Joint load reduction is effective for alleviating OA pain. Treatment options for joint unloading include braces and HTO, both of which may be impractical for patients. The purpose of the present study was to examine the biomechanical rationale of a practical, partial unloading implant (KineSpring® System, Moximed) for knee OA. Device durability was tested by cyclically loading bone-implant constructs through simulated use for at least 10 million cycles. Joint load reduction with the implant was quantified by measuring changes in medial and lateral knee compartment loads generated by cadaver knees in simulated gait. Safety of the device was tested by 3, 6, and 12 month follow-up of implants in an in vivo ovine model. Surgical technique and device safety and efficacy were assessed in human clinical studies. The unloader device survived over 15 million cycles of simulated use without failure. In the simulated gait cadaver model, the unloading device significantly reduced medial compartment (29 ± 13 lbs, p<0.05) and overall knee joint loads during the stance phase of gait testing but did not significantly increase lateral compartment loading. Chronic ovine implants demonstrated good tolerance of the implant with normal wound healing and secure device fixation. Clinical experience (n=49) demonstrated uneventful device implantation. Unlike HTO, the implantation technique for the unloader does not alter joint alignment. This surgical technique avoids removal of bone, ligament, and cartilage, thus preserving future primary arthroplasty, if required. Early-term clinical experience also demonstrates good outcomes for patients, the earliest of whom are beyond 2.6 years with the implant. This unloading device offers a practical and attractive treatment option for patients with medial knee OA: load reduction without load transfer, durability, preservation of downstream treatment options, safety, and early-term efficacy.
Opening wedge high tibial osteotomy (OWHTO) is a treatment option for medial compartment osteoarthritis of the knee in the young active adult. Limited evidence exists in the literature regarding return to activities following OWHTO. We performed a retrospective study of local patients who underwent OWHTO from 2005 – 2012 assessing post-operative return to sporting function. Patients with additional knee pathology, surgery or alternative issues affecting activity were excluded. 110 patients met inclusion criteria, 75 were successfully contacted. Mean improvement in pain score = 4.8/10 (95%CI 4.2 to 5.4, p<0.01). Mean pre-operative KOS-SAS score = 0.5/2, mean post-operative KOS-SAS score = 1.1/2, mean change in KOS-SAS score following OWHTO = 0.6 (95% CI 0.5 to 0.7, p<0.01). Mean pre-morbid Tegner score = 5.9/10, pre-operative = 2.7/10, post-operative = 4.2/10. Mean change in Tegner score following OWHTO = 1.5 (95% CI 1 to 1.9, p<0.01). Following OWHTO 25% of patients achieved pre-morbid Tegner scores. Patient BMI, age, type of implant or graft used had no significant effect on outcome. OWHTO can temporarily improve pain, activity and sporting levels in young patients with isolated medial compartment knee OA. Return to pre-morbid activity levels and even high level sports function is possible although not the norm.
Unicompartmental knee arthroplasty (UKA) is the preferred treatment for anterior medial knee osteoarthritis (OA) owing to the rapid postoperative recovery. However, the risk factors for UKA failure remain controversial. The clinical data of Oxford mobile-bearing UKAs performed between 2011 and 2017 with a minimum follow-up of five years were retrospectively analyzed. Demographic, surgical, and follow-up data were collected. The Cox proportional hazards model was used to identify the risk factors that contribute to UKA failure. Kaplan-Meier survival was used to compare the effect of the prosthesis position on UKA survival.Aims
Methods
The management of disabling osteoarthritis of the knee following ipsilateral femoral fracture malunion can be difficult. This study presents the results of seven such patients treated by femoral shaft osteotomy in the fracture region and with locked intramedullary nail fixation. Seven patients with malunited femoral shaft fractures presenting with knee symptoms between 1992 and 1999 were treated by femoral shaft osteotomy. The presenting knee symptoms and function were graded from 0–4. All patients underwent open femoral shaft osteotomy at the apex of the deformity and fixation was by locked intramedullary nailing. The patients were followed up until osteotomy union and reviewed clinically and radiologically with particular emphasis on knee symptoms and function. There were six males and one female. The mean age at presentation was 48 years and the mean time from fracture 28 years. (Range 13–37 years). The mean knee alignment angle preoperatively was 5 degrees varus (range 0–12). The mean time to osteotomy union was 28 months. The mean knee alignment angle postoperatively was 2 degrees valgus. (range 5 degrees varus-5 degrees valgus). Five of the seven patients reported excellent pain relief and functional improvement. One patient had serious vascular complication and now has a stiff but pain free knee. One patient who presented with very advanced OA has since undergone an uncomplicated total knee arthroplasty after osteotomy union and nail removal. These patients presenting with severe disability at an age that would be too young for total knee replacement are difficult to manage. Five out seven patients in these series are symptomatically improved to return to their old occupation. The knee replacement has been delayed in these by a mean of five years. Their eventual knee replacement is likely to have been made less difficult as a result of alignment correction.
Cartilage diseases have a significant impact on the patient's quality of life and are a heavy burden for the healthcare system. Better understanding, early detection and proper follow-up could improve quality of life and reduce healthcare related costs. Therefore, the aim of this study was to evaluate if difference between osteoarthritic (OA) and non-osteoarthritic (non-OA) knees can be detected quantitatively on cartilage and subchondral bone levels with advanced but clinical available imaging techniques. Two OA (mean age = 88.3 years) and three non-OA (mean age = 51.0 years) human cadaveric knees were scanned two times. A high-resolution peripheral quantitative computed tomography (HR-pQCT) scan (XtremeCT, Scanco Medical AG, Switzerland) was performed to quantify the bone microstructure. A contrast-enhanced clinical CT scan (GE Revolution Evo, GE Medical Systems AG, Switzerland) was acquired with the contrast agent Visipaque 320 (60 ml) to measure cartilage. Subregions dividing the condyle in four parts were identified semi-automatically and the images were segmented using adaptive thresholding. Microstructural parameters of subchondral bone and cartilage thickness were quantified. The overall cartilage thickness was reduced by 0.27 mm between the
Intra-articular injection is a common way to deliver biologics to joints, but their effectiveness is limited by rapid clearance from the joint space. This barrier can be overcome by genetically modifying cells within the joint such that they produce anti-arthritic gene products endogenously, thereby achieving sustained, therapeutic, intra-articular concentrations of the transgene products without re-dosing. A variety of non-viral and viral vectors have been subjected to preclinical testing to evaluate their suitability for delivering genes to joints. The first transfer of a gene to a human joint used an ex vivo protocol involving retrovirally transduced, autologous, synovial fibroblasts. Recent advances in vector technology allow in vivo delivery using adeno-associated virus (AAV). We have developed an AAV vector encoding the interleukin-1 receptor antagonist (AAV.IL-1Ra) for injection into joints with osteoarthritis (OA). It showed efficacy and safety in equine and rat models of OA, leading to a recently-completed, investigator-initiated, Phase I, dose-escalation clinical trial in 9 subjects with mid-stage
The knee joint has also a periarticular adipose tissue, which is known as Hoffa's fat pad (IPFP). IPFP has a dual function in the joint it reduces the concentration of Nitric Oxide, the release of glycosaminoglycans and the expression of MMP1 in the cartilage, but it also contains MSC and macrophages. Our hypothesis is that synovial fluid contains elements, not all of which are understood, which act as messengers and alter the “homeostasis” of the knee and the metabolism of all the cellular components of the joint, including the MSC of Hoffa's fat pad, thus making them another piece in the puzzle as far as
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
Aims. The primary aim of the study was to perform an analysis to identify the cost per quality-adjusted life-year (QALY) of robot-assisted unicompartmental knee arthroplasty (rUKA) relative to manual total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) for patients with isolated medial compartment osteoarthritis (OA) of the knee. Secondary aims were to assess how case volume and length of hospital stay influenced the relative cost per QALY. Patients and Methods. A Markov decision analysis was performed, using known parameters for costs, outcomes, implant survival, and mortality, to assess the cost-effectiveness of rUKA relative to manual TKA and UKA for patients with isolated medial compartment
Aims. Many patients undergoing total knee arthroplasty (TKA) have severe osteoarthritis (OA) in both knees and may consider either simultaneous or staged bilateral TKA. The implications of simultaneous versus staged bilateral TKA for return to work are not well understood. We hypothesized that employed patients who underwent simultaneous bilateral TKA would have significantly fewer days missed from work compared with the sum of days missed from each operation for patients who underwent staged bilateral TKA. Methods. The prospective arthroplasty registry at the Hospital for Special Surgery was used. Baseline characteristics and patient-reported outcome scores were evaluated. We used a linear regression model, adjusting for potential confounding variables including age, sex, preoperative BMI, and type of work (sedentary, moderate, high activity, or strenuous), to analyze time lost from work after simultaneous compared with staged bilateral TKA. Results. We identified 152 employed patients who had undergone simultaneous bilateral TKA and 61 who had undergone staged bilateral TKA, and had completed the registry’s return to work questionnaire. The simultaneous group missed a mean of 46.2 days (SD 29.1) compared with the staged group who missed a mean total of 68.0 days of work (SD 46.1) when combining both operations. This difference was statistically significant (p < 0.001). In multivariate mixed regression analysis adjusted for age, sex, BMI, American Society of Anesthesiologists status, and type of work, the simultaneous group missed a mean of 16.9 (SD 5.7) fewer days of work compared with the staged group (95% confidence interval 5.8 to 28.1; p = 0.003). Conclusion. Employed patients undergoing simultaneous bilateral TKA missed a mean of 17 fewer days of work as a result of their surgical treatment and rehabilitation compared with those undergoing staged bilateral TKA. This information may be useful to surgeons counselling employed patients with bilateral
Aims. Recent studies have suggested that corticosteroid injections into the knee may harm the joint resulting in cartilage loss and possibly accelerating the progression of osteoarthritis (OA). The aim of this study was to assess whether patients with, or at risk of developing, symptomatic osteoarthritis of the knee who receive intra-articular corticosteroid injections have an increased risk of requiring arthroplasty. Methods. We used data from the Osteoarthritis Initiative (OAI), a multicentre observational cohort study that followed 4,796 patients with, or at risk of developing, osteoarthritis of the knee on an annual basis with follow-up available up to nine years. Increased risk for symptomatic OA was defined as frequent knee symptoms (pain, aching, or stiffness) without radiological evidence of OA and two or more risk factors, while OA was defined by the presence of both femoral osteophytes and frequent symptoms in one or both knees. Missing data were imputed with multiple imputations using chained equations. Time-dependent propensity score matching was performed to match patients at the time of receving their first injection with controls. The effect of corticosteroid injections on the rate of subsequent (total and partial) knee arthroplasty was estimated using Cox proportional-hazards survival analyses. Results. After removing patients lost to follow-up, 3,822 patients remained in the study. A total of 249 (31.3%) of the 796 patients who received corticosteroid injections, and 152 (5.0%) of the 3,026 who did not, had knee arthroplasty. In the matched cohort, Cox proportional-hazards regression resulted in a hazard ratio of 1.57 (95% confidence interval (CI) 1.37 to 1.81; p < 0.001) and each injection increased the absolute risk of arthroplasty by 9.4% at nine years’ follow-up compared with those who did not receive injections. Conclusion. Corticosteroid injections seem to be associated with an increased risk of knee arthroplasty in patients with, or at risk of developing, symptomatic
Aims. This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Methods. Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs. Results. We detected 1,212 DEmRNAs and 49 DElncRNAs in
The aim of this study was to examine the loading
of the other joints of the lower limb in patients with unilateral osteoarthritis
(OA) of the knee. We recruited 20 patients with no other symptoms
or deformity in the lower limbs from a consecutive cohort of patients
awaiting knee replacement. Gait analysis and electromyographic recordings were
performed to determine moments at both knees and hips, and contraction
patterns in the medial and lateral quadriceps and hamstrings bilaterally.
The speed of gait was reduced in the group with OA compared with
the controls, but there were only minor differences in stance times
between the limbs. Patients with
There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA. A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers. During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an
Aims. The patient-acceptable symptom state (PASS) is a level of wellbeing, which is measured by the patient. The aim of this study was to determine if the proportion of patients who achieved an acceptable level of function (PASS) after medial unicompartmental knee arthroplasty (UKA) was different based on the status of the anterior cruciate ligament (ACL) at the time of surgery. Methods. A total of 114 patients who underwent UKA for isolated medial osteoarthritis (OA) of the knee were included in the study. Their mean age was 65 years (SD 10). No patient underwent a bilateral procedure. Those who had undergone ACL reconstruction during the previous five years were excluded. The Knee injury Osteoarthritis Outcome Score Activities of Daily Living (KOOS ADL) function score was used as the primary outcome measure with a PASS of 87.5, as described for total knee arthroplasty (TKA). Patients completed all other KOOS subscales, Lysholm score, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Veterans Rand 12-item health survey score. Failure was defined as conversion to TKA. Results. Survivorship at ten years was 97% in both the ACL-deficient and ACL-intact groups. The mean survival was 16.1 years (95% confidence interval (CI) 15.3 to 16.8) for the ACL-deficient group and 15.6 years (95% CI 14.8 to 16.361) for the ACL-intact group (p = 0.878). At a mean of nine years (SD 3.5) in the ACL-deficient group, 32 patients (87%) reached the PASS for the KOOS ADL. In the ACL-intact group, at a mean of 8.6 years (SD 3) follow-up, 63 patients (85%) reached PASS for the KOOS ADL. There was no significant difference in the percentage of patients who reached PASS for all KOOS subscales and Lysholm between the two groups. Conclusion. PASS was achieved in 85% of all UKAs for KOOS ADL, similar to reports for TKA. Fixed-bearing, medial, non-robotically-assisted UKA resulted in 97% survival at ten years in both the ACL-deficient and ACL-intact groups. There was no significant difference in all outcomes between the two groups. Understanding PASS will allow better communication between surgeons and patients to improve the surgical management of patients with single compartment
Aims. The aim of this study was to estimate time to arthroplasty among patients with hip and knee osteoarthritis (OA), and to identify factors at enrolment to first-line intervention that are prognostic for progression to surgery. Methods. In this longitudinal register-based observational study, we identified 72,069 patients with hip and knee OA in the Better Management of Patients with Osteoarthritis Register (BOA), who were referred for first-line OA intervention, between May 2008 and December 2016. Patients were followed until the first primary arthroplasty surgery before 31 December 2016, stratified into a hip and a knee OA cohort. Data were analyzed with Kaplan-Meier and multivariable-adjusted Cox regression. Results. At five years, Kaplan-Meier estimates showed that 46% (95% confidence interval (CI) 44.6 to 46.9) of those with hip OA, and 20% (95% CI 19.7 to 21.0) of those with knee OA, had progressed to arthroplasty. The strongest prognostic factors were desire for surgery (hazard ratio (HR) hip 3.12 (95% CI 2.95 to 3.31), HR knee 2.72 (95% CI 2.55 to 2.90)), walking difficulties (HR hip 2.20 (95% CI 1.97 to 2.46), HR knee 1.95 (95% CI 1.73 to 2.20)), and frequent pain (HR hip 1.56 (95% CI 1.40 to 1.73), HR knee 1.77 (95% CI 1.58 to 2.00)). In hip OA, the probability of progression to surgery was lower among those with comorbidities (e.g. ≥ four conditions; HR 0.64 (95% CI 0.59 to 0.69)), with no detectable effects in the knee OA cohort. Instead, being overweight or obese increased the probability of
Several attempts have been made to treat medial compartment
We report on the 5 year results of a randomized study comparing TKR performed using conventional instrumentation versus electromagnetic computer-assisted surgery. This study analysed patient reported outcome measures (PROMs) at 5 years utilising the American Knee Society Score (AKSS), Oxford Knee Score (OKS), the Short Form 36 score and range of motion (ROM). Of the 200 patients enrolled 125 completed 5 year follow up, 62 in the navigated group and 63 in the conventional group. There were 28 deceased patients, 29 withdrawals and 16 lost to follow-up. There was improvement in clinical function in most PROMs from 1-5 year follow up across both groups. OKS improved from a mean of 26.6 (12–55) to 35.1 (5–48). AKSS increased from 75.3 (0–100) to 78.4 (−10–100), SF36 from 58.9 (2.5–100) to 53.2 (0–100). ROM improved by an average 7 degrees from 110 degrees to 117 degrees (80–135). There was no statistically significant difference in PROMs between the groups at 5 years. Patients undergoing revision surgery were identified from the dataset and global PACS. There were no revisions within 5 years in the navigated group and 3 revisions in the conventional group, two for infection and one for mid-flexion instability, giving an all cause revision rate of 3.06% at 5 years for this group. There appears to be no significant advantage in clinical function for patients undergoing TKR for