Biomarkers and surgical predictors in temporomandibular joint disease

Background: Temporomandibular joint (TMJ) disc displacement (DD) is associated with pain and impaired function and has two main sub-diagnoses, DD with or without reduction (DDwR/DDwoR). DD synovial tissue has been sparsely investigated, and further characterisation is needed. Patients with TMJ diseases might need surgery, with arthroscopy being the most common approach. However, no patient-specific surgical predictors have been identified, guiding the clinician in prognosticating the outcome.

Aim: To develop tissue-based diagnostic criteria for patients with DD of the TMJ, and to identify factors that may predict TMJ surgical therapy outcome.

Material and methods: All included studies contain patients operated with arthroscopy or discectomy, due to DDwR, DDwoR, osteoarthritis, or chronic inflammatory arthritis. Surgical outcome in the retrospective study I (n = 224), and the prospective observational cohort studies II (n = 93) and IV (n = 100) were correlated to a predefined set of patient-specific variables. Synovial tissue biopsies were harvested and analysed in studies III (n = 63) and IV. The cytokine profile of patients with DDwR was compared to that of DDwoR in study III, and protein concentrations were correlated to surgical outcome in study IV.

Results: Masticatory muscle palpation pain had a positive association to surgical outcome in studies I, II, and IV. TMJ disability, TMJ psychosocial impact, global pain, and age might be promising predictors, but needs further verification. Significant concentration differences between DDwR and DDwoR were found in 15/28 tested cytokines. Only three cytokines, interferon gamma-induced protein 10 (IP-10) (P = 0.024), osteoprotegerin (OPG) (P = 0.046), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.001) had lower concentrations in DDwoR compared to DDwR. In study IV, higher concentrations of interleukin 8 (IL-8) (P = 0.049), lumican (P = 0.037), matrix metalloproteinase 7 (MMP-7) (P = 0.038), and tissue inhibitor of metalloproteinase 2 (TIMP-2) (P = 0.015) were associated with an inferior surgical outcome.

Conclusions: Bilateral muscle palpation pain seems to be a predictor of unfavourable outcome indicating the surgeon to reconsider further non-invasive treatment. Furthermore, IL-8, lumican, MMP-7, and TIMP-2 were positively correlated to outcome and may serve as predictors for surgical outcome. The inflammatory profile was found to differ between DDwoR and DDwR, further establishing the difference between the two states. Other studies indicate that higher concentrations of IP-10, OPG, and RANTES could have been expected in DDwoR, which is why this contradictory result might indicate biomarker potential.

List of scientific papers

I. Ulmner M, Kruger-Weiner C, Lund B. Patient-specific factors predicting outcome of temporomandibular joint arthroscopy: a 6-year retrospective study. J Oral Maxillofac Surg. 2017;75(8):1643.e1-1643.e7.
https://doi.org/10.1016/j.joms.2017.04.005

II. Ulmner M, Kruger-Weiner C, Lund B. Predictive factors in temporomandibular joint arthroscopy: a prospective cohort short-term outcome study. Int J Oral Maxillofac Surg. 2020;49(5):614-620.
https://doi.org/10.1016/j.ijom.2019.09.002

III. Ulmner M, Sugars R, Naimi-Akbar A, Suslu S, Reseland JE, Kruger-Weiner C, Lund B. Synovial tissue cytokine profile in disc displacement of the temporomandibular joint. J Oral Rehabil. 2020 Jul 8.
https://doi.org/10.1111/joor.13051

IV. Ulmner M, Sugars R, Naimi-Akbar A, Tudzarovski N, Kruger-Weiner C, Lund B. Synovial tissue proteins and patient-specific variables as predictive factors for temporomandibular joint surgery. [Submitted]