Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular joint. Part II: mandibular growth

Abstract

Background: Temporomandibular joint (TMJ) arthritis in children causes alterations in the craniomandibular growth. Resultant abnormalities include; condylar erosions, a posterior mandibular rotation pattern, micrognathia, malocclusion with an anterior open bite, altered joint and muscular function occasionally associated with pain. These alterations may be prevented by early aggressive anti-inflammatory intervention. Previously, we have shown that intra-articular (IA) corticosteroid reduces TMJ inflammation but causes additional mandibular growth inhibition in young rabbits. Local blockage of TNF-alpha may be an alternative treatment approach against TMJ involvement in juvenile idiopathic arthritis (JIA). We evaluated the anti-inflammatory effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in young rabbits in terms of mandibular growth. This article (Part II) presents the data and discussion on the effects on facial growth. In Part I the anti-inflammatory effects of systemic and IA etanercept administration are discussed.

Methods: Arthritis was induced and maintained in the TMJs of 10-week old pre-sensitized rabbits (n = 42) by four repeated IA TMJ injections with ovalbumin, over a 12-week period. One group was treated weekly with systemic etanercept (0.8 mg/kg) (n = 14), another group (n = 14) received IA etanercept (0.1 mg/kg) bilaterally one week after induction of arthritis and one group (n = 14) served as an untreated arthritis group receiving IA TMJ saline injections. Head computerized tomographic scans were done before arthritis was induced and at the end of the study. Three small tantalum implants were inserted into the mandible, serving as stable landmarks for the super-impositions. Nineteen variables were evaluated in a mandibular growth analysis for inter-group differences. All data was evaluated blindedly. ANOVA and T-tests were applied for statistical evaluation using p < 0.05 as significance level.

Results: Significant larger mandibular growth disturbances were observed in the group receiving IA saline injections compared with the systemic etanercept group. The most pronounced unfavourable posterior mandibular rotation pattern was observed in the group receiving IA saline injections.

Conclusion: Intervention with systemic etanercept monotherapy equivalent to the recommended human dose allows a mandibular growth towards an original morphology in experimental TMJ arthritis. Systemic administrations of etanercept are superior to IA TMJ administration of etanercept in maintaining mandibular vertical growth.

Figure 1

Flow chart illustrating the study design.

Figure 2

Anatomical landmarks. Cm (Condylar midpoint), Ar1 (Articulare 1), Ar2 (Articulare 2), Go (Gonion), Ba (Basion point), Inc (Incisal point), Mol (Molar point). The implant points were located on the right side: ImpA (Implant A) and ImpB (Implant B). The following two lines were defined: ML (Mandibular line) from Go to Ba, defined at the right side; IL (Implant line) going through ImpA-ImpB. For specific definitions of the anatomical landmarks see Stoustrup et al. 2008 [12].

Figure 3

Angles and transverse variables measured. Angle1: Cm-ImpA-ImpB; Angle2: Go-ImpA-ImpB; Angle3: Cm-Go-Ba; Condylar distance (CD): Cm_right-Cm_left; Gonial distance (GD): Go_right-Go_left.

Figure 4

Vertical variables measured. Total posterior mandible height (TPMH): Cm-Go; Collum mandibular height 1 (CMH1): Cm-Ar1; Collum mandibular height 2 (CMH2): Cm-Ar2; Ramus height 1 (RH1): Ar1-Go; Ramus height 2 (RH2): Ar2-Go; Mandibular body height 1 (MBH1) Inc ⊥ IL; Mandibular body height 2 (MBH2): Mol ⊥ ML; Dentoalveolar height (DAH): Mol ⊥ IL; Height of angular notch (ANH): Inc ⊥ ML.

Figure 5

Sagittal variables measured. Mandibular length 1 (ML1) Go-ImpB; Mandibular length 2 (ML2) Ar1-ImpB; Mandibular length 3 (ML3) Ar2-ImpB; Total mandibular length (TML) Cm-ImpB; Implant distance (ID): ImpA-ImpB. Figures from Stoustrup et al. 2008 [12].

Figure 6

The relative growth of the total posterior mandibular height (TPMH). The growth of this variable was significantly larger (p < 0.05) in the systemic etanercept group (TPMH 12.6% [CI-95: 11.0–13.1]) compared with the IA saline group (TPMH 10.4% [CI-95: 9.2–11.5]). A non-significant trend (p < 0.1) towards a difference in the relative TPMH growth was observed between the systemic etanercept group (TPMH 12.6% [CI-95: 11.0–13.1]) and the IA etanercept group (TPMH 10.8% [CI-95: 9.2–12.2]).

Figure 7

The findings of this study. Intervention with systemic etanercept monotherapy equivalent to the recommended human dose allows mandibular growth towards an original morphology by significantly improved growth of the total posterior mandibular height (see TPMH variable at small arrow). Systemic etanercept (0.8 mg/kg weekly) administration is superior to IA TMJ etanercept administration at times of inflammatory flares in maintaining mandibular vertical growth. All three groups demonstrated an unfavourable clockwise posterior mandibular rotation pattern, illustrated by an opening of Angle 3 (large arrow). The most pronounced posterior mandibular rotation was observed in the IA saline group in which a closing of Angle 2 also occurred.