Comparison of Hyaluronic Acid, Injectable Platelet-Rich Fibrin, and Prolotherapy in TMJ Arthrocentesis

Temporomandibular joint (TMJ) disorders represent a heterogeneous group of conditions affecting the temporomandibular joint, masticatory muscles, and associated structures. These disorders are among the most common causes of chronic orofacial pain and functional impairment. Patients with temporomandibular joint disorders frequently present with symptoms such as joint pain, limited mouth opening, joint sounds, and impaired mandibular movements, which may significantly affect quality of life. The pathophysiology of TMJ disorders is multifactorial and may involve internal derangements of the joint, inflammatory processes, biomechanical alterations, and degenerative changes within the joint structures.

Conservative treatment approaches, including patient education, pharmacologic therapy, occlusal splints, and physiotherapy, are generally considered the first-line management for temporomandibular joint disorders. However, a subset of patients may not achieve adequate symptom relief with conservative treatment. In such cases, minimally invasive surgical procedures, such as temporomandibular joint arthrocentesis, are frequently recommended. Arthrocentesis is a minimally invasive procedure that involves lavage of the superior joint space to remove inflammatory mediators, release adhesions, reduce intra-articular pressure, and improve joint mobility. This technique has been widely used in the management of internal derangements and other temporomandibular joint pathologies and has demonstrated favorable clinical outcomes in terms of pain reduction and functional improvement.

In recent years, several intra-articular adjunctive therapies have been introduced to enhance the therapeutic effects of TMJ arthrocentesis. Hyaluronic acid is one of the most commonly used agents due to its viscoelastic, lubricating, and anti-inflammatory properties. Intra-articular hyaluronic acid injections may help restore the physiological properties of synovial fluid, improve joint lubrication, and contribute to pain reduction and functional recovery. Injectable platelet-rich fibrin (i-PRF) is an autologous platelet concentrate that contains a high concentration of growth factors and cytokines that may promote tissue healing, angiogenesis, and regenerative processes within the joint structures. Dextrose prolotherapy has also gained interest as a regenerative injection therapy that may stimulate fibroblast activity, enhance connective tissue repair, and potentially improve joint stability and function.

Although these intra-articular treatment modalities have been increasingly used in clinical practice, the available evidence regarding their comparative effectiveness when used in conjunction with TMJ arthrocentesis remains limited. Most previous studies have evaluated these therapies separately, and there is a lack of prospective comparative studies assessing different intra-articular adjuncts within the same clinical study design.

The aim of this study was to compare the clinical outcomes of temporomandibular joint arthrocentesis performed alone and arthrocentesis combined with different intra-articular adjunctive treatments, including hyaluronic acid, injectable platelet-rich fibrin (i-PRF), and dextrose prolotherapy. Patients diagnosed with temporomandibular joint disorders and presenting with joint pain and functional limitation were included in the study according to predefined inclusion and exclusion criteria. Following clinical and radiological evaluation, eligible patients were allocated into four treatment groups: arthrocentesis alone, arthrocentesis combined with hyaluronic acid injection, arthrocentesis combined with injectable platelet-rich fibrin (i-PRF), and arthrocentesis combined with dextrose prolotherapy.

All procedures were performed under standardized clinical conditions. Temporomandibular joint arthrocentesis was carried out using a conventional two-needle technique to irrigate the superior joint space. Following lavage, the designated intra-articular agent was administered according to the treatment group. Clinical outcomes were evaluated using standardized parameters including pain intensity assessed by visual analog scale (VAS), maximum mouth opening, and functional improvement of mandibular movements. Patients were followed at predefined postoperative intervals, and the changes in clinical parameters were analyzed to assess treatment effectiveness.

The results of this study are expected to provide comparative clinical data regarding the effectiveness of different intra-articular adjunctive therapies used with temporomandibular joint arthrocentesis. The findings may contribute to the current evidence base and assist clinicians in selecting the most appropriate minimally invasive treatment strategy for patients with temporomandibular joint disorders.

• Temporomandibular Joint Arthrocentesis (Procedure): Temporomandibular joint arthrocentesis was performed using a standard two-needle technique to lavage the superior joint space and remove inflammatory mediators.
• Hyaluronic Acid (Orthovisc) (Drug): Intra-articular injection of hyaluronic acid (Orthovisc) into the temporomandibular joint following arthrocentesis.
• Injectable Platelet-Rich Fibrin (i-PRF) (Biological): Autologous injectable platelet-rich fibrin prepared from the patient's venous blood and injected intra-articularly into the temporomandibular joint following arthrocentesis.
• Dextrose prolotherapy (DPT) (Drug): Intra-articular injection of dextrose solution administered as prolotherapy into the temporomandibular joint following arthrocentesis.

Primary outcomes

• Change in Pain Intensity (Visual Analog Scale, VAS) [Baseline, 1 week, 1 month, and 3 months]: Pain intensity was assessed using a Visual Analog Scale (VAS) to evaluate changes in pain levels after temporomandibular joint arthrocentesis alone or in combination with intra-articular hyaluronic acid, injectable platelet-rich fibrin (i-PRF), or dextrose prolotherapy. The Visual Analog Scale (VAS) is presented as a 0-10 numeric rating scale, where 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores indicate greater pain severity.
• Change in Maximum Mouth Opening [Baseline, 1 week, 1 month, and 3 months]: Maximum mouth opening (MMO) was measured clinically in millimeters to evaluate improvement in mandibular mobility after temporomandibular joint arthrocentesis alone or in combination with intra-articular hyaluronic acid, injectable platelet-rich fibrin (i-PRF), or dextrose prolotherapy.

Secondary outcomes

• Change in Jaw Functional Limitation Scale Score (JFLS-8) [Baseline, 1 month, and 3 months (The 1-week assessment was not performed because the questionnaire evaluates symptoms over the preceding month; therefore, a 1-week measurement could cause temporal overlap and affect response interpretation.)]: Functional limitation assessed using the 8-item Jaw Functional Limitation Scale (JFLS-8). Each item is scored on a 0-10 numeric rating scale, where 0 indicates no functional limitation and 10 indicates severe functional limitation. Higher scores indicate greater functional impairment.
• Change in Graded Chronic Pain Scale Score (GCPS 2.0) [Baseline, 1 month, and 3 months (The 1-week assessment was not performed because the questionnaire evaluates symptoms over the preceding month; therefore, a 1-week measurement could cause temporal overlap and affect response interpretation.)]: Pain-related disability assessed using the Graded Chronic Pain Scale version 2.0 (GCPS 2.0). The scale evaluates chronic pain intensity and pain-related disability. Higher scores represent greater pain severity and functional disability.
• Change in Pain Drawing Score [Baseline, 1 week, 1 month, and 3 months]: Pain distribution assessed using the Pain Drawing Questionnaire, where patients mark painful areas on a standardized body diagram. Larger marked areas indicate wider pain distribution.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Patients presenting with temporomandibular joint (TMJ) pain, limited mouth opening, and/or unilateral joint pain
* Patients diagnosed with internal derangement of the temporomandibular joint classified as DC/TMD
* Patients who did not respond adequately to conservative treatment modalities
* Patients who underwent temporomandibular joint magnetic resonance imaging (MRI) evaluation
* Individuals aged 18-65 years

Exclusion Criteria:

* Individuals who did not provide informed consent or were unwilling to participate in the study
* Patients whose primary source of pain was myofascial pain dysfunction or cervical-origin pain
* Pregnant or breastfeeding patients
* Patients with a known allergy to any of the injected solutions used in the study
* Patients with systemic joint diseases such as rheumatoid arthritis
* Patients with acute infection in the temporomandibular joint region
* Patients with hematological disorders
* Patients with a history of previous temporomandibular joint surgery
* Patients with tumors or malignant neoplasms involving the temporomandibular joint
* Patients with a history of oral or maxillofacial trauma affecting the temporomandibular joint
* Patients who were unable to cooperate with clinical examination or follow-up procedures

• Emel Bulut, DDS, PhD, Principal investigator, Ondokuz Mayıs University