Treatment of temporomandibular joint osteoarthritis: systematic review of the literature and evaluation of the effects of simvastatin on human osteoblasts in vitro
Drug Therapy. Osteoarthritis. Temporomandibular Joint. Simvastatin. Osteoblasts.
Osteoarthritis of the temporomandibular joint (TMJ-OA) is a chronic, non-infectious, focal degenerative disease associated with the subchondral bone remodeling with functional dysregulation of osteoblasts. Studies suggest that statins are promising candidates for new drugs for osteoarthritis (OA) because of their effects on modulating the inflammatory response. Therefore, the present study aimed to carry out a systematic review of the scientific literature to answer which drugs would be available for the treatment of OA. Furthermore, we also sought to use an experimental approach to evaluate the in vitro effects of simvastatin on human osteoblasts. For the systematic review, search strategies were used in the MEDLINE, Cochrane Central, Web of Science, BBO, and EMBASE databases, including articles until July 2022. After analyzing the abstracts, and applying the inclusion and exclusion criteria, 6 studies met the established eligibility criteria. The methodological assessment was performed using the Jadad Scale, the analysis for risk of bias was determined by the table for risk of bias, and the analysis of evidence was determined by the GRADE tool. The analysis of the studies revealed that pharmacological treatment caused a decrease in pain intensity in all evaluated studies, with emphasis on the high level of evidence according to the GRADE tool for intra-articular treatment with sodium hyaluronate associated with therapy with oral glucosamine. In the experimental approach of the present study, the human osteoblast lineage MG-63 was used to evaluate in vitro the effects of simvastatin. Our results demonstrated that concentrations of 1-10 μM of simvastatin did not affect the cell viability of osteoblasts. However, when the morphology of osteoblasts was evaluated, it was observed that simvastatin altered the morphology of the cells as the polarized shape was replaced by an increase in the number of cells with a rounded profile. This change in morphology was also observed when cells were stimulated with LPS. However, when evaluating the phagocytic capacity of these cells, treatment with simvastatin was not able to induce/alter the phagocytosis of zymosan particles. In another experimental set, LPS-stimulated production of nitric oxide by osteoblasts was inhibited by treatment with simvastatin. Taken together, the results of this study demonstrate that the scientific literature gathered in the systematic review presents therapeutic alternatives that support the improvement of pain and noise in TMJ-OA. However, studies with detailed standardized variables and methods are necessary to reduce the risk of bias found, which may compromise the conclusion of a certain therapeutic option for clinical practice. In addition, the importance of correlation of clinical studies with biomarkers evaluated in vitro is emphasized that can contribute to the analysis of drugs aimed at preventing and/or stagnating the progression of TMJ-OA. Therefore, we demonstrated in vitro that simvastatin proved to be a promising candidate for a drug that modulates some osteoblast functions, indicating the potential for clinical use in TMJ-OA.