Does injection of plasma rich in growth factors after temporomandibular joint arthroscopy improve outcomes in patients with Wilkes stage IV internal derangement? A randomized prospective clinical study

Abstract

The aim of this study was to evaluate the efficacy of injection of plasma rich in growth factors (PRGF) after temporomandibular joint (TMJ) arthroscopy in patients with Wilkes stage IV internal derangement. Ninety-two patients were randomized to two experimental groups: group A (42 joints) received injections of PRGF, group B (50 joints) received saline injections. Pain intensity on a visual analogue scale (VAS) and maximum mouth opening (MMO, mm) were measured before and after surgery and compared by analysis of variance (ANOVA). The mean age of patients was 35.8 years (range 17–67 years); 86 were female. Significant reductions in pain were noted in both groups after surgery: VAS 7.9 preoperative and 1.4 at 24 months postoperative. Significantly better clinical results were achieved in group A than in group B only at 6 and 12 months postoperative; no significant difference was noted at 18 or 24 months after the surgical intervention. MMO increased after surgery in both groups: 26.2 mm preoperative and 36.8 mm at 24 months postoperative. No significant differences in MMO were found when the two groups of patients were compared. In conclusion, the injection of PRGF does not add any significant improvement to clinical outcomes at 2 years after surgery in patients with advanced internal derangement of the TMJ.

It has been suggested that disc displacement without reduction (DDwoR) might progress to osteoarthrosis (OA). In cases of longstanding DDwoR, magnetic resonance imaging (MRI) signs of OA are frequently noted; however, these radiological signs can appear in patients diagnosed with disc displacement with reduction (DDwR) and even in patients with a normal disc position. Thus, disc displacement is only one cause of OA, which can result from a multitude of primary joint lesions.

The majority of patients with internal derangement of the temporomandibular joint (TMJ) improve clinically with non-surgical treatments that include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), occlusal splints, and physiotherapy. When these treatment modalities fail to improve the patient’s clinical situation, different minimally invasive techniques, such as the injection of diverse substances into the joint, arthrocentesis, and arthroscopy with lysis and lavage, have exhibited good clinical results in relieving pain and improving functional outcomes. None of these surgical procedures modify the abnormal position of the articular disc or enter the inferior joint compartment, which might be one of the reasons for the poor clinical outcomes that are observed in some cases in which the internal derangement progresses to disc perforation, OA, and mandibular asymmetry.

Most previously published studies have failed to demonstrate any differences in the outcomes of arthroscopy with lysis and lavage compared to operative arthroscopic surgery. Recently, descriptions of new surgical arthroscopic techniques that use coblation technology, new stabilization sutures, and pins have been reported, and the efficacies of these new techniques require verification over the long term.

The use of plasma rich in growth factors (PRGF) is an autologous biological therapy that is based on the use of the patient’s own plasma, platelet-derived growth factors, and endogenous fibrin scaffolds for regenerative purposes. Recent data support the application of platelet-rich plasma (PRP) products as an effective and safe method in the treatment of the initial stages of knee OA. Furthermore, some randomized clinical studies have concluded that PRGF exhibits superior clinical results compared to hyaluronic acid (HA) in alleviating the symptoms of mild to moderate osteoarthritis of the knee.

The aim of this prospective clinical study was to evaluate the efficacy of PRGF injections at the end of arthroscopic surgery in patients with disc displacement and MRI signs of condylar OA of the TMJ.

Materials and methods

Patients with internal derangement of the TMJ (DDwoR) and OA of the mandibular condyle (Wilkes stage IV) who had failed to respond to non-surgical treatments (NSAIDs, physiotherapy, and occlusal splints) for at least 6 months were assessed for this prospective randomized controlled clinical study. The study was approved by the reference ethics committee of the study hospital and all patients provided written informed consent before entering into the study. The recruitment of patients began in January 2008 and finished in December 2011.

Consecutive patients were assessed against defined inclusion and exclusion criteria and only those meeting the necessary criteria were included in the study. All patients completed the 2 years of follow-up. The inclusion criteria were as follows: unilateral joint involvement and MRI signs of anterior DDwoR (ADDwoR) with degenerative alterations of the bony components of the joint (OA). The exclusion criteria were as follows: bilateral joint involvement, prior TMJ surgery (including infiltrations and arthrocentesis), history of mandibular fracture, presence of known connective tissue or autoimmune diseases, concurrent use of steroids, muscle relaxants, or narcotics, major psychiatric disease, contraindications for imaging, and the presence of a medical contraindication to the treatment.

All of the patients were assessed clinically according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) specifications, and the following variables were recorded: joint pain using a visual analogue scale (VAS) (0–10), joint noises (clicking, crepitus, or none), duration of the symptoms, and maximum mouth opening (MMO) measured as the distance between the upper and lower incisors. The different clinical parameters were recorded by the same observer (staff maxillofacial surgeon not blinded to the surgical procedure) before surgery and at 3, 6, 12, 18, and 24 months of follow-up.

MRI images were obtained using a Philips Achieva 1.5T scanner (release 3.2 level 3; Philips Medical Systems, Netherlands) with the following parameters: a pseudodynamic sagittal survey at four consecutive oral apertures and fast field echo (FFE) sequences, with a repeat time (TR) of 1/4 200 ms and echo times (TEs) of 1/4 15 and 1/4 50 ms. MRI images were also obtained in the coronal plane. The morphological characteristics of the articular disc (normal, biconvex, biplanar, folded, amorphous, or other), the position and mobility of the disc (normal, anteriorly displaced with or without reduction, anteromedial or anterolateral disc displacement, pure medial or lateral disc displacement, normal mobility, hypomobility, or fixed), the morphological appearance of the joint (normal, intra-articular effusion, or free bodies), and the bone morphology (normal, or signs of OA including deformity, erosions, osteophytes, cysts, and bone marrow changes (sclerosis, oedema)) were studied before surgery and at 2 years after surgery.

Ninety-two patients fulfilled the inclusion criteria and consented to participate in this study. The patients were randomized to the two experimental groups using specific software (Random Allocation Software). The patients were blinded to which arm they were in. The patients assigned to group A received injections of PRGF in both the superior and inferior joint spaces at the end of the arthroscopic treatment, under direct arthroscopic view. The other group of patients (group B, control group) received an injection of 5 ml of 5% sodium chloride in the inferior joint compartment.

With regard to the arthroscopy, all operations were performed under general anaesthesia as ambulatory procedures by a single surgeon in a single hospital using the same types of instruments. The double-channel arthroscopic technique with two 2.3-mm cannulae was used in all cases. A 1.9-mm Dyonics 30° arthroscope (Smith & Nephew, Melbourne, Australia) was employed. Exploration of the superior joint space was performed, and the following arthroscopic findings were recorded: hypervascularization of the posterior disc attachment, synovitis and hyperemia of the capsule, the presence of adhesions, perforation of the disc, and fibrillation or denudation of the bone. After lysis and lavage of the superior joint space, a coblation probe (ArthroCare System 2000; ArthoCare, Sunnyvale, CA, USA) was used to release the anterior attachment of the disc and a portion of the lateral pterygoid muscle (capsulotomy with myotomy) ( Fig. 1 ) . Posterior mobilization of the disc was performed with a blunt probe, and then superficial vaporization of the posterior disc attachment was performed ( Fig. 2 ) . In group A, the inferior joint space was entered under arthroscopic guidance using a spinal gauge inserted through the disc in the intermediate joint space to infiltrate 5 ml of PRGF, and the remaining PRGF was injected into the superior joint space before withdrawing the arthoscopic cannula ( Fig. 3 ). In group B, 5 ml of 5% sodium chloride was injected into the inferior joint compartment using the same surgical procedure as that used in group A patients (Fig. 3 ).

Fig. 1
Arthroscopic surgical technique. (A) Release of the anterior disc attachment with a coblation probe. (B) The lateral pterygoid muscle is exposed (*).

Fig. 2
(A) Synovitis grade III–IV of the posterior disc attachment. (B) Coagulation of the posterior disc attachment with a coblation probe. (C) Absence of synovitis after coagulation.

Fig. 3
The inferior joint compartment was entered using a spinal needle to infiltrate 5 ml of PRGF.

To prepare the PRGF (PGGF-Endoret, BTI, Vitoria, Spain), 36 ml of peripheral blood was extracted from each patient by venipuncture directly into four extraction tubes containing 3.8% sodium citrate as anticoagulant. The extracted blood was centrifuged at 580 g for 8 min at room temperature in a BTI Biotechnology Institute system centrifuge (BTI, Vitoria, Spain), in the same surgical theatre. Once the blood tubes were centrifuged, the plasma fractions were separated by pipetting under strictly sterile conditions. Only the 2 ml of plasma that was rich in platelets remaining above the red series was obtained; the leukocytes were avoided. Prior to infiltration, all of the 2-ml fractions were placed together in a single tube (for a total volume of 8 ml), with gentle inversion of the tube in a sterile glass container in which it was activated before infiltration via the addition of 400 μl of calcium chloride.

In the immediate post-surgical period (2 weeks), all patients received NSAIDs, consumed a soft diet, and underwent physical therapy (thermal applications and range of motion and isometric exercises). Occlusal splint therapy (flat plane) was advised only for patients in whom parafunctional activity had been diagnosed previously (24% of the patients). There was no significant difference in postoperative management between the groups.

Descriptive statistics for categorical and continuous variables were calculated. To assess the significance of trends over time in terms of each variable (i.e., MMO and VAS pain ratings), general linear models were derived. Comparisons of the mean values of the variables were performed with one-way analysis of variance (ANOVA). All significance tests were performed based on a probability of type I error of 0.05 or less. SPSS version 16.0 software (SPSS Inc., Chicago, IL, USA) was used for all statistical analyses.

Results

A total of 92 patients underwent randomization and treatment and completed the follow-up. No patient was excluded. The mean age of the patients was 35.8 years (range 17–67 years). The majority of the patients were female (86 patients). Preoperatively, no significant difference was found between the groups of patients regarding age, pain, or MMO ( Table 1 ). The duration of symptoms before the first visit ranged from 9 months to 15 years (mean 35.4 months).

Table 1
Comparison of the two study groups at baseline. a
PRGF group Control group
Age, years, mean ± SD 36.7 ± 6.3 34.8 ± 7.9
Sex, female/male 40/2 47/3
Left joint 17 19
Right joint 25 31
Pain, VAS 7.7 ± 1.6 8.1 ± 1.9
MMO, mm 26.4 ± 6.3 27.2 ± 7.6
MRI showing DDwoR + OA 42 50
Patients/joints 42 50
PRGF, plasma rich in growth factors; SD, standard deviation; VAS, visual analogue scale; MMO, maximum mouth opening; MRI, magnetic resonance imaging; DDwoR, disc displacement without reduction; OA, osteoarthrosis.

a No significant differences were observed between the groups of patients with regard to age, sex, pain, or MMO.

Among the 92 joints treated, 42 were randomized to group A and these patients received injections of PRGF in both joint compartments. The other 50 joints were assigned to group B and these patients received injections of saline. There were 56 right joint procedures and 36 left joint interventions.

Preoperative magnetic resonance images (MRI) revealed that all the joints had discs that were anteriorly displaced without reduction and with OA of the bony components of the joint. Effusion was observed in 62 joints before surgery. There was no statistically significant difference in preoperative MRI signs between the two groups ( Table 2 ). MRI obtained 2 years after surgery revealed six joints with anterior DDwR (ADDwR) and 86 with ADDwoR. In the six displaced cases, biplanar disc morphologies rather than folded disc morphologies appeared after the surgeries. The number of joints with effusion in the superior joint compartment decreased from 62 before surgery to only 16 after arthroscopy. Moreover, normalization of the bony components of the joints (absence of bone marrow changes) was noted in 12 joints at 2 years after the initial surgical procedure ( Table 2 ).

Table 2
Comparison of MRI findings obtained preoperatively and at 2 years postoperative in the two groups of patients (group A: with injection of PRGF in both compartments; group B: control group); N = 92 joints.
Disc position Disc morphology Effusion Bone morphology Total
Normal DDwR DDwoR Normal Abnormal No Yes Normal OA signs a
Planar Folded Other
Preop. 92 21 61 10 30 62 92 92
Group A 42 9 28 4 13 29 42
Group B 50 12 33 6 17 33 50
Postop. 6 86 27 52 15 76 16 * 12 80 * 92
Group A 2 40 12 25 7 40 2 10 32
Group B 4 46 15 27 8 36 14 2 48
MRI, magnetic resonance imaging; PRGF, platelet rich in growth factors; DDwR, disc displacement with reduction; DDwoR, disc displacement without reduction; OA, osteoarthrosis; Preop., preoperative; Postop., postoperative.

a Presence of osteophytes, bone deformity, bone marrow changes.

* P < 0.05.

With regard to the main arthroscopic findings, anterior disc displacement was observed in all of the cases studied (‘roofing’ of 0 in 100% of the joints). Grades I–II synovitis (increased vascularity and capillary hyperemia) was observed in 38 (41.3%) of the joints, whereas synovitis of grades III–IV (generalized capillary hyperemia, effusion, and debris) was noted in 54 (58.7%). All of the joints with grade III–IV synovitis exhibited joint effusion on the preoperative MRI. Chondromalacia of grades I–II (softening/furrowing) was present in 43 (46.7%) of the joints, and grades III–IV (ulceration–fibrillation/subchondral bone exposure) was present in 32 (34.8%) of the joints. Osteophytes over the eminence were observed in two cases. Adherences within the superior joint space were observed in 17 cases (18.5%), and fibrous obliteration of the superior joint space was noted in only one joint. Posterior disc perforations were present in six of the joints studied ( Table 3 ). No significant differences were found between the groups.

Table 3
Arthroscopic findings in the two groups of patients (group A: with injection of PRGF in both compartments; group B: control group); N = 92 joints.
‘Roofing’ a Synovitis b Chondromalacia c Osteophytes Adherences Disc perforation
100–50 50–25 25–0 I–II III–IV I–II III–IV
Total 92 38 54 43 32 2 17 6
Group A 42 18 24 18 14 1 6 2
Group B 50 20 30 25 18 1 11 4
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Jan 16, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Does injection of plasma rich in growth factors after temporomandibular joint arthroscopy improve outcomes in patients with Wilkes stage IV internal derangement? A randomized prospective clinical study
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