Aims. MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms. Methods. Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG. Results. miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines (IL-6, IL-1β, TNF-α) and pain-related factors (TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα. Conclusion. Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα-CCL2/CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548–557

Introduction. The commonest causes of revision of Unicompartmental Knee Replacement (UKR) in National Registers are loosening and pain. Cementless UKR was introduced to address loosening and was found, in small randomised studies, to have better radiographic fixation than Cemented UKR. Although non-significant these studies also suggested the clinical outcome was better with cementless. The aim of this larger study was to compare the pain and function of cementless and cemented UKR at five years. Methods. 263 Cemented and 266 Cementless UKR of identical design, implanted by four high volume surgeons for the same indications, were reviewed by independent physiotherapists at five years. Revision, re-operation, Oxford Knee Score (OKS), American Knee Society score (AKSS) and EQ-5D were assessed. Two pain specific scores were also used: Pain Detect (PD) and Intermittent and Constant Osteoarthritis Pain (ICOAP). The pain scores were normalised onto a scale of 0 to 100 with 100 being the best. The cemented cohort was mainly implanted before the cementless, although there was considerable overlap. To explore whether differences were due to progressive improvement in surgical practice with time each cohort was divided into early and late subgroups. Results. Pre-operatively there were no differences between the devices in patient demographics or scores. At 5 years there were no differences in revision rate (0.8%), re-operation rate (2.2%) or medical complication rate (4%). The Cementless had significantly (p<0.05) better OKS (43 v 41), AKSS and EQ5D. There were significantly (p=0.03) fewer cementless cases with unexplained pain (2.3% v 6%). The cementless had significantly (p<0.002), less ‘strongest’ (84 v 76) and ‘average’ (90 v 85) pain as assessed by PD and less chronic (97 v 92) and intermittent (93 v 86) pain as assessed by ICOAP. Subgroup analysis found no significant differences in outcome between the early and late subgroups within the cohorts, whereas there were significant differences in outcomes between the late subgroup of the cemented cohort and the early subgroup of the cementless cohort. Discussion and Conclusion. Almost all outcome scores were significantly better following cementless compared to cemented UKR, suggesting that the cementless is better than cemented. However, as the cemented cases were mainly implanted before the cementless, it could be the difference was due to other factors, such as surgical technique or rehabilitation, that improved with time. This is unlikely to be the case as there were no differences between the early and late subgroups within the cohorts whereas there were differences between the late subgroup of the cemented cohort and the early subgroup of the cementless cohort which were implanted at a similar time. Although the functional scores following cementless are significantly better than cemented, the differences are similar to or smaller than the minimally clinical important difference (MCID) for these scores. In contrast there is significantly less pain following the cementless and the differences tended to be greater than the MCID. This suggests that Cementless UKR is associated with appreciably less pain and slightly better function than Cemented UKR. For figures, tables, or references, please contact authors directly

Background. This article reviews four commonly used approaches to assess patient responsiveness to a treatment or therapy [Return To Normal (RTN), Minimal Important Difference (MID), Minimal Clinically Important Difference (MCID), OMERACT-OARSI (OO)], and demonstrates how each of the methods can be formulated in a multi-level modelling (MLM) framework. Methods. Data from the Arthroplasty Pain Experience (APEX) cohort study was used. Patients undergoing total hip and knee replacement completed the Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire prior to surgery and then at 3, 6 and 12 months after surgery. We compare baseline scores, change scores, and proportion of individuals defined as “responders” using traditional and multi-level model (MLM) approaches to patient responsiveness. Results. Using existing approaches, baseline and change scores are underestimated, and the variance of baseline and change scores overestimated in comparison to MLM approaches. MLM increases the proportion of individuals defined as responding in RTN, MID, and OO criteria compared to existing approaches. Using MLM with the MCID criteria reduces the number of individuals identified as responders. Conclusion. MLM improves the estimation of the standard deviation of baseline and change scores by explicitly incorporating measurement error into the model, and avoiding regression to the mean when making individual predictions. Using refined definitions of responsiveness may lead to a reduction in misclassification when attempting to predict who does and does not respond to an intervention, and clarifies the similarities between existing methods. Approvals. The APEX trials were registered as an International Standardised Randomised Controlled Trial (96095682), approved by Southampton and South West Hampshire Research Ethics Committee (09/H0504/94) and all participants provided informed written consent

Background. Chronic pain after joint replacement is common, affecting approximately 10% of patients after total hip replacement (THR) and 20% of patients after total knee replacement (TKR). Heightened generalised sensitivity to nociceptive input could be a risk factor for the development of this pain. The primary aim of this study was to investigate whether preoperative widespread pain sensitivity was associated with chronic pain after joint replacement. Methods. Data were analysed from 254 patients receiving THR and 239 patients receiving. TKR. Pain was assessed preoperatively and at 12 months after surgery using the Western Ontario and McMaster Universities Osteoarthritis Pain Scale. Preoperative widespread pain sensitivity was assessed through measurement of pressure pain thresholds (PPTs) at the forearm using an algometer. Statistical analysis was conducted using linear regression and linear mixed models, and adjustments were made for confounding variables. Results. In both the THR and TKR cohort, lower PPTs (heightened widespread pain. sensitivity) were significantly associated with higher preoperative pain severity. Lower PPTs were also significantly associated with higher pain severity at 12 months after surgery in the THR cohort. However, PPTs were not associated with the change in pain severity from preoperative to 12 months postoperative in either the TKR or THR cohort. Conclusions. These findings suggest that although preoperative widespread pressure pain sensitivity is associated with pain severity before and after joint replacement, it is not a predictor of the amount of pain relief that patients gain from joint replacement surgery, independent of preoperative pain severity. Level of Evidence. 2. Approvals. The APEX trials were registered as an International Standardised Randomised Controlled Trial (96095682), approved by Southampton and South West Hampshire Research Ethics Committee(09/H0504/94) and all participants provided informed written consent

Introduction. The pathogenesis of primary knee osteoarthritis is due to excess mechanical loading of the articular cartilage. Previous studies have assessed the impact of muscle forces on tibiofemoral kinematics and force distribution. A cadaveric study was performed to evaluate the effect of altering the moment arm of the iliotibial band (ITB) on knee biomechanics. Method. A robotic system consisting of a 6-DOF manipulator capable of measuring forces on the medial and lateral condyle of a cadaveric knee at various flexion angles and muscle forces was utilized [1]. The system measured the compartment forces at flexion angles between 0° and 30° under 3 simulated loading conditions (300N quadriceps, 100N hamstrings and: i. 0N ITB; ii. 50N ITB; iii. 100N ITB). Eight fresh frozen human cadaver knee specimens (4 males, 4 females); age range 36 – 50 years; weight range 49 – 90 kg; height range 154 – 190 cm were used in the study. The ITB and associated lateral soft tissue structures were laterally displaced from the lateral femoral condyle by fixing a metal implant (like in Figure 1) to the distal lateral femur. Mechanical loads on the medial and lateral compartments (with and without the implant) were measured using piezoelectric pressure sensors. Results. For each specimen, lateral displacement of the ITB due to the implant was measured (15 – 20 mm). The % average unloading of the medial compartment for all the specimens ranged from 34% – 65% (Figure 2). Also observed was a concomitant increase in lateral compartment load. Medial unloading was even observed with no ITB force (0N) which indicates a role for other lateral structures attached to the ITB in unloading the medial compartment [2]. In addition, under these non-weight bearing conditions, on average, there was an increase in valgus tibial angulation through the flexion range. Discussion. Increasing mechanical leverage of muscles across a joint is accomplished in nature through sesamoid bones (e.g., patella) which increase the muscle moment arm. By increasing the moment arm of the ITB and lateral soft tissue structures by lateralizing these structures, our model demonstrates a 34–65% unloading of the medial compartment. Studies of knee braces and weight loss have shown that reducing mechanical load on the medial condyle by even 10% provides clinical benefits in terms of reduced pain and improved function. Based on the results of this study, unloading the medial compartment by displacing the ITB laterally may be a means of treating medial osteoarthritis (Figure 3). A prospective, multi-center, non-randomized, open label, single-arm study is currently underway to establish the safety and efficacy of providing medial osteoarthritis pain relief by displacing the ITB using Cotera, Inc.'s Latella™ Knee Implant

Background. The trapeziometacorpal joint (TMJ) of the thumb is a common site of primary osteoarthritis. Pain, crepitis and instability secondary to subluxation are common symptoms associated with TMJ arthritis. Conservative therapy help to control symptoms however with time, many patients progress with pain, deformity and functional limitation. The goals of operative intervention are to restore stability and strength, decrease pain and to provide a functional range of motion. Francobal-prosthesis may fulfil these criterions. Technique. We implanted the prosthesis through a dorso-radial straight longitudinal or slightly curved skin incision. A dorsal capsulotomy is performed and at this step adduction deformity should be addressed. An osteotomy of the proximal surface of the first metacarpal is made perpendicular to the long axis of the medullary cavity followed by reaming of the medullary cavity and then a trial fit. This is followed by preparation of the trapezium including removing any osteophytes, drilling of a cavity. Dental burs may be used at this step to deepen the cavity. The process of cementation started by cementation of the cup with its opening neutral to the joint surface, and if there is any muscle tension, bone is removed from the metacarpal before the metacarpal component is cemented. Reduction is achieved by snapping. The capsule and wound are closed and the thumb is immobilised in an adduction splint for ten days. Results. Results showed marked improvement of pain in many patients with high rate of satisfaction. No restriction of movement or instability was observed. In some cases, loosening of the shaft was noticed. However, this does not affect the overall function. Discussion. De La Caffini`re-prosthesis presents one of the operative options in the management of trapeziometacorpal joint (TMJ). Arthritis, however, this operation is recommended only in selective cases where skaphoid-trapezium-trapezoid (STT) joints are not involved

Purpose: To quantify the amount of agreement among UK orthopaedic surgeons regarding the natural history and treatment including surgery and rehabilitation of the ACL deficient knee. Methods: Following from Marx et al (Arthroscopy. 2003 Sep;19(7):762–70) a surgeon mail survey was performed to 360 members of the British Association for Surgery of the Knee. Surgeons who had treated ACL deficient patients in the last year were asked to complete the survey. Thirty questions were included to determine the surgeons’ opinions regarding the natural history of the ACL deficient knee, indications for surgery and patient selection, surgical treatment and rehabilitation. Clinical agreement was present when 80% or more agreed on the same response option. Results: 150 surgeons in total responded to the survey; 121 had treated ACL deficient patients in the past year. The mean age was 48.9 years and 83% considered their practice to be a subspecialty in knee surgery. The mean number of ACL reconstructions performed in the past year was 41 (range 1–210). Clinical agreement was present for 12 (40%) of the 30 questions; surgeons disagreed on 18 (60%) of the questions. Conclusions: Similar significant variation regarding the management of ACL injuries is seen among members of BASK as among members of the American Academy of Orthopaedic Surgeons (AAOS). Clinical disagreement included whether ACL deficient patients can participate in all recreational sporting activities, that ACL reconstruction reduces the rate of arthrosis in the ACL deficient knee, and the use of bracing in non-surgically treated ACL deficient knees. Surgeons also disagreed about age, open growth plates, radiographic evidence of osteoarthrosis, pain, and, repairable and unrepairable meniscal tears in ACL deficient patients

Purpose: To quantify the amount of agreement among UK orthopaedic surgeons regarding the natural history and treatment including surgery and rehabilitation of the ACL deficient knee. Methods: Following from Marx et al (Arthroscopy. 2003 Sep;19(7):762–70) a surgeon mail survey was performed to 360 members of the British Association for Surgery of the Knee. Surgeons who had treated ACL deficient patients in the last year were asked to complete the survey. Thirty questions were included to determine the surgeons’ opinions regarding the natural history of the ACL deficient knee, indications for surgery and patient selection, surgical treatment and rehabilitation. Clinical agreement was present when 80% or more agreed on the same response option. Results: 150 surgeons in total responded to the survey; 121 had treated ACL deficient patients in the past year. The mean age was 48.9 years and 83% considered their practice to be a subspecialty in knee surgery. The mean number of ACL reconstructions performed in the past year was 41 (range 1–210). Clinical agreement was present for 12 (40%) of the 30 questions; surgeons disagreed on 18 (60%) of the questions. Conclusions: Similar significant variation regarding the management of ACL injuries is seen among members of BASK as among members of the American Academy of Orthopaedic Surgeons (AAOS). Clinical disagreement included whether ACL deficient patients can participate in all recreational sporting activities, that ACL reconstruction reduces the rate of arthrosis in the ACL deficient knee, and the use of bracing in non-surgically treated ACL deficient knees. Surgeons also disagreed about age, open growth plates, radiographic evidence of osteoarthrosis, pain, and, repairable and unrepairable meniscal tears in ACL deficient patients

Aims

We assessed the long-term outcomes of a large cohort of patients who have undergone a periacetabular osteotomy (PAO), and sought to validate a patient satisfaction questionnaire for use in a PAO cohort.

Background. Osteoarthritis (OA) pain treatment has limitations in terms of serious adverse effects and low efficacy. We aimed to evaluate efficacy and safety of naproxen sodium/codeine phosphate combination in these patients. Methods. In this prospective, randomised, double blind, placebo controlled clinical trial, 135 patients with osteoarthritis, who were 40–65 years; applied to our institution's orthopaedics outpatient clinic; had grade 1, 2, or 3 primary osteoarthritis diagnosed in last 1 year; and had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score≥40, and Visual Analogue Scale score≥40, were enrolled. Subjects were randomised (1:1) to placebo (n= 67) or combination (n= 68) arms, in which 550 mg naproxen sodium/30mg codeine phosphate was given orally twice a day for 7 days. Rescue medicine was 500 mg paracetamol (max= 6 tablets/day). Demographic characteristics, medical history, adverse events, VAS and WOMAC scores were collected in study visits performed within 10 days. The study was approved by local institutional ethics committee and written informed consents were obtained from all participants. Results. Patients were evenly matched in both arms. The mean age was 52.3±6.6 years (89.7% female). WOMAC and VAS scores decreased significantly within each group (p<0.001 for all). For the study group (n=43) the mean (+ SD) and median (min-max) VAS Score was −29.8 (+21.0) and −30 (−70−0), respectively. In contrast, for the control group (n=36) the mean and median (min-max) VAS Score was −16.1 (+24.4) and −12.5 (−65−40), respectively. WOMAC score was decreased more in combination group (p= 0.044). Changes in VAS scores between visits were significantly different (more in combination receivers) between groups (p= 0.018). Ratio of patients requiring no rescue medicine was higher among combination receivers than controls (64.8% vs. 35.2%, respectively). Most common adverse events were constipation, dyspepsia, and somnolence; no fatality was encountered. Conclusions. Naproxen sodium/codeine phosphate combination is effective and safe in osteoarthritis patients. Level of Evidence. Level 1

Aims

The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms.

Aims

To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope.

Patient-reported outcome measures (PROMs) are being used increasingly in total knee arthroplasty (TKA). We conducted a systematic review aimed at identifying psychometrically sound PROMs by appraising their measurement properties. Studies concerning the development and/or evaluation of the measurement properties of PROMs used in a TKA population were systematically retrieved via PubMed, Web of Science, Embase, and Scopus. Ratings for methodological quality and measurement properties were conducted according to updated COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Of the 155 articles on 34 instruments included, nine PROMs met the minimum requirements for psychometric validation and can be recommended to use as measures of TKA outcome: Oxford Knee Score (OKS); OKS–Activity and Participation Questionnaire (OKS-APQ); 12-item short form Knee Injury and Osteoarthritis Outcome (KOOS-12); KOOS Physical function Short form (KOOS-PS); Western Ontario and McMaster Universities Arthritis Index-Total Knee Replacement function short form (WOMAC-TKR); Lower Extremity Functional Scale (LEFS); Forgotten Joint Score (FJS); Patient’s Knee Implant Performance (PKIP); and University of California Los Angeles (UCLA) activity score. The pain and function subscales in WOMAC, as well as the pain, function, and quality of life subscales in KOOS, were validated psychometrically as standalone subscales instead of as whole instruments. However, none of the included PROMs have been validated for all measurement properties. Thus, further studies are still warranted to evaluate those PROMs. Use of the other 25 scales and subscales should be tempered until further studies validate their measurement properties.

Cite this article: Bone Joint Res 2021;10(3):203–217.

Aims

Neither a surgeon’s intraoperative impression nor the parameters of computer navigation have been shown to be predictive of the outcomes following total knee arthroplasty (TKA). The aim of this study was to determine whether a surgeon, with robotic assistance, can predict the outcome as assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain (KPS), one year postoperatively, and establish what factors correlate with poor KOOS scores in a well-aligned and balanced TKA.

Aims

The primary aim of this study was to assess whether pain in the contralateral knee had a clinically significant influence on the outcome of total knee arthroplasty (TKA) according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Secondary aims were to: describe the prevalence of contralateral knee pain; identify if it clinically improves after TKA; and assess whether contralateral knee pain independently influences patient satisfaction with their TKA.