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Objective: Knee Osteoarthritis (KOA) is a debilitating degenerative joint ailment afflicting millions of patients. Numerous studies have assessed the efficacy of mesenchymal stem cells (MSCs) derived from various sources for KOA treatment, yet direct comparisons are scarce and inconsistent. Furthermore, network meta-analysis (NMA) conclusions require updating, while the safety of MSCs therapy remains contentious. This study evaluates therapeutic approaches involving MSCs from different sources in patients with KOA through randomized controlled trials (RCTs) and cohort studies. The objective is to compare the effectiveness and safety of MSCs strategies from various sources for KOA treatment., Methods: A systematic literature review was conducted to identify RCTs and cohort studies comparing different sources of MSCs in KOA patients. A randomized effects network meta-analysis was used to concurrently evaluate both direct and indirect comparisons across all protocols., Results: The NMA included 16 RCTS and reported 1005 participants. Adipose-derived mesenchymal stem cells (AD-MSCs) were the most effective treatment, showing significant improvements in the Visual Analogue Scale (VAS), the Short Form 36 (SF-36 scale), the International Knee Literature Committee Knee Evaluation Scale (IKDC subjective scores), and the Knee Injury and OA Outcome Score (KOOS). The probabilities are P = 85.3, P = 70.5, P = 88 and P = 87, respectively. Compared with placebo, AD-MSCs resulted in a VAS Score (SMD 0.97; 95%CI 0.37, 1.57), IKDC subjective scores (SMD -0.71; 95%CI -1.20, -0.21) was significantly reduced. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) showed significant improvements in the University of Western Ontario and McMaster University OA (WOMAC) (P = 91.4). Compared with placebo, UC-MSCs had a higher WOMAC Score (SMD 1.65; 95%CI 0.27, 3.03) and ranked first. Compared with MSCs, placebo emerged as the safer option (P = 74.9), with a notable reduction in AEs associated with HA treatment (RR 0.77; 95%CI 0.61, 0.97). AD-MSCs were found to have the least favorable impact on AEs with a probability of P = 13.3., Conclusions: This network meta-analysis established that MSCs offer pain relief and enhance various knee scores in KOA patients compared to conventional treatment. It also identifies other therapeutic avenues warranting further exploration through high-quality studies. Nonetheless, it underscores the necessity to emphasize the potential complications and safety concerns associated with MSCs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control ( n = 12), L0.3: 0.3 mg/kg/day ( n = 15), L1.0: 1.0 mg/kg/day ( n = 14), and L3.0: 3.0 mg/kg/day ( n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

Introduction: it is estimated that 302 million people worldwide are affected by osteoarthritis, corresponding to 60% osteoarthritis (OA) of the knee, which responsible 80% of disability in older adults, hence the importance of the association of the sign with the early inflammatory process in OA., Objective: to determine the association of digital pressure sign in patients with and without osteoarthritis of the knee., Material and Methods: this was an observational, comparative cross-sectional study, carried out in patients with and without a diagnosis of knee OA, to whom the digital pressure sign was determined. The sample was calculated with the formula for two proportions, obtaining a total of 40 participants per group, obtained by non-probabilistic sampling for convenience. The statistical analysis included frequencies, percentages, 2 and OR. The bioethics regulations in force were respected., Results: the study included 80 participants, with a median age of 48.9 years (RQI 46-53.7), 73.1% were predominantly female sex (38), and a statistically significant association was found between patients with OA and the presence of digital pressure sign, 2 4.62 and p value = 0.41, OR of 2.65., Conclusions: the presence of digital pressure sign increases the probability of having OA 2.65 times more.

Background: End-stage osteoarthritis of the knee (OAK) is often treated by total knee arthroplasty (TKA). This intervention can significantly improve quality of life. However, many patients are dissatisfied with the outcome of surgery. One of the factors related to dissatisfaction is the of lack integration of patients' preferences, habits and values that are not addressed by physicians. To develop realistic expectations, affected patients need evidence-based information. Our aim was to explore the information needs of patients with OAK to support the development of decision aids and consent forms to promote informed decision-making. Additionally, we investigated whether the information needs during the Covid-19 pandemic differ from those before the pandemic., Methods: The qualitative research design included a social media analysis of Facebook groups. Facebook groups were selected according to the following criteria: Thematic relevance, English or German language, at least one new post per week, from period before and after the start of the Covid-19 pandemic in March 2020. Thematically relevant group posts were analysed according to the content-structuring content analysis of Kuckartz using MaxQDA., Results: Out of 448 identified Facebook groups, we screened seven for relevant posts and a total of 77 posts out of 6 groups were selected. The following eight categories were derived during the coding process: access to health care, disease information, TKA indication and contraindication, TKA outcome and quality of life, information needs regarding conservative therapy, strain, attitude towards TKA and attitude towards conservative therapy. The analysis showed that patients with OAK need information about the benefits and risks of TKA and conservative therapies., Conclusion: This study provides information on the information needs of patients with OAK in order to decide between TKA or conservative therapy. Patients need information about treatment options in due consideration of their immediate living situation to be reliably able to assess potential outcomes. Such Information about TKA should enable patients to assess the individual prognosis with comprehensible and relevant outcome measures. Also, they should be formulated with the living environment of the patients in mind and be linked to possible fears and negative previous experiences with treatments., (© 2024. The Author(s).)

Objective: Meta-analysis of the comparative efficacy of Oxford unicompartmental knee arthroplasty (OUKA) for the treatment of spontaneous osteonecrosis of the knee (SONK) and medial knee osteoarthritis (MKOA)., Methods: A computerized search was conducted for literature related to OUKA treatments of SONK and MKOA across various databases, including the China National Knowledge Infrastructure, WAN FANG, VIP, SinoMed, Cochrane Library, PubMed, Embase, and Web of Science, covering the period from each database's inception to September 2023. Literature screening, quality assessment and data extraction were performed according to the inclusion and exclusion criteria. After extracting the literature data, RevMan 5.4 software was applied to analyse the postoperative knee function score, postoperative knee mobility, postoperative pain, bearing dislocation rate, aseptic loosening, postoperative progression of posterolateral arthritis, and revision rate., Result: A total of 9 studies were included, including 6 cohort studies and 3 matched case‒control studies. A total of 1544 knees were included, including 183 in the SONK group and 1361 in the MKOA group. The meta-analysis results showed that the SONK and MKOA groups showed a significant difference in postoperative knee function scores [MD = 0.16, 95% CI (- 1.20, 1.51), P = 0.82], postoperative knee mobility [MD = - 0.05, 95% CI (- 1.99. 1.89), P = 0.96], postoperative pain [OR = 0.89, 95% CI (0.23, 3.45), P = 0.87], rate of bearing dislocation [OR = 1.28, 95% CI (0.34, 4.81), P = 0.71], aseptic loosening [OR = 2.22, 95% CI (0.56, 8.82), P = 0.26], postoperative posterolateral arthritis progression [OR = 2.14, 95% CI (0.47, 9.86), P = 0.33], and revision rate [OR = 1.28, 95% CI (0.53, 3.04), P = 0.58] were not statistically significant., Conclusion: OUKA treatment with SONK and MKOA can achieve similar satisfactory clinical results., (© 2024. The Author(s).)

Background/aim: Osteoarthritis is one of the most common degenerative conditions that causes pain, stiffness, and decreased functionality. The management of knee osteoarthritis necessitates collaboration among specialists from different disciplines, considering the primary clinical manifestations and functional level of the disease. The aim of this study was to highlight the disparities in postoperative outcomes between knee arthroplasty procedures with and without non-steroidal anti-inflammatory drugs (NSAIDs). The study specifically focuses on the immediate advantages and outcomes observed at the 6-month milestone., Patients and Methods: This study followed 713 patients who were randomly divided into two groups: a group that did not receive non-steroidal anti-inflammatory drugs (N-NSAIDs) consisting of 394 patients, and a group that received non-steroidal anti-inflammatory drugs (NSAIDs) comprising 319 patients. The study spanned a duration of 5 years (2018-2022), with patients being followed and evaluated for up to 6 months after the surgery., Results: It was observed that, from a therapeutic standpoint, the use of injectable treatments decreased. Significantly better differences were recorded in the N-NSAIDs group regarding return to pre-osteoarthritis activities at 6 months and reduced or absent night pain at 3 months (p<0.05)., Conclusion: Statistically significant improvements were observed in the N-NSAIDs group concerning the ability to resume pre-osteoarthritis activities within 6 months, as well as a reduction or absence of nighttime pain within 3 months., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: A double level osteotomy (DLO) may be indicated in patients with genu varum when the deformity involves both the tibia and femur. These patients, who are often young and active, have a high functional demand and hope for a rapid return to sport. The purpose of our study was to assess return to sport and functional outcomes following DLO for symptomatic genu varum., Materials and Methods: A total of 40 patients (mean age 45.5±2 years) who underwent a DLO between 2018 and 2020, performed in 2 different hospitals, were reviewed after a minimum follow-up of 1-year. The mean initial varus was 11±2°. The type of sport and frequency of participation (UCLA activity score) as well as time to return to sport and level of activity recovered were defined as the primary endpoints. Functional scores were also assessed with the knee injury and osteoarthritis outcome score (KOOS)., Results: At the last follow-up, 87.5% (n=35) of patients reported that they had returned to sport. The mean time to return to sport was 6±1 months with a significant difference (p<0.001) between the pre- and postoperative UCLA activity scores. There was a strong correlation between the presence of a joint line obliquity >3° and decreased functional outcomes (p<0.0001). The overall KOOS score improved (p<0.001) by a mean of 38.6 points after the correction. The 8 lateral cortical fractures (Takeuchi type I and II) and the 2 medial cortical fractures (Nakayama type 1) that were found had no impact on functional outcomes (p>0.05)., Conclusion: Our findings demonstrated that DLO provided rapid return to sport, thus making it possible to meet the functional demands and expectations of patients., Level of Evidence: IV; Retrospective study., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Knee osteoarthritis (KOA) is a high-priority problem among the aging population. While exercise has been shown to be beneficial in management of the disease, scalable and low-cost interventions to improve exercise in this population are lacking. Recent controversy over the value of corticosteroid injections for palliation has also arisen. Therefore, we designed a randomized, double-blind, placebo-controlled clinical trial with a 2-period crossover design to study (1) behavioral incentives to promote exercise and (2) corticosteroid injections to reduce pain and improve function in patients with KOA when compared to lidocaine only., Methods: The study design is a pragmatic factorial and crossover randomized clinical trial. Patients with KOA who are deemed eligible by their provider to receive knee injections and are able to walk without assistive devices will be recruited from clinical practices at four sites within the Veterans Affairs (VA) Health System in the USA. In total, 220 participants will be randomized to receive social incentives with gamification (i.e., incorporation of game elements) to promote exercise and compared to controls that receive a Fitbit but no incentive. Each patient will also be assigned to receive a blinded corticosteroid injection and a lidocaine-only injection in random order. The primary outcomes are the change in average daily step counts from baseline and the change in Knee Osteoarthritis Outcome Score (KOOS) from baseline. The study team will continuously collect step count, heart rate, and sleep data using activity monitors and patient-reported outcomes using the Way to Health (WTH) platform at two four-week intervals over eight months of follow-up. Mixed effects regression incorporating all available data points will be used for analysis., Discussion: The "Marching on for Veterans with Osteoarthritis of the Knee" (MOVE-OK) trial will take a pragmatic approach to evaluate (1) whether incentives based on behaviorally enhanced gamification can improve physical activity in this patient population and (2) whether corticosteroids injections reduce pain and disability in patients with KOA. Results of this trial will help to direct clinical practice and inform management guidelines., Trial Registration: ClinicalTrials.gov NCT05035810 . Registered on 5 September 2021., (© 2022. The Author(s).)

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.

Background: Knee osteoarthritis (OA) and depression are both major health issues influencing the quality of elderly life. The aim of the present study was to explore the prevalence of depression and the factors influencing depression in community-dwelling elderly patients with OA of the knee in China., Methods: We conducted a cross-sectional descriptive study. The study included 214 participants aged 60 and older diagnosed with OA of the knee. The depression of the elderly was measured by using the Geriatric Depression Scale (GDS). Participants were asked to complete a demographic questionnaire, the GDS, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the society dimension of Arthritis Impact Measurement Scales 2 (AIMS2). In addition, the participants performed a timed up and go test (TUG) and the stair-climb test (SCT)., Results: The average age of the participants was 69.2 ± 7.63 years old, their body mass index (BMI) was 25.2 ± 3.85, and their disease duration was 5.9 ± 7.72 years. The mean total score of the GDS was 4.43 ± 2.89, and the GDS scores correlated positively with pain (r = 0.45, P < 0.001), stiffness (r = 0.40, P < 0.001), physical function (r = 0.52, P < 0.001),TUG (r = 0.35, P < 0.001), and SCT (r = 0.47, P < 0.001) and negatively with social support (r = - 0.35, P < 0.001).Analysis using multiple regression demonstrated that physical function, social support, and SCT explained 36.8% of the variance in depression., Conclusions: Our findings suggested that physical function, social support, and lower extremity strength were predictors of depressive symptoms in community-dwelling elderly people with OA of the knee. Focusing on this elderly group with increasing functional exercise, positive social interaction and support, and lower limb muscle strength training should help in the prevention of depression., (© 2022. The Author(s).)

Objective: To investigate the effects of electrical dry needling (DN) plus corticosteroid injection (CSI) on pain, physical function, and global change in patients with osteoarthritis of the knee (KOA)., Design: A prospective, single-blinded, randomized controlled trial., Setting: Pain treatment clinic., Participants: Sixty patients with KOA were randomly assigned to the electrical dry needling plus corticosteroid injection (electrical-DN+CSI) group or CSI group., Interventions: The CSI group received glucocorticoid injection only once during the trial, and the electrical-DN+CSI group received glucocorticoid injection combined with 4 sessions of electrical-DN., Main Outcomes Measures: The primary outcome was the numerical rating scale at 3 months. The secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index, the time to complete the Timed Up and Go test, and the score of the global rating of change scale at 3 months. A generalized linear mixed-effects model was used to analyze the repeated measurement data., Results: Baseline characteristics and measurements were similar in the 2 groups. The group by time interaction effect was significant for all variables (P<.05). The electrical-DN+CSI group obtained a more significant reduction in pain intensity and more significant improvement in dysfunction than the CSI group at 3 months (P<.05). The median global rating of change score for the CSI group was +3 (somewhat better), and that for the electrical-DN+CSI group was +4 (moderately better)., Conclusion: Electrical-DN therapy at myofascial trigger points combined with CSI is more effective at alleviating pain, improving dysfunction, and creating global change than CSI alone for patients with KOA. Electrical-DN may be an essential part of treatment for KOA rehabilitation., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to compare any differences in the primary outcome (biphasic flexion knee moment during gait) of robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) at one year post-surgery., Methods: A total of 76 patients (34 bi-UKA and 42 TKA patients) were analyzed in a prospective, single-centre, randomized controlled trial. Flat ground shod gait analysis was performed preoperatively and one year postoperatively. Knee flexion moment was calculated from motion capture markers and force plates. The same setup determined proprioception outcomes during a joint position sense test and one-leg standing. Surgery allocation, surgeon, and secondary outcomes were analyzed for prediction of the primary outcome from a binary regression model., Results: Both interventions were shown to be effective treatment options, with no significant differences shown between interventions for the primary outcome of this study (18/35 (51.4%) biphasic TKA patients vs 20/31 (64.5%) biphasic bi-UKA patients; p = 0.558). All outcomes were compared to an age-matched, healthy cohort that outperformed both groups, indicating residual deficits exists following surgery. Logistic regression analysis of primary outcome with secondary outcomes indicated that the most significant predictor of postoperative biphasic knee moments was preoperative knee moment profile and trochlear degradation (Outerbridge) (R 2 = 0.381; p = 0.002, p = 0.046). A separate regression of alignment against primary outcome indicated significant bi-UKA femoral and tibial axial alignment (R 2 = 0.352; p = 0.029), and TKA femoral sagittal alignment (R 2 = 0.252; p = 0.016). The bi-UKA group showed a significant increased ability in the proprioceptive joint position test, but no difference was found in more dynamic testing of proprioception., Conclusion: Robotic arm-assisted bi-UKA demonstrated equivalence to TKA in achieving a biphasic gait pattern after surgery for osteoarthritis of the knee. Both treatments are successful at improving gait, but both leave the patients with a functional limitation that is not present in healthy age-matched controls. Cite this article: Bone Joint J  2022;103-B(4):433-443.

Recent literature suggests that sarcopenia, often represented by low lower limbs muscle mass and strength, can be considered a potential risk factor for knee osteoarthritis (OA), but the available literature is still limited. We therefore aimed to investigate whether sarcopenia is associated with a higher risk of radiographic (ROA) and symptomatic knee OA (SxOA) in a large cohort of North American people in the context of the OA initiative. Sarcopenia at baseline was diagnosed in case of low skeletal muscle mass (i.e., lower skeletal mass index) and poor performance in the chair stands test. The outcomes of interest for this study included ROA (radiographical osteoarthritis) if a knee developed a Kellgren and Lawrence (KL) grade ≥2 at follow-up, and SxOA (symptomatic osteoarthritis) defined as new onset of a combination of painful knee OA. Altogether, 2,492 older participants (mean age: 68.4 years, 61.4% females) were included. At baseline, sarcopenia was present in 6.1% of the population. No significant difference in ROA prevalence was observed between those with and without sarcopenia (p=0.76), whilst people with sarcopenia reported a significant higher prevalence of SxOA (p<0.0001). Using a logistic regression analysis, adjusting for potential confounders at baseline and the diagnosis of sarcopenia during follow-up, sarcopenia was associated with a higher incidence of knee SxOA (odds ratio, OR=2.29; 95%CI [confidence interval]: 1.42-3.71; p=0.001), but not knee ROA (OR=1.48; 95%CI: 0.53-4.10; p=0.45). In conclusion, sarcopenia could be associated with a higher risk of negative knee OA outcomes, in particular symptomatic forms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Veronese, Stefanac, Koyanagi, Al-Daghri, Sabico, Cooper, Rizzoli, Reginster, Barbagallo, Dominguez, Smith and Maggi.)

Objective: Obesity is a known risk factor for knee osteoarthritis (OA). Diabetes has been associated with progression of OA and metformin is the first-line treatment in type 2 diabetes. The effect of the body mass index (BMI) and metformin on the expression of certain matrix genes in human chondrocytes is unclear. The purpose of this study was to investigate the effect of BMI and metformin on the expression of matrix genes in primary human chondrocytes., Design: Adult female patients undergoing knee arthroplasty for end-stage OA were enrolled. Primary chondrocytes were cultivated and stimulated with metformin. Matrix gene expression was analyzed using polymerase chain reaction. Clinical data were used in multivariable regression models to assess the influence of BMI and metformin stimulation on gene expression., Results: A total of 14 patients were analyzed. BMI was a predictor of increased expression in ADAMTS5 (β = -0.11, P = 0.03). Metformin slightly reduced expression in ADAMTS5 (β = 0.34, P = 0.04), HIF-1a (β = 0.39, P = 0.04), IL4 (β = 0.30, P = 0.02), MMP1 (β = 0.47, P < 0.01), and SOX9 (β = 0.37, P = 0.03). The hip-knee-ankle angle and proton pump inhibitors (PPIs) intake were associated with reduced SOX9 expression (β = 0.23, P < 0.01; β = 2.39, P < 0.01). Higher C-reactive protein (CRP) levels were associated with increased MMP1 expression (β = -0.16, P = 0.02)., Conclusion: We found that BMI exerts a destructive effect via induction of ADAMTS5. Metformin reduced the expression of catabolic genes ADAMTS5 and MMP1 and might play a role in disease prevention. Limb malalignment and PPI intake was associated with a reduced expression of SOX9, and higher CRP levels correlated with increased MMP1 expression, indicating a destructive process.

Objective: Assess how treatment with the viscosupplement hylan G-F 20 relates to opioid prescriptions and intraarticular corticosteroid injections (IACS) in patients with osteoarthritis of the knee (OAK)., Design: Case-crossover; adult patients with OAK identified in a claims database were treated with hylan G-F 20 from July 1, 2007, to June 29, 2017. Opioid or IACS prescriptions in the 6 months before treatment were compared to the 6 months after. Patients with comorbid conditions requiring pain medications were excluded, resulting in a 29,395-patient cohort. Four subgroups were investigated: patients with (1) opioids before hylan G-F 20 (OB; n = 6,609); (2) opioids before and after hylan G-F 20 (OBF; n = 3,320); (3) IACS before hylan G-F 20 (CB; n = 11,162); and (4) IACS before and after hylan G-F 20 (CBF; n = 2,810). All opioids were converted to morphine milligram equivalents (MME)., Results: OB subgroup patients had a significant decrease ( P < 0.01) in total MME (-14.0%), MME per day (-14.2%) and opioid prescription days (-12.6%) after treatment versus before. Only 50.2% of patients prescribed opioids before hylan G-F 20 were prescribed an opioid after treatment. OBF subgroup patients had a significant increase ( P < 0.01) in opioid prescription days (7.8%) before versus after treatment. There was a significant decrease ( P < 0.01) in the number of IACS after versus before treatment for the Total Cohort (-56.1%), and subgroups CB (-72.6%) and CBF (-4.1%). A total of 74.8% of patients receiving an IACS before treatment did not receive an IACS after treatment., Conclusions: Hylan G-F 20 is associated with a reduction in opioid prescriptions and IACS in OAK patients.

Aims: The aim of this study was to compare the clinical outcomes of robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) during the first six weeks and at one year postoperatively., Methods: A per protocol analysis of 76 patients, 43 of whom underwent TKA and 34 of whom underwent bi-UKA, was performed from a prospective, single-centre, randomized controlled trial. Diaries kept by the patients recorded pain, function, and the use of analgesics daily throughout the first week and weekly between the second and sixth weeks. Patient-reported outcome measures (PROMs) were compared preoperatively, and at three months and one year postoperatively. Data were also compared longitudinally and a subgroup analysis was conducted, stratified by preoperative PROM status., Results: Both operations were shown to offer comparable outcomes, with no significant differences between the groups across all timepoints and outcome measures. Both groups also had similarly low rates of complications. Subgroup analysis for preoperative psychological state, activity levels, and BMI showed no difference in outcomes between the two groups., Conclusion: Robotic arm-assisted, cruciate-sparing bi-UKA offered similar early clinical outcomes and rates of complications to a mechanically aligned TKA, both in the immediate postoperative period and up to one year following surgery. Further work is required to identify which patients with osteoarthritis of the knee will derive benefit from a cruciate-sparing bi-UKA. Cite this article: Bone Joint J  2021;103-B(10):1561-1570.

In the knee joint, articular cartilage injury can often lead to osteoarthritis of the knee (OAK). Currently, no point-of-care treatment can completely address OAK symptoms and regenerate articular cartilage to restore original functions. While various cell-based therapies are being developed to address OAK, exosomes containing various components derived from their cells of origin have attracted attention as a cell-free alternative. The potential for exosomes as a novel point-of-care treatment for OAK has been studied extensively, especially in the context of intra-articular treatments. Specific exosomal microRNAs have been identified as possibly effective in treating cartilage defects. Additionally, exosomes have been studied as biomarkers through their differences in body fluid composition between joint disease patients and healthy subjects. Exosomes themselves can be utilized as a drug delivery system through their manipulation and encapsulation of specific contents to be delivered to specific cells. Through the combination of exosomes with tissue engineering, novel sustained release drug delivery systems are being developed. On the other hand, many of the functions and activities of exosomes are unknown and challenges remain for clinical applications. In this review, the possibilities of intra-articular treatments utilizing exosomes and the challenges in using exosomes in therapy are discussed.

Aims: To assess the prevalence, health care resource utilization (HCRU), and economic burden of disease among Medicare beneficiaries with a principal diagnosis of osteoarthritis (OA) of the knee., Materials and Methods: Patients with a principal diagnosis of knee OA were identified from the 5% noninstitutional sample file within 2009 and 2014 Medicare fee-for-service Limited Data Sets. A complete medical benefit record for each individual was generated by linking patient data across corresponding institutional claims from inpatient, outpatient, skilled nursing facility, and home health care services. The study revealed the prevalence and HCRU among Medicare knee OA patients, as well as the patient-level burden of disease by comparing HCRU and costs between knee OA patients and matched control patients., Results: The prevalence of principal diagnosis of knee OA among Medicare beneficiaries increased from 5.9% in 2009 to 6.2% in 2014. Total disease-related claims for the knee OA population was approximately 8 million in 2009 and 9 million in 2014. The average Medicare reimbursement per claim was $12,085 in the inpatient setting, $5,563 in skilled nursing facilities, $2,742 in home health care, $264 in the outpatient setting and $147 in noninstitutional office visits in 2014. Overall, the average total expense per knee OA patient in 2014 was $15,558, an increase of $5,364 compared to the matched control patient., Conclusions: Many Medicare beneficiaries received care for knee OA, and these patients had significantly greater HCRU than those with the absence of knee OA, totaling over $34 billion in healthcare expenditures in 2014.

The aim of this non-inferiority study was to evaluate and compare the effects of Tiszasüly and Kolop mud pack therapy on pain, function and quality of life in patients with knee osteoarthritis. In this double-blind, randomised, follow-up study, 60 patients with knee osteoarthritis were treated with either Tiszasüly hot mud pack (group 1) or with Kolop hot mud pack (group 2) on 10 occasions for 2 weeks (10 working days). One hundred millimetre visual analogue scale (VAS) for knee pain, the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Knee injury and Osteoarthritis Outcome Score (KOOS), the Lequesne Index for physical function and EuroQoL-5D for quality-of-life measurements were recorded at baseline, at the end of treatment (week 2) and 3 months later (week 12). In both groups, all measured parameters improved significantly from the baseline until the end of treatment and during the follow-up period (p < 0.05). There were no significant differences between the groups in terms of the WOMAC, KOOS, EQ-5D and Lequesne Index at any visits. Knee pain improved in both groups at week 2 and week 12; the only significant difference visible between the groups was at the end of the treatment in favour of the Tiszasüly mud pack group (p = 0.009). Tiszasüly and Kolop mud packs both have a favourable effect on knee pain, physical function and quality of life in patients with knee osteoarthritis. Our results proved non-inferiority of Tiszasüly mud pack.

Objective: To test the acceptability and feasibility of self-administered acupressure as an intervention for knee pain among middle-aged and older adults with knee osteoarthritis (KOA)., Methods: In this pilot randomized controlled trial, 35 participants with KOA were randomized to receive self-administered acupressure (n = 17, two self-administered acupressure training sessions followed by self-practice for 6 weeks) or knee health education (n = 18, two health education sessions about KOA management followed by self-care for 6 weeks). Current pain intensity (primary outcome) was measured using a Numeric Rating Scale (NRS) at baseline and weeks 1, 2, 4 and 6 (post-intervention). Secondary outcome measures included worst and least pain intensity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion (ROM) of the knee joints and Short-Form Six-Dimension (SF-6D) scores for health-related quality of life., Results: Participants in both groups attended all training sessions. In the self-administered acupressure group, all subjects mastered the acupressure technique and passed a consistency check. Both groups showed a decreasing trend in current knee pain intensity measured using NRS post-intervention. A medium between-group effect size (0.40) was found, but between-group differences were not statistically significant. The other secondary outcome measures were also comparable between both groups post-intervention (all p > 0.05)., Conclusion: A two-session self-administered acupressure training was acceptable to and feasible in participants with KOA. The data generated allowed for calculation of a sample size for a definitive randomized controlled trial (RCT) to confirm whether self-acupressure is effective for pain management in KOA. Furthermore trials with adequate power and longer follow-up periods are warranted.

Background: Periprosthetic bone mineral density (BMD) may influence implant fixation and subsequent loosening. Unicompartmental knee arthroplasty (UKA) restores normal knee kinematics and load distribution to the surrounding bone. We studied the influence of systemic and periprosthetic BMD of the proximal tibia on migration of the tibial component of cemented medial UKA., Methods: The cohort was dichotomized into a normal BMD group (T-score ≥ -1; n = 37) and a low BMD group (T-score < -1; n = 28) according to World Health Organization criteria. BMD of the proximal tibia and migration of the tibial component were measured with dual X-ray absorptiometry scans and stereoradiographs with 2-year follow-up., Results: Patients with normal systemic BMD had an 11% to15% higher BMD in all regions of interest (ROIs) compared to patients with low systemic BMD throughout follow-up. Over time, a decrease in periprosthetic BMD in ROI 1-3 was seen for both groups. The operated knees and contralateral knees showed a similar reduction in BMD in all ROIs between preoperative and 24 months. Between 12 and 24 months, the normal BMD group migrated (maximal total point motion) 0.03 mm (95% confidence interval, -0.01, 0.08) and the low BMD group migrated 0.02 mm (95% confidence interval, -0.03, 0.07). Migration over time was not influenced by change in periprosthetic BMD., Conclusion: Migration of cemented medial tibial UKA was low until 24 months and was neither affected by preoperative systemic BMD nor affected by postoperative change in periprosthetic BMD. This suggests good long-term fixation despite an index difference in proximal tibial BMD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To treat the increasing number of patients with osteoarthritis (OA) of the knee, high-volume institutions rely on central referral services as first contact point. Depending on the grading of arthritis, patients will be referred to a nonoperative or operative care provider. The present study reports on a simple 5-step questionnaire to identify patients with OA (Kellgren/Lawrence [KL] grade ≥2) of the knee to improve efficiency of referrals., Methods: We included 998 patients who contacted the physician referral service at the author's institution complaining of knee pain and divided them into 2 groups. The study group included patients with an appointment and consisted of 646 patients (345 women [53.4%] and 301 men [46.6%]). X-rays of the knee were graded according to the KL classification system. The control group of patients who did not make an appointment consisted of 352 patients (187 women [53.1%] and 165 men [46.9%]). These patients were contacted to evaluate whether they had been diagnosed with OA of the knee since their initial call, to assure that the study group was not exposed to a selection bias., Results: Logistic regression revealed 5 questions as significant predictors for OA of the knee (KL grade ≥2). When combining both groups, an 86.9% sensitivity, a 73.3% specificity, and an 84.3% overall accuracy were reached, when patients answered 3 or more questions positively., Conclusion: The present study revealed a simple 5-step questionnaire to identify patients with OA of the knee. Implementation of the questionnaire has the potential to improve the accuracy of referral processes and streamline organization before the first appointment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To compare the effectiveness of intra-articular injection (IAI) with Botulinum toxin type A (BTA), triamcinolone hexacetonide (TH), and saline in primary knee osteoarthritis., Design: A randomized controlled trial, with blinded patients and assessor., Setting: Outpatient rheumatology service., Subjects: Patients with knee osteoarthritis grades II and III., Interventions: Patients received IAI with 100 IU BTA, 40 mg TH, or isotonic saline solution (SS) 0.9%., Main Measures: Patients were assessed at baseline and at 4, 8, and 12 weeks with the following instruments: visual analog scale for pain during movement (VASm; primary outcome) and visual analog scale for pain at rest (VASr), Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, 6-minute walk test, Timed Up and Go test, Short Form (SF)-36 questionnaire, range of motion of knee, and ultrasound (US) measurement of synovial hypertrophy., Results: In total, 105 patients were randomized, with 35 in each group; 96 were female (91.4%) and 9 were male (8.6%), with a mean age of 64.2 years (±6.9). At 12 weeks, the TH group showed better results only for VASm. At four weeks, the TH group showed better results than the BTA and SS groups for VASm (-68.9% (37.8) vs. -35.3% (40.3) vs. -35.9% (51.4)), WOMAC pain (-56.0% (30.7) vs. -30.8% (34.3) vs. -30.0% (39.9)), WOMAC stiffness (-53.4% (38.4) vs. -17.2% (59.3) vs. -17.3% (78.1)), WOMAC function (-48.2% (34.6) vs. 30.8% (33.6) vs. -13.6% (64.9)), WOMAC total score (-51.2% (31.0) vs. -30.9% (30.0) vs. -18.8% (54.8)), and US measurement of synovial hypertrophy (-11.6% (44.9) vs. -1.5% (47.9) vs. +28.6% (81.3))., Conclusion: IAI with TH had a higher effectiveness than that with TBA or SS in the short-term assessment (four weeks) for pain in movement, WOMAC, and US measurement of synovial hypertrophy.

Background: In the progression of osteoarthritis (OA) of the knee, a correlation between meniscal posterior segment injuries and medial meniscal extrusion has been reported, but there have been few reports on the relationship with the meniscal shape. The purpose of this study was to clarify the features of the meniscal shape involved in the progression of knee OA., Methods: Data were obtained from the Osteoarthritis Initiative (OAI) database. We defined two sets of subjects. One set included 455 knees of subjects whose OA grade on the Kellgren Lawrence (KL) scale progressed in 24 months from baseline and the other set consisted of 455 knees with no progression. The OA progressed subjects were divided to three groups: the "OA change group", KL0 and KL1 knees that progressed to KL2 and KL3; the "mild change group", KL2 knees that progressed to KL3; and the "severe change group", KL2 and KL3 knees that progressed to KL4. The no progression set was divided into three groups whose OA grade remained unchanged. We used magnetic resonance imaging data and manually measured seven items (longitudinal diameter [LD], anterior wedge thickness, anterior wedge width, posterior wedge width, posterior wedge thickness, anterior wedge angle, posterior wedge angle) from the sagittal slice and the extrusion from the coronal slice. These measurements were compared between knees with and without OA progression., Results: In the "OA change group" and "mild change group", the anterior and posterior wedge widths and the extrusion were significantly larger, but the anterior and the posterior wedge angles were significantly smaller. In the "severe change group," the LD and the extrusion were significantly larger. In each group, there was no uniform tendency for the correlation coefficient of the parameters evaluated., Conclusions: Our findings suggested (1) a larger meniscal LD at the baseline predicted progression of knee OA after 24 months and (2) a larger meniscal width and smaller meniscal angle predicted progression of knee OA after 24 months.

Background: Evaluation of knee and lower limb function alone is not sufficient to assess gait. For accurate assessment of gait abnormality, gait oscillation should also be measured. The goal of this analysis was to assess the influence of the knee joint on gait oscillation during gait and stair-stepping in patients with osteoarthritis of the knee., Methods: In 33 patients diagnosed with knee osteoarthritis and 33 healthy adults as the control group, we examined acceleration (anterior and lateral directions) and gait barycentric factors (single-support phase and ratio of center of gravity maximum values) during gait and stair-stepping., Results: Acceleration in the anterior direction in the sacral region was greater in healthy adults than in osteoarthritis (OA) patients during gait and stair-down. Acceleration in the anterior direction in the dorsal vertebral region was greater in OA patients than in healthy adults during (up and down) stair-stepping. Acceleration in the lateral direction in the sacral region was greater in healthy adults than in OA patients during stair-up. Acceleration in the lateral direction in the dorsal vertebral region was greater in OA patients than in healthy adults during stair-stepping. The single-support phase was close to 1 for gait and stair-stepping in healthy adults and OA patients. The single-support time was largely the same for gait and stair-stepping in healthy adults. On the other hand, the single-support time was longer for stair-stepping than for gait in OA patients. The ratio of the center of gravity maximum values was greater for the sacral region than for the dorsal vertebral region. There was a significant difference in the stair-stepping ratio of the center of gravity maximum values between healthy adults and OA patients for the sacral region., Conclusion: We considered that knee OA influenced acceleration in the anterior and lateral direction in the dorsal vertebral and the ratio of the center of gravity maximum values on gait oscillation.

Purpose: Osteoarthritis of the knee is a common disease, often associated with a Baker's cyst. Besides osteoarthritis, also other joint pathologies of the knee can be causative for a Baker's cyst. Radiotherapy is known to be an effective treatment for osteoarthritis, with an anti-inflammatory effect. As the excessive production of synovia usually is associated with intraarticular inflammation, our hypothesis was that radiotherapy might positively influence the synovial production and reduce the volume of a Baker's cyst., Materials and Methods: We performed a prospective trial, including 20 knees receiving radiotherapy for knee arthritis. Besides documentation of NRS (numeric rating scale), WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and Knee Society Score, the volume of the Baker's cyst was calculated for a short- (6 to 12 weeks) and long-term (9 to 12 months) follow-up. Ultrasonic volumetry was performed using an ultrasound device with a high-resolution multifrequency linear probe (6-9 MHz)., Results: Low-dose radiotherapy improved NRS, WOMAC score and Knee Society Score significantly. The mean volume of Baker's cyst decreased from 22.3 ml to 10.7 respectively 3.1 ml during follow-up. A decrease in volume of more than 25% compared to the baseline could be achieved for 75% of the patients in the short-term and 79% of the patients in the long-term follow up., Conclusion: Radiotherapy of knee osteoarthritis is an effective treatment that decreases the volume of a Baker's cyst. Most patients respond to the treatment. Whether radiotherapy is an effective treatment for Baker's cyst without associated osteoarthritis has to be further examined.

Objective: Aim of this trial was to compare efficacy of activated platelet-rich plasma against hyaluronic acid as intra-articular injections to people with osteoarthritis of the knee., Design: Phase-2 randomized controlled trial, with blind patients and outcome assessors., Setting: Outpatient rehabilitation service; years 2011-2013., Subjects: Patients with knee osteoarthritis grades 2-3 at magnetic resonance imaging (MRI) were included after consent and randomized. Target sample size was 25 patients per group., Interventions: Patients received three activated platelet-rich plasma (intervention group) or hyaluronic acid (controls) intra-articular injections at 4-week intervals., Main Measures: Main outcome measure was proportion of patients with >1 grade improvement at six months from last injection, as assessed by a radiologist blind to study group. Patients were evaluated over time clinically and with functional scales (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm, Tegner, American Knee Society Score (AKSS), Lequesne, visual analogue scale (VAS) for pain)., Results: Overall, 30 patients were randomized to intervention and 28 to control group. For primary outcome, 28 patients (29 knees) in the intervention and 22 (25 knees) in the control group were available. Patients with at least 1 grade improvement at repeat MRI were 14 (48.3%) in the intervention and 2 (8%) in the control group ( P < 0.003). Improvement in symptoms and functional scales was consistently higher in the intervention group. No side-effects were observed in either group., Conclusion: Activated platelet-rich plasma reduces articular damage as evident at MRI, as soon as six months after treatment; it reduces pain and improves patient's function and overall quality of life.

Background: Asporin is a novel extracellular matrix protein (ECM) with an important role in the development of osteoarthritis (OA), because it has been reported that functional polymorphisms in the aspartic acid repeat (D) of the asporin gene (ASPN) are associated with susceptibility to OA., Aim: This study was planned to investigate the association of the ASPN polymorphism with primary OA of the knee in a Mexican population, including several countryside regions., Methods: We conducted a case-control study in which 93 cases with primary OA of the knee and 118 controls were included. Cases included patients > 40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee of ≥ 2. Controls were subjects > 40 years of age with a radiologic score of < 2. The D repeat polymorphism was genotyped and logistic regression was developed to evaluate risk magnitude., Results: The D14 allele was more common in our cases and was associated with an increased risk for developing OA, while the frequencies of the remaining alleles did not exhibit differences., Conclusion: Our data suggest that the D14 allele of the ASPN polymorphism could exert an influence on primary OA of the knee etiology in a Mexican Mestizo population., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Background: Osteoarthritis (OA) of the knee is a degenerative, painful pathology, needing conservative treatment for symptoms' relief., Objective: Comparing the effects of Extracorporeal shockwave therapy (ESWT) and Kinesiotherapy (KIN) on perceived health and range of motion (ROM) of the affected knee., Method: A pilot randomized controlled trial with concealed allocation, assessor blinding, intention-to-treat analysis. Forty participants, aged 40-75 with OA of the knee were randomized to an ESWT and a KIN groups. The ESWT group completed 5 interventions for 5 weeks, the KIN group completed the same number of interventions. All evaluations were performed at baseline and after the treatment for: perceived health (Western Ontario and McMaster Universities questionnaire - WOMAC), range of motion (ROM)., Results: After the intervention the statistical significant between groups differences favoring the ESWT were found in the WOMAC with regard to pain (p< 0.000), stiffness (p= 0.018), physical function (p< 0.000), total score (p< 0.000), extension and flexion of the affected knee (p= 0.015, p< 0.000) respectively., Conclusions: ESWT improves WOMAC and ROM better then KIN on the affected knee in patients with OA of the knee.

This meta-analysis was performed to determine the effect of balneotherapy on relieving pain and stiffness and improving physical function, compared to controls, among patients with knee osteoarthritis. We searched electronic databases for eligible studies published from 2004 to December 31, 2016, with language restrictions of English or Japanese. We screened publications in Medline, Embase, Cochrane library, and the Japan Medical Abstracts Society Database using two approaches, MeSH terms and free words. Studies that examined the effect of balneotherapy for treating knee osteoarthritis of a ≥2-week duration were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used as the outcome measure. A total of 102 publications were assessed according to the exclusion criteria of the study; eight clinical trial studies, which comprised a total of 359 cases and 375 controls, were included in this meta-analysis. The meta-analysis analyzed improvement in WOMAC score at the final follow-up visit, which varied from 2 to 12 months post-intervention. Our meta-analysis indicates that balneotherapy was clinically effective in relieving pain and stiffness, and improving function, as assessed by WOMAC score, compared to controls. However, there was high heterogeneity (88 to 93%). It is possible that balneotherapy may reduce pain and stiffness, and improve function, in individuals with knee osteoarthritis, although the quality of current publications contributes to the heterogeneity observed in this meta-analysis.

Purpose: Tibial condylar valgus osteotomy (TCVO) is a type of opening-wedge high tibial osteotomy for advanced medial knee osteoarthritis (OA) with subluxated lateral joint. We report the concept, the current surgical technique with a locking plate, and the short-term clinical and radiological results of this procedure., Methods: 11 knees with medial OA and a widened lateral joint were treated by TCVO (KL stage III: 6, IV: 5). In this procedure, by the L-shaped osteotomy from the medial side of the proximal tibia to the intercondylar eminence and the valgus correction, lateralization of the mechanical axis and reduction of the subluxated lateral joint are obtained with early postoperative weight-bearing. Before, 6 months, 1, and 5 years after the operation, a visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), alignment of the lower extremity, and congruency and stability of the femorotibial joint were investigated., Results: The VAS improved from an average of 73 mm to 13 mm, and the total WOMAC score from 52 to 14 before to 5 years after the operation, respectively. The mechanical axis changed from 1 to 60%, and the FTA changed from 186° to 171°. The joint line convergence angle (JLCA) changed from 6° to 1°, and the angle difference of JLCA between varus and valgus stress improved from 8° to 4° after the procedure., Conclusion: Improvements in pain and activities of daily living were observed by TCVO along with valgus correction of the lower extremity and stabilization of the femorotibial joint.

This study aimed to determine the factors associated with response to intra-articular steroid injection (IASI) in patients with knee joint osteoarthritis. One hundred seventy-four female patients, age ranging from 30 to 80 years, diagnosed to have osteoarthritis of the knee joint, were given IASI. Response to IASI was assessed by using WOMAC and VAS at 2 weeks, 4 weeks and 3 months. At 3 months, the subjects were categorized as responders, partial responders and non-responders to treatment by IASI. Various factors were narrowed down to see their effect on response, namely age, BMI, smoking habits, comorbidities, presence of clinical effusion, radiographic score, local knee tenderness, range of movement and socioeconomic status. One hundred twenty-four patients completed the study. 16.1 % showed 50 % or more improvement in WOMAC score at 3 months post IASI therapy, whereas 38.7 % of OA patients had more than 50 % improvement in VAS score. Out of all factors, range of movement, local knee tenderness and radiographic score of the affected joint are the three parameters which can predict the improvement in WOMAC score after 3 months of IASI therapy (P = 0.013, P = 0.045 and P = 0.000, respectively). Age of the patient can predict improvement in VAS at 3 months post IASI (P = 0.027). We conclude that age, range of movement, local knee tenderness and radiographic score of the affected joint can predict response to IASI after 3 months of IASI therapy.

Background: In placebo-controlled RCT of symptomatic treatment in osteoarthritis (OA) the extent of pain reduction is heterogeneous, the pooled effect size rather small. Pain reduction is typically higher in knee than in hip trials. The recommended trial duration is 3 months, but in knee OA the best treatment effect vs placebo is observed at 2 weeks. We hypothesized that the placebo response differs in knee vs hip OA., Objective: We performed a meta-analysis to describe the time course of pain in placebo groups of trials in knee and hip OA over 3 months., Methods: A systematic search of PubMed, MEDLINE and Google Scholar of placebo-controlled cox-2 inhibitor (coxib) RCT (from 1999 to 2007) of hip and knee OA was performed. Pain levels (visual analogue scale [VAS], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in the placebo groups at different measurement time points were extracted, expressed as weighted mean at weeks 2, 4, 6-8 and 12-13., Results: Twenty-one studies included 3064 knee OA patients and 608 hip OA patients. For knee OA, pain (VAS) decreased from 15 mm at week 2, to 20 mm at week 6-8, and 21 mm at week 12-13. For hip OA patients, pain decreased by 12 mm, 14 mm and 14 mm, respectively., Conclusion: Pain decreased in both knee and hip OA patients treated with placebo at 2 weeks, but further decreases up to week 12 occurred only in knee OA, especially for pain VAS, resulting in a time dependent impact on the magnitude of treatment outcome. Primary endpoint pain should be assessed at 2-4 weeks., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Fructosamine is a glycated protein that reflects blood glucose control over the last 2-3 weeks. There are no studies that address the impact of intra-articular injection (IAI) of methylprednisolone acetate (MPA) on fructosamine levels among patients with type-2 diabetes and osteoarthritis of the knee (OAK). Non-selected patients attending the rheumatology or orthopedic clinic with type-2 diabetes and painful OAK, who failed non-steroidal anti-inflammatory drugs (NSAIDS) and physical therapy, were asked to participate in our study. After consent blood tests were drown for fructosamine, hemoglobin A1c (HbA1c) level, complete blood count, lipid profile, serum albumin, serum protein, c-reactive protein, and erythrocyte sedimentation rate. Demographic and different clinical parameters were also documented. Immediately after that, patients had IAI of 80 mg of MPA at the knee joint (group 1). Two to three weeks later, the same blood tests were repeated (except for HbA1c). Age- and sex-matched group of patients with type-2 diabetes and painful OAK attending the same clinics, but who were managed by NSAIDS were asked to participate as a control group (group 2) and had the same evaluation at enrollment and 2-3 weeks later, after consent. Eighteen patients from either group completed the study. Mean fructosamine level in group 1 patients was 263.7 ± 31.8 mg% prior to the IAI vs. 274.6 ± 39.3 mg% (p = 0.035), 2-3 weeks later, while mean fructosamine level in the control group (group 2) at enrollments was 274.2 ± 31.2 mg% vs. 269 ± 30.2 mg%, p = 0.509, 2-3 weeks later. There was no significant change in any other parameter tested at enrollment in either group, compared to those obtained 2-3 weeks afterwards. Body mass index was on the edge of significance as a predictor for a significant change in fructosamine level in group 1 patients. IAI of 80 mg of MPA in patients with type-2 diabetes and OAK had resulted in a significant, though mild increase in fructosamine levels 2-3 weeks later.

Objective: To determine the effect of a progressive resistance exercise (PRE) program on women with osteoarthritis (OA) of the knee., Methods: Eligible subjects included women aged 40 to 70 years with pain between 3 and 8 on a 10-cm pain scale. Among the 144 subjects screened, 60 met the eligibility criteria and were randomized to the experimental group (EG) or control group (CG). Subjects in the EG participated in a 12-week PRE program twice a week and CG remained on a waiting list for physical therapy. The PRE program consisted of strengthening exercises for knee extensors, knee flexors, hip abductors and hip adductors, all performed with 50% and 70% of the one-repetition maximum (1RM) using machines with free weights. Resistance was reevaluated every two weeks. Assessments of pain, muscle strength, walking distance, function and quality of life were performed at baseline, six weeks and 12 weeks by a blinded assessor., Results: Twenty-nine female subjects were randomly assigned to the EG and 31 were randomly assigned to the CG. Repeated-measures ANOVA revealed significantly better results in the EG pain (from 7.0±1.3 to 4.3±3.1 in the EG and from 7.0±1.2 to 6.6±1.5 in the CG - p<0.001), function (p<0.001), some domains of quality of life (physical function: p=0.002; physical role limitation: p=0.002; and pain: p=0.044) and muscle strength (extensors: p<0.001; flexors: p=0.002; and abductors: p<0.001)., Conclusion: The PRE program was effective in reducing pain and improving function, some quality of life domains and strength in women with OA of the knee., (© The Author(s) 2014.)

Objectives: The knee can be injected at different anatomic sites with or without image-guidance. We undertook a systematic review to determine the accuracy of intra-articular knee injection (IAKI) and whether this varied by site, use of image-guidance, and experience of injectors, and whether accuracy of injection, site, or use of image-guidance influenced outcomes following IAKIs., Methods: Medline, Embase, AMED, CINAHL, Web of Knowledge, Cochrane Central Registers for Controlled Trials up to Dec 2012 were searched for studies that evaluated either accuracy of IAKIs or outcomes related to accuracy, knee injection sites, or use of image-guidance. Within-study and between-study analyses were performed., Results: Data from 23 publications were included. Within-study analyses suggested IAKIs at the superomedial patellar, medial midpatellar (MMP), superolateral patellar (SLP) and lateral suprapatellar bursae sites were more accurate when using image-guidance than when blinded (ranges of pooled risk difference 0.09-0.19). Pooling data across studies suggested blinded IAKIs at the SLP site were most accurate (87%) while MMP (64%) and anterolateral joint line (ALJL) sites were (70%) least accurate. Overall about one in five blinded IAKIs were inaccurate. There was some evidence that experience of the injector was linked with improved accuracy for blinded though not image-guided injections. Based on a small number of studies, short but not longer-term outcomes for ultrasound-guided were found to be superior to blinded IAKIs., Conclusions: Image-guided IAKIs are modestly more accurate than blinded IAKIs especially at the MMP and ALJL sites. Blinded injections at SLP site had good accuracy especially if performed by experienced injectors. Further studies are required to address the question whether accurate localization is linked with an improved response., (© 2013 The Authors. Published by Elsevier HS Journals, Inc. All rights reserved.)

Objectives: This paper aimed to systematically review and meta-analyze the effectiveness of Tai Chi for osteoarthritis of the knee., Methods: MEDLINE, the Cochrane Library, EMBASE, Scopus, PsycInfo and CAMBASE were screened through April 2013. Randomized controlled trials (RCTs) comparing Tai Chi to control conditions were included. Two authors independently assessed risk of bias using the risk of bias tool recommended by the Cochrane Back Review Group. Outcome measures included pain, physical functional, joint stiffness, quality of life, and safety. For each outcome, standardized mean differences and 95% confidence intervals were calculated., Results: 5 RCTs with a total of 252 patients were included. Four studies had a low risk of bias. Analysis showed moderate overall evidence for short-term effectiveness for pain, physical function, and stiffness. Strong evidence was found for short-term improvement of the physical component of quality of life. No long-term effects were observed. Tai Chi therapy was not associated with serious adverse events., Conclusion: This systematic review found moderate evidence for short-term improvement of pain, physical function and stiffness in patients with osteoarthritis of the knee practicing Tai Chi. Assuming that Tai Chi is at least short-term effective and safe it might be preliminarily recommended as an adjuvant treatment for patients with osteoarthritis of the knee. More high quality RCTs are urgently needed to confirm these results., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: IA steroid injections (IASIs) have been shown to relieve pain in knee OA and are widely used in clinical practice. There is, however, evidence of some variation in response. Knowledge of predictors of response could aid in the selection of patients for this therapy. The aim of this systematic review was to determine factors associated with response to IASI in knee OA., Methods: Medline, Embase, AMED, CINAHL, Web of Science and Cochrane Central Registers for Controlled Trials up to January 2012 were searched with additional hand searches of relevant articles. Studies included were those that involved adults diagnosed with knee OA in whom IASIs were administered and factors that predicted treatment response were investigated., Results: Eleven publications meeting these criteria were reviewed and relevant information extracted. It was not possible to pool the results because of the different predictors studied, variable outcome measures, different criteria for symptom change and missing data. Given the relative paucity of data and small heterogeneously designed studies, it was difficult to identify predictors of response. Data from individual publications, although not consistent across studies, suggest that the presence of effusion, withdrawal of fluid from the knee, severity of disease, absence of synovitis, injection delivery under US guidance and greater symptoms at baseline may all improve the likelihood of response to IASI., Conclusion: Further larger-scale studies using standardized methods are required to characterize predictors of response and should focus on synovitis, effusion, pain and structural severity of disease. Such data would help in better targeting therapy to those most likely to benefit.