A protocol for a randomized clinical trial assessing the efficacy of hypertonic dextrose injection (prolotherapy) in chronic ankle instability.

BACKGROUND: Lateral ankle sprain (LAS) is a common injury. Conservative care is not uniformly effective. Chronic ankle instability (CAI) results in up to 70% of patients with LAS in the physically active population. LAS, together with subsequent osteochondral lesions and pain in many patients, leads to the development of post-traumatic osteoarthritis, resulting in a substantial direct and indirect personal and societal health burden. Dextrose prolotherapy (DPT) is an injection-based therapy for many chronic musculoskeletal conditions but has not been tested for CAI. This protocol describes a randomized controlled trial to test the efficacy of DPT versus normal saline (NS) injections for chronic ankle instability (CAI). METHODS AND ANALYSIS: A single-center, parallel-group, randomized controlled trial will be conducted at a university-based primary care clinic in Hong Kong. A total of 114 patients with CAI will be randomly allocated (1:1) to DPT and NS groups. The primary outcome will be the Cumberland Ankle Instability Tool scores at 1 year. The secondary outcomes will be the number of re-sprains in 1 year, the Star Excursion Balance Test, the 5-level of EuroQol 5-dimension questionnaire, and the Foot and Ankle Ability Measure. All outcomes will be evaluated at baseline and at 16, 26, and 52 weeks using a linear mixed model. DISCUSSION: We hypothesized the DPT is a safe, easily accessible, and effective treatment for patients with CAI. This RCT study will inform whether DPT could be a primary non-surgical treatment for CAI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040213 . Registered on 25 November 2020.

Vague Posterior Knee Discomfort in a Soccer Player: A Clinical Vignette.

A 24-yr-old male soccer player presented with a 7-yr history of left posterior knee "looseness." Evaluation 7 yrs ago, at the time of initial injury, revealed atraumatic anterior and posterior cruciate ligament sprains. On representation, the patient described the pain as a constant, dull ache, 3/10, but his biggest complaint was this feeling of "instability" and looseness where his knee would "buckle" 3-4 times a week. Physical examination was positive for grade 1 posterior drawer and grade 1 posterior sag signs. Reverse KT-1000 testing showed a 3-mm side-to-side difference. Sonographic evaluation confirmed magnetic resonance imaging findings of posterior cruciate ligament laxity and buckling and a small cystic lesion abutting the posteromedial margin of the distal 1/3 of the posterior cruciate ligament. After a trial of physical therapy, the patient elected to undergo experimental injection of dextrose hyperosmolar solution. This resulted in resolution of the cyst and reverse KT-1000 measurements improved to a side-to-side difference of 1 mm. The patient's subjective feeling of looseness and instability resolved by 7 wks.

The efficacy of dextrose prolotherapy over placebo for temporomandibular joint hypermobility: A systematic review and meta-analysis.

OBJECTIVE: The aim of the systematic review was to analyse the available evidence in order to assess the efficacy of dextrose prolotherapy in improving outcomes in temporomandibular joint (TMJ) hypermobility patients as compared to placebo. METHODS: An electronic search of PubMed, Scopus, CENTRAL and Google scholar databases was performed for English language papers published up to February 2018. Randomised clinical trials (RCTs) and controlled clinical trials (CCTs) comparing dextrose prolotherapy with placebo for TMJ hypermobility were included. RESULTS: Three RCTs were included in the review. Frequency of subluxation/dislocation was reported by two trials which found no difference between dextrose and placebo. A statistical significant difference in reduction of MMO with the use of dextrose prolotherapy was seen on pooling of data (random: MD = -3.32, 95% CI -5.26 to -1.28; P = 0.0008; I2  = 0%). A statistical significant difference in pain reduction was also seen with dextrose as compared to placebo (random: MD = -1, 95% CI -1.58 to -0.42; P = 0.0007; I2  = 0%). CONCLUSION: Within the limitations of the study, dextrose prolotherapy may cause significant reduction in mouth opening and pain associated with TMJ hypermobility. Conclusions with regard to reduction of episodes of subluxation/dislocation cannot be drawn. There is a need of more high-quality RCTs with larger sample size and homogenous prolotherapy protocol to draw stronger conclusions on the effect of dextrose prolotherapy in patients with TMJ hypermobility.

Long-term therapeutic effects of dextrose prolotherapy in patients with hypermobility of the temporomandibular joint: a single-arm study with 1-4 years' follow up.

The aim was to analyse the short-term and long-term therapeutic efficacy of dextrose prolotherapy for dislocation or subluxation (hypermobility) of the temporomandibular joint (TMJ). Sixty-one patients with symptomatic hypermobility of the TMJ were included in this single-arm prospective study, in which they were each given four sessions of intra-articular and pericapsular injections six weeks apart. Each injection comprised 10% dextrose/mepivacaine solution 3ml. Clinical outcomes including severity of pain on movement according to the numerical rating scale (NRS), maximal interincisal opening, clicking, and frequency of locking were measured before treatment (T1), during treatment (T2) (just before the third session of injections), at the short-term follow-up (T3) (three months after treatment), and at the long-term follow-up (T4) (1-4 years after treatment). Condylar translation and osseous changes of each joint were evaluated at T1 and T4 using tomography. There was significant reduction in all variables by T2 (p<0.001, p<0.001, p=0.006, and p<0.001). The pain scores (p<0.001) and clicking (p<0.001) had decreased significantly by T3. Linear tomograms of each joint at T1 and T4 showed no alteration in the morphology of the bony components of the joint, and at T4, tomographic open views of all joints showed condylar hypertranslation. Dextrose prolotherapy provided significant and sustained reduction of pain and recovery of constitutional symptoms associated with symptomatic hypermobility of the TMJ without changing either the position of the condyle or the morphology of the bony components of the joint.

Modified dextrose prolotherapy for recurrent temporomandibular joint dislocation.

Conservative interventions with simple procedures and predictable benefits are expected by patients with recurrent dislocation of the temporomandibular joint (TMJ). We have introduced a modified technique of prolotherapy that comprises injection of lignocaine and 50% dextrose at a single site in the posterior periarticular tissues. We studied the effects in 45 younger patients (age range 17-59 years) with non-neurogenic recurrent dislocation of the TMJ, and confirmed the therapeutic effect after more than a year's follow-up. There were appreciable improvements in the number of episodes of dislocation and clicking after the injection. The overall success rate, defined as the absence of any further dislocation or subluxation for more than 6 months, was 41/45 (91%). Of the 41 rehabilitated patients, 26 (63%) required a single injection, 11 (27%) had 2 treatments, and 4 (10%) needed a third injection. All patients tolerated the injections well. The modified dextrose prolotherapy is simple, safe, and cost-effective for the treatment of recurrent dislocation of the TMJ.

The efficacy of dextrose prolotherapy for temporomandibular joint hypermobility: a preliminary prospective, randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: The aim of this study was to assess the efficacy of dextrose prolotherapy for the treatment of temporomandibular joint (TMJ) hypermobility. PATIENTS AND METHODS: A prospective, randomized, double-blind clinical study using a placebo control was carried out. Twelve patients with painful subluxation or dislocation of the TMJ were randomly assigned to 1 of 2 equal-sized groups. Patients in the active group received 4 injections of dextrose solution (2 mL of 10% dextrose and 1 mL of 2% mepivacaine) for each TMJ, each 6 weeks apart, whereas patients in the placebo group received injections of placebo solution (2 mL of saline solution and 1 mL of 2% mepivacaine) on the same schedule. A verbal scale expressing TMJ pain on palpation, maximal mouth opening (MMO), clicking sound, and frequency of luxations (number of locking episodes per month) were assessed at each injection appointment just before the injection procedure and 3 months after the last injection. The collected data were then statistically analyzed. RESULTS: By the end of the study, each group showed significant improvement in TMJ pain on palpation and number of locking episodes and insignificant improvement in clicking sound. With the exception of the MMO, there were no statistically significant differences throughout the study intervals between the active and placebo groups. The active group showed a significant reduction in MMO at the 12th week postoperatively. Differences compared with mean baseline value remained significant at the end of the follow-up period. On the other hand, the placebo group showed an insignificant difference in MMO throughout the study periods. For the last 2 intervals, the placebo group showed statistically significantly higher mean MMO values than the active group. By the end of the 12th postoperative week, the percentages of decrease in MMO were significantly greater in the active group. CONCLUSION: Prolotherapy with 10% dextrose appears promising for the treatment of symptomatic TMJ hypermobility, as evidenced by the therapeutic benefits, simplicity, safety, patients' acceptance of the injection technique, and lack of significant side effects. However, continued research into prolotherapy's effectiveness in patient populations with large sample sizes and long-term follow-up is needed.

Case series on chronic whiplash related neck pain treated with intraarticular zygapophysial joint regeneration injection therapy.

BACKGROUND: Although in clinical use, there is only 1 published case report on the efficacy of intraarticular regeneration injection therapy (RIT) (a.k.a. prolotheraphy). This report supports a rationale for future clinical trials of this technique. OBJECTIVE: To assess the efficacy of intraarticular zygapophysial joint RIT in patients with chronic whiplash related neck pain that failed other conservative and interventional procedures. Patients were treated with intraarticular RIT and reassessed over 1 year. DESIGN: Retrospective case review of prospective data. MATERIALS AND METHODS: Eighteen consecutive patients were treated with intraarticular prolotherapy by placing 0.5 - 1mL of 20% dextrose solution into each zygapophysial joint, after confirmation of intraarticular location with radiographic contrast, using 25-gauge spinal needles and fluoroscopic guidance. Solution was prepared by diluting D50W with 1% lidocaine. RESULTS: Fifteen patients completed treatment. Three patients had bilateral treatment, leaving 18 sides for analysis. Mean Neck Disability Index (NDI) pre-treatment was 24.71 and decreased post-treatment to 14.21 (2 months), 13.45 (6 months), 10.94 (12 months). Average change NDI=13.77 (p<0.0001) baseline versus 12 months. Symptoms for 14 patients were from motor vehicle accident, of which 13 were in litigation. Patients attending physiotherapy over the course of treatment had better outcomes than those without physiotherapy. Women needed more injections (5.4) than men (3.2) p=0.0003. CONCLUSION: Intraarticular RIT improved pain and function in this case series. The procedure appears safe, more effective than periarticular RIT, and lasted as long, or longer, than those patients with previous radiofrequency neurotomy. Concurrent physiotherapy helped reduce post-procedure neck stiffness. Future trials should consider gender when deciding how many treatments to administer. Litigation was not a barrier to recovery.

Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity.

CONTEXT: Use of dextrose prolotherapy. Prolotherapy is defined as injection that causes growth of normal cells or tissue. OBJECTIVE: Determine the 1 and 3 year efficacy of dextrose injection prolotherapy on anterior cruciate ligament (ACL) laxity. After year 1, determine patient tolerance of a stronger dextrose concentration (25% versus 10%). DESIGN: Prospective consecutive patient trial. SETTING: Outpatient physical medicine clinic. PATIENTS OR OTHER PARTICIPANTS: Eighteen patients with 6 months or more of knee pain plus ACL knee laxity. This laxity was defined by a KT1000 anterior displacement difference (ADD) of 2 mm or more. INTERVENTION: Intraarticular injection of 6-9 cc of 10% dextrose at months 0, 2, 4, 6, and 10. Injection with 6 cc of 25% dextrose at 12 months. Then, depending on patient preference, injection of either 10% or 25% dextrose every 2-4 months (based on patient preference) through 36 months. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) for pain at rest, pain on level surfaces, pain on stairs, and swelling. Goniometric flexion range of motion, and KT1000-measured ADD were also measured. All measurements were obtained at 0, 6, 12 and 36 months. RESULTS: Two patients did not reach 6 month data collection, 1 of whom was diagnosed with disseminated cancer. The second was wheelchair-bound and found long-distance travel to the clinic problematic. Sixteen subjects were available for data analysis. KT1000 ADD, measurement indicated that 6 knees measured as normal (not loose) after 6 months, 9 measured as normal after 1 year (6 injections), and 10 measured as normal at 3 years. At the 3 year follow-up, pain at rest, pain with walking, and pain with stair use had improved by 45%, 43%, and 35% respectively. Individual paired t tests indicated subjective swelling improved 63% (P = .017), flexion range of motion improved by 10.5 degrees (P = .002), and KT1000 ADD improved by 71% (P = .002). Eleven out of 16 patients preferred 10% dextrose injection. CONCLUSION: In patients with symptomatic anterior cruciate ligament laxity, intermittent dextrose injection resulted in clinically and statistically significant improvement in ACL laxity, pain, swelling, and knee range of motion.