Pharmacological interventions for early-stage frozen shoulder: a systematic review and network meta-analysis.

OBJECTIVES: To evaluate the efficacy of pharmacological interventions for treating early-stage, pain predominant, adhesive capsulitis, also known as frozen shoulder. METHODS: We performed a systematic review in accordance with PRSIMA guidelines. Searches were conducted on PUBMED, EMBASE and Cochrane Central Register of Controlled Trials on the 24th of February 2022. Outcomes were shoulder pain, shoulder function and range of movement. Synthesis involved both qualitative analysis for all studies and pairwise meta-analyses followed by a network meta-analysis for randomised controlled trials (RCTs). RESULTS: A total of 3,252 articles were found, of which 31 met inclusion criteria, and 22 of these were RCTs. Intraarticular (IA) injection of corticosteroids (8 RCTS, 340 participants) and IA injection of platelet-rich plasma (PRP) (3 RCTs, 177 participants) showed benefit at 12 weeks compared with physical therapy in terms of shoulder pain and function, while oral non-steroidal anti-inflammatories (NSAIDs) (2 RCTs, 44 participants) and IA injection of hyaluronate (2 RCTs, 42 participants) did not show a benefit. Only IA PRP showed benefit over physical therapy for shoulder range of movement. CONCLUSION: These results shows that IA corticosteroids IA PRP injections are beneficial for early-stage frozen shoulder. These findings should be appraised with care considering the risk of bias, heterogeneity, and inconsistency of the included studies. We believe that research focused on early interventions for frozen shoulder could improve patient outcomes and lead to cost-savings derived from avoiding long-term disability. Further well-designed studies comparing with standardised physical therapy or placebo are required to improve evidence to guide management.

Genetic insights into the association between serum cytokines and frozen shoulder risk: A bidirectional mendelian randomization study.

BACKGROUND: Although existing studies have indicated a connection between chronic low-grade inflammation and the onset of frozen shoulder (FS), the precise causal relationship between distinct circulating inflammatory factors and FS has yet to be thoroughly evaluated. In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between systemic cytokines and FS. METHODS: A genome-wide association dataset comprising 41 serum cytokines from 8,293 individuals of Finnish descent was utilized, along with FS data from the UK Biobank included 10,104 FS cases and 451,099 controls. The primary MR method was the inverse variance weighted approach, and four additional MR techniques (MR-Egger, weighted median, simple mode, and weighted mode) were also employed to support and validate the findings. Heterogeneity and horizontal pleiotropy assessments were assessed using Cochrane's Q and MR-Egger intercept tests. Moreover, a series of sensitivity analyses were conducted to strengthen the accuracy and credibility of these findings. RESULTS: Based on the IVW method, genetically predicted increasing levels of growth regulated oncogene alpha (GROa) (OR=1.08, 95 % CI 1.02-1.13, P=0.005), interferon gamma-induced protein 10 (IP-10) (OR=1.09, 95 % CI 1.02-1.17, P=0.010), regulated on activation, C-C Motif Chemokine Ligand 5 (CCL5) (OR=1.11, 95 % CI 1.03-1.20, P=0.007) were suggestively associated with an increased risk of FS. Reverse MR analysis revealed no significant causal effect of FS on the 41 systemic inflammatory factors. No heterogeneity or horizontal pleiotropy was observed in our analysis. CONCLUSION: This study established a causal association between 41 systemic inflammatory factors and FS, indicating that elevated levels of GROa, IP-10 and CCL5 were associated with a higher risk of FS. Further research is warranted to explore the potential of these biomarkers as early predictors and therapeutic targets for FS.

Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting.

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder.

Corticosteroid Injection Methods for Frozen Shoulder: A Network Meta-analysis.

OBJECTIVE: To investigate the efficacy of corticosteroid (CS) injection methods for frozen shoulder. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched up to May 6, 2023. STUDY SELECTION: Randomized controlled trials (RCTs) that investigated CS injection methods for frozen shoulder were included. DATA EXTRACTION: Data were extracted independently by 2 authors. Risk of bias was assessed using the RoB 2 tool. DATA SYNTHESIS: A random-effects network meta-analysis was performed within a frequentist framework. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. A total of 66 RCTs involving 4491 patients were included. For short-term outcomes, 4-site injection (vs placebo [PLA]: standardized mean difference [SMD]=-2.20, 95% confidence interval [CI], -2.81 to -1.59 in pain; SMD=2.02; 95% CI, 1.39-2.65 in global function) was the most effective (low certainty). Rotator interval injection was the optimal treatment with moderate to high certainty (vs PLA: SMD=-1.07, 95% CI, -1.51 to -0.64 in pain; SMD=0.94, 95% CI, 0.49-1.40 in global function). For midterm outcomes, 4-site injection was most effective (vs PLA: SMD=-1.71, 95% CI, -2.41 to -1.01 in pain; SMD=2.22, 95% CI, 1.34-3.09 in global function; low certainty). Distension via rotator interval (D-RI) was the optimal treatment with moderate to high certainty (vs PLA: SMD=-1.10, 95% CI, -1.69 to -0.51 in pain; SMD=1.46, 95% CI, 0.73-2.20 in global function). Distension and intra-articular injection via anterior or posterior approaches produced effects equivalent to those of rotator interval injection and D-RI. CONCLUSIONS: Rotator interval injection, distension, and intra-articular injection had equivalent effects on symptom relief. More RCTs are required to validate the superiority of multisite injections.

Rotator Interval vs Posterior Approach Ultrasound-guided Corticosteroid Injections in Primary Frozen Shoulder: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the efficacy of rotator interval (RI) vs posterior approach (PA) ultrasound (US) guided corticosteroid injections into the glenohumeral (GH) joint in primary frozen shoulder (PFS). DATA SOURCES: A systematic literature search for all relevant studies on Medline, Scopus, Embase, Web of Science, and Cochrane Central, up to January 2023 was conducted. STUDY SELECTION: Randomized controlled trials that directly compared the US-guided corticosteroid injection into the RI and GH joint using PA in patients clinically and radiographically diagnosed with PFS. DATA EXTRACTION: The primary outcome was pain, and the secondary outcomes were function, and range of motion (ROM). Two authors independently assessed the risk of bias using the Cochrane risk-of-bias tool version 2. A random-effects model and generic inverse variance method were performed. Effect sizes were estimated using mean difference (MD) and standardized mean difference (SMD). DATA SYNTHESIS: A total of 5 clinical trials involving 323 subjects were included for the meta-analysis. US-guided corticosteroid injections into the RI revealed significant pain relief (MD 1.33 [95% confidence interval (CI) 0.20 to 2.46]; P=.02) and significant functional improvement (SMD 1.31 [95% CI 0.11 to 2.51]; P=.03) compared with the PA after 12 weeks. CONCLUSION: The results suggest the injection of corticosteroid into RI space is more effective than PA after 12 weeks in improving both pain and functional scores in patients with PFS.

Pharmacoacupuncture for the Treatment of Frozen Shoulder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Pharmacoacupuncture (PA) is an alternative injection therapy for a broad range of conditions. This meta-analysis evaluates the effectiveness and safety of PA in treating frozen shoulder (FS) and aims to standardise PA characteristics in clinical practice. METHODS: Randomized controlled trials (RCTs) assessing PA for FS were systematically reviewed from seven electronic databases up to August 31, 2023. Outcomes measured included the visual analogue scale (VAS) or numerical rating scale (NRS), effective rate, Constant-Murley Score (CMS), Shoulder Pain and Disability Index (SPADI), ROM, quality of life (QoL), and adverse events. Data analysis was conducted using RevMan 5.3, with the risk of bias in each trial evaluated using Cochrane's risk of bias tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool assessed the quality of evidence. RESULTS: Thirteen RCTs involving 1034 patients met the inclusion criteria, with eleven RCTs and 872 patients included in the meta-analysis. PA showed low-quality evidence of improvement in VAS, effective rate, CMS Total, and CMS Pain. Moderate-quality evidence indicated improvement in CMS ADL and CMS Mobility. PA was effective in four SF-36 subscales: physical function, social role function, mental health, and emotional role function. No significant difference in CMS strength was observed. One trial reported mild anaphylaxis reaction to bee venom as an adverse event. CONCLUSION: PA may offer potential benefits as an alternative injection therapy for FS patients. Further well-designed RCTs with rigorous methodology are required to substantiate its therapeutic efficacy and clinical utility. REGISTRATION: PROSPERO (CRD42023445708).

Factors associated with frozen shoulder in adults: a retrospective study.

OBJECTIVE: This study aims to explore the risk factors associated with frozen shoulder patients and further analyze the relationship between gender and diabetes with frozen shoulder. METHOD: We have reviewed the data of 1205 frozen shoulder patients in China's Xinjiang region from 2018 to 2023. The collected information included patients' gender, occupation, place of origin, marital status, age, the season of disease onset, duration of illness, etiology, surgical history, hypertension, diabetes, respiratory diseases, knee joint disease, hyperlipidemia, cardiovascular diseases, cervical spondylosis, lumbar disc herniation, rheumatoid arthritis, hyperuricemia, sleep quality, smoking and alcohol consumption, and constipation. We have used multifactor logistic regression analysis to identify the risk factors for a frozen shoulder. RESULTS: Single-factor logistic regression analysis showed that the number of females, patients with diabetes, knee joint disease, constipation, and patients with poor sleep quality in the observation group are higher than in the control group (P < 0.05). There were no statistically significant differences between the two groups in terms of occupation, place of origin, marital status, age, season of disease onset, duration of illness, etiology, surgical history, hypertension, respiratory diseases, hyperlipidemia, cardiovascular diseases, cervical spondylosis, lumbar disc herniation, rheumatoid arthritis, hyperuricemia, smoking, and alcohol consumption history (P > 0.05). Multivariate analysis showed that the final model included four variables: gender, diabetes history, sleep, and constipation. Among them, the OR values of gender and diabetes history were more significant than 1, indicating that they were independent risk factors for frozen shoulder, while the OR values of sleep and constipation were less than 1, suggesting that they were negatively associated with the occurrence of frozen shoulder. CONCLUSION: The results of this study suggest that gender and diabetes are independent risk factors for frozen shoulder. Additionally, poor sleep quality and constipation also can be correlated with the occurrence of a frozen shoulder.

Causal associations of hypothyroidism with frozen shoulder: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Many studies have investigated the association between hypothyroidism and frozen shoulder, but their findings have been inconsistent. Furthermore, earlier research has been primarily observational, which may introduce bias and does not establish a cause-and-effect relationship. To ascertain the causal association, we performed a two-sample bidirectional Mendelian randomization (MR) analysis. METHODS: We obtained data on "Hypothyroidism" and "Frozen Shoulder" from Summary-level Genome-Wide Association Studies (GWAS) datasets that have been published. The information came from European population samples. The primary analysis utilized the inverse-variance weighted (IVW) method. Additionally, a sensitivity analysis was conducted to assess the robustness of the results. RESULTS: We ultimately chose 39 SNPs as IVs for the final analysis. The results of the two MR methods we utilized in the investigation indicated that a possible causal relationship between hypothyroidism and frozen shoulder. The most significant analytical outcome demonstrated an odds ratio (OR) of 1.0577 (95% Confidence Interval (CI):1.0057-1.1123), P = 0.029, using the IVW approach. Furthermore, using the MR Egger method as a supplementary analytical outcome showed an OR of 1.1608 (95% CI:1.0318-1.3060), P = 0.017. Furthermore, the results of our sensitivity analysis indicate that there is no heterogeneity or pleiotropy in our MR analysis. In the reverse Mendelian analysis, no causal relationship was found between frozen shoulders and hypothyroidism. CONCLUSION: Our MR analysis suggests that there may be a causal relationship between hypothyroidism and frozen shoulder.

Rehabilitation in subjects with frozen shoulder: a survey of current (2023) clinical practice of Italian physiotherapists.

OBJECTIVE: Frozen Shoulder (FS) is a musculoskeletal pathology that leads to disability, functional decline, and a worsening in quality of life. Physiotherapists are the primary professionals involved in the treatment of FS, and it is essential to determine if their practice aligns with evidence-based suggestions. AIM: The aim is to assess the knowledge, skills, and operational strategies of Italian physiotherapists regarding FS and compare them with the existing literature. METHODS: A web-based, anonymous, and voluntary cross-sectional survey was developed and administered to Italian physiotherapists to evaluate their clinical practices. RESULTS: A total of 501 physiotherapists (38.5% female), completed the survey. More than half were under 35 years old (67.8%), declared working in private practice settings or being self-employed (57.1%), and were primarily engaged with musculoskeletal patients (81.8%). For subjects with FS at their first access, 21.4% identified X-rays as the most useful imaging technique to recognize pathologies beyond rehabilitation competence. In terms of general management, the majority reported working with an orthopaedic or physiatrist (47.5%) or in a multidisciplinary team (33.5%). Regarding manual therapy techniques, 63.3% of physiotherapists preferred intense degree mobilization, posterior direction, and moderate pain at the end of the range of motion for low irritable/high stiffness FS; however, there is a lack of consensus for managing very irritable/low stiffness FS. The majority of physiotherapists (57.7%) concurred that stretching improves the balance between metalloproteinase and its inhibitors. Additionally, 48.3% of physiotherapists selected mobile phone videos and messages to improve patients' compliance with exercises at home and for motivational/educational purposes. DISCUSSION AND CONCLUSION: The clinical practices of Italian physiotherapists in FS subjects sometimes deviate from evidence-based recommendations. While some discrepancies may be attributed to the existing uncertainties in the literature regarding knowledge and management strategies for FS patients, the authors recommend a stronger adherence to evidence-based practice.

Arthroscopic capsular release is more effective in pain relief than conservative treatment in patients with frozen shoulder.

BACKGROUND: Frozen shoulder is a common medical condition, but the ideal therapeutic method is yet to be determined. Our aim was to analyze the pain-relieving effect of different treatment options used for the management of this disease. METHODS: Medical records of 59 patients (22 male, 37 female, average age: 55.5 years ±9.9) with early stage primary frozen shoulder were evaluated, their demographic data, physical examination, concomitant diseases and treatment specific data were registered. Life quality and the level of pain were assessed using the Oxford Shoulder Score (OSS) and Numeric Rating Scale (NRS). Different treatment modalities and their effect on pain relief were recorded. Any existing correlation between life quality, pain and demographic data, concomitant diseases or the therapeutic method used was investigated. RESULTS: The level of pain measured on NRS improved from 7.9 ± 1.6 to 1.9 ± 2.2. The most effective therapeutic method in terms of pain relief was surgery, followed by physiotherapy and intraarticular steroid injection (NRS score after treatment: 2 - p < 0.0001; 3.3 - p < 0.0001; 4.9 - p < 0.0001, respectively). Non-steroidal anti-inflammatory drugs (NSAIDs) did not reduce pain significantly. OSS improved from 24 to 43.6 and was not affected by the investigated variables, time to recovery was not influenced by the demographic data, the type of treatment or concomitant diseases. CONCLUSIONS: Arthroscopic capsular release, physiotherapy and intraarticular steroid injection outperformed physical therapy and NSAID treatment in terms of pain relief. Despite of slight but persistent post-therapeutic pain found in half of the cases, treatment was considered satisfactory by the patients. Nor patient specific neither therapy specific data had a significant effect on the course of the disease.

Translational targeting of inflammation and fibrosis in frozen shoulder: Molecular dissection of the T cell/IL-17A axis.

Frozen shoulder is a common fibroproliferative disease characterized by the insidious onset of pain and restricted range of shoulder movement with a significant socioeconomic impact. The pathophysiological mechanisms responsible for chronic inflammation and matrix remodeling in this prevalent fibrotic disorder remain unclear; however, increasing evidence implicates dysregulated immunobiology. IL-17A is a key cytokine associated with inflammation and tissue remodeling in numerous musculoskeletal diseases, and thus, we sought to determine the role of IL-17A in the immunopathogenesis of frozen shoulder. We demonstrate an immune cell landscape that switches from a predominantly macrophage population in nondiseased tissue to a T cell-rich environment in disease. Furthermore, we observed a subpopulation of IL-17A-producing T cells capable of inducing profibrotic and inflammatory responses in diseased fibroblasts through enhanced expression of the signaling receptor IL-17RA, rendering diseased cells more sensitive to IL-17A. We further established that the effects of IL-17A on diseased fibroblasts was TRAF-6/NF-κB dependent and could be inhibited by treatment with an IKKß inhibitor or anti-IL-17A antibody. Accordingly, targeting of the IL-17A pathway may provide future therapeutic approaches to the management of this common, debilitating disease.

Genetic causal association between frozen shoulder and carpal tunnel syndrome: a two-sample mendelian randomization.

OBJECTIVE: Observational studies have suggested an association between frozen shoulder (FS) and carpal tunnel syndrome (CTS). However, due to challenges in establishing a temporal sequence, the causal relationship between these two conditions remains elusive. This study, based on aggregated data from large-scale population-wide genome-wide association studies (GWAS), investigates the genetic causality between FS and CTS. METHODS: Initially, a series of quality control measures were employed to select single nucleotide polymorphisms (SNPs) closely associated with the exposure factors. Two-sample Mendelian randomization (MR) was utilized to examine the genetic causality between FS and CTS, employing methods including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode approaches. Subsequently, sensitivity analyses were conducted to assess the robustness of the MR analysis results. RESULTS: IVW analysis results indicate a positive causal relationship between CTS and FS (p < 0.05, OR > 1), while a negative causal relationship between the two conditions was not observed. Heterogeneity tests suggest minimal heterogeneity in our IVW analysis results (p > 0.05). Multivariable MR testing also indicates no pleiotropy in our IVW analysis (p > 0.05), and stepwise exclusion tests demonstrate the reliability and stability of the MR analysis results. Gene Ontology (GO) pathway analysis reveals enrichment of genes regulated by the associated SNPs in the TGFß-related pathways. CONCLUSION: This study provides evidence of the genetic causal association between frozen shoulder and carpal tunnel syndrome and provides new insights into the genetics of fibrotic disorders.

Ultrasound-guided hydrodilatation for adhesive capsulitis: capsule-preserving versus capsule-rupturing technique.

OBJECTIVE: To compare the clinical efficacy of capsule-rupturing versus capsule-preserving ultrasound-guided hydrodilatation in patients with shoulder adhesive capsulitis (AC). To determine potential factors affecting the outcome over a 6-month follow-up. MATERIALS AND METHODS: Within a 2-year period, 149 consecutive patients with AC were prospectively enrolled and allocated into (i) group-CR, including 39 patients receiving hydrodilatation of the glenohumeral joint (GHJ) with capsular rupture and (ii) group-CP, including 110 patients treated with GHJ hydrodilatation with capsular preservation. Demographics, affected shoulder, and AC grade were recorded. Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and visual analog scale (VAS) were used for clinical assessment at baseline/1/3/6 months. Comparisons were performed with Mann-Whitney U test and Kolmogorov-Smirnov test. Linear regression was used to identify predictors of outcome. P value < 0.05 defined significance. RESULTS: DASH and VAS scores in both groups improved significantly compared to baseline (P < 0.001) and were significantly lower in the CP compared to CR group at all time-points following intervention (P < 0.001). Capsule rupture was a significant predictor of DASH score at all time-points (P < 0.001). DASH scores correlated to initial DASH score at all time-points (P < 0.001). DASH/VAS scores at 1 month were correlated to the AC grade (P = 0.025/0.02). CONCLUSION: GHJ hydrodilatation results in pain elimination and functional improvement till the mid-term in patients with AC, with improved outcome when adopting the capsule-preserving compared to the capsule-rupturing technique. Higher initial DASH score is predictive of impaired functionality in the mid-term.

MR imaging signs of shoulder adhesive capsulitis: analysis of potential differentials and improved diagnostic criteria.

OBJECTIVE: To evaluate the prevalence of shoulder adhesive capsulitis (AC) signs on MR studies of patients with various common shoulder conditions. METHODS: MR images of 316 patients were retrospectively evaluated. Patients were divided into three groups: controls (66 patients), clinical AC (63 patients), and study group (187 patients). The final diagnosis of AC was reached clinically. The study group was composed of patients with focal and massive rotator cuff tears, active hydroxyapatite deposition disease, fractures around the shoulder, and post-surgery. The following AC signs were evaluated: inferior glenohumeral ligament (IGHL) thickening; coracohumeral ligament (CHL) thickening; and hyperintensity of the inferior glenohumeral ligament, which was graded in four classes. RESULTS: The IGHL signal intensity was statistically higher in patients with fractures than in controls (P = 0.008). There was no statistically significant difference in IGHL signal between the AC group and patients with massive rotator cuff tears and active hydroxyapatite deposition disease (P > 0.1). IGHL thickness in patients with fractures, massive rotator ruptures, and active hydroxyapatite deposition disease was significantly higher compared to controls (P < 0.02) and significantly lower compared to the AC group (P < 0.0001). Based on these findings, a grading system for fibro-inflammatory capsular changes is proposed. CONCLUSION: MR AC signs are frequent in patients with shoulder conditions other than AC; however, in these patients, capsular changes are less prominent than in patients with clinical AC.

Efficacy of Combining Acupuncture and Physical Therapy for the Management of Patients With Frozen Shoulder: A Systematic Review and Meta-Analysis.

BACKGROUND: Frozen shoulder, a debilitating condition causing pain and restricted joint mobility, often challenges conventional physical therapy methods. This study investigates the efficacy of combined acupuncture and physical therapy regimen, as opposed to physical therapy alone, for pain reduction and improvement of the clinical effective rate and the range of motion in patients with frozen shoulder. METHODS: A systematic search of PubMed, Scopus, Cochrane Trial, and Web of Science databases was done for randomized controlled trials, quasi-experimental, and nonrandomized studies, reporting data of adult (>18 years) patients with frozen shoulder who received physical therapy with or without acupuncture. Outcomes of interest were pain, clinical effective rate, active and passive range of motion. Data were analyzed using STATA software, employing a random-effects model and standardized mean differences (SMD) and odds ratios (OR) for outcome measures. RESULTS: A total of 13 studies were included. The combined approach significantly reduced pain (SMD = -0.891) with considerable heterogeneity (I² = 85.3%) and improved clinical effective rates (OR = 3.693, I² = 0%). Significant improvements were also observed in active and passive range of motion, with varying degrees of heterogeneity. CONCLUSION: The combination of acupuncture and physical therapy is more effective than physical therapy alone in managing pain, improving clinical effective rates, and enhancing range of motion in patients with frozen shoulder. These findings suggest that incorporating acupuncture into standard rehabilitation protocols could enhance patient outcomes.

A high level of scientific evidence is available to guide treatment of primary shoulder stiffness: The SIAGASCOT consensus.

PURPOSE: Shoulder stiffness (SS) is a condition characterised by active and passive restricted glenohumeral range of motion, which can occur spontaneously in an idiopathic manner or be associated with a known underlying aetiology. Several treatment options are available and currently no consensus has been obtained on which treatment algorithm represents the best choice for the patient. Herein we present the results of a national consensus on the treatment of primary SS. METHODS: The project followed the modified Delphi consensus process, involving a steering, a rating and a peer-review group. Sixteen questions were generated and subsequently answered by the steering group after a thorough literature search. A rating group composed by professionals specialised in the diagnosis and treatment of shoulder pathologies rated the question-answer sets according to the scientific evidence and their clinical experience. RESULTS: Recommendations were rated with an average of 8.4 points out of maximum 9 points. None of the 16 answers received a rating of less than 8 and all the answers were considered as appropriate. The majority of responses were assessed as Grade A, signifying a substantial availability of scientific evidence to guide treatment and support recommendations encompassing diagnostics, physiotherapy, electrophysical agents, oral and injective medical therapies, as well as surgical interventions for primary SS. CONCLUSIONS: A consensus regarding the conservative and surgical treatment of primary SS could be achieved at a national level. This consensus sets basis for evidence-based clinical practice in the management of primary SS and can serve as a model for similar initiatives and adaptable guidelines in other European countries and potentially on a global scale. LEVEL OF EVIDENCE: Level I.

Ultrasound-guided corticosteroid injection in the coracohumeral ligament in patients with Adhesive Capsulitis of the shoulder: A double-blinded, sham-controlled randomized study.

BACKGROUND: Contracture and thickening of the coracohumeral ligament (CHL) occur in patients with adhesive capsulitis. This adversely affects the movement and function of the shoulder joint. There is limited evidence that explores the effectiveness of an isolated steroid injection into CHL in combination with physical therapy. This prospective randomized control trial aimed to evaluate the clinical effects of ultrasound-guided corticosteroid injection compared to a sham injection into the CHL in subjects with adhesive capsulitis. METHODS: Forty patients (23 males, 52.2 ± 8 years of age) with unilateral adhesive capsulitis (with 5.4 ± 2 months mean duration of symptoms) were randomly assigned to either the experimental or control group. Both groups received ultrasound-guided injections into the CHL. The experimental group (n=20) received corticosteroids and the control group (n=20) received a sham lidocaine injection. All subjects underwent supervised conventional physical therapy three times a week for 3 months. Subjects were evaluated for improvements in pain, range of motion, and disability at 6 and 12 weeks as compared to pre-injection baseline measurements. Data were compared statistically across groups and times at p<0.05. The CHL thickness was compared at baseline across sides using paired t-tests. RESULTS: The experimental group showed statistically greater improvements in pain, functional scores, flexion, abduction, internal and external rotation range of motion at 12 weeks compared to the control group. Pain reduction was observed in both groups at 6 and 12 weeks, but the experimental group exhibited significantly greater reductions. The CHL was significantly thicker on the affected side as compared to the unaffected side (p<0.001). DISCUSSION AND CONCLUSION: This study partially supported the hypothesis. Notably, significant improvements in pain, range of motion, and functional scores were observed at 12 weeks in the experimental group. The greater improvements in pain and external rotation may have resulted in lower disability scores in the experimental group. The results emphasize the importance of targeted intervention into the CHL.

Decreased prevalence of new-onset adhesive capsulitis in patients prescribed angiotensin receptor blockers.

BACKGROUND: Angiotensin receptor blockers (ARBs) are commonly prescribed antihypertensive agents that have well-known antifibrotic properties. The purpose of this study was to examine the association between ARB use and the rates of new-onset adhesive capsulitis as well as adhesive capsulitis requiring operative treatment. METHODS: Using a large national insurance database, a randomly generated cohort of patients with at least 3 continuous months of ARB use between January 2010 and December 2019 (n = 1,000,000) was compared to a separate randomly generated cohort without ARB use (n = 3,000,000). Rates of newly diagnosed adhesive capsulitis and associated manipulation under anesthesia (MUA) and/or arthroscopic capsulotomy were calculated over a 1- and 2-year period following the completion of at least 3 continuous months of ARB therapy. Rates were compared using multivariable logistic regression to control for demographics and comorbidities. Both unadjusted and adjusted odds ratios and 95% confidence intervals were calculated and reported for each comparison. Statistical significance was set at P <.05. RESULTS: The mean age in the ARB cohort was 61.8 years (standard deviation [SD] = 10.0), whereas in the control cohort, it was 54.8 years (SD = 12.3) (P < .001). The ARB cohort had significantly lower rates of newly diagnosed adhesive capsulitis compared with the control cohort at both 1 year (0.15% vs. 0.55%, P < .001) and 2 years (0.3% vs. 0.78%, P < .001). Similar findings were observed for the arthroscopic capsular release/MUA cohort associated with adhesive capsulitis. After adjusting for confounding factors, the lower rates of adhesive capsulitis and arthroscopic capsular release/MUA associated with adhesive capsulitis in the ARB cohort remained statistically significant (P < .001). CONCLUSION: Patients prescribed ARBs experienced a decreased rate of newly diagnosed adhesive capsulitis, as well as adhesive capsulitis requiring surgical intervention when compared to a control cohort. These findings suggest a potential protective effect of ARBs against the development of adhesive capsulitis. Further investigations are warranted to elucidate the underlying mechanisms and establish a causal relationship.

Matrix metalloproteinase-1 and matrix metalloproteinase-9 are highly expressed in the joint capsule of diabetic frozen shoulder.

BACKGROUND: The pathophysiology of frozen shoulder (FS) involves abnormal expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) that lead to capsular fibrosis. However, there has been little concern for why diabetic FS has more protracted fibrotic condition. The objective of this study was to compare the expression levels of MMPs and TIMPs in the joint capsule of patients with diabetic and nondiabetic FS. MATERIALS AND METHODS: Samples of capsular tissue were collected from 20 patients with FS (10 diabetic patients; diabetic group and 10 nondiabetic patients; nondiabetic group) and 10 patients (control group) with chronic anterior shoulder instability. Quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot analysis were performed to determine the expression levels of mRNA and protein for MMP-1, 3, 9, 13, 14, and TIMP-1, 2. RESULTS: The results of quantitative real-time reverse transcriptase-polymerase chain reaction showed significantly higher expression levels of all MMPs and TIMP-1 and significantly lower expression levels of TIMP-2 in the joint capsule of patients in the diabetic or nondiabetic groups compared with the control group. Significantly higher expression levels of MMP-1, 9, 14, and TIMP-1 were detected in the diabetic group compared with the nondiabetic group. The results of Western blot analysis showed significantly higher levels of MMP-3, 13, 14, and TIMP-1 in the joint capsule of patients in the diabetic or nondiabetic groups compared with the control group. However, no significant differences of protein levels of them were observed between diabetic and nondiabetic groups. CONCLUSIONS: The findings of this study demonstrate the potential involvement of MMP-1 and 9 in the pathophysiology of diabetic FS. These findings may be helpful in identification of therapeutic targets for development of novel treatments for this protracted chronic fibrosing condition.

Type 2 diabetes and fasting glycemic traits are causal factors of frozen shoulder: a 2-sample Mendelian randomization analysis.

BACKGROUND: The causal relationship between type 2 diabetes (T2D) and frozen shoulder is unclear. This study aims to explore the genetic causal association between T2D and glycemic traits (fasting glucose [FG], fasting insulin [FI], glycated hemoglobin [HbA1c], and 2-hour postprandial glucose [2hGlu]) on frozen shoulder. METHODS: Using 2-sample Mendelian randomization (MR), we analyzed nonconfounded estimates of the effects of T2D and glycemic traits on frozen shoulder. Single-nucleotide polymorphisms (SNPs) strongly associated (P < 5 × 10-8) with exposures from genome-wide association studies (GWAS) were identified. We employed fixed effect mode inverse variance weighting (IVW-FE), random effect mode IVW (IVW-MRE), MR-Egger, and weighted median to assess the association of exposures and outcome. Sensitivity analysis was conducted to test for heterogeneity and multidirectionality bias in MR. RESULTS: We found a significant genetic causal correlation between T2D (IVW-MRE P = .007, odds ratio [OR] 1.093, 95% confidence interval [CI] 1.03-1.16), FG (IVW-FE P < .001, OR 1.455, 95% CI 1.173-1.806), and frozen shoulder, but no evidence for causal correlation between FI, HbA1c, and 2hGlu and frozen shoulder. Although there was certain heterogeneity, sensitivity analysis reveals no deviation from the MR assumptions. CONCLUSION: This study supports a genetic causal relationship between T2D and FG and frozen shoulder.