Aims. Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. Methods. A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections. Results. A total of 102 patients were recruited. The follow-up period was 12 months, at intervals of six weeks, 12 weeks, six months, and 12 months. KOOS-Total significantly improved in all groups at these time intervals compared to pre-injection. There was an improvement in EQ-5D-5L index scores in saline and single injection groups, but not in the multiple injection group. Comparison of treatment groups showed no additional beneficial effect of single or multiple PRP injections above that displayed in the saline injection group. Subjective patient satisfaction and recommendation of treatment received demonstrated a similar pattern in all the groups. There was no indication of superiority of either single or multiple PRP injections compared to saline injections. Conclusion. There is no evidence that single or multiple PRP had any additional beneficial effect compared to saline injection up to 12 months, follow-up after treatment of early stage symptomatic OA of the knee. Cite this article: Bone Joint J 2022;104-B(6):663–671

Aims. Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. Methods. This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included. Results. In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months. Conclusion. Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes. Cite this article: Bone Joint J 2024;106-B(6):532–539

Aims. To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture. Methods. A randomized multicentre two-arm parallel-group, participant- and assessor-blinded superiority trial was undertaken. Recruitment commenced on 28 July 2015 and two-year follow-up was completed in 21 October 2019. Participants were 230 adults aged 18 years and over, with acute Achilles tendon rupture managed with non-surgical treatment from 19 UK hospitals. Exclusions were insertion or musculotendinous junction injuries, major leg injury or deformity, diabetes, platelet or haematological disorder, medication with systemic corticosteroids, anticoagulation therapy treatment, and other contraindicating conditions. Participants were randomized via a central online system 1:1 to PRP or placebo injection. The main outcome measure was Achilles Tendon Rupture Score (ATRS) at two years via postal questionnaire. Other outcomes were pain, recovery goal attainment, and quality of life. Analysis was by intention-to-treat. Results. A total of 230 participants were randomized, 114 to PRP and 116 to placebo. Two-year questionnaires were sent to 216 participants who completed a six-month questionnaire. Overall, 182/216 participants (84%) completed the two-year questionnaire. Participants were aged a mean of 46 years (SD 13.0) and 25% were female (57/230). The majority of participants received the allocated intervention (219/229, 96%). Mean ATRS scores at two years were 82.2 (SD 18.3) in the PRP group (n = 85) and 83.8 (SD 16.0) in the placebo group (n = 92). There was no evidence of a difference in the ATRS at two years (adjusted mean difference -0.752, 95% confidence interval -5.523 to 4.020; p = 0.757) or in other secondary outcomes, and there were no re-ruptures between 24 weeks and two years. Conclusion. PRP injection did not improve patient-reported function or quality of life two years after acute Achilles tendon rupture compared with placebo. The evidence from this study indicates that PRP offers no patient benefit in the longer term for patients with acute Achilles tendon rupture. Cite this article: Bone Joint J 2022;104-B(11):1256–1265

A total of 159 patients (84 women and 75 men, mean age of 53 (20 to 87)) with subacromial impingement were randomised to treatment with subacromial injections using lidocaine with one of hyaluronic acid (51 patients), corticosteroid (53 patients) or placebo (55 patients). Patients were followed up for 26 weeks. The primary outcome was pain on a visual analogue score (VAS), and secondary outcomes included the Constant Murley score, shoulder pain score, functional mobility score, shoulder disability questionnaire and pain-specific disability score. The different outcome measures showed similar results. After three, six and 12 weeks corticosteroid injections were superior to hyaluronic acid injections and only at six weeks significantly better than placebo injections. The mean short-term reduction in pain on the VAS score at 12 weeks was 7% (. sd. 2.7; 97.5% confidence interval (CI) 0.207 to 1.55; p = 0.084) in the hyaluronic acid group, 28% (. sd. 2.8; 97.5% CI 1.86 to 3.65; p < 0.001) in the corticosteroid group and 23% (. sd. 3.23; 97.5% CI 1.25 to 3.26; p < 0.001) in the placebo group. At 26 weeks there was a reduction in pain in 63% (32 of 51) of patients in the hyaluronic acid group, 72% (38 of 53) of those in the corticosteroid group and 69% (38 of 55) of those in the placebo group. We were not able to show a convincing benefit from hyaluronic acid injections compared with corticosteroid or placebo injections. Corticosteroid injections produced a significant reduction in pain in the short term (three to 12 weeks), but in the long term the placebo injection produced the best results

A Morton's neuroma is a painful forefoot disorder characterised by plantar pain and toe paraesthesia. Many treatments have been tried including modification of shoe wear, injections and surgery. The results from different treatment modalities are extremely variable in the scientific literature. We reviewed 79 patients who presented with an ultrasound proven Morton's Neuromata at an average of 60 months following treatment in a patient blind randomised trial. 35 had surgery with resection of the Morton's Neuromata. We compared the results of the patients who had had a steroid injection and surgery, a steroid injection alone, a placebo injection and then surgery and a placebo injection alone. We looked at the requirement for further consultations, pain scores, activity restrictions, footwear restriction, overall satisfaction with their treatment and overall quality of life scores. We found no significant difference between the groups. Overall 80% of the surgical patients had a good or excellent result and 67% of the non- operatively managed patients had a good or excellent result. There was no difference in their quality of life scores. Previous studies have shown little benefit in steroid injections in the treatment of Morton's Neuromata. We conclude at the five year mark there is no significant differences between operating on Morton's Neuromata and treating them conservatively. Further research should focus on comparing operative vs conservative treatment in the short to medium term. In order to justify the risks and costs of surgery

The December 2022 Sports Roundup³⁶⁰ looks at: Anterior cruciate ligament (ACL) repair with dynamic intraligamentary stabilization or anterior ACL at five years?; Femoroacetabular impingement in mild osteoarthritis: is hip arthroscopy the answer?; Steroids in Achilles tendinopathy: A randomized trial.

Aim: To assess the efficiency of pre-emptive analgesia in a clinical setting as opposed to closely controlled animal models, looking at postoperative pain scores, total analgesia requirement and amount of general anaesthetic agent required during surgery. Methods and Results. Subject to exclusions, 40 patients undergoing day-case arthroscopy of the knee (mean age 44 years, ASA grade 1–2) were randomized into two treatment groups. All patients had general anaesthesia. The trial group received an injection of 15mI 0.5% Bupivicaine / 1/200,000 adrenaline pre-emptively. After surgery a placebo injection was given of 15ml normal saline in an identical manner. The control group received the opposite order. Additional post-operative analgesia, if required, was administered in recovery. This was recorded, also total dose of propofol used, time to awakening, visual analogue pain score at 15 / 30 / 60 minutes, postoperative nausea and vomiting at 30 minutes and the number of delayed discharges. Although no difference was observed in postoperative pain scores at 15, 30 or 60 minutes, a trend for the trial group to require less analgesia in recovery was observed (Chi squared =9.74, p=0. 1) but this was not statistically significant. There was no difference in mean dose of propofol used in either group, 15mg/kg/hr (. sd. =2.85) trial versus 14.6mg/kg/hr (. sd. =1.96) control. Conclusion: Local anaesthetic given pre-emptively appears to be no more effective at controlling pain in the immediate postoperative period than the current standard practice of postoperative injection. It’s effect in clinical practice may be less dramatic than that observed in more controlled animal models and a larger study may be required to show a statistically significant difference

Objective: In the absence of dependable and reproducible non-surgical treatment alternatives for osteoarthritis (OA), new approaches are needed. A new therapy, based on the intra-articular injection of autologous conditioned serum (ACS), is used in several European countries. ACS is generated by incubating venous blood with medical grade glass beads. Peripheral blood leukocytes produce elevated amounts of endogenous anti-inflammatory cytokines such as interleukin-1 receptor antagonist (IL-1Ra) that are recovered in the serum(. 1. ). In the present study, the clinical efficacy and safety of intra-articular injections of ACS were compared to intra-articular hyaluronan (HA), and placebo (saline) in patients with confirmed knee OA. Study Methods: In a prospective, randomized, patient- and observer-blind, placebo-controlled trial with three parallel groups, 399 patient knees with OA were included in an intention to treat (ITT-) analysis. Efficacy was assessed by patient-administered outcome instruments (WOMAC, VAS, SF-8, GPA) after 7, 13 and 26 weeks. The frequency and severity of adverse events were used as safety parameters. Results: In all treatment groups, intra-articular injections produced a significant reduction in WOMAC-scores and weight-bearing pain (VAS), as well as improvement in health-related quality of life. However, responses to ACS were far stronger. The superiority of ACS and either HA or placebo was statistically significant for all outcome measures and all time points. The mean improvement for patients treated with HA and placebo was half that in the ACS-group (p< 0.001). No significant differences between HA treatment and placebo injections (p> 0,05, at all time points and all outcome measures) were recorded. Frequency of adverse advents (AE) was comparable in the ACS- and the placebo-group (p> 0,05), whereas there were significantly more AE in the HA-group (p< 0,05 for the comparison with ACS and placebo). Conclusion: Patients with OA of the knee treated by intra-articular injection of ACS showed significantly better clinical improvement during 26 weeks observation compared to patients injected with HA or placebo. The results demonstrate that ACS is highly effective and well tolerated in the management of chronic, idiopathic OA of the knee. So far, the efficacy of ACS is defined through improvement in clinical signs and symptoms, particularly pain. It remains to be determined whether there are disease-modifying, chondroprotective, or even chondroregenerative, sequelae

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering interventions for treating distal femur fractures in adults; ultrasound and shockwave therapy for acute fractures in adults; and local corticosteroid injection versus placebo for carpal tunnel syndrome

Introduction: Analgesia from controlled injections of local anaesthetic into the lumbar zygapohysial joint (z-joint) has been accepted as the standard for diagnosis of z-joint pain. Little is known about the placebo-response rate. Aim of this pilot study is to validate the fluoroscopically controlled z-joint-injection (ZJI) as an instrument for diagnosis of degenerative symptomatic z-joint disease. Material and Methods: Due to degenerative lumbar spine syndrome 50 z-joints (L5/5: 27; L5/S1 23) were injected three times in a single blinded trial bilaterally. According to a randomisation protocol, using the oblique needle technique the ZJI were done with an local anaesthetic (LA: 1.5 ml 0.5% Scandicain), a saline placebo (sodium: 1.5ml 0.9% NaCl) and with no agent (sicca punction). The pain level before and after the injections (30 min, 1 and 2–3 hours) was documented by the patient on a 10pts.-VAS. Improvement in the pain level after an FJI is defined as responder. A responder reacts false positive if the degree of effectiveness of the placebo-FJI is the same or better than the response to LA. A patient reacts false negative if the pain diminution after LA application is lower than after placebo. Results: Preliminary results regarding the reactions 30 min after injection are presented. 26% were non-responder and 52.9% LA-responder. The sicca response rate was 38%, for sodium it was 46%. Reaction after sicca-FJI was false positive in 24%, after sodium-FJI in 32% of cases. 38% reacted false negative to LA-injection. The order of the agent application didn’t have significant influence on the responder rates and also not on the extent of contradictory effects. Conclusions: Despite numerous examinations none could sufficiently evaluate accurate reliable predictors for positive ZJI-responders till now. This is confirmed by our high LA-non-responder-rate of 48.1%. However, only a placebo injection can absolutely exclude a true placebo response. Placebo responses seem to be common. High specificity (minimization of the false positive results) and sensitivity (minimization of the false negative results) are characters for a good diagnostic test. In literature, the specificity of the intraarticular facet block as a diagnostic test for facet joint disease is currently unknown. Capsular rupture with epidural and periarticular diffusion is probably responsible for many false positive findings. Regarding our results, the validity of only one ZJI is not acceptable and shouldn’t be consulted as a diagnostic method for the identification of a facet joint syndrome, therefore. Pain relief after ZJI is a poor predictor of clinical outcome of posterolateral lumbosacral fusions when based on single blocks. Corresponding further examinations are necessary also regarding the ZJI-reliability

Aims

The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

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To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytren’s disease (DD) and the value of further research from an NHS perspective.

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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).

Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair. Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed. Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections. Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors