Aims. Frozen shoulder is a common, painful condition that results in impairment of function. Corticosteroid injections are commonly used for frozen shoulder and can be given as glenohumeral joint (GHJ) injection or suprascapular nerve block (SSNB). Both injection types have been shown to significantly improve shoulder pain and range of motion. It is not currently known which is superior in terms of relieving patients’ symptoms. This is the protocol for a randomized clinical trial to investigate the clinical effectiveness of corticosteroid injection given as either a GHJ injection or SSNB. Methods. The Therapeutic Injections For Frozen Shoulder (TIFFS) study is a single centre, parallel, two-arm, randomized clinical trial. Participants will be allocated on a 1:1 basis to either a GHJ corticosteroid injection or SSNB. Participants in both trial arms will then receive physiotherapy as normal for frozen shoulder. The primary analysis will compare the Oxford Shoulder Score (OSS) at three months after injection. Secondary outcomes include OSS at six and 12 months, range of shoulder movement at three months, and Numeric Pain Rating Scale, abbreviated Disabilities of Arm, Shoulder and Hand score, and EuroQol five-level five-dimension health index at three months, six months, and one year after injection. A minimum of 40 patients will be recruited to obtain 80% power to detect a minimally important difference of ten points on the OSS between the groups at three months after injection. The study is registered under ClinicalTrials.gov with the identifier NCT04965376. Conclusion. The results of this trial will demonstrate if there is a difference in shoulder pain and function after GHJ injection or SSNB in patients with frozen shoulder. This will help provide effective treatment to patients with frozen shoulder. Cite this article: Bone Jt Open 2023;4(3):205–209

Our aim was to compare the outcome of arthroscopic release for frozen shoulder in patients with and without diabetes. We prospectively compared the outcome in 21 patients with and 21 patients without diabetes, two years post-operatively. The modified Constant score was used as the outcome measure. The mean age of the patients was 54.5 years (48 to 65; male:female ratio: 18:24), the mean pre-operative duration of symptoms was 8.3 months (6 to 13) and the mean pre-operative modified Constant scores were 36.6 (standard deviation (. sd. ) 4.6) and 38.4 (. sd. 5.7) in the diabetic and non-diabetic groups, respectively. The mean modified Constant scores at six weeks, six months and two years post-operatively in the diabetics were 55. 6 (. sd. 4.7), 67. 4 (. sd. 5.6) and 84. 4 (. sd. 6.8), respectively; and in the non-diabetics 66.8 (. sd. 4.5), 79.6 (. sd. 3.8) and 88.6 (. sd. 4.2), respectively. A total of 15 (71%) of diabetic patients recovered a full range of movement as opposed to 19 (90%) in the non-diabetics. There was significant improvement (p < 0.01) in the modified Constant scores following arthroscopic release for frozen shoulder in both groups. The results in diabetics were significantly worse than those in non-diabetics six months post-operatively (p < 0.01) with a tendency towards persistent limitation of movement two years after operation. These results may be used when counselling diabetic patients for the outcome after arthroscopic treatment of frozen shoulder. Cite this article: Bone Joint J 2014;96-B:1355–8

Aims. To achieve expert clinical consensus in the delivery of hydrodilatation for the treatment of primary frozen shoulder to inform clinical practice and the design of an intervention for evaluation. Methods. We conducted a two-stage, electronic questionnaire-based, modified Delphi survey of shoulder experts in the UK NHS. Round one required positive, negative, or neutral ratings about hydrodilatation. In round two, each participant was reminded of their round one responses and the modal (or ‘group’) response from all participants. This allowed participants to modify their responses in round two. We proposed respectively mandating or encouraging elements of hydrodilatation with 100% and 90% positive consensus, and respectively disallowing or discouraging with 90% and 80% negative consensus. Other elements would be optional. Results. Between 4 August 2020 and 4 August 2021, shoulder experts from 47 hospitals in the UK completed the study. There were 106 participants (consultant upper limb orthopaedic surgeons, n = 50; consultant radiologists, n = 52; consultant physiotherapist, n = 1; extended scope physiotherapists, n = 3) who completed round one, of whom 97 (92%) completed round two. No elements of hydrodilatation were “mandated” (100% positive rating). Elements that were “encouraged” (≥ 80% positive rating) were the use of image guidance, local anaesthetic, normal saline, and steroids to deliver the injection. Injecting according to patient tolerance, physiotherapy, and home exercises were also “encouraged”. No elements were “discouraged” (≥ 80% negative rating) although using hypertonic saline was rated as being “disallowed” (≥ 90% negative rating). Conclusion. In the absence of rigorous evidence, our Delphi study allowed us to achieve expert consensus about positive, negative, and neutral ratings of hydrodilatation in the management of frozen shoulder in a hospital setting. This should inform clinical practice and the design of an intervention for evaluation. Cite this article: Bone Jt Open 2022;3(9):701–709

Frozen shoulder is a recognised complication following simple arthroscopic shoulder procedures, but its exact incidence has not been reported. Our aim was to analyse a single-surgeon series of patients undergoing arthroscopic subacromial decompression (ASD; group 1) or ASD in combination with arthroscopic acromioclavicular joint (ACJ) excision (group 2), to establish the incidence of frozen shoulder post-operatively. Our secondary aim was to identify associated risk factors and to compare this cohort with a group of patients with primary frozen shoulder. We undertook a retrospective analysis of 200 consecutive procedures performed between August 2011 and November 2013. Group 1 included 96 procedures and group 2 104 procedures. Frozen shoulder was diagnosed post-operatively using the British Elbow and Shoulder Society criteria. A comparative group from the same institution involved 136 patients undergoing arthroscopic capsular release for primary idiopathic frozen shoulder. . The incidence of frozen shoulder was 5.21% in group 1 and 5.71% in group 2. Age between 46 and 60 years (p = 0.002) and a previous idiopathic contralateral frozen shoulder (p < 0.001) were statistically significant risk factors for the development of secondary frozen shoulder. Comparison of baseline characteristics against the comparator groups showed no statistically significant differences for age, gender, diabetes and previous contralateral frozen shoulder. . These results suggest that the risk of frozen shoulder following simple arthroscopic procedures is just over 5%, with no increased risk if the ACJ is also excised. Patients aged between 46 and 60 years and a previous history of frozen shoulder increase the relative risk of secondary frozen shoulder by 7.8 (95% confidence interval (CI) 2.1 to 28.3)and 18.5 (95% CI 7.4 to 46.3) respectively. Cite this article: Bone Joint J 2015; 97-B:963–6

Aims. This systematic review places a recently completed multicentre randomized controlled trial (RCT), UK FROST, in the context of existing randomized evidence for the management of primary frozen shoulder. UK FROST compared the effectiveness of pre-specified physiotherapy techniques with a steroid injection (PTSI), manipulation under anaesthesia (MUA) with a steroid injection, and arthroscopic capsular release (ACR). This review updates a 2012 review focusing on the effectiveness of MUA, ACR, hydrodilatation, and PTSI. Methods. MEDLINE, Embase, PEDro, Science Citation Index, Clinicaltrials.gov, CENTRAL, and the World Health Organization (WHO) International Clinical Trials Registry were searched up to December 2018. Reference lists of included studies were screened. No language restrictions applied. Eligible studies were RCTs comparing the effectiveness of MUA, ACR, PTSI, and hydrodilatation against each other, or supportive care or no treatment, for the management of primary frozen shoulder. Results. Nine RCTs were included. The primary outcome of patient-reported shoulder function at long-term follow-up (> 6 months and ≤ 12 months) was reported for five treatment comparisons across four studies. Standardized mean differences (SMD) were: ACR versus MUA: 0.21 (95% confidence interval (CI) 0.00 to 0.42), ACR versus supportive care: -0.13 (95% CI -1.10 to 0.83), and ACR versus PTSI: 0.33 (95% CI 0.07 to 0.59) and 0.25 (95% CI -0.34 to 0.85), all favouring ACR; MUA versus supportive care: 0 (95% CI -0.44 to 0.44) not favouring either; and MUA versus PTSI: 0.12 (95% CI -0.14 to 0.37) favouring MUA. None of these differences met the threshold of clinical significance agreed for the UK FROST and most confidence intervals included zero. Conclusion. The findings from a recent multicentre RCT provided the strongest evidence that, when compared with each other, neither PTSI, MUA, nor ACR are clinically superior. Evidence from smaller RCTs did not change this conclusion. The effectiveness of hydrodilatation based on four RCTs was inconclusive and there remains an evidence gap. Cite this article: Bone Jt Open 2021;2(9):773–784

Aims. Early large treatment effects can arise in small studies, which lessen as more data accumulate. This study aimed to retrospectively examine whether early treatment effects occurred for two multicentre orthopaedic randomized controlled trials (RCTs) and explore biases related to this. Methods. Included RCTs were ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation), a two-arm study of surgery versus non-surgical treatment for proximal humerus fractures, and UK FROST (United Kingdom Frozen Shoulder Trial), a three-arm study of two surgical and one non-surgical treatment for frozen shoulder. To determine whether early treatment effects were present, the primary outcome of Oxford Shoulder Score (OSS) was compared on forest plots for: the chief investigator’s (CI) site to the remaining sites, the first five sites opened to the other sites, and patients grouped in quintiles by randomization date. Potential for bias was assessed by comparing mean age and proportion of patients with indicators of poor outcome between included and excluded/non-consenting participants. Results. No bias in treatment effect was observed overall for the CI site, or the first five sites, compared with the remaining sites in either trial. An early treatment effect on the OSS was observed for the first quintile of participants recruited to ProFHER only (clinically relevant difference of seven points). Selection bias for age was observed in the ProFHER trial only, with slightly younger patients being recruited into the study. Both trials showed some selection bias for markers of poor prognosis, although these did not appear to change over time. Conclusion. No bias in treatment effects overall were found at the CI or early sites set-up. An early treatment effect was found in one of the two trials, which was likely a chance effect as this did not continue during the study. Selection bias was observed in both RCTs, however this was minimal and did not impact on outcome. Cite this article: Bone Jt Open 2023;4(2):96–103

Aims. A pragmatic multicentre randomized controlled trial, UK FROzen Shoulder Trial (UK FROST), was conducted in the UK NHS comparing the cost-effectiveness of commonly used treatments for adults with primary frozen shoulder in secondary care. Methods. A cost utility analysis from the NHS perspective was performed. Differences between manipulation under anaesthesia (MUA), arthroscopic capsular release (ACR), and early structured physiotherapy plus steroid injection (ESP) in costs (2018 GBP price base) and quality adjusted life years (QALYs) at one year were used to estimate the cost-effectiveness of the treatments using regression methods. Results. ACR was £1,734 more costly than ESP ((95% confidence intervals (CIs) £1,529 to £1,938)) and £1,457 more costly than MUA (95% CI £1,283 to £1,632). MUA was £276 (95% CI £66 to £487) more expensive than ESP. Overall, ACR had worse QALYs compared with MUA (-0.0293; 95% CI -0.0616 to 0.0030) and MUA had better QALYs compared with ESP (0.0396; 95% CI -0.0008 to 0.0800). At a £20,000 per QALY willingness-to-pay threshold, MUA had the highest probability of being cost-effective (0.8632) then ESP (0.1366) and ACR (0.0002). The results were robust to sensitivity analyses. Conclusion. While ESP was less costly, MUA was the most cost-effective option. ACR was not cost-effective. Cite this article: Bone Jt Open 2021;2(8):685–695

Aims. Manipulation under anaesthetic (MUA) is a recognised form of treatment for patients with a frozen shoulder. However, not all patients benefit. Some have persistent or recurrent symptoms. There are no clear recommendations in the literature on the optimal management of recurrent frozen shoulder after a MUA. We aimed to address this issue in this study. Patients and Methods. We analysed a prospectively collected, single-surgeon, consecutive series of patients who underwent MUA for frozen shoulder between January 1999 and December 2015. The Oxford Shoulder Scores (OSS) and range of movement were the outcome measures. . Results. A total of 730 patients (792 shoulders) underwent MUA during the study period. A further MUA was undertaken in 141 shoulders (17.8%), for which we had complete data for 126. The mean improvement in OSS for all patients undergoing MUA was 16 (26 to 42), and the mean post-operative OSS in those requiring a further MUA was 14 (28 to 42; t-test, no difference between mean improvements, p = 0.57). Improvement was seen after a further MUA, regardless both of the outcome of the initial MUA, and of the time of recurrence. Patients with type-1 diabetes mellitus were at a 38% increased risk of requiring a further MUA, compared with the 18% increased risk of the group as a whole (p < 0.0001). Conclusion. Patients with a poor outcome or recurrent symptoms of a frozen shoulder after a MUA should be offered a further MUA with the expectation of a good outcome and a low complication rate. Cite this article: Bone Joint J 2017;99-B:812–17

Frozen shoulder is commonly encountered in general orthopaedic practice. It may arise spontaneously without an obvious predisposing cause, or be associated with a variety of local or systemic disorders. Diagnosis is based upon the recognition of the characteristic features of the pain, and selective limitation of passive external rotation. The macroscopic and histological features of the capsular contracture are well-defined, but the underlying pathological processes remain poorly understood. It may cause protracted disability, and imposes a considerable burden on health service resources. Most patients are still managed by physiotherapy in primary care, and only the more refractory cases are referred for specialist intervention. Targeted therapy is not possible and treatment remains predominantly symptomatic. However, over the last ten years, more active interventions that may shorten the clinical course, such as capsular distension arthrography and arthroscopic capsular release, have become more popular. . This review describes the clinical and pathological features of frozen shoulder. We also outline the current treatment options, review the published results and present our own treatment algorithm.

There are many types of treatment used to manage the frozen shoulder, but there is no consensus on how best to manage patients with this painful and debilitating condition. We conducted a review of the evidence of the effectiveness of interventions used to manage primary frozen shoulder using the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Physiotherapy Evidence Database, MEDLINE and EMBASE without language or date restrictions up to April 2009. Two authors independently applied selection criteria and assessed the quality of systematic reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. Data were synthesised narratively, with emphasis placed on assessing the quality of evidence. In total, 758 titles and abstracts were identified and screened, which resulted in the inclusion of 11 systematic reviews. Although these met most of the AMSTAR quality criteria, there was insufficient evidence to draw firm conclusions about the effectiveness of treatments commonly used to manage a frozen shoulder. This was mostly due to poor methodological quality and small sample size in primary studies included in the reviews. We found no reviews evaluating surgical interventions. More rigorous randomised trials are needed to evaluate the treatments used for frozen shoulder

Aims. The primary aim of this study was to evaluate the efficacy of distension arthrography in the treatment of adhesive capsulitis of the shoulder. The secondary aim was to assess which patient and procedural factors predicted the recurrence of symptoms after the procedure. Methods. All patients referred to our shoulder clinic over a ten-year period, between 2008 and 2018, with a clinical diagnosis of capsulitis and symptoms persisting for more than six months, were offered treatment with a distension arthrogram. All procedures were performed by one of five musculoskeletal radiologists, with a combination of steroid, local anaesthetic, and a distention volume of 10 ml, 30 ml, or 50 ml. Patient demographics, procedural details, recurrence of symptoms, and the need for further intervention were evaluated. Results. A total of 2,432 distension arthrograms were performed during the study period. The mean time between arthrography and analysis was 5.4 years (SD 4.4; 1 to 11). Recurrent symptoms occurred in 184 cases (7.6%), all of whom had a repeat distension arthrogram at a median of nine months (interquartile range (IQR) 6.0 to 15.3). The requirement for further intervention for persistent symptoms following arthrography was significantly associated with diabetes (p < 0.001) and bilateral capsulitis (p < 0.001). The volume of distension, either with air or saline, showed a dose-dependent advantage. Distension of 50 ml versus 30 ml showed a significantly decreased odds ratio for recurrence of 2.2 (95% confidence interval (CI) 1.6 to 3.0; p < 0.001). Capsule rupture (p = 0.615) or steroid dose (p = 0.275) did not significantly affect the rate of recurrence. There were no infections or neurovascular injuries. Following the second distension arthrogram, the symptoms resolved in 137 cases (74.5%) with no further intervention being required. An arthroscopic capsular release was ultimately required in 41 cases, comprising 1.7% of the entire cohort. Conclusion. We found a low rate of repeat intervention following distension arthrography in patients with adhesive capsulitis of the shoulder, at long term follow-up. Greater volumes of distension are associated with lower rates of recurrence independent of capsule rupture. Cite this article: Bone Joint J 2020;102-B(5):606–610

We treated 22 patients with a diagnosis of primary frozen shoulder resistant to conservative treatment by manipulation under anaesthetic and arthroscopic release of the rotator interval, at a mean time from onset of 15 months (3 to 36). Biopsies were taken from this site and histological and immunocytochemical analysis was performed to identify the types of cell present. The tissue was characterised by the presence of fibroblasts, proliferating fibroblasts and chronic inflammatory cells. The infiltrate of chronic inflammatory cells was predominantly made up of mast cells, with T cells, B cells and macrophages also present. The pathology of frozen shoulder includes a chronic inflammatory response with fibroblastic proliferation which may be immunomodulated

The effect of timing of a manipulation under anaesthetic (MUA) and injection of corticosteroid and local anaesthetic for the treatment of frozen shoulder has attracted little attention to date. All studies describe a period of conservative treatment before proceeding to an MUA. Delay has been associated with a poorer outcome. We present a retrospective review of a prospectively collected, single-surgeon, consecutive series of 246 patients with a primary frozen shoulder treated by MUA within four weeks of presentation. The mean duration of presenting symptoms was 28 weeks (6 to 156), and time to initial post-operative assessment was 26 days (5 to 126). The Oxford shoulder score (OSS) improved by a mean of 16 points (Wilcoxon signed-ranks test, p < 0.001) with a mean OSS at this time of 43 (7 to 48). Linear regression analysis showed no correlation between the duration of presenting symptoms and OSS at initial follow-up (R2 < 0.001) or peri-operative change in OSS (R2 < 0.001) or OSS at long-term follow-up (R2 < 0.03). Further analysis at a mean of 42 months (8 to 127) revealed a sustained improvement with a mean OSS of 44 (16 to 48). A good outcome follows an MUA and injection of corticosteroid and local anaesthetic in patients with primary frozen shoulder, independent of the duration of the presenting symptoms, and this improvement is maintained in the long term

Aims. Our aim was to investigate the prevalence of Propionibacterium (P.) acnes in the subcutaneous fat and capsule of patients undergoing shoulder surgery for frozen shoulder or instability. Patients and Methods. A total of 46 patients undergoing either an arthroscopic capsular release or stabilisation had biopsies taken from the subcutaneous fat and capsule of the shoulder at the time of surgery. These samples were sent for culture in enrichment, and also for Nucleic Acid Amplification testing. The prevalence of P. acnes and other microbes was recorded. Fisher's exact test of binary variables was used to calculate the association with significance set at p < 0.05. Assessment of influence of independent variables including a pre-operative glenohumeral injection, fat colonisation and gender, was undertaken using binary linear regression. Results. A total of 25 patients (53%) had P. acnes in one or more tissue samples and 35 (74%) had other bacterial species. The same microbe was found in the subcutaneous fat and the capsule in 13 patients (28%). There was no statistically significant association between the surgical pathology and capsular colonisation with P. acnes (p = 0.18) or mixed identified bacterial species (p = 0.77). Male gender was significantly associated with an increased capsular colonisation of P. acnes (odds ratio (OR) 12.38, 95% confidence interval (CI) 1.43 to 106.77, p = 0.02). A pre-operative glenohumeral injection was significantly associated with capsular P. acnes colonisation (OR 5.63, 95% CI 1.07 to 29.61, p = 0.04. Positive fat colonisation with P. acnes was significantly associated with capsular P. acnes (OR 363, 95% CI 20.90 to 6304.19, p < 0.01). Regression models pseudo R. 2. found fat colonisation with P. acnes to explain 70% of the variance of the model. Patients who had a pre-operative glenohumeral injection who were found intra-operatively to have fat colonisation with P. acnes had a statistically significant association with colonisation of their capsule with P. acnes (OR 165, 95% CI 13.51 to 2015.24, p < 0.01). Conclusion. These results show a statistically significant association between subcutaneous skin P. acnes culture and P. acnes capsular culture, especially when the patient has undergone a previous injection. The results refute the hypothesis that P. acnes causes frozen shoulder. Cite this article: Bone Joint J 2017;99-B:1067–72

Aims. Ultrasound (US)-guided injections are widely used in patients with conditions of the shoulder in order to improve their accuracy. However, the clinical efficacy of US-guided injections compared with blind injections remains controversial. The aim of this study was to compare the accuracy and efficacy of US-guided compared with blind corticosteroid injections into the glenohumeral joint in patients with primary frozen shoulder (FS). Methods. Intra-articular corticosteroid injections were administered to 90 patients primary FS, who were randomly assigned to either an US-guided (n = 45) or a blind technique (n = 45), by a shoulder specialist. Immediately after injection, fluoroscopic images were obtained to assess the accuracy of the injection. The outcome was assessed using a visual analogue scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the subjective shoulder value (SSV) and range of movement (ROM) for all patients at the time of presentation and at three, six, and 12 weeks after injection. Results. The accuracy of injection in the US and blind groups was 100% (45/45) and 71.1% (32/45), respectively; this difference was significant (p < 0.001). Both groups had significant improvements in VAS pain score, ASES score, SSV, forward flexion, abduction, external rotation, and internal rotation throughout follow-up until 12 weeks after injection (all p < 0.001). There were no significant differences between the VAS pain scores, the ASES score, the SSV and all ROMs between the two groups at the time points assessed (all p > 0.05). No injection-related adverse effects were noted in either group. Conclusion. We found no significant differences in pain and functional outcomes between the two groups, although an US-guided injection was associated with greater accuracy. Considering that it is both costly and time-consuming, an US-guided intra-articular injection of corticosteroid seems not always to be necessary in the treatment of FS as it gives similar outcomes as a blind injection. Cite this article: Bone Joint J 2021;103-B(2):353–359

This study prospectively evaluated the outcome of manipulation under anaesthesia and hydrodilatation as treatments for adhesive capsulitis. A total of 36 patients (38 shoulders) were randomised to receive either method, with all patients being treated in stage II of the disease process. The mean age of the patients was 55.2 years (44 to 70) and the mean duration of symptoms was 33.7 weeks (12 to 76). Eighteen shoulders (17 patients) underwent manipulation under anaesthesia and 20 (19 patients) had hydrodilatation. There were three insulin-dependent diabetics in each group. The mean visual analogue score in the manipulation under anaesthesia group was 5.7 (3 to 8.5; n = 18) before treatment, 4.7 (0 to 8.5; n = 16) at two months (paired t-test p = 0.02), and 2.7 (0 to 9; n = 16) at six months (paired t-test, p = 0.0006). The mean score in the hydrodilatation group was 6.1 (4 to 10; n = 20) before treatment, 2.4 (0 to 8; n = 18) at two months (paired t-test, p = 0.001), and 1.7 (0 to 7; n = 18) at six months (paired t-test, p = 0.0006). The visual analogue scores in the hydrodilatation group were significantly better than in the manipulation under anaesthesia group over the six-month follow-up period (p < 0.0001). The mean Constant score in those manipulated was 36 (26 to 66) before treatment, 58.5 (24 to 90) at two months (paired t-test, p = 0.001) and 59.5 (23 to 85) at six months (paired t-test, p = 0.0006). In the hydrodilatation group it was 28.8 (18 to 55) before treatment, 57.4 (17 to 80) at two months (paired t-test, p = 0.0004) and 65.9 (28 to 92) at six months (paired t-test, p = 0.0005). The Constant scores in the hydrodilatation group were significantly better than in the manipulated group over the six-month period of follow-up (p = 0.02). The range of movement improved in all patients over the six months, but was not significantly different between the groups. At the final follow-up, 94% of patients (17 of 18) were satisfied or very satisfied after hydrodilatation compared with 81% (13 of 16) of those receiving a manipulation. Most of our patients were treated successfully, but those undergoing hydrodilatation did better than those who were manipulated

The purpose of this study was to evaluate the expression of acid-sensing ion channels (ASICs) in the capsule and synovial fluid of patients with frozen shoulder. Capsular tissue and synovial fluid were obtained from 18 patients with idiopathic frozen shoulder (FS group) and 18 patients with instability of the shoulder (control group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule were determined using the reverse transcriptase-polymerase chain reaction, immunoblot analysis, and immunohistochemistry (IHC). The concentrations in synovial fluid were evaluated using an enzyme-linked immunosorbent assay. . The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule were significantly increased in the FS group compared with the control group. The protein levels of these three ASICs were also increased. The increased expressions were confirmed by IHC. Of the ASICs, ASIC3 showed the greatest increase in both mRNA and levels of expression compared with the control group. The levels of ASIC1 and ASIC3 in synovial fluid were significantly increased in the FS group. . This study suggests that ASICs may play a role as mediators of inflammatory pain and be involved in the pathogenesis of frozen shoulder. Cite this article: Bone Joint J 2015;97-B:824–9

Frozen shoulder is a chronic fibrosing condition of the capsule of the joint. The predominant cells involved are fibroblasts and myofibroblasts which lay down a dense matrix of type-I and type-III collagen within the capsule. This subsequently contracts leading to the typical features of pain and stiffness. Cytokines and growth factors regulate the growth and function of the fibroblasts of connective tissue and remodelling of the matrix is controlled by the matrix metalloproteinases (MMPs) and their inhibitors. Our aim was to determine whether there was an abnormal expression or secretion of cytokines, growth factors and MMPs in tissue samples from 14 patients with frozen shoulder using the reverse transcription/polymerase chain reaction (RT/PCR) technique and to compare the findings with those in tissue from four normal control shoulders and from five patients with Dupuytren’s contracture. Tissue from frozen shoulders demonstrated the presence of mRNA for a large number of cytokines and growth factors although the frequency was only slightly higher than in the control tissue. The frequency for a positive signal for the proinflammatory cytokines Il-1β and TNF-α and TNF-β, was not as great as in the Dupuytren’s tissue. The presence of mRNA for fibrogenic growth factors was, however, more similar to that obtained in the control and Dupuytren’s tissue. This correlated with the histological findings which in most specimens showed a dense fibrous tissue response with few cells other than mature fibroblasts and with very little evidence of any active inflammatory cell process. Positive expressions of the mRNA for the MMPs were also increased, together with their natural inhibitor TIMP. The notable exception compared with control and Dupuytren’s tissue was the absence of MMP-14, which is known to be a membrane-type MMP required for the activation of MMP-2 (gelatinase A). Understanding the control mechanisms which play a part in the pathogenesis of frozen shoulder may lead to the development of new regimes of treatment for this common, protracted and painful chronic fibrosing condition

We prospectively studied 50 patients with the diagnosis of primary frozen shoulder. The serum lipid levels were measured in 43 of these patients and compared with those in 43 age-matched and sex-matched control subjects. The fasting serum triglyceride and cholesterol levels were significantly elevated in the frozen-shoulder group (cholesterol p < 0.01; triglyceride p < 0.02)

In a series of 12 patients with inoperable gastric carcinoma who had treatment with a synthetic matrix metalloproteinase inhibitor (Marimastat) for more than one month, six developed a frozen shoulder or a condition resembling Dupuytren’s disease. This suggests that the matrix metalloproteinases, a family of naturally occurring proteinases, may be involved in the pathogenesis of these two conditions. Our observation opens avenues for further research which could lead to local or systemic therapeutic interventions for frozen shoulder and Dupuytren’s disease