Comparison of the effect of prolotherapy and paraffin wax for hand osteoarthritis.

OBJECTIVE: Hand osteoarthritis (OA) is associated with considerable disability, especially in the elderly patient population. Paraffin wax (PW) and prolotherapy (P) are non-pharmacological treatment methods used in this setting. This study aimed to compare the therapeutic efficacy of P and PW in hand osteoarthritis. PATIENTS AND METHODS: This study was designed as a single-center, randomized-controlled trial conducted at our Physical Medicine and Rehabilitation Clinic between February 2019 and July 2020. Patients with bilateral hand OA were divided into PW and P treatment groups. The PW group was treated 5 days per week for 2 weeks. The P group received an injection of dextrose solution into the ligaments of painful joints once weekly for three weeks. Visual analog scale (VAS), Duruoz Hand Index (DHI) scale, hand dynamometer for grip strength, and pinch meter for lateral pinch were used for baseline and post-treatment follow-up assessments. RESULTS: Overall, 42 patients were included. The VAS scores significantly decreased in both PW and P groups (p=0.024 and p=0.014). Baseline and third-month post-treatment VAS scores did not significantly differ (p=0.581). The DHI scores improved significantly in both groups (p<0.001 and p<0.001), being higher in the P than in the PW group (p=0.042). Right- and left-hand grip strength increased significantly in PW and P groups (p<0.001, p=0.001; p=0.013, p=0.002, respectively). CONCLUSIONS: Both treatment methods were effective regarding pain and grip strength; however, P improved the hand functions more significantly.

Hypertonic glucose in the treatment of low back pain: A randomized clinical trial.

BACKGROUND: Chronic low back pain (LBP) is defined as pain lasting longer than 3 months and is one of the conditions with the most significant social impact. Treatment is complex and includes proliferative agents used in prolotherapy. The mechanism is not known, but osmotic agents (hypertonic solutions of dextrose or glucose) cause cellular rupture and an inflammatory response that releases cytokines and growth factors that lead to scarring and reinnervation. METHODS: Patients with chronic LBP (>12 weeks) who were non-traumatic and unresponsive to at least 1 month of physical therapy were selected. All patients were followed up at a return visit at 1, 3, and 6 months for pain assessment using validated pain questionnaires and scales. RESULTS: Nineteen patients were included in the conservative group and 19 in the glucose group, with the majority being women (57.9%). The patients were between 47 and 59 years of age (39.5%), mixed race (76.33%), married or in a committed relationship (73.7%), and had completed the study for 5.2 years. Overall mean body mass index was 27.3 ± 4.4 kg/m 2 and was higher in the conservative group (28.0 ± 4.7 kg/m 2 ). The groups showed differences in Visual Analog Scale scores, with median and amplitude values close to each other between the time points evaluated and increasing values in the glucose group, which had significantly higher values for this scale at the third evaluation ( P = .031). When comparing the Rolland-Morris scale scores between the groups, there was a significant difference only in the 3-m assessment ( P = .021). In the follow-up assessment, both groups showed significant improvement between T0 and the other assessment time points ( P < .05) in all evaluations. CONCLUSION: Both groups significantly improved on the evaluated scales during follow-up. Overall, no effects were attributable to the glucose components or the prolotherapy protocol.

Effect of dextrose prolotherapy on internal derangement of the temporomandibular joint.

OBJECTIVE: This study aimed to evaluate the effect of dextrose prolotherapy in treating internal derangement of the temporomandibular joint. PATIENTS AND METHODS: A total of 20 patients with temporomandibular joint internal derangement were enrolled in the study. The diagnosis of internal derangement was confirmed by magnetic resonance imaging (MRI). The posterior and anterior disc attachment, as well as the most tender part of the masseter muscle, were injected with 12.5% dextrose. Pain, maximum mouth opening, clicking, and deviation were assessed immediately before treatment, as well as at 2-, 4-, and 12- weeks post-treatment. RESULTS: There was a significant improvement in the four clinical variables at the three-time intervals. Pain at two weeks was reduced by 60% (6 vs. 3.75) and by 200% (6 vs. 1.9) at 4 weeks. The maximum mouth opening was increased by 6.4 mm at 2 weeks and 7.85 mm at 4 weeks. The percentage of patients with clicking decreased from 70%, preoperatively- to 50% at 2 weeks, 15% at 4 weeks, and 5% at 12 weeks. The ratio of patients with deviation was decreased from 80% preoperatively to 35% at 2 weeks, 15% at 4 weeks, and 5% at 12 weeks. CONCLUSIONS: Prolotherapy is a safe and effective treatment for alleviating the symptoms of internal derangement of the temporomandibular joint.

The effect of dextrose prolotherapy versus placebo/other non-surgical treatments on pain in chronic plantar fasciitis: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Prolotherapy is the injection of a small volume of sclerosing or irritant solutions into an injured tissue. We aimed to investigate the effect of dextrose prolotherapy (DPT) versus placebo/other non-surgical treatments on pain in chronic plantar fasciitis. METHODS: We searched seven electronic databases (PubMed/MEDLINE, Web of Science, EMBASE, Scopus, ProQuest, CENTRAL, PEDro) from inception to December 31, 2021 with no language restriction for publications comparing the effect of DPT with placebo/other non-surgical treatments in patients with chronic plantar fasciitis. Our primary outcome was pain and the secondary outcomes were foot function and plantar fascia thickness. The risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: Overall, eight studies with a total of 449 patients were included in the meta-analysis. All the included studies reported short-term pain. A large effect size (dppc2 = -0.97, 95% confidence interval [CI] -1.84 to -0.10) was observed favoring the use of DPT to reduce pain in patients with chronic plantar fasciitis in the short-term. The results for foot function improvement (dppc2 = -1.28, 95% CI -2.49 to -0.07) and plantar fascia thickness reduction (dppc2 = -1.02, 95% CI -1.99 to -0.05) in the short-term were also in favor of DPT. CONCLUSIONS: Since almost all the included studies had high risk of bias and multiple trials lacked long-term follow-ups, further high-quality research is required to determine the long-term effects of DPT vs placebo/other non-surgical interventions.

Botulinum Toxin Versus Dextrose Prolotherapy: Which is More Effective for Temporomandibular Joint Subluxation? A Randomized Clinical Trial.

PURPOSE: Botulinum toxin type A (BTX-A) therapy or dextrose prolotherapy (DP) has been used to treat temporomandibular joint (TMJ) disorders. However, the superiority of one method over the other has not been studied in patients with TMJ subluxation. Therefore, this study aims to answer the following clinical question: among patients with TMJ subluxation, do those undergoing BTX-A injection into lateral pterygoid muscles, compared to those undergoing intra- and periarticular DP injections, have better outcomes in terms of locking episodes and patient satisfaction? METHODS: A randomized clinical trial was implemented in adult patients with TMJ subluxation. The sample was composed of patients with TMJ subluxation with painful open-locking during wide mouth opening and/or yawning at baseline. The subjects were treated randomly with one of two treatment techniques with equal numbers as follows: one-session BTX-A injection into lateral pterygoid muscles (BTX-A group) or three sessions of dextrose injections around TMJ (prolotherapy group). The predictor variable was the treatment technique (BTX-A or prolotherapy injections). The primary outcome variable was the frequency of locking episodes. The secondary outcome variable was patient satisfaction. The primary outcome variable was recorded at baseline and 8-12 months following the injections. The secondary outcome variable was recorded only 8-12 months following the injections. Descriptive and bivariate statistics were computed. The data were analyzed with the Wilcoxon and Mann-Whitney U tests. RESULTS: The baseline sample was composed of 30 patients with TMJ subluxation. However, the follow-up sample comprised 25 subjects: 11 (9 females, 2 males; 25.64 years) in the BTX-A group and 14 (10 females, 4 males; 32.37 years) in the prolotherapy group. Locking episodes decreased significantly in the two groups with no significant difference (P < .01). Seven patients in the BTX-A group (7 of 11 patients; 63.6 percent) and eight (8 of 14 patients; 57.1 percent) in the prolotherapy group reported no complaint of locking at the end of follow-up, with no significant difference between the groups (P > .05). Patient satisfaction showed no significant difference between the groups (P > .05). CONCLUSION: These findings suggested that BTX-A injection is no more effective than DP for any outcome variables of TMJ subluxation assessed.

Prolotherapy: A Narrative Review of Mechanisms, Techniques, and Protocols, and Evidence for Common Musculoskeletal Conditions.

Prolotherapy is a nonsurgical regenerative technique that allows small amounts of irritant solution to be injected into the site of painful tendon and ligament insertions to promote the growth of healthy cells and tissues. The goal of prolotherapy is to stimulate growth factors that may strengthen attachments and reduce pain. Prolotherapy injection technique is centered around a focused physical examination and strong anatomic knowledge for maximized results. Prolotherapy is beneficial in a variety of different musculoskeletal conditions, including, but not limited to, lateral epicondylosis, rotator cuff tendinopathy, plantar fasciitis, Achilles tendinopathy, osteoarthritis, low back pain, sacroiliac joint pain, and TMJ laxity.

Comparing dextrose prolotherapy with other substances in knee osteoarthritis pain relief: A systematic review.

The objective of this study is to compare the effectiveness of dextrose-prolotherapy with other substances for pain relief in patients with primary knee osteoarthritis. The literature screening was done in January 2021 through Medline (PubMed), EMBASE, and Database of the National Institute of Health based on the following criteria: randomized clinical trials that subjected patients with primary knee osteoarthritis who underwent treatment with dextrose-prolotherapy and other substances for pain relief. Paired reviewers independently identified 3381 articles and included 8 trials that met the eligibility criteria. According to the findings of this review, participants that underwent dextrose-prolotherapy showed improvements between baseline and posterior assessments and when compared to saline injections, but when compared to other substances, the results were not clear. Although dextrose-prolotherapy is a useful treatment method by itself, it is still not possible to clearly affirm that it is superior or inferior to its counterparts. There is an urgent need for further studies to bring more evidence to the field.

Dextrose prolotherapy for pain and dysfunction of the TMJ reducible disc displacement: A randomized, double-blind clinical study.

To assess the efficacy of dextrose prolotherapy on the clinical signs and symptoms of patients having disc displacement with reduction (DDWR). This prospective, randomized, double-blind clinical study included thirty patients suffering from bilateral DDWR. The patients were randomly divided into two equal groups. After induction of local anesthesia, each joint was injected in two sites; one in the superior joint space and the other in the retrodiscal tissue, using 25% dextrose solution in group I and normal saline in group II. Pain intensity, maximal interincisal opening (MIO), and joint sounds (JS) were evaluated preoperatively, 1 week after each injection, and 3 months and 6 months after the last injection. Patients in group I showed significant improvement in pain and MIO, and higher satisfaction with treatment than patients in group II. Compared to saline injection, dextrose injection resulted in an improvement in JS but without significant difference within and between groups. Intra-articular injection of 25% dextrose is effective in the treatment of pain and dysfunction of TMJ DDWR as shown by significant improvement in pain and MIO and patient satisfaction. The technique is simple, easy to do, safe and should be adopted whenever appropriate.

Effectiveness, Compliance, and Safety of Dextrose Prolotherapy for Knee Osteoarthritis: A Meta-Analysis and Metaregression of Randomized Controlled Trials.

OBJECTIVES: This study assessed the effectiveness, compliance, and safety of dextrose prolotherapy for patients with knee osteoarthritis. DATA SOURCES: PubMed, EMBASE, the Cochrane Library Database, and the Scopus database from their inception to December 31, 2021. METHODS: This study was conducted in accordance with the guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Randomized controlled trials regarding the effectiveness of dextrose prolotherapy in knee osteoarthritis were identified. The included trials were subjected to meta-analysis. Risk of bias was assessed using the Cochrane risk of bias tool. Subgroup and random-effects metaregression analyses were performed to explore any heterogeneity (I2) of treatment effects across studies. RESULTS: A total of 14 trials enrolling 978 patients were included in the meta-analysis. Compared with placebo injection and noninvasive control therapy, dextrose prolotherapy had favorable effects on pain, global function, and quality of life during the overall follow-up. Dextrose prolotherapy yielded greater reductions in pain score over each follow-up duration than did the placebo. Compared with other invasive therapies, dextrose prolotherapy generally achieved comparable effects on pain and functional outcomes for each follow-up duration.Subgroup results indicated that combined intra-articular and extra-articular injection techniques may have stronger effects on pain than a single intra-articular technique. CONCLUSIONS: Dextrose prolotherapy may have dose-dependent and time-dependent effects on pain reduction and function recovery, respectively, in patients with knee osteoarthritis. Due to remarkable heterogeneity and the risk of biases across the included trials, the study results should be cautiously interpreted.

Identification of early response to hypertonic dextrose prolotherapy markers in knee osteoarthritis patients by an inflammation-related cytokine array.

BACKGROUND: Osteoarthritis (OA) is one of the most common forms of arthritis, and hypertonic dextrose prolotherapy has long been used clinically to treat knee OA. The aim of this study was to investigate the inflammation-related protein-expression profile characterizing the efficacy of the hypertonic dextrose prolotherapy in knee OA as prognostic markers. METHODS: OA patients over the age of 65 were recruited for Western Ontario McMaster University Osteoarthritis (WOMAC) index, knee X-ray evaluation and knee joint synovial fluid analysis before and after hypertonic dextrose prolotherapy. The expressions of inflammation-related factors were measured using a novel cytokine antibody array methodology. The cytokine levels were quantified by quantitative protein expression and analyzed by ELISA using the patients' knee-joint synovial fluid. RESULTS: The WOMAC Index and minimum joint space width before receiving the intra-articular injection and at 2-week intervals were compared. Twelve patients who received OA intervention were enrolled and finally a clinical evaluation of 12 knee joints and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose prolotherapy, the OA patients clearly demonstrated a significant improvement in WOMAC index and increasing tendency in the medial minimum joint space width after intervention. Meanwhile, we observed a significantly associated tendency between hypertonic dextrose treatment of knee OA and the upregulation of MMP2, TIMP-1, EGF, CXCL9 and IL-22. CONCLUSION: The findings provide knee OA patients receiving hypertonic dextrose prolotherapy, which is accompained by the improvemeny of knee symptoms and associated tendency of upregulation of MMP2, EGF, CXCL 9 and IL-22.

Meta-analysis of clinical trials focusing on hypertonic dextrose prolotherapy (HDP) for knee osteoarthritis.

Hypertonic dextrose prolotherapy (HDP) is an injection of a concentrated dextrose solution for the purpose of local treatment of musculoskeletal pain and possible enhancement of repair mechanisms. This systematic review and meta-analysis examines the clinical utility of HDP injection for treatment of knee osteoarthritis (OA). Randomized controlled trials (RCTs) utilizing HDP to treat knee OA were retrieved from MEDLINE, EMBASE, and Cochrane Library (CENTRAL). Identification and inclusion of RCTs utilizing intra-articular and extra-articular administration of HDP vs administration of other injectate or physical therapy as control for knee OA were included. Primary clinical outcomes were changes in knee WOMAC, pain and function score. Secondary outcomes were adverse events related to HDP. For continuous outcomes with same or different measurements, we calculated, respectively the weighted mean difference (WMD) or the standardized mean difference (SMD), respectively. Results were pooled using DerSimonian and Laird random effect models across the included studies and heterogeneity between studies was estimated using the I2 index. Five studies comprising a total of 319 treated patients met inclusion criteria and were included in the final analysis. At a mean of 22.8 weeks follow-up, HDP treatment significantly improved total WOMAC score (WMD = 13.77, 95% CI: 6.75-20.78; p < 0.001; I2 = 90%), pain (SMD = 1.33, 95% CI: 0.49-2.17; p < 0.001; I2 = 91%) and knee function (SMD = 1.30, 95% CI: 0.45-2.14; p < 0.001; I2 = 91%) compared with control group. There were no severe adverse events related to dextrose injection reported in all the included studies. HDP is a promising treatment for knee OA with a reasonable safety profile. Further research in mechanism of HDP activity and long-term follow-up study will be needed for exploring this novel therapy modality.

Efficacy of hypertonic dextrose injection (prolotherapy) in temporomandibular joint dysfunction: a systematic review and meta-analysis.

Hypertonic dextrose prolotherapy (DPT) has been reported to be effective for temporomandibular disorders (TMDs) in clinical trials but its overall efficacy is uncertain. To conduct a systematic review with meta-analysis of randomized controlled trials (RCTs) to synthesize evidence on the effectiveness of DPT for TMDs. Eleven electronic databases were searched from their inception to October, 2020. The primary outcome of interest was pain intensity. Secondary outcomes included maximum inter-incisal mouth opening (MIO) and disability score. Studies were graded by "Cochrane risk of bias 2" tool; if data could be pooled, a meta-analysis was performed. Ten RCTs (n = 336) with some to high risk of bias were included. In a meta-analysis of 5 RCTs, DPT was significantly superior to placebo injections in reducing TMJ pain at 12 weeks, with moderate effect size and low heterogeneity (Standardized Mean Difference: - 0.76; 95% CI - 1.19 to - 0.32, I2 = 0%). No statistically significant differences were detected for changes in MIO and functional scores. In this systematic review and meta-analysis, evidence from low to moderate quality studies show that DPT conferred a large positive effect which met criteria for clinical relevance in the treatment of TMJ pain, compared with placebo injections.Protocol registration at PROSPERO: CRD42020214305.

Hypertonic Dextrose Stimulates Chondrogenic Cells to Deposit Collagen and Proliferate.

OBJECTIVE: Hypertonic dextrose (HD) injections (prolotherapy) for osteoarthritis are reported to reduce pain. Cartilage regeneration is hypothesized as a mechanism. This in vitro study identifies an HD concentration that stimulates chondrogenic cells to increase metabolic activity and assesses whether this concentration affects collagen deposition and proliferation. DESIGN: ATDC5 chondrogenic cells were cultured in normoglycemic DMEM/F12 medium, treated with concentrations of HD (4-400 mM), and assessed with PrestoBlue. Advanced light microscopy was used to conduct live imaging of collagen deposition through second harmonic generation microscopy (SHG) and proliferation via 2-photon excitation microscopy. Proliferation was additionally assessed with hemocytometer counts. RESULTS: A linear regression model found that, relative to the 4 mM baseline control, cells treated with 200 mM had a higher mean absorbance (P = 0.023) and cells treated with 250 mM were trending toward a higher mean absorbance (P = 0.076). Polynomial regression interpolated 240 mM as producing the highest average absorbance. Hemocytometer counts validated 250 mM as stimulating proliferation compared with the 4 mM control (P < 0.01). A concentration of 250 mM HD led to an increase in collagen deposition compared with that observed in control (P < 0.05). This HD concentration also led to increases in proliferation of ATDC5 cells relative to that of control (P < 0.001). CONCLUSIONS: A 250 mM HD solution appears to be associated with increased metabolic activity of chondrocytes, increased collagen deposition, and increased chondrocyte proliferation. These results support clinical prolotherapy research suggesting that intra-articular HD joint injections reduce knee pain. Further study of HD and cellular processes is warranted.

Efficacy of prolotherapy in comparison to other therapies for chronic soft tissue injuries: A systematic review and network meta-analysis.

INTRODUCTION: Prolotherapy and other injections, primarily acting on pathways associated with maladaptive tissue repair, are recommended for recalcitrant chronic soft tissue injuries (CSTI). However, selection of injection is challenging due to mixed results. This network meta-analysis (NMA) aimed to compare prolotherapy with other therapies, particularly injections, for CSTI and establish robustness of the results. METHODOLOGY: Pubmed, Medline, SPORTDiscus and Google scholar were searched from inception to 4th January 2021 for randomised controlled trials (RCTs) involving injection therapies (e.g. blood derivatives, corticosteroid, hyaluronic acid, botulinum toxin) for CSTI. The primary and secondary outcomes were pain and function, respectively, at (or nearest to) 6 months. Effect size (ES) was presented as standardised mean difference with 95% confidence interval (CI). Frequentist random effect NMA was used to generate the overall estimates, subgroup estimates (by region and measurement time point) and sensitivity analyses. RESULTS: A total of 91 articles (87 RCTs; 5859 participants) involving upper limb (74%), lower limb (23%) and truncal/hip (3%) injuries were included. At all time points, prolotherapy had no statistically significant pain benefits over other therapies. This observation remained unchanged when tested under various assumptions and with exclusion of studies with high risk of bias. Although prolotherapy did not offer statistically significant functional improvement compared to most therapies, its ES was consistently better than non-injections and corticosteroid injection for both outcomes. At selected time points and for selected injuries, prolotherapy demonstrated potentially better pain improvement over placebo (<4 months: shoulder [ES 0.65; 95% CI 0.00 to 1.30]; 4-8 months: elbow [ES 0.91; 95% CI 0.12 to 1.70]; >8 months: shoulder [ES 2.08; 95% CI 1.49, to 2.68]). Injections generally produced greater ES when combined with non-injection therapy. CONCLUSION: While clinical outcomes were generally comparable across types of injection therapy, prolotherapy may be used preferentially for selected conditions at selected times.

The effectiveness of PROLOTHERAPY for recalcitrant Medial TIBIAL Stress Syndrome: a prospective consecutive CASE series.

BACKGROUND: Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries in sporting populations. It accounts for between 6 and 16% of all running injuries, and up to 53% of lower leg injuries in military recruits. Various treatment modalities are available with varying degrees of success. In recalcitrant cases, surgery is often the only option. OBJECTIVE: To evaluate whether ultrasound-guided injection of 15% dextrose for treatment of recalcitrant MTSS decreases pain and facilitates a return to desired activity levels for those who may otherwise be considering surgery or giving up the sport. METHOD: The study design was a prospective consecutive case series involving eighteen patients: fifteen male and three female; (mean age = 31.2 years) with recalcitrant MTSS. They were referred from sports injury clinics across the UK, having failed all available conservative treatment. INTERVENTION: An ultrasound-guided sub-periosteal injection of 15% dextrose was administered by the same clinician (NP) along the length of the symptomatic area. Typically, 1 mL of solution was injected per cm of the symptomatic area. MAIN OUTCOME MEASURES: Pain was assessed using a 10-cm visual analog scale (VAS) at baseline, short-term, medium-term (mean 18 weeks), and long-term (mean 52 weeks) follow-up. Symptom resolution and return to activity were measured using a Likert scale at medium and long-term follow-up. Statistical analyses were performed using SPSS for Mac version 19.0.0 (IBM, New York, NY, US). The Shapiro-Wilk test was used to evaluate the normality of the distribution of data. Friedman's non-parametric test was used to compare the within-patient treatment response over time. Post-hoc Wilcoxon signed-rank tests with Bonferroni corrections were performed to determine VAS average pain response to treatment over five paired periods. RESULTS: Patients reported a significant (p < 0.01) reduction in median VAS pain score at medium and long-term follow-up compared to baseline. Median improvement per patient was 4.5/10. Patients rated their condition as 'much improved' at medium-term follow-up and the median return to sports score was 'returned to desired but not pre-injury level' at medium-term and long-term follow-up. No adverse events were reported. CONCLUSIONS: Ultrasound-guided 15% dextrose prolotherapy injection has a significant medium-term effect on pain in MTSS. This benefit may be maintained long-term; however, more robust trials are required to validate these findings in the absence of controls. CLINICAL RELEVANCE: Clinicians should consider the use of ultrasound-guided injection of 15% dextrose as a viable treatment option to reduce pain and aid return to activity for patients with recalcitrant MTSS.

Changes in levels of cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen in subjects with knee osteoarthritis after dextrose prolotherapy: A randomized controlled trial.

OBJECTIVE: To assess the effects of dextrose prolotherapy in patients with knee osteoarthritis on the levels of serum cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen, and on the Western Ontario McMaster Universities Index and numerical rating scale score for pain. METHODS: A randomized controlled trial, in which participants were randomly allocated into 2 groups, receiving injections of either hyaluronic acid or dextrose prolotherapy. The hyaluronic acid group received 5 injections, 1 each on weeks 1, 2, 3, 4 and 5, and the dextrose prolotherapy group received 3 injections, 1 each on weeks 1, 5 and 9. Serum cartilage oligomeric proteinase, urinary C-terminal telopeptide of type II collagen, Western Ontario McMaster Universities Index score, and numerical rating scale score for pain were measured at baseline and 3 weeks after the last injection. Comparative analysis was conducted using Wilcoxon test within groups and analysis of covariance (ANCOVA) test between groups. RESULTS: A total of 47 participants (21 allocated to hyaluronic acid, 26 allocated to dextrose prolotherapy) completed the protocol. Both interventions resulted in significant improvements in numerical rating scale scores for pain, total Western Ontario McMaster Universities Index scores, and its subscales score. However, the dextrose prolotherapy outperformed hyaluronic acid in numerical rating scale score for pain and level of urinary C-terminal telopeptide of type II collagen, with score changes differences of 0.93 (p = 0.042) and 0.34 (p = 0.048), respectively. No significant changes in level of serum cartilage oligomeric proteinase were found in either group. CONCLUSION: Dextrose prolotherapy is an alternative injection therapy for knee osteoarthritis, which was found to be associated with a significant reduction in urinary C-terminal telopeptide of type II collagen compared with hyaluronic acid injection. Neither injection method resulted in reduced serum cartilage oligomeric proteinase.

Effects of Hyperosmolar Dextrose Injection in Patients With Rotator Cuff Disease and Bursitis: A Randomized Controlled Trial.

OBJECTIVE: To determine whether dextrose prolotherapy offers clinical benefits in patients with shoulder pain and bursitis. DESIGN: Double-blinded, randomized controlled trial. SETTING: Outpatient rehabilitation department of a single medical center. PARTICIPANTS: Patients (N=50) who had received a diagnosis of shoulder pain and bursitis through clinical tests and ultrasound examination. INTERVENTIONS: Participants were randomly assigned to the 15% dextrose injection (D15W) group or the placebo group to receive either D15W or normal saline injection, respectively. All participants received ultrasound-guidance bursal injection every 2 weeks for a total of 3 injections. MAIN OUTCOME MEASURES: The primary outcome was maximal pain level while performing activities. The secondary outcomes included resting pain level, function and disability assessment results, and ultrasonographic parameters. Participants were followed up for 3 months after completion of the injection course. RESULTS: No significant differences in baseline characteristics were observed between the D15W and placebo groups. Significant time effects were observed for all outcome parameters (all P<.05); however, time × group effects were nonsignificant for all outcomes, except for tissue elasticity (P=.026). CONCLUSIONS: Supporting evidence is insufficient regarding the clinical benefits of 15% dextrose bursal injection administered through 3 sessions in patients with chronic shoulder pain and bursitis. The findings indicate that these injections may increase the tissue stiffness of the supraspinatus tendon, as indicated by elastography assessment results, but further research is required to determine the nature of such changes in elastography findings.

Effects of dextrose prolotherapy on tendinopathy, fasciopathy, and ligament injuries, fact or myth?: A systematic review and meta-analysis.

OBJECTIVES: Prolotherapy or proliferative therapy is a treatment option for damaged connective tissues involving the injection of a solution (proliferant) which theoretically causes an initial cell injury and a subsequent "proliferant" process of wound healing via modulation of the inflammatory process. Nonetheless, the benefits of dextrose prolotherapy have not been adequately evaluated. Therefore, the present study assesses the effectiveness and superiority of prolotherapy separately in treating dense fibrous connective tissue injuries. METHODS: PubMed, Scopus, and Embase were searched from the earliest record to February 18, 2019. This study included randomized controlled trials whichBoth analysis at individual studies level and pooled meta-analysis were performed. RESULTS: Ten trials involving 358 participants were included for review. At study level, the majority of comparisons did not reveal significant differences between dextrose prolotherapy and no treatment (or placebo) regarding pain control. The meta-analysis showed dextrose prolotherapy was effective in improving activity only at immediate follow-up (i.e., 0-1 month) (standardized mean difference [SMD]: 0.98; 95% confidence interval [CI]: 0.40-1.50; I = 0%); and superior to corticosteroid injections only in pain reduction at short-term follow-up (i.e., 1-3 month) (SMD: 0.70; 95% CI: 0.14-1.27; I = 51%). No other significant SMDs were found in this analysis. CONCLUSIONS: There is insufficient evidence to support the clinical benefits of dextrose prolotherapy in managing dense fibrous tissue injuries. More high-quality randomized controlled trials are warranted to establish the benefits of dextrose prolotherapy. REVIEW REGISTRATION: PROSPERO (CRD42019129044).

Dextrose Prolotherapy Versus Lidocaine Injection for Temporomandibular Dysfunction: A Pragmatic Randomized Controlled Trial.

Objective: Several intraarticular injections, including dextrose and lidocaine, are reported to reduce pain and dysfunction in temporomandibular dysfunction (TMD) and increase maximal jaw opening; our goal was to determine whether dextrose/lidocaine outperforms sterile water/lidocaine for TMD. Design: Pragmatic randomized controlled trial. Setting: Outpatient clinic. Subjects: Chronic (≥3 months) of moderate-to-severe (≥6/10) jaw or facial pain meeting research-specific TMD criteria. Intervention: Blinded intraarticular dextrose prolotherapy (DPT) (20% dextrose/0.2% lidocaine) versus intraarticular lidocaine (0.2% lidocaine in sterile water) at 0, 1, and 2 months. Participants were then unblinded and offered DPT by request for 9 additional months. Main outcome measures: Primary: Numerical Rating Scale (0-10 points) score for facial pain and jaw dysfunction; percentage achieving ≥50% improvement in pain and dysfunction (0, 3, and 12 months). Secondary: Maximal interincisal opening (MIO; 0 and 3 months). Intention-to-treat analysis was by joint using mixed-model regression. Results: Randomization of 29 participants (25 female, 47 ± 17 years, 43 joints) produced similar groups. Three-month pain and dysfunction improvements were similar, but more DPT-treated joints improved by ≥50% in pain (17/22 vs. 6/21; p = 0.028). The MIO improved in both groups (5.6 ± 5.8 mm vs. 5.1 ± 7.0 mm; p = 0.70). From 3 to 12 months, minimal DPT was received by original DPT and lidocaine recipients, 0.5 ± 0.9 and 0.6 ± 1.5 injections, respectively, with only 2 out of 21 joints in the original lidocaine group receiving more than 1 dextrose injection after 3 months. Twelve-month analysis revealed that joints in the original DPT group improved more in jaw pain (4.8 ± 2.4 points vs. 2.6 ± 2.9 points; p = 0.026) and jaw dysfunction (5.3 ± 2.6 points vs. 2.7 ± 2.3 points; p = 0.013). More DPT than lidocaine-treated joints improved by ≥50% in both pain (19/22 vs. 5/21; p = 0.003) and dysfunction (17/22 vs. 7/21; p = 0.040). There were no adverse events; satisfaction was high. Conclusions: Intraarticular DPT resulted in clinically important and statistically significant improvement in pain and dysfunction at 12 months compared to lidocaine injection (ClinicalTrials.gov identifier NCT01617356).

Efficacy of Intra-Articular Hypertonic Dextrose (Prolotherapy) for Knee Osteoarthritis: A Randomized Controlled Trial.

PURPOSE: To test the efficacy of intra-articular hypertonic dextrose prolotherapy (DPT) vs normal saline (NS) injection for knee osteoarthritis (KOA). METHODS: A single-center, parallel-group, blinded, randomized controlled trial was conducted at a university primary care clinic in Hong Kong. Patients with KOA (n = 76) were randomly allocated (1:1) to DPT or NS groups for injections at weeks 0, 4, 8, and 16. The primary outcome was the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 0-100 points) pain score. The secondary outcomes were the WOMAC composite, function and stiffness scores; objectively assessed physical function test results; visual analogue scale (VAS) for knee pain; and EuroQol-5D score. All outcomes were evaluated at baseline and at 16, 26, and 52 weeks using linear mixed model. RESULTS: Randomization produced similar groups. The WOMAC pain score at 52 weeks showed a difference-in-difference estimate of -10.34 (95% CI, -19.20 to -1.49, P = 0.022) points. A similar favorable effect was shown on the difference-in-difference estimate on WOMAC function score of -9.55 (95% CI, -17.72 to -1.39, P = 0.022), WOMAC composite score of -9.65 (95% CI, -17.77 to -1.53, P = 0.020), VAS pain intensity score of -10.98 (95% CI, -21.36 to -0.61, P = 0.038), and EuroQol-5D VAS score of 8.64 (95% CI, 1.36 to 5.92, P = 0.020). No adverse events were reported. CONCLUSION: Intra-articular dextrose prolotherapy injections reduced pain, improved function and quality of life in patients with KOA compared with blinded saline injections. The procedure is straightforward and safe; the adherence and satisfaction were high.