Steroid Route for Experimental Temporomandibular Joint Arthritis Treatment: Bone Growth

Objectives: Juvenile idiopathic arthritis often affects the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. This study evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ.
Methods: Joint inflammation was initiated by injecting 2 doses of complete Freund's adjuvant (CFA) at one month intervals into the right TMJs of 24 growing Sprague-Dawley male rats (left side controls). Four additional rats were left untreated. With the second CFA injection, three equal groups received: 1) intra-articular 5 mg P-DEX, 2) tail vein 15 mg P-DEX, or 3) nothing additional to CFA. Animals were euthanized 28 days later and heads stored in 10% formalin prior to radiographic measurement of ramus height (Cs-Golnf) and micro-computed tomography analysis of condylar width (CW), bone volume (BV), and bone density (BD). Inflammation-targeting of systemic P-DEX was confirmed by IVIS IRDye imaging. Groups were compared using analysis of variance.
Results: CFA treatment caused a significant reduction in Cs-Golnf (p < 0.05), but neither route of P-DEX administration caused further significant growth retardation. A systemic effect was noted in both routes of steroid application (reductions in contralateral control Cs-Golnf relative to no treatment, p < 0.05), yet more contralateral growth was seen relative to both of their steroid treatment sides (p < 0.01), indicating a concentrated effect in the inflamed TMJ. CW did not vary in response to CFA or either P-DEX route. However, BV and BD were significantly reduced in both inflamed and control condyles as a result of either steroid application (p < 0.05).
Conclusions: A high-dose systemic administration of inflammation-targeting P-DEX has a similar impact on TMJ bone growth as an intra-articular injection.