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The Bone & Joint Journal
Vol. 104-B, Issue 11 | Pages 1256 - 1265
1 Nov 2022
Keene DJ Alsousou J Harrison P O’Connor HM Wagland S Dutton SJ Hulley P Lamb SE Willett K

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


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 532 - 539
1 Jun 2024
Lei T Wang Y Li M Hua L

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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_V | Pages 8 - 8
1 Mar 2012
Cowie J Thomson C McKinley J
Full Access

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


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 158 - 158
1 Jul 2002
Fagan DJ Martin W Smith A
Full Access

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


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 151 - 151
1 Mar 2006
Schuetz U Richter M Dreinhoefer K Puhl W Koepp H
Full Access

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


Bone & Joint Open
Vol. 3, Issue 11 | Pages 898 - 906
15 Nov 2022
Dakin H Rombach I Dritsaki M Gray A Ball C Lamb SE Nanchahal J

Aims

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.

Methods

We used data from the Repurposing anti-TNF for Dupuytren’s disease (RIDD) randomized controlled trial of intranodular adalimumab injections in patients with early-stage progressive DD. RIDD found that intranodular adalimumab injections reduced nodule hardness and size in patients with early-stage DD, indicating the potential to control disease progression. A within-trial cost-utility analysis compared four adalimumab injections with no further treatment against standard care alone, taking a 12-month time horizon and using prospective data on EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and resource use from the RIDD trial. We also developed a patient-level simulation model similar to a Markov model to extrapolate trial outcomes over a lifetime using data from the RIDD trial and a literature review. This also evaluated repeated courses of adalimumab each time the nodule reactivated (every three years) in patients who initially responded.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 340 - 347
22 Apr 2022
Winkler T Costa ML Ofir R Parolini O Geissler S Volk H Eder C

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.

Methods

HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 99 - 99
1 Mar 2008
Haque T Hamdy R Kotsiopriftis M Lauzier D Nakada S
Full Access

Bone Morphogenetic Protein 7 (BMP7) is a powerful osteoinductive substance that could stimulate bone formation in difficult conditions including distraction osteogenesis. However, to be effective, large unphysiological doses are required. Blocking the expression of BMP antagonists could amplify the effects of BMP7, allowing smaller doses of BMP7 to be used without altering its osteogenic potential. In this study, BMP7 antagonist Noggin was shown to be upregulated following BMP7 injection in a rabbit distraction osteogenesis model suggesting a role for Noggin in controlling BMP7 activity. Blocking Noggin expression may thus permit smaller doses of BMP7 to be used effectively. Distraction osteogenesis (DO) is an excellent method to form new bone. However, the long duration the external fixator has to be kept on until the new bone consolidates, could lead to numerous problems. BMP7 may accelerate bone formation in DO. However, large doses of BMP7 may be necessary. In this study, we investigated the expression of BMP7 antagonist Noggin in DO. Noggin may control BMP7 activity through a negative feedback mechanism. Blocking Noggin may amplify the effects of BMP7, thus permitting the use of smaller doses of BMP7 effectively in DO. Using smaller doses of BMP7 – while maintaining its powerful effects – may decrease side effects and render this drug more affordable economically. Noggin is normally expressed in DO. Its expression is upregulated by local application of BMP7. Its expression is co-localized to the same cells that express BMP7 and its receptors. The right tibia of sixteen rabbits was lengthened using a uniplanar fixator. The rabbits were divided into two groups: one received seventy-five micrograms recombinant BMP7 and the other placebo. All injections were performed one week after start of distraction. Rabbits were sacrificed ten minutes, one day, two days and two weeks following the injections. The expression of Noggin was studied in the distracted tissue by immunohistochemistry. Noggin may play a role in DO. Blocking its action may have huge clinical implications, by permitting the use of smaller – but equally effective – amounts of BMP7. Funding: CIHR, FRSQ and Shriners of North America


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1297 - 1302
3 Oct 2020
Kurosaka K Tsukada S Ogawa H Nishino M Nakayama T Yoshiya S Hirasawa N

Aims

Although periarticular injection plays an important role in multimodal pain management following total hip arthroplasty (THA), there is no consensus on the optimal composition of the injection. In particular, it is not clear whether the addition of a corticosteroid improves the pain relief achieved nor whether it is associated with more complications than are observed without corticosteroid. The aim of this study was to quantify the safety and effectiveness of cortocosteroid use in periarticular injection during THA.

Methods

We conducted a prospective, two-arm, parallel-group, randomized controlled trial involving patients scheduled for unilateral THA. A total of 187 patients were randomly assigned to receive periarticular injection containing either a corticosteroid (CS group) or without corticosteroid (no-CS group). Other perioperative interventions were identical for all patients. The primary outcome was postoperative pain at rest during the initial 24 hours after surgery. Pain score was recorded every three hours until 24 hours using a 100 mm visual analogue scale (VAS). The primary outcome was assessed based on the area under the curve (AUC).


Bone & Joint 360
Vol. 8, Issue 1 | Pages 37 - 39
1 Feb 2019


Bone & Joint 360
Vol. 7, Issue 4 | Pages 3 - 8
1 Aug 2018
White TO Carter TH


Bone & Joint 360
Vol. 5, Issue 6 | Pages 27 - 29
1 Dec 2016


Bone & Joint Research
Vol. 5, Issue 1 | Pages 11 - 17
1 Jan 2016
Barlow JD Morrey ME Hartzler RU Arsoy D Riester S van Wijnen AJ Morrey BF Sanchez-Sotelo J Abdel MP

Aims

Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone.

Methods

A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis.


Bone & Joint 360
Vol. 5, Issue 6 | Pages 18 - 21
1 Dec 2016


Bone & Joint Research
Vol. 2, Issue 10 | Pages 227 - 232
1 Oct 2013
Kearney RS Parsons N Costa ML

Objectives

To conduct a pilot randomised controlled trial to evaluate the feasibility of conducting a larger trial to evaluate the difference in Victorian Institute of Sports Assessment-Achilles (VISA-A) scores at six months between patients with Achilles tendinopathy treated with a platelet-rich plasma (PRP) injection compared with an eccentric loading programme.

Methods

Two groups of patients with mid-substance Achilles tendinopathy were randomised to receive a PRP injection or an eccentric loading programme. A total of 20 patients were randomised, with a mean age of 49 years (35 to 66). All outcome measures were recorded at baseline, six weeks, three months and six months.


Bone & Joint 360
Vol. 2, Issue 2 | Pages 18 - 20
1 Apr 2013

The April 2013 Wrist & Hand Roundup360 looks at: whether botox is just for Hollywood; supercharging nerve repairs; YouTube research; options for Keinbock’s disease; volar plates; driving and plasters; symptomatic radial malunion; and MRI and acute scaphoid fractures.