contributing to Class II correction in Herbst appliance treatment were evaluated quantitatively on lateral roentgenograms. The material consisted of forty-two Class II. Division 1 malocclusion cases. Twenty-two of these were treated with the Herbst appliance for 6 months. The other twenty cases served as a control group. The results of the investigation revealed the following: (1) Bite jumping with the Herbst appliance resulted in Class 1 occlusal relationships in all treated cases. (2) The improvement in occlusal relationships was about equally a result of skeletal and dental changes. (3) Class II molar correction averaging 6.7 mm. was mainly a result of a 2.2 mm. increase in mandibular length, a 2.8 mm. distal movement of the maxillary molars, and a 1.0 mm. mesial movement of the mandibular molars. (4) Overjet correction averaging 5.2 mm. was mainly a result of a 2.2 mm. increase in mandibular length and a 1.8 mm. mesial movement of the mandibular incisors. (5) Anterior condylar displacement (0.3 mm.), redirection of maxillary growth (0.4 mm.), and distal movement of the maxillary incisors (0.5 mm.) were of minor importance in the improvement in molar and incisor relationships seen. (6) A direct relationship existed between the amount of bite jumping at the start of treatment and the treatment effects on the occlusion and on mandibular growth. For a maximal treatment response, it is suggested that the Herbst appliance be constructed with the mandible jumped anteriorly as much as possible, namely, to an incisal edge-to-edge position. The clinician should be aware of the dental changes occurring during Herbst appliance treatment and make sure that these changes are not incongruous with his over-all treatment goal."

"The aim of the present study was to investigate the temporal pattern of expression of VEGF (Vascular Endothelial Growth Factor) and new bone formation in the condyle during forward mandibular positioning. The importance of vascularization during endochondral ossification was investigated during natural growth of the condyle and compared to that after forward mandibular positioning. The goal was to further our understanding of the cellular responses during functional appliance therapy with a view to extending the experiment into maturity. One hundred and fifty 35 days old Sprague-Dawley rats, 100 fitted with a bite-jumping appliance and 50 untreated, were divided into 10 groups. One group was sacrificed on each of experimental days 3, 7, 14, 21, 30, 33, 37, 44, 51 and 60 respectively. Sagittal sections were cut and stained with VEGF antibodies and Periodic acid and Schiff's reagent (PAS). Each section was quantitatively analyzed with a computer assisted analyzing program and the temporal sequence of expression of VEGF and new bone formation during natural growth and after mandibular forward positioning was compared. There was significant increase in both vascularization and mandibular bone growth upon forward mandibular positioning and the highest amount of both were expressed in the posterior region of the condyle. The highest acceleration of vascularization preceded that of new bone formation. Forward mandibular positioning was found to solicit a sequence of cellular events leading to increased vascularization and subsequently new bone formation resulting in enhanced condylar growth."

"Postnatal partial inhibition of VEGF expression was found to cause stunted body growth, impaired organ development and increased mortality."

"During the late stages of somatic growth, quantitative analysis of the temporal expression of VEGF, in rat condyles past the growth spurt was consistently higher in the posterior region when compared to anterior and middle regions. The pattern of new bone formation in the condyle throughout the same period followed a similar pattern.
After the peak height velocity, both VEGF and bone formation showed a gradual decrease concomitant with the slow down of the growth."

"The posterior region of the condyle showed the highest amount of VEGF expression during natural growth and during advancement. Interestingly, the highest amount of bone formed during natural growth and in response to advancement also occurred in the posterior region of the condyle. Such a close correlation could be explained by the fact that new blood vessels contribute to the population size of non-differentiated mesenchymal cells"

"connective tissues of the invading blood vessels are repository of undifferentiated mesechymal cells"

"VEGF could be the regulator of the process of recruiting new blood vessels into the hypertrophic cartilage matrix of the condyle"

"mechanical strain produced by mandibular advancement [may cause] an increase in the expression of VEGF by hypertrophic chondrocytes and subsequently lead to an increase in vascular invasion into the hypertrophic cartilage layer in the condyle."<-this may not be the only effect though.

"The type of collagenous matrix that forms in the human condyle in situations of repair is known to be type III collagen{up in LSJL}. Type III collagen is the emergency type of collagen that occurs during bone repair as well as bone development. The reason that type III collagen is a good candidate for the repair bone matrix is that the nature of the cross links to stabilize the collagen molecules to form collagen fibrils are weaker than those present in type I collagen matrix. This makes its removal at a later stage and its replacement by the more stable type I collagen matrix an easier process. Type III collagen is then removed at a later stage and replaced with Type I collagen, the more permanent type of collagen matrix and the most stable due to its very strong cross links."

Temporomandibular synovial fluid pressure response to altered mandibular positions.

"Hydrostatic synovial fluid pressure within the superior aspect of the temporomandibular joint space of the growing pig, Sus scrofa domesticus, was examined in response to various acute and chronic alterations of mandibular position. Bilateral measurements of pressure were recorded with chronically implanted wick catheters in three 8-week-old pigs before and at the time of appliance placement and then at 2-day intervals until the animals were 20 weeks old. Besides confirming the observations of a previous study, we noted that forward positioning of the mandible caused an increase in synovial fluid pressure that decayed to baseline levels within 2 hours. Posterior positioning of the mandible effected a larger increase in pressure that partially decayed over 2 hours but did not return to baseline levels over the entire course of the experiment."

This is a very relevant experiment and unfortunately I couldn't get the full study.

VEGF and bone formation in the glenoid fossa during forward mandibular positioning.

"The temporal pattern of vascular endothelial growth factor (VEGF) expression and bone formation in the glenoid fossa during natural growth was identified and compared with that during forward mandibular positioning. We randomly divided 150 female Sprague-Dawley rats, 35 days old, into 10 experimental and 10 control groups. Appliances were fitted to position the mandible forward in the experimental groups. The rats were then killed at different times. Sections were cut and stained with anti-VEGF antibodies to evaluate VEGF expression, and with periodic acid and Schiff's reagent to evaluate new bone formation. Both VEGF expression and newly formed bone were measured by a computer-assisted image analyzing system. during natural growth and forward mandibular positioning, VEGF expression and new bone formation were highest in the posterior region of the glenoid fossa. There were significant increases of VEGF and new bone formation in the experimental groups compared with the controls. The highest amount of VEGF expression occurred before the highest amount of bone formation was reached. Forward mandibular positioning causes significant increases in vascularization and new bone formation in the glenoid fossa. A close correlation exists between vascularization and bone formation."

"an increase of 170% in the VEGF expression [has been attributed to] mandibular advancement"

Skeletal effects of bite jumping therapy on the mandible - removable vs. fixed functional appliances.

"The data for removable and fixed functional appliances were respectively comprehended and analyzed with regard to their attributes in mandibular growth modification. Furthermore, numerous reported findings were assessed by relating them to some important factors influencing the effects of bite jumping, such as treatment timing, treatment duration and post-treatment follow-up, to allow for a more objective and accurate evaluation.
The key differences between removable and fixed appliances are working hours (intermittent vs. continuous), length of treatment time (long vs. short), optimal treatment timing (before puberty growth vs. at or after puberty spurt), and mode of bite-jumping (considerable vertical opening vs. limited vertical opening). These different features lead to different treatment effects on mandibular and TMJ growth, such as the intensity of possibly increased growth (clinically less significant vs. significant), the direction of enhanced growth (vertical vs. horizontal), and the stability of treatment changes (unstable vs. stable). The short-term or long-term post-treatment relapse mainly relates to the rebound of dental position.
The immediate effects of bite jumping functional appliances on the mandibular growth enhancement are convincing during actual treatment. This extra gain of growth might be sustainable during the short-term and long-term post-treatment period."

"In an attempt to elucidate the mechanism by which mesenchymal cells proliferate and differentiate in response to mandibular protrusion, the temporal sequence of cellular changes in posterior aspect of TMJ in rats [was identified]. The mesenchymal cells were found to be stretched and oriented in the direction of the pull, which might trigger the biophysiological path of mesenchymal cells differentiating into bone making cells in TMJ."

"[Some studies have] found no growth stimulation on a short-term basis. A limited number of studies on long-term effects of removable BJFA on mandibular growth have almost invariably reported some relapse after 3–20 years after treatment"

[Expression of BMP/Smads in rabbit condylar cartilage during mandibular forward positioning].

"To identify the relationship between the expression of BMP/Smads in condylar cartilage and condylar growth modifications in rabbits during mandibular forward positioning.
Sixty male rabbits with 8 weeks of age were randomly divided into the experimental group (n=36) and control group (n=24). The mandibles of rabbits in the experimental groups were induced to forward position by a functional appliance. The rabbits in the experimental group and control group were sacrificed after 3 days and 1, 2, 4, 8, 12 weeks, respectively. The expression of BMP-2, Smad1/5, 4 and 6 in condylar cartilage was examined by immunohistochemical staining.
The expression of BMP-2, Smad1/5, 4 and 6 was mainly found in the chondrocytes from the transitional zone and hypertrophic zone, and was also found in the chondrocytes and osteoblasts of the mineralized zone. Compared with those of the age-matched controls, the positive signals for BMP-2, Smad1/5, 4 and 6 in the experimental animals were stronger at early stage, coinciding with the remodeling in condylar cartilage after functional appliance.
The expression of BMP-2, Smad1/5, 4 and 6 is associated with the adaptive remodeling of the condylar cartilage after functional appliance."

Again an important study and I can't find the full version.

"Adaptive remodelling of the condylar cartilage in response to mandibular protrusion constitutes the rationale for bite-jumping appliances to solicit growth modification. By investigating the expression of type X collagen and capillary endothelium, this study was designed to evaluate the osteogenic transition of chondrogenesis during adaptive remodelling of condylar cartilage and compare it with that under natural condylar growth. One hundred female Sprague-Dawley rats, 35 days of age, were divided into five experimental groups (n = 15, fitted with bite-jumping appliances) where condylar adaptation was created by forward repositioning of the mandible, and five control groups (n = 5) where the condyles underwent natural growth. The animals were sacrificed at 3, 7, 14, 21 and 30 days and 7 mum serial sections of the condyles were processed for in situ hybridization and immunohistochemical analyses. The expression of type X collagen in the hypertrophic zone and capillary endothelium in the erosive zone of condylar cartilage were examined to evaluate osteogenic transition, a critical programme leading to endochondral ossification.  (1) The temporal pattern of the expression of type X collagen and capillary endothelium during condylar adaptation coincided with that during natural condylar growth. (2) The amount of the expression of these two factors during condylar adaptation was significantly higher than that during natural growth. It is suggested that condylar adaptation in growing rats triggered by mandibular forward positioning enhances osteogenic transition which eventually results in increased bone formation."

"Using an animal model where the condyle is deviated from the fossa, it has been found that mesenchymal cells in the articular layer are stretched and reorientated towards the pull, leading to an increased mesenchyme population and an enhanced differentiation into chondrocytes, which subsequently results in an adaptive remodelling "<-maybe this can occur within the epiphyseal bone marrow as well.

Forward mandibular positioning up-regulates SOX9 and type II collagen expression in the glenoid fossa.

"the purpose of this study was to investigate the temporal pattern of expression of two key chondrogenesis markers-SOX9 and its target gene, type II collagen-in the glenoid fossa by immunostaining in a 35-day-old Sprague Dawley rat model during both natural growth and forward mandibular positioning. The expression of both factors was up-regulated when the mandible was positioned forward, indicating an enhancement of chondrocyte differentiation and chondroid matrix formation. Our results indicate that chondroid bone formation in the glenoid fossa in response to forward mandibular positioning is regulated by molecular markers indicative of endochondral ossification."

"Expression of SOX9 was found to be localized in both the mesenchymal cells and hypertrophic chondrocytes"

Replicating mesenchymal cells in the condyle and the glenoid fossa during mandibular forward positioning.

"The purpose of this study was to identify and quantify the temporal sequence of replicating mesenchymal cells during natural growth and mandibular advancement in the condyle and the glenoid fossa. One hundred fifty 35-day-old female Sprague-Dawley rats were randomly divided into 10 experimental groups (10 rats each) and 10 control groups (5 rats each). The experimental groups were fitted with appliances that positioned the mandible forward. One hour before the rats were killed, bromodeoxyuridine (BrdU) was intravenously injected into them. Sections were cut and stained with anti-BrdU antibody to evaluate the number of replicating mesenchymal cells. Cellular uptake of BrdU was quantified with the Leica Qwin (Leica Microsystem Imaging Solutions, Cambridge, United Kingdom) system.  the numbers of replicating mesenchymal cells during natural growth were highest in the posterior region of the condyle and the anterior region of the glenoid fossa. In the experimental groups, the posterior region had the highest number of replicating cells for both the condyle and the glenoid fossa, with the condyle having 2 to 3 times more replicating cells than the glenoid fossa. The number of replicating mesenchymal cells, which is genetically controlled, influences the growth potential of the condyle and the glenoid fossa. Mandibular protrusion leads to an increase in the number of replicating cells in the temporomandibular joint. Individual variations in the response to growth modification therapy could be a result of the close correlation between mesenchymal cell numbers and growth."

"an increase in the mitotic activity of mesenchymal cells in the condyle in response to mandibular advancement with an increase in the thickness of the prechondroblastic and chondroblastic zones, and [there was] an increase in DNA synthesis only when the mandible was positioned distally instead {although there have been conflicting reports}."

"In some sections, clusters of mesenchymal cells could be observed that resembled the initial stages of cell condensation"

"The number of mesenchymal cells in anyone is genetically controlled. In a study of genetic and environmental control of variations in neuron cell numbers in mice, it was found that genetic factors are the most important in controlling this variation. Heritable influences were found to contribute
to 76% of the variance, and up to 90% is attributable to genetic factors in a broad sense.  Nongenetic factors were still appreciable and account for a coefficient of variation that averages approximately
3.6%. Similarly, variations in mesenchymal cell numbers would be greatly influenced by genetic factors that might explain the variations in patients’ responses to growth modification."

<-In chinese unfortunately.

"Identical bite-jumping appliances were fixed to upper incisors of animals in experimental groups, causing a continuous mandibular forward positioning. Histological sections were performed through mandibular condyle and were stained with HE under the same condition. Chondrogenesis was quantified by measuring the area of cells in resting, proliferative, hypertrophic and erosive zones in the superioposterior region.
1. comparison among experimental groups revealed a fluctuation in proliferative zone, with 21-day group being the greatest (0.058 +/- 0.004 mm2) and 14-day the least (0.012 +/- 0.001 mm2). A change in erosive zone was also depicted by a peak of 0.112 +/- 0.001 mm2 in 7-day group and a bottom of 0.018 +/- 0.002 mm2 in 14-day group. 2. comparison among the control groups manifested stable zonation, except for a slump of proliferative zone descending from 0.069 +/- 0.005 mm2 in 3-day group to 0.009 +/- 0.001 mm2 in 21-day group. 3. comparison between experimental and control groups demonstrated significant discrepancy in proliferative zone, hypertrophic zone and erosive zone.
Mandibular forward positioning stimulates and accelerates cartilaginous remodeling in mandibular condyle."

The adaptive remodeling of condylar cartilage---a transition from chondrogenesis to osteogenesis.

"Mandibular condylar cartilage is categorized as articular cartilage but markedly distinguishes itself in many biological aspects, such as its embryonic origin, ontogenetic development, post-natal growth mode, and histological structures. The most marked uniqueness of condylar cartilage lies in its capability of adaptive remodeling in response to external stimuli during or after natural growth. The adaptation of condylar cartilage to mandibular forward positioning constitutes the fundamental rationale for orthodontic functional therapy, which partially contributes to the correction of jaw discrepancies by achieving mandibular growth modification. The adaptive remodeling of condylar cartilage proceeds with the biomolecular pathway initiating from chondrogenesis and finalizing with osteogenesis. During condylar adaptation, chondrogenesis is activated when the external stimuli, e.g., condylar repositioning, generate the differentiation of mesenchymal cells in the articular layer of cartilage into chondrocytes, which proliferate and then progressively mature into hypertrophic cells. The expression of regulatory growth factors, which govern and control phenotypic conversions of chondrocytes during chondrogenesis, increases during adaptive remodeling to enhance the transition from chondrogenesis into osteogenesis, a process in which hypertrophic chondrocytes and matrices degrade and are replaced by bone. The transition is also sustained by increased neovascularization, which brings in osteoblasts that finally result in new bone formation beneath the degraded cartilage."

"The repositioning of the mandibular condyle in adult rats led to a reactivation of chondrogenesis in condylar cartilage which otherwise is at resting status, and finally results in increased bone formation"<-so stretching the mandible seems to result in endochondral ossification of the articular cartilage.

"the chondrogenic activity of BMP-2 in vitro involves the action of the cell-cell adhesion protein, N-cadherin, which functionally complexes with beta-catenin"

"the change of condyle position relative to the glenoid fossa constitutes an important trigger for [the endochondral ossification related adaptation of the mandible]. The deviation of the condyle from the glenoid fossa by mandibular forward translation is the basis for orthodontic functional therapy, which aims to enhance condylar growth and therefore to eliminate the discrepancy between upper and lower jaws."

"a decrease in compressive loading enhances condylar growth, whereas an increase in loading inhibits growth"

Changes in condylar cartilage after anterior mandibular displacement in juvenile pigs.

"Twenty juvenile pigs were randomly divided into two experimental groups, where the treatment group was fitted with mandibular advancement splints, and the control group was not. Changes in the mRNA content of condylar cartilage tissue was then were measured after 4weeks of treatment.
The temporal pattern of the expression of Col1 and MMP13 during condylar adaptation coincided with that during natural condylar growth. The amount of the expression of Col10 during condylar adaptation was significantly lower, whereas the expression of Col2, MMP8 and VEGF was significantly higher compared to natural growth.
It is suggested that condylar adaptation in growing pigs triggered by mandibular forward positioning results not only from passive adaptation of cartilage, but also involves growth affected processes. Mechanical strain produced by mandibular advancement induced remodelling and revascularization in the posteriocranial mandibular condyle."

"The mandibular condylar cartilage serves as both an articular condyle, and as a growth centre in the juvenile mandible."

Dentoskeletal effects and facial profile changes in young adults treated with the Herbst appliance.

"Early adolescent subjects in the permanent dentition who had been treated with the Herbst appliance were used for comparison. Lateral headfilms from before and after an average treatment period of 8.5 months for the young adults and 7.1 months for the adolescents were evaluated. All adult and adolescent subjects were treated to either Class I or overcorrected Class I occlusal relationships. In both groups the improvement in sagittal incisor and molar relationships was achieved more by dental changes than by skeletal ones. The amount of skeletal change contributing to overjet and molar correction was smaller in the young adult group (22% and 25%, respectively) than in the early adolescent group (39% and 41%, respectively). Skeletal and soft tissue facial profile convexity was reduced in adults and adolescents. Facial profile improvement did not differ between the two groups."

Young adults were defined as individuals who had a fused radius(arm) bone.  Young adults ranged from 13.6-19.8.

Adolescents increased in mandibular length by +2.5mm more than young adults.  young adults still increased in mandibular length by 1.5mm.

Zones of undifferentiated mesenchyme and undifferentiated growth cartilage are seen in the adult condyle.

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