Carpaine alleviates tendinopathy in mice by promoting the ubiquitin-proteasomal degradation of p65 via targeting the E3 ubiquitin ligase LRSAM1.

BACKGROUND: Currently, there are no specific drugs or targets available for the treatment of tendinopathy. However, inflammation has recently been found to play a pivotal role in tendinopathy progression, thereby identifying it as a potential therapeutic target. Carpaine (CA) exhibits potential anti-inflammatory pharmacological properties and may offer a therapeutic option for tendinopathy. PURPOSE: This study aimed to investigate the effectiveness of CA in addressing tendinopathy and uncovering its underlying mechanisms. METHODS: Herein, the efficacy of CA by local administration in vivo in comparison to the first-line drug indomethacin was evaluated in a mouse collagenase-induced tendinopathy (CIT) model. Furthermore, IL-1ß induced a simulated pathological inflammatory microenvironment in tenocytes to investigate its underlying mechanisms in vitro. Further confirmation experiments were performed by overexpressing or knocking down the selective targets of CA in vivo. RESULTS: The findings demonstrated that CA was dose-dependent in treating tendinopathy and that the high-dose group outperformed the first-line drug indomethacin. Mechanistically, CA selectively bound to and enhanced the activity of the E3 ubiquitin ligase LRSAM1 in tendinopathy. This effect mediated the ubiquitination of p65 at lysine 93, subsequently promoting its proteasomal degradation. As a result, the NF-κB pathway was inactivated, leading to a reduction in inflammation of tendinopathy. Consequently, CA effectively mitigated the progression of tendinopathy. Moreover, the LRSAM1 overexpression demonstrated effectiveness in mitigating the tendinopathy progression and its knockdown abolished the therapeutic effects of CA. CONCLUSION: CA attenuates the progression of tendinopathy by promoting the ubiquitin-proteasomal degradation of p65 via increasing the enzyme activity of LRSAM1. The exploration of LRSAM1 has also unveiled a new potential target for treating tendinopathy based on the ubiquitin-proteasomal pathway.

Examining the Potential of Vitamin C Supplementation in Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs.

Because equine tendinopathies are slow to heal and often recur, therapeutic strategies are being considered that aid tendon repair. Given the success of utilizing vitamin C to promote tenogenesis in other species, we hypothesized that vitamin C supplementation would produce dose-dependent improvements in the tenogenic properties of tendon proper (TP) and peritenon (PERI) cells of the equine superficial digital flexor tendon (SDFT). Equine TP- and PERI-progenitor-cell-seeded fibrin three-dimensional constructs were supplemented with four concentrations of vitamin C. The gene expression profiles of the constructs were assessed with 3'-Tag-Seq and real-time quantitative polymerase chain reaction (RT-qPCR); collagen content and fibril ultrastructure were also analyzed. Moreover, cells were challenged with dexamethasone to determine the levels of cytoprotection afforded by vitamin C. Expression profiling demonstrated that vitamin C had an anti-inflammatory effect on TP and PERI cell constructs. Moreover, vitamin C supplementation mitigated the degenerative pathways seen in tendinopathy and increased collagen content in tendon constructs. When challenged with dexamethasone in two-dimensional culture, vitamin C had a cytoprotective effect for TP cells but not necessarily for PERI cells. Future studies will explore the effects of vitamin C on these cells during inflammation and within the tendon niche in vivo.

The JUMPFOOD study: additional effect of hydrolyzed collagen and vitamin C to exercise treatment for patellar tendinopathy (jumper's knee) in athletes-study protocol for a double-blind randomized controlled trial.

BACKGROUND: Patellar tendinopathy (PT) is a common problem in jumping athletes. Management can be challenging and treatment outcome is not always successful. In combination with tendon loading exercises, hydrolyzed collagen/vitamin C supplementation appears to have a promising effect on the recovery of tendinopathy. The aim of this study is to evaluate whether the use of oral supplementation of hydrolyzed collagen and vitamin C in combination with progressive tendon loading exercises (PTLE) is superior to PTLE and placebo on VISA-P score (which rates pain, function, sports participation) after 24 weeks for athletes with PT. METHODS: The JUMPFOOD study is a double-blinded, two-armed randomized controlled trial, in which the effectiveness of oral supplementation of hydrolyzed collagen/vitamin C combined with PTLE compared to PTLE with placebo on pain and recovery of function in athletes with PT will be investigated. Seventy-six athletes aged 16-40 years, with symptoms of PT for at least 12 weeks, who play sports at least once a week will be included. All participants will receive education, advice with regard to load management and a PTLE program according to the Dutch guidelines for anterior knee pain. In addition, the intervention group will receive daily 10 g hydrolyzed collagen and 40 mg vitamin C supplementation for 24 weeks whereas the control group receives 10 g maltodextrin placebo supplementation. Measurements will take place at baseline and at 12 and 24 weeks' follow-up. Primary outcome is the VISA-P score, which evaluates pain, function, and sports participation. For secondary outcome measures, data with regard to pain during functional tests, flexibility measurements, blood withdrawals, imaging characteristics of the tendon, and health questionnaires will be collected. During the follow-up period, participants will register sports participation, amount of training and tendon load, pain during sports, co-medication, and side-effects in a digital weekly diary. DISCUSSION: The JUMPFOOD study is the first large RCT to study the effectiveness of hydrolyzed collagen/vitamin C supplementation in combination with the PTLE program in athletes with patellar tendinopathy. If supplementation of collagen/vitamin C appears to be effective, this treatment can be implemented in daily sports medicine practice to improve the treatment outcome of patients with PT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05407194. Registered on 7 June 2022.

Combined extract (Curcuma longa-Glycyrrhiza glabra) alleviates the inflammations of Achilles tendinopathy in Wistar rats.

OBJECTIVE: Achilles tendinopathy is a frequent pathological condition in adults with overused ankles, causing microtrauma, inducing tenocyte apoptosis and inflammatory response. Common treatment involves oral prescription or injection of anti-inflammatory agents, surgery, or shock-wave therapy. However, prolonged administration is not advisable due to adverse effects. Therefore, a novel and safe regimen is needed. Curcuma longa and Glycyrrhiza glabra extracts are known for their anti-inflammatory effects owing to their active compounds (curcumin and glycyrrhizin, respectively). This study aimed to determine the effect of combined extracts of Curcuma longa and Glycyrrhiza glabra on tendon healing in an animal model of Achilles tendinopathy (Wistar rats). MATERIALS AND METHODS: This study took place from February to May 2022 and compared the regimens administered to 32 animal models of Wistar rats with 4 healthy rats as a control group to determine the most effective therapeutic regimen: immobilization, immobilization with ibuprofen, or immobilization with the combined extract. The outcomes were measured to find which intervention provided the lowest inflammatory markers [High Mobility Group Box-1 (HMGB-1), Tumor Necrosis Factor-α (TNF-α), Chemokin motif ligand 12 (CXCL-12)], and improved tissue morphology represented by the BONAR score, decreased cross-sectional area (CSA), and increased Macrophage 2 (M2) differentiation. RESULTS: After Achilles tendinopathy was induced, total immobilization (I1) was proven to be the most effective with the lowest CSA, whereas immobilization+175 mg/kg Curcuma longa+110 mg/kg Glycyrrhiza glabra extract (I5) was the most effective with the lowest HMGB-1 levels and the lowest CXCL-12 levels. Immobilization+131 mg/kg Curcuma longa+82.5 mg/kg Glycyrrhiza glabra extract (I6) was the most effective with the lowest Bonar score, while immobilization+87.5 mg/kg Curcuma longa+55 mg/kg Glycyrrhiza glabra extract (I7) was proven to be the most effective with the highest M2 coverage area and the lowest TNF-α levels. CONCLUSIONS: We found that combined extract therapy was the most effective intervention for treating Achilles tendinopathy due to its ability to provide the lowest inflammatory markers.

Can Achilles tendinosis be treated effectively with lidocaine and glucose infiltrations, and if so, is the effect lasting? A longitudinal, observational on 27 consecutive patients.

OBJECTIVE: Our aim was to add to the small but growing body of evidence on the effectiveness of ultrasound-guided Achilles intratendinous hyperosmolar dextrose prolotherapy and introduce a novel, preceding step of paratenon hydrodissection with lidocaine in patients with chronic Achilles tendinosis resistant to rehabilitation therapy. METHODS: We conducted a longitudinal, observational study on 27 consecutive patients diagnosed with Achilles tendinosis, in whom conservative treatment, ie, physiotherapy or shock wave therapy, had failed. A 2% lidocaine paratenon anesthesia and hydrodissection was followed by ultrasound-guided, intratendinous injections of 25% glucose every 5 weeks. Visual analogue scales (VAS) were used for pain assessment at rest, for activities of daily living, and after moderate exercise at the begining and at the end of the treatment. Moreover, tendon thickness and vascularisation were recorded at baseline and final treatment consultation. Effectiveness was estimated from scoring and relative pain reduction using a 95% CI. The non-parametric Wilcoxon test and a general linear model for repeated measures were applied. Statistical significance was established as p < 0.05. RESULTS: A median of 5 (1-11) injection consultations per patient were required. Pain scores decreased significantly in all three conditions (p < 0.001). Relative reductions were 75% in pain at rest (95% CI;61-93%), 69% in pain with daily living activities (95% CI; 55-83%), and 70% in pain after moderate exercise (95% CI; 57-84%). Tendon neo-vascularisation was significantly reduced (p < 0.001). We did not observe significant changes in tendon thickness (p = 0.083). CONCLUSIONS: Achilles tendinosis treatment with paratenon lidocaine hydrodissection and subsequent prolotherapy with hyperosmolar glucose solution is safe, effective, inexpensive, and virtually painless with results maintained over time.

Emerging Treatment Options for Chronic Tendinopathy of the Foot: A Clinical Vignette.

ABSTRACT: The patient is a 65-year-old female recreational skier and avid walker who presented with a several-month history of right ankle and foot pain. The patient's pain began without inciting event and was described as a constant aching pain aggravated by downhill walking and alleviated with rest. She was diagnosed with right distal tibialis anterior tendinopathy with partial thickness tear noted on magnetic resonance imaging and musculoskeletal ultrasound. Given symptoms recalcitrant to conservative measures, the patient opted to pursue an ultrasound-guided prolotherapy injection and a course of physical therapy; unfortunately, she did not have any improvement in symptoms. The patient subsequently underwent ultrasound-guided percutaneous ultrasonic tenotomy and debridement of the distal tibialis anterior tendon, followed by a postprocedure rehabilitation protocol of physical therapy with transition to home exercise program with complete resolution of her pain. Prolotherapy, and percutaneous ultrasonic tenotomy and debridement are two treatment modalities that show promise in the treatment of painful, chronic tendinopathy.

Is Curcumine Useful in the Treatment and Prevention of the Tendinopathy and Myotendinous Junction Injury? A Scoping Review.

Physical activity in general and sports in particular, is a mechanism that produces stress and generates great force in the tendon and in the muscle-tendon unit, which increases the risk of injury (tendinopathies). Eccentric and repetitive contraction of the muscle precipitates persistent microtraumatism in the tendon unit. In the development of tendinopathies, the cellular process includes inflammation, apoptosis, vascular, and neuronal changes. Currently, treatments with oral supplements are frequently used. Curcumin seems to preserve, and even repair, damaged tendons. In this systematic review, we focus more especially on the benefits of curcumin. The biological actions of curcumin are diverse, but act around three systems: (a) inflammatory, (b) nuclear factor B (NF-κB) related apoptosis pathways, and (c) oxidative stress systems. A bibliographic search is conducted under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a basis for reporting reliable systematic reviews to perform a Scoping review. After analysing the manuscripts, we can conclude that curcumin is a product that demonstrates a significant biological antialgic, anti-inflammatory, and antioxidant power. Therefore, supplementation has a positive effect on the inflammatory and regenerative response in tendinopathies. In addition, curcumin decreases and modulates the cell infiltration, activation, and maturation of leukocytes, as well as the production of pro-inflammatory mediators at the site of inflammation.

Tendon injections - upper extremity.

Imaging-guided tendon procedures aim to reduce pain and increase function by controlling inflammation and stimulating healing. Ultrasound is the preferable guiding modality due to its high resolution and real-time demonstration of the tendinous anatomy and needle positioning. The technique includes appropriate patient positioning, which varies depending on the targeted tendon, as well as sterile and proper draping. For most procedures, we prefer the "in-plane" approach, which demonstrates the entire needle as it advances through different tissue layers. Upper limb injections commonly use corticosteroids and anesthetics with different reported short- and long-term results depending on the tendon treated; better results are obtained in the treatment of tenosynovitis (sliding tendons such as trigger finger and De Quervain's tenosynovitis). Shoulder and elbow tendinopathies (anchor tendons) may also benefit from injections containing irritants or healing stimulants such as dextrose (prolotherapy) and platelet-rich plasma or by the stimulation of healing via tendon perforations (fenestration). The hyaluronic acid injection has also been used in the treatment of both tenosynovitis and tendinopathies. For tendons passing through osteofibrous tunnels, an additional release may be performed, and the techniques are discussed in this review. Therefore, this article provides practicing musculoskeletal radiologists and trainees with a comprehensive review of tendon injection musculoskeletal image-guided procedures.

The Role of Hyaluronic Acid for Soft Tissue Indications: A Systematic Review and Meta-Analysis.

CONTEXT: Soft tissue injuries are often treated with injectables such as corticosteroids and platelet-rich plasma (PRP) to reduce inflammation and promote healing. There is increasing evidence examining the use of hyaluronic acid (HA) for the management of soft tissue injuries. OBJECTIVE: To evaluate the treatment effect and role of HA for available soft tissue indications. DATA SOURCES: A search of PubMed, MEDLINE, EMBASE, and CENTRAL from the inception date of each database through February 24, 2021, was conducted for all randomized controlled trials (RCTs) involving the use of HA for soft tissue indications. Two reviewers independently screened articles for eligibility and extracted data from included studies for analysis. We assessed risk of bias for all included studies and pooled outcomes using a fixed-effects model. Outcomes (ie, function and pain relief) were categorized to short-term (<6 weeks, 6-12 weeks) and mid-term (>12 weeks) data. We present effect estimates as mean differences (MDs) and standardized mean differences (SMDs) and present the estimate of effect of HA for available indications in relation to available comparators. STUDY DESIGN: Meta-analysis of RCTs. LEVEL OF EVIDENCE: Level 1. RESULTS: Of the 6930 articles screened, 19 RCTs (n = 1629 patients) were eligible and included in this review. HA was evaluated across a variety of soft tissue indications including rotator cuff disease, elbow pain, ankle sprains, Achilles tendinopathy, patellar tendinopathy, and trigger finger. Of the 19 RCTs, 11 were placebo-controlled and 9 used active comparators (PRP, cortisone, prolotherapy, or extracorporeal shockwave therapy). The pooled treatment effect of HA across most soft indications against placebo and active comparators demonstrated benefit in short-term pain <6 weeks (MD visual analogue scale [VAS] 2.48, 95% CI 2.31-2.65) and 6 to 12 weeks (MD VAS 2.03, 95% CI 1.86-2.20). Mid-term pain relief also favored HA over comparators across indications >12 weeks from administration (MD VAS 3.57, 95% CI 3.35-3.78). High heterogeneity was present with rotator cuff (10 trials, I2 = 94%), and elbow tendinopathy (2 trials, I2 = 99%). We identified uncertain benefit for trigger finger (2 trials, I2 = 67%). Heterogeneity for ankle sprains, patellar tendinopathy and Achilles tendinopathy could not be assessed as they only had 1 trial each. CONCLUSION: This systematic review and meta-analysis support HA's efficacy in the treatment of a variety of soft tissue indications. Understanding the relative effects of HA to other injectable modalities requires additional, large trials.

Effect of Vitamin C on Tendinopathy Recovery: A Scoping Review.

Tendinopathies represent 30-50% of all sports injuries. The tendon response is influenced by the load (volume, intensity, and frequency) that the tendon support, resulting in irritability and pain, among others. The main molecular component of tendons is collagen I (60-85%). The rest consist of glycosaminoglycans-proteoglycans, glycoproteins, and other collagen subtypes. This study's aim was to critically evaluate the efficacy of vitamin C supplementation in the treatment of tendinopathies. At the same time, the study aims to determine the optimal conditions (dose and time) for vitamin C supplementation. A structured search was carried out in the SCOPUS, Medline (PubMed), and Web of Science (WOS) databases. The inclusion criteria took into account studies describing optimal tendon recovery when using vitamin C alone or in combination with other compounds. The study design was considered, including randomized, double-blind controlled, and parallel designs in animal models or humans. The main outcome is that vitamin C supplementation is potentially useful as a therapeutic approach for tendinopathy recovery. Vitamin C supplementation, alone or in combination with other products, increases collagen synthesis with a consequent improvement in the patient's condition. On the other hand, vitamin C deficiency is mainly associated with a decrease in procollagen synthesis and reduced hydroxylation of proline and lysine residues, hindering the tendon repair process.

Modulation of Inflammation by Plant-Derived Nutraceuticals in Tendinitis.

Tendinitis (tendinopathy) is a pro-inflammatory and painful tendon disease commonly linked with mechanical overuse and associated injuries, drug abuse, and lifestyle factors (including poor diet and physical inactivity) that causes significant healthcare expenditures due to its high incidence. Nuclear factor kappa B (NF-κB) is one of the major pro-inflammatory transcription factors, along with other inflammation signaling pathways, triggered by a variety of stimuli, including cytokines, endotoxins, physical and chemical stressors, hypoxia, and other pro-inflammatory factors. Their activation is known to regulate the expression of a multitude of genes involved in inflammation, degradation, and cell death. The pathogenesis of tendinitis is still poorly understood, whereas efficient and sustainable treatment is missing. Targeting drug suppression of the key inflammatory regulators represents an effective strategy for tendinitis therapy, but requires a comprehensive understanding of their principles of action. Conventional monotherapies are often ineffective and associated with severe side effects in patients. Therefore, agents that modulate multiple cellular targets represent therapeutic treatment potential. Plant-derived nutraceuticals have been shown to act as multi-targeting agents against tendinitis via various anti-oxidant and anti-inflammatory mechanisms, whereat they were able to specifically modulate numerous signaling pathways, including NF-κB, p38/MAPK, JNK/STAT3, and PI3K/Akt, thus down-regulating inflammatory processes. This review discusses the utility of herbal nutraceuticals that have demonstrated safety and tolerability as anti-inflammatory agents for the prevention and treatment of tendinitis through the suppression of catabolic signaling pathways. Limitations associated with the use of nutraceuticals are also described.

Effects of Hypertonic Dextrose Injection (Prolotherapy) in Lateral Elbow Tendinosis: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review the effectiveness of hypertonic dextrose prolotherapy (DPT) on pain intensity and physical functioning in patients with lateral elbow tendinosis (LET) compared with other active non-surgical treatments. DATA SOURCES: Systematic search of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Web of Science, PubMed, Dimensions, Global Health, NHS Health Technology Assessment, Allied and Complementary Medicine, and OVID nursing database from inception to June 15, 2021, without language restrictions. STUDY SELECTION: Two reviewers independently identified parallel or crossover randomized controlled trials that evaluated the effectiveness of DPT in LET. The search identified 245 records; data from 8 studies (354 patients) were included. DATA EXTRACTION: Two reviewers independently extracted data and assessed included studies. The Cochrane Risk of Bias 2 tool was used to evaluate risk of bias. The Grading of Recommendation Assessment, Development, and Evaluation approach was used to assess quality of the evidence. DATA SYNTHESIS: Pooled results favored the use of DPT in reducing tennis elbow pain intensity compared with active controls at 12 weeks postenrollment, with a standardized mean difference of -0.44 (95% confidence interval, -0.88 to -0.01, P=.04) and of moderate heterogeneity (I2=49%). Pooled results also favored the use of DPT on physical functioning compared with active controls at 12 weeks, with Disabilities of the Arm, Shoulder and Hand scores achieving a mean difference of -15.04 (95% confidence interval, -20.25 to -9.82, P<.001) and of low heterogeneity (I2=0.0%). No major related adverse events have been reported. CONCLUSIONS: DPT is superior to active controls at 12 weeks for decreasing pain intensity and functioning by margins that meet criteria for clinical relevance in the treatment of LET. Although existing studies are too small to assess rare adverse events, for patients with LET, especially those refractory to first-line treatments, DPT can be considered a nonsurgical treatment option in carefully selected patients. Further high-quality trials with comparison with other injection therapies are needed.

Effect of Hypertonic Dextrose Injection on Pain and Shoulder Disability in Patients with Chronic Supraspinatus Tendinosis: A Randomized Double-Blind Controlled Study.

OBJECTIVES: To investigate the effect of hypertonic dextrose injection on pain and disability in patients with chronic supraspinatus tendinosis. The secondary aim was to evaluate its effect on the tendon range of motion (ROM) and morphology. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Outpatient clinic. PARTICIPANTS: Individuals (N=57) with symptomatic chronic supraspinatus tendinosis. INTERVENTIONS: Participants were randomly administered ultrasound-guided injections of 20% hypertonic dextrose (study group, n=29) or 5% normal saline (control group, n=28). MAIN OUTCOME MEASURES: The primary outcome measure was visual analog scale (VAS) scores for pain and Shoulder Pain and Disability Index (SPADI) scores. Secondary outcomes included the ROM and ultrasound examination findings of the supraspinatus tendon at baseline and at 2, 6, and 12 weeks postintervention. RESULTS: The study group exhibited significant improvements in the VAS (mean difference [MD], -2.1; 95% confidence interval [CI], -2.7 to -1.4; P<.001) and SPADI (MD, -11.6; 95% CI, -16.5 to -6.7; P<.001) scores compared with baseline scores at week 2. However, the effect was not sustained to week 6. Flexion ROM increased at weeks 2 (MD, 14.1; 95% CI, 5.7-22.5; P<.001) and 6 (MD, 8.9; 95% CI, 2.4-15.4; P=.003) compared with baseline. The thickness of the supraspinatus tendon improved at weeks 6 (MD, .50; 95% CI, .26-.74; P<.001) and 12 (MD, .61; 95% CI, .37-.84; P<.001) compared with baseline. The ratio of histograms also improved at weeks 6 (MD, .19; 95% CI, .06-.32; P=.002) and 12 (MD, .26; 95% CI, .10-.41; P<.001) compared with baseline. CONCLUSION: Hypertonic dextrose injection could provide short-term pain and disability relief in patients with chronic supraspinatus tendinosis. Ultrasound imaging at week 6 revealed changed tendon morphology.

Efficacy of hypertonic dextrose infiltrations for pain control in rotator cuff tendinopathy: systematic review and meta-analysis.

INTRODUCTION: The aim of our study was to assess the efficacy of hypertonic dextrose infiltrations for pain control in individuals with rotator cuff tendinopathy and to assess the characteristics of the treatment and the presence of side effects or adverse reactions through a systematic review and meta-analysis. METHODS: The search for the articles was performed in the electronic databases PUBMED, EMBASE, SCOPUS, SCIELO, DIALNET and Google Scholar, published up to August 2020. The keywords used were "prolotherapy" or "proliferation therapy" or "hypertonic dextrose infiltrations" or "hypertonic dextrose injection" and "Rotator Cuff" or "Rotator Cuff Injury" or "Rotator Cuff Tear" or "Rotator Cuff Tendinosis" or "supraspinatus". The effectiveness of hypertonic dextrose infiltrations was expressed as standardized mean difference (d) and 95% CI. RESULTS: In the pooled analysis, hypertonic dextrose infiltrations were an effective intervention to reduce long-term pain in patients with rotator cuff tendinopathy when compared to controls; furthermore, in the individual analyses, hypertonic dextrose infiltrations were more effective in the short, medium and long terms than non-invasive treatments, and more effective in the long-term than infiltrations with local anesthetics. On the other hand, hypertonic dextrose infiltrations were not more effective than injections with corticosteroids or PRP. Finally, no complications or serious adverse effect were observed when hypertonic dextrose infiltrations were used. CONCLUSIONS: We found that hypertonic dextrose infiltrations reduced pain in individuals with rotator cuff in the long-term. Hypertonic dextrose infiltrations could be an alternative to non-invasive treatments when no favorable results can be achieve. However, due to the small number of studies included in this meta-analysis, new studies are necessary to clarify the efficacy and safety of this intervention.

Curcuminoids and Boswellia serrata extracts combination decreases tendinopathy symptoms: findings from an open-label post-observational study.

Background: To investigate the effects of 1-month treatment in addition to standard care with a food supplement containing both Curcuma longa and Boswellia serrata extracts on tendinopathy symptoms.Method: This open-label, non-controlled, post-observational study included 670 patients suffering from tendinopathy recruited at different sites by Belgian general practitioners. Patients received a medical prescription for 1-month treatment with two tablets twice a day of a pharmaceutical grade food supplement containing both C. longa and B. serrata extracts. Pain and functional limitation were evaluated using a visual analog scale at the inclusion and 1-month treatment later. Patient satisfaction, concomitant drugs intake and side effects were also recorded.Results: After 1-month treatment, pain and functional limitation were significantly improved whatever the cause of tendinopathy, its localization, and the duration of symptoms. The pain score decreased from 6.16 ± 1.53 to 2.98 ± 1.64 (p < .0001), yielding a drop of 51.6% and the functional limitation score fell after 1-month treatment from 5.96 ± 1.73 to 2.88 ± 1.67 (p < .0001) corresponding to a drop of 51.6%. The percentage of patients taking at least one concomitant treatment at the end of the treatment period had decreased from 81.3% to 61.8% (p < .0001). Only 43 (6.5%) patients reported side effects. No severe adverse effects related to the product were reported.Conclusion: The combination of C. longa and B. serrata extracts improves symptoms in patients suffering of tendinopathy and shows a good safety. Although its effect will have to be confirmed in randomized controlled trials, it can be considered as a helpful support of standard symptomatic treatments for tendinopathies. HighlightsTendinopathy is a common disease representing 30% of all consultations with a general practitioner for musculoskeletal disorders.The combination of Curcuminoids and Boswelliaserrata extracts are efficient on tendinopathy symptoms in support of standard symptomatic treatments.The combination of Curcuminoids and B. Serrata extract is safe and can be administrated for at least 1 month in addition of analgesic and non-steroidal anti-inflammatory drugs.

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).

Current pharmacological approaches to the treatment of tendinopathy.

INTRODUCTION: Tendinopathies are common in elite and recreational athletes: traditionally considered overuse injuries, they involve excessive tensile loading and subsequent breakdown of the loaded tendon. Many pharmacological treatments have been proposed for the management of tendinopathy, with no agreement regarding the overall best option available both for Achilles and patellar tendinopathy. AREAS COVERED: The present article reports the best scientific evidence regarding the efficacy and safety of different pharmacological treatments in different types of tendinopathy, focusing on Achilles and patellar tendinopathy, the conditions on which more studies have been published. EXPERT OPINION: No univocal evidence exists regarding the best non-operative management, which includes non-steroidal anti-inflammatory drugs, platelet-rich plasma, high volume image-guided injections, hyaluronic acid, and prolotherapy, for tendinopathy (in particular Achilles and patellar tendinopathies) as a suitable alternative to the commonly used eccentric loading rehabilitation regimen. It is unclear whether the combination of pharmacological substances with physical therapy would produce better results than physical therapy alone. There is an overall lack of published well-performed randomized controlled trials comparing the various options available for the management of tendinopathy, studying large cohorts of patients for adequately long follow-up periods and with well-validated standardized scores and scales.

Effectiveness of Dextrose Prolotherapy for Rotator Cuff Tendinopathy: A Systematic Review.

OBJECTIVE: To systematically review and evaluate the efficacy and complication profile of prolotherapy using hyperosmolar dextrose solution injection for rotator cuff tendinopathy. LITERATURE SURVEY: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (from inception to 1 July, 2019). METHODOLOGY: A comprehensive search was completed to identify randomized controlled trials addressing prolotherapy using hyperosmolar dextrose solution for rotator cuff tendinopathy. Two reviewers independently screened the titles, abstracts, and full texts, and then extracted data from eligible studies. All reported outcome measures and complications were analyzed descriptively. SYNTHESIS: Five studies satisfied inclusion criteria. Included studies analyzed a total of 272 participants with a final follow-up ranging from 6 weeks to 12 months. Prolotherapy differed greatly among studies. Two studies used a multisite enthesis injection protocol while the other three used ultrasound-guided protocols. Two of the studies used an intrasubstance supraspinatus injection and three used a supraspinatus enthesis injection. Control groups consisted of nonoperative rehabilitation including physical therapy and medical management in three studies, supraspinatus saline enthesis injection in one study, and corticosteroid injection in one study. There was statistically significant improvement in pain intensity with multisite injection protocols compared to physical therapy and medical management in both studies. Ultrasound-guided supraspinatus injection trials did not find any statistically significant difference in pain intensity, range of motion, strength, function, or ultrasound characteristics compared to controls of enthesis saline injection or corticosteroid. The complication rate was low, with only 6/272 participants experiencing adverse events consisting of transient increase in pain for 1 to 2 days postintervention. CONCLUSIONS: Prolotherapy with hyperosmolar dextrose solution is a potentially effective adjuvant intervention to physical therapy for patients with rotator cuff tendinopathy ranging from tendinosis to partial-thickness and small full-thickness tears. Further studies are necessary to determine effects in subpopulations as well as optimal technique including dextrose concentration, volume, and location.

Tendinopathy: Pathophysiology, Therapeutic Options, and Role of Nutraceutics. A Narrative Literature Review.

Tendinopathies are very common in general population and a huge number of tendon-related procedures take place annually worldwide, with significant socio-economic repercussions. Numerous treatment options are commonly used for tendon disorders. Besides pharmacological and physical therapy, nutrition could represent an additional tool for preventing and treating this complex pathology that deserve a multidisciplinary approach. In recent years, nutraceutical products are growing up in popularity since these seem to favor the prevention and the healing processes of tendon injuries. This narrative literature review aims to summarize current understanding and the areas of ongoing research about the management of tendinopathies with the help of oral supplementation.

Magnolol prevents ossified tendinopathy by inhibiting PGE2-induced osteogenic differentiation of TDSCs.

Magnolol is a compound that is extracted from magnolia, is used in Chinese medicine and is a type of lignan. Magnolol has various anti-inflammation, anti-proliferation and pro-autophagy effects. Ossified tendinopathy affects many athletes and people with repetitive tendon injuries. Ossified tendinopathy is a tremendous economic burden, and no effective and safe drugs are available to prevent the pathogenesis of ectopic ossification. In this study, we aimed to study how magnolol affects ossified tendinopathy by evaluating its effects on osteogenic differentiation of tendon-derived stem cells (TDSCs). Our data suggested that magnolol attenuated ectopic ossification in the Achilles tendon caused by Achilles tenotomy. Magnolol inhibited PGE2-induced ALP activity and prevented calcium deposits in TDSCs in vitro. Magnolol also exerted inhibitory effects on expression of osteogenic factors, such as Runx2, OCN, and BMP2 in vivo. Further investigation revealed the underlying mechanism by which magnolol prevents PGE2-induced ectopic ossification. Specifically, magnolol inhibits PGE2-induced PI3K/AKT/ß-catenin pathway activation in TDSCs. Our findings demonstrated that magnolol inhibited ossified tendinopathy through preventing osteogenic differentiation of TDSCs via downregulation PGE2-induced PI3K/AKT/ß-catenin pathways.