Viscosupplementation with High Molecular Weight Hyaluronic Acid for Hip Osteoarthritis: a Systematic Review and Meta-Analysis of Randomised Control Trials of the Efficacy on Pain, Functional Disability, and the Occurrence of Adverse Events.

PURPOSE OF THE STUDY: Hip osteoarthritis (OA) has a prevalence of around 6.4% and is the second most commonly affected joint. This review aims to assess the clinical outcomes of intra-articular high molecular weight hyaluronic acid (HMWHA) in the management of hip osteoarthritis. MATERIAL AND METHODS: We conducted a comprehensive search across PubMed, Google Scholar, and the Cochrane Library for randomised trials investigating the effectiveness of high molecular weight hyaluronic acid (HMWHA) in the treatment of hip osteoarthritis. Quality and risk of bias assessments were performed using the Cochrane RoB2 tool. To synthesise the data, we utilised the Standardised Mean Difference (SMD) for assessing pain relief through the Visual Analogue Scale (VAS) and the Lequesne index (LI) for evaluating functional outcomes. Risk Ratio (RR) was calculated to assess the occurrence of complications. RESULTS: A total of four studies involving HMWHA and control groups were included. The standardised mean difference (SMD) for the Visual Analogue Scale (VAS) (SMD -0.056; 95% CI; -0.351, 0.239; p = 0.709) and the Lequesne index (SMD -0.114; 95% CI; -0.524, 0.296; p = 0.585) were not statistically significant. Analysis for complications demonstrated an overall relative risk ratio (RR) of 0.879 (95% CI; 0.527, 1.466; p = 0.622), and was not statistically significant. DISCUSSION AND CONCLUSIONS: Intra-articular HMWHA in hip OA can significantly reduce pain and improve functional recovery when compared with the condition before treatment. However, there is no significant difference between HMWHA, or saline, or other therapeutic treatments. Currently, available evidence indicates that intra-articular HMWHA in hip OA would not increase the risk of adverse events. KEY WORDS: hip osteoarthritis, hyaluronic acid, intra-articular, molecular weight, viscosupplementation.

Clinical efficacy of multiple intra-articular injection for hip osteoarthritis.

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

Fluoroscopy-guided triple hip block for patients with hip osteoarthritis: A new approach.

Hip osteoarthritis (OA) is found in approximately 10% of the population and often causes disability and social limitations in elderly patients. Intra-articular injections are among the most frequently applied interventional treatments for the hip joint. Femoral and obturator sensorial nerve blocks have also been reported to be effective for both diagnostic and therapeutic purposes. A single needle insertion was performed for the blockage of the hip joint and sensory branches. For the sensory branch of the femoral nerve, the needle is advanced at nearly a 45-degree angle toward below the anterior inferior iliac spine near the anterolateral edge of the hip joint. For the sensory branch of the obturator nerve, the needle is advanced at nearly an angle of 45 degrees toward the area below the junction of the pubis and ischium. Finally, for joint injection, the same needle was advanced toward the midline of the anterior femoral head-neck junction at a steeper angle, and blocks were applied. Three patients with hip osteoarthritis were injected with this method and well-being was achieved in a 3-month follow-up. We think that blockage of the hip joint and peripheral sensory branches with a single needle insertion is a fast and effective method. However, prospective controlled studies are needed to determine the efficacy and safety of the method.

Association of Pharmacologic Treatment of Depression/Anxiety With Initial Patient-Reported Outcome Measures in Patients With Hip and Knee Osteoarthritis.

INTRODUCTION: Depression and anxiety are common comorbidities that may exacerbate osteoarthritis (OA)-related pain. We aim to evaluate the effect of pharmacologic treatment of depression/anxiety on hip and knee patient-reported outcome measures (PROMs). METHODS: A multi-institutional PROMs database was queried for patients with depression or anxiety and hip or knee OA who completed a PROMs questionnaire at an initial orthopaedic visit between January 2015 and March 2023. Data on demographics, comorbidities, and duration of pharmacologic treatment of depression/anxiety were obtained. Patients were stratified into three cohorts based on treatment duration. PROMs were compared across cohorts. RESULTS: Two thousand nine hundred sixty patients who completed PROMs at their initial orthopaedic visit had both OA and depression/anxiety. One hundred thirty-four (4.5%) received pharmacologic treatment of depression/anxiety for < 1 year, versus 196 (6.6%) for more than 1 year. In unadjusted analyses, patients with pharmacologic treatment had significantly lower Patient-Reported Outcomes Measurement Information System (PROMIS)-Physical (39.8 [IQR 34.9, 44.9] vs 42.3 [37.4, 47.7], P < 0.001) and PROMIS-Mental (43.5 [36.3, 50.8] vs 48.3 [41.1, 53.3], P < 0.001) scores than those without treatment. After adjusting for demographics and comorbidities, only differences in PROMIS-Mental scores remained statistically significant, with pharmacologic treatment associated with lower scores (ß = -2.26, 95% CI, [-3.29, -1.24], P < 0.001). On secondary analysis including duration of pharmacologic treatment, < 1 year of treatment was associated with significantly lower PROMIS-Mental scores than those not treated (ß = -4.20, 95% CI [-5.77, -2.62], P < 0.001) while scores of patients with more than 1 year of treatment did not differ significantly from those without treatment. CONCLUSION: :Our results indicate that pharmacologic treatment of depression/anxiety is associated with improved psychological health but not with improved physical symptoms related to OA. We observed a nonsignificant trend that patients with depression/anxiety who warrant pharmacologic treatment tend to have worse physical symptoms than those who do not; however, unadjusted analyses suggest this is a complex relationship beyond the isolated effect of pharmacologic treatment.

Proteome-Wide Mendelian Randomization and Colocalization Analysis Identify Therapeutic Targets for Knee and Hip Osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease. Although some biomarkers and drug targets of OA have been discovered and employed, limitations and challenges still exist in the targeted therapy of OA. Mendelian randomization (MR) analysis has been regarded as a reliable analytic method to identify effective therapeutic targets. Thus, we aimed to identify novel therapeutic targets for OA and investigate their potential side effects based on MR analysis. In this study, two-sample MR, colocalization analysis, summary-data-based Mendelian randomization (SMR) and Mendelian randomization phenome-wide association study (MR-PheWAS) were conducted. We firstly analyzed data from 4907 plasma proteins to identify potential therapeutic targets associated with OA. In addition, blood expression quantitative trait loci (eQTLs) data sources were used to perform additional validation. A protein-protein interaction (PPI) network was also constructed to delve into the interactions among identified proteins. Then, MR-PheWASs were utilized to assess the potential side effects of core therapeutic targets. After MR analysis and FDR correction, we identified twelve proteins as potential therapeutic targets for knee OA or hip OA. Colocalization analysis and additional validation supported our findings, and PPI networks revealed the interactions among identified proteins. Finally, we identified MAPK3 (OR = 0.855, 95% CI: 0.791-0.923, p = 6.88 × 10-5) and GZMK (OR = 1.278, 95% CI: 1.131-1.444, p = 8.58 × 10-5) as the core therapeutic targets for knee OA, and ITIH1 (OR = 0.847, 95% CI: 0.784-0.915, p = 2.44 × 10-5) for hip OA. A further MR phenome-wide association study revealed the potential side effects of treatments targeting MAPK3, GZMK, and ITIH1. This comprehensive study indicates twelve plasma proteins with potential roles in knee and hip OA as therapeutic targets. This advancement holds promise for the progression of OA drug development, and paves the way for more efficacious treatments of OA.

Population Pharmacokinetics of Fasinumab in Healthy Volunteers and Patients With Pain Due to Osteoarthritis of the Knee or Hip.

Osteoarthritis (OA) pain management options are currently limited. Fasinumab, an anti-nerve growth factor monoclonal antibody, has been investigated in healthy volunteers and patients with OA-related pain, among other conditions. Data from 12 Phase I-III clinical trials of 92 healthy volunteers and 7430 patients with OA were used to develop a population pharmacokinetic model to characterize fasinumab concentration-time profiles and assess the covariates' effect on fasinumab pharmacokinetic parameters. Participants received single or repeated fasinumab doses intravenously (IV)/subcutaneously (SC), based on body weight (0.03-1 mg/kg IV or 0.1-0.3 mg/kg SC)/fixed dose (9-12 mg IV or 1-12 mg SC). Fasinumab concentration-time data following IV and SC administration in healthy volunteers and patients with OA-related pain were adequately described by a 2-compartment model. Bioavailability increased with higher doses; estimated at 55.1% with 1 mg SC dose, increasing in a greater-than-proportional manner above this. Body weight had the largest predicted impact on fasinumab steady-state exposures, participants at the 5th and 95th percentiles had a 43%-45% higher/22%-23% lower exposure versus reference, respectively. Other covariates had small but clinically irrelevant impacts.

Melatonin is a potential novel analgesic agent for osteoarthritis: Evidence from cohort studies in humans and preclinical research in rats.

Melatonin exhibits potential for pain relief and long-term safety profile. We examined the analgesic effects of oral melatonin on osteoarthritis (OA) and investigated the underlying mechanism. Using data from a UK primary care database, we conducted a cohort study in individuals with OA to compare the number of oral analgesic prescriptions and the risk of knee/hip replacement between melatonin initiators and hypnotic benzodiazepines (i.e., active comparator) initiators using quantile regression models and Cox-proportional hazard models, respectively. To elucidate causation, we examined the effects of melatonin on pain behaviors and explored several metabolites that may serve as potential regulatory agents of melatonin in the monoiodoacetate rat model of OA. Using data from another community-based cohort study, that is, the Xiangya OA Study, we verified the association between the key serum metabolite and incident symptomatic knee OA. Compared with the hypnotic benzodiazepines cohort (n = 8135), the melatonin cohort (n = 813) had significantly fewer subsequent prescriptions of oral analgesics (50th percentile: 5 vs. 7, 75th percentile: 19 vs. 29, and 99th percentile: 140 vs. 162) and experienced a lower risk of knee/hip replacement (hazard ratio = 0.47, 95% Cl: 0.30-0.73) during the follow-up period. In rats, oral melatonin alleviated pain behaviors and increased serum levels of glycine. There was an inverse association between baseline serum glycine levels and the risk of incident symptomatic knee OA in humans (n = 760). In conclusion, our findings indicate that oral melatonin shows significant potential to be a novel treatment for OA pain. The potential role of glycine in its analgesic mechanism warrants further investigation.

Effects of Analgesics on Self-Reported Physical Function and Walking Ability in People With Hip or Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Hip and knee osteoarthritis are among the leading causes of global disability, and one of the main aims of the management is to improve physical function. The objective of this review was to investigate the effect of analgesics on physical function (self-reported physical function and walking ability). METHODS: A systematic review and meta-analysis of the findings were performed. Randomized controlled trials investigating the effect of analgesics on self-reported physical function and walking ability were included. Analgesics were orally administered acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), or opioids. Data were pooled in a random-effects model, and the standardized mean difference (SMD) with 95% CI was calculated (SMDs: 0.2-0.4 = small, 0.5-0.7 = medium, and ≥0.8 = large effect sizes). The quality of the evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: A total of 1454 studies were identified, of which 33 were included. On self-reported physical function, the results showed low- to moderate-quality evidence for a small beneficial effect of acetaminophen (SMD = -0.13 [95% CI = -0.26 to 0.00]), NSAIDs (SMD = -0.32 [95% CI = -0.37 to -0.27]), or opioids (SMD = -0.20 [95% CI = -0.32 to -0.09]). There was moderate-quality evidence for a small effect of NSAIDs on pain during walking (SMD = -0.34 [95% CI = -0.45 to -0.23]). CONCLUSION: In people with hip or knee osteoarthritis, there was low- to moderate-quality evidence for small beneficial effects of analgesics on physical function and walking ability. IMPACT: Analgesics may improve physical function by reducing pain during exercise and walking.

Use of prescribed analgesics before and after exercise therapy and patient education in patients with knee or hip osteoarthritis.

The aim of this study was to investigate utilisation patterns of prescribed analgesics before, during, and after an exercise therapy and patient education program among patients with knee or hip osteoarthritis. This cohort study is based on data from the nationwide Good Life with osteoarthritis in Denmark (GLA:D®) patient-register linked with national health registries including data on prescribed analgesics. GLA:D® consists of 8-12 weeks of exercise and patient education. We included 35,549 knee/hip osteoarthritis patients starting the intervention between January 2013 and November 2018. Utilisation patterns the year before, 3 months during, and the year after the intervention were investigated using total dispensed defined daily doses (DDDs) per month per 1000 population as outcome. During the year before the intervention, use of prescribed paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids increased with 85%, 79% and 22%, respectively. During the intervention, use of paracetamol decreased with 16% with a stable use the following year. Use of NSAIDs and opioids decreased with 38% and 8%, respectively, throughout the intervention and the year after. Sensitivity analyses indicated that the prescription of most analgesics changed over time. For paracetamol, NSAIDs, and opioids, 10% of analgesic users accounted for 45%, 50%, and 70%, respectively, of the total DDDs dispensed during the study period. In general, analgesic use increased the year before the intervention followed by a decrease during the intervention and the year after. A small proportion of analgesic users accounted for half or more of all paracetamol, NSAIDs, and opioids dispensed during the study period.

Efficacy of Herbal Medicine in Hand Osteoarthritis: A Narrative Review.

OBJECTIVE: Osteoarthritis (OA) is one of the most prevalent joint disorders in the world that has placed an enormous economic and social burden on governments and healthcare sectors in many countries. Hand OA (HOA) is the most common peripheral arthritis, which is less investigated than knee and hip OA. Due to limited approved drug choices and adverse effects of long-term use of current regimens, we aimed to review the existing evidence that were used as oral herbal medicine to treat HOA. METHODS: The PubMed database was searched for both observational and interventional studies that have investigated herbal medicine safety and efficacy in HOA, written in English and published between 2010 and 2022. RESULTS: A total of 5 original articles fulfilled the inclusion criteria, and each article assessed a different herbal regimen. Overall, it seems desirable to add specific herbal treatments to the regimen of HOA patients, specifically in case of early stages of HOA. CONCLUSION: Currently, the need for a low-risk alternative treatment in HOA patients is felt more than ever. There are reliable references relating to the safety of Korean red ginseng, GCSB-5, XLGB, and GS-GCu in these patients, although their efficacy was limited. Additionally, herbs like curcumin and Boswellia serrata have positively affected patients with knee osteoarthritis. However, there is a lack of strong evidence supporting their effectiveness in hand osteoarthritis (HOA). This emphasizes the potential benefits that these herbs may have for HOA patients.

Efficacy of trigger point dry needling on pain and function of the hip joint: a systematic review of randomized clinical trials.

OBJECTIVE: The objective of this study was to assess the evidence for the impact of dry needling (DN) on hip pain and function. METHODS: Medline/PubMed, Embase, Scopus, Web of Science and Cochrane CENTRAL databases were searched systematically through June 2022 for randomized clinical trials (RCTs) investigating the impact of DN on hip pain and function. Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess risk of bias. Descriptive analysis was conducted to explain the outcomes and adverse events of DN in hip joint diseases. Meta-analysis was not feasible due to significant heterogeneity. RESULTS: A total of seven eligible studies (including 273 patients) were included out of 2152 screened records. Five studies were in participants with hip osteoarthritis (OA; n = 3), greater trochanteric pain syndrome (GTPS; n = 1) or piriformis syndrome (n = 1); the other two studies were conducted in healthy athletes (n = 2). Two articles assessed changes in participants' short-term visual analog scale (VAS) scores (<1 week), one of which showed that DN significantly reduced pain (P < 0.05). One-week VAS scores were analyzed in three studies, all of which demonstrated reduced scores following DN (P < 0.05). Hip range of motion (ROM) and muscle force were also improved following DN. No serious side effects were reported. CONCLUSION: DN may be safe and effective at relieving hip pain and improving hip function. DN performs significantly better than several different types of control intervention (including sham DN, no treatment, corticosteroid injections and laser). Strong evidence (high degree of certainty around the results) is lacking, and future studies should ideally use longer follow-up periods and larger sample sizes. REVIEW REGISTRATION NUMBER: CRD42022297845 (PROSPERO).

A Tale of Bilateral Rapidly Progressive Osteoarthritis of the Hip-It Is Not Always the Steroid Injection: A Case Report.

ABSTRACT: Rapidly progressive osteoarthritis of the hip is an unusual subset of hip osteoarthritis in which a >2 mm/yr rate of joint space narrowing occurs. Rapidly progressive osteoarthritis of the hip has been associated with intra-articular steroid injection, with the incidence of rapidly progressive osteoarthritis of the hip after intra-articular steroid injection ranging from 2.8% to 21%. The occurrence of rapidly progressive osteoarthritis of the hip unrelated to intra-articular steroid injection is rare, and not frequently reported. This report presents a unique case of rapidly progressive osteoarthritis of the hip in the bilateral hips of one patient. The first hip developed rapidly progressive osteoarthritis of the hip within 6 mos after an intra-articular steroid injection. Three years later, the second hip developed rapidly progressive osteoarthritis of the hip within 4 mos without any injection or use of systemic steroid medication. The etiology of rapidly progressive osteoarthritis of the hip in the absence of intra-articular steroid injection is unclear, and this case presents the opportunity to observe the development of rapidly progressive osteoarthritis of the hip due to different causes within the same individual.

Ultrasound guided injection with Collagen-based Medical Device: real-life evaluation of efficacy and safety in hip osteoarthritis.

AIMS: Data regarding the treatment of hip osteoarthritis (OA) with collagen-based extracellular bio-scaffolds are lacking. We evaluated the treatment of hip OA with ultrasound guided intraarticular injections of Collagen-based Medical Device (CMD). MATERIAL AND METHODS: Forty-four patients with Kellgren-Lawrence grade (KLG) I or II were selected, and 20/44 randomly selected patients (CMD group), were treated with 2 weekly consecutive ultrasound guided intraarticular injections of CMD (MD-HIP, Guna S.p.a. Milan, Italy). An additional 24/44 patients were treated with oral non-steroidal anti-inflammatory drugs (NSAIDs) daily (NSAIDs group). Clinical assessment, X-rays and ultrasound evaluation were performed at baseline, and after 1 month in both groups, and after 3 months in the CMD group. Outcome measures were general pain VAS (0-10), the whole WOMAC score, and the WOMAC specific subscores. RESULTS: CMD and NSAIDs group were homogenous for age, gender, VAS pain and WOMAC scores. The CMD group had significant improvement of the VAS pain (p<0.0001), global WOMAC score (p<0.0001) and WOMAC function (p<0.0001) from baseline to the 1st month, with further improvement from the 1st to the 3rd month (p<0,001; p<0.01; p<0.03, respectively). Significant improvement in WOMAC pain (p<0.0001) and WOMAC stiffness (p<0.0001) was detected at 1st month, with no significant change at 3rd month. In the NSAIDs group significant improvement in WOMAC function was detected after 1 month (p=0.021) only. No adverse events were recorded in the CMD and NSAIDs group. CONCLUSION: The ultrasound guided intraarticular hip injections of CMD resulted in significant improvement in VAS pain and WOMAC scores compared to treatment with oral NSAIDs.

Experiences of living with hip osteoarthritis and of receiving advice, education and ultrasound-guided intra-articular hip injection in the hip injection trial. A qualitative study.

OBJECTIVES: The Hip Injection Trial (HIT) compared the effectiveness of adding a single ultrasound-guided intra-articular injection of either corticosteroid and local anaesthetic or local anaesthetic alone to advice and education among people with hip osteoarthritis (OA). This nested qualitative study explored participants' experiences of living with hip OA and of the trial treatment they received. METHOD: Semi-structured telephone interviews were undertaken with a purposeful sample of trial participants after a 2-month trial follow-up. Interviewers were blinded to which injection participants had received. Thematic analysis using constant comparison was undertaken prior to knowing the trial results. RESULTS: 34 trial participants were interviewed across all arms. OA causes pain, physical limitations, difficulties at work, lowered mood, and disrupted sleep. Those who received advice and education alone felt that they had not received 'treatment' and described little/no benefit. Participants in both injection groups described marked improvements in pain, physical function, and other aspects of life (e.g., sleep, confidence). The perceived magnitude of benefit appeared greater among those who received the corticosteroid injection; however, the length of benefit varied in both injection groups. There was uncertainty about the longer-term benefits of injection and repeated injections. CONCLUSION: Hip OA is highly burdensome. Participants perceived little/no benefit from advice and education alone but reported marked improvements when combined with either injection. However, the magnitude of benefit was greater among those who received corticosteroid. The varying duration of response to injection and uncertainty regarding longer-term benefits of injection and repeated injections suggests that these areas are important for future research. TRIAL REGISTRATION: EudraCT 2014-003412-37; ISRCTN50550256.

How safe are intra-articular corticosteroid injections to the hip?

BACKGROUND: Intra-articular corticosteroid injections (ICSI) are an effective symptomatic treatment for osteoarthritis of the hip. However, the safety of ICSI has been questioned and a relatively high risk for septic arthritis, rapidly progressive osteoarthritis (RPIO) and periprosthetic joint infections (PJI) in patients undergoing subsequent total hip arthroplasty (THA) have been suggested. METHODS: This is a retrospective evaluation of 682 hips that underwent ICSI with 40 mg of Triamcinolone for primary osteoarthritis of the hip. All ICSI were performed using sterile techniques, the number of ICSI in each hip and the cumulative corticosteroid dosage were assessed. Pre- and post-injection radiographs were compared to identify cases with RPIO. Native joint septic arthritis, surgical site infections and PJI were identified by chart review. RESULTS: 4 hips (0.6%) developed RPIO 2-4 months following ICSI. The cumulative Triamcinolone dose was not associated with the development of RPIO (p = 0.281). 1 case was diagnosed with septic arthritis and treated with staged THA, there were no signs of infection at a 5 years follow-up. 483 hips (75.7%) underwent THA, including 199 hips with THA less than 3 months following ICSI and 181 hips with > 1 ICSI prior to THA. There were 3 superficial surgical site infections/wound dehiscence and no PJI. CONCLUSION: The rate of RPIO was 0.6%. The current findings suggest that if ICSI is performed under sterile conditions, the risk for septic arthritis or PJI following THA, even in patients with multiple ICSI or ICSI within 3 months prior to surgery, is minimal.

Characterization of adverse joint outcomes in patients with osteoarthritis treated with subcutaneous tanezumab.

OBJECTIVE: Due to the risk of rapidly progressive osteoarthritis (RPOA), the phase III studies of subcutaneous (SC) tanezumab in patients with moderate to severe hip or knee osteoarthritis (OA) included comprehensive joint safety surveillance. This pooled analysis summarizes these findings. METHOD: Joint safety events in the phase III studies of SC tanezumab (2 placebo- and 1- nonsteroidal anti-inflammatory drug [NSAID]-controlled) were adjudicated by a blinded external committee. Outcomes of RPOA1 and RPOA2, primary osteonecrosis, subchondral insufficiency fracture, and pathological fracture comprised the composite joint safety endpoint (CJSE). Potential patient- and joint-level risk factors for CJSE, RPOA, and total joint replacement (TJR) were explored. RESULTS: Overall, 145/4541 patients (3.2%) had an adjudicated CJSE (0% placebo; 3.2% tanezumab 2.5 mg; 6.2% tanezumab 5 mg; 1.5% NSAID). There was a dose-dependent risk of adjudicated CJSE, RPOA1, and TJR with tanezumab vs NSAID. Patient-level cross-tabulation found associations between adjudicated RPOA with more severe radiographic/symptomatic (joint pain, swelling, and physical limitation) OA. Risk of adjudicated RPOA1 was highest in patients with Kellgren-Lawrence (KL) grade 2 or 3 OA at baseline. Risk of adjudicated RPOA2 or TJR was highest in patients with KL grade 4 joints at baseline. A higher proportion of joints with adjudicated RPOA2 had a TJR (14/26) than those with adjudicated RPOA1 (16/106). CONCLUSION: In placebo- and NSAID controlled studies of SC tanezumab for OA, adjudicated CJSE, RPOA, and TJR most commonly occurred in patients treated with tanezumab and with more severe radiographic or symptomatic OA. NCT02697773; NCT02709486; NCT02528188.

The impact of moderate to severe osteoarthritis on the physical performance and quality of life: a cross-sectional study in Greek patients (PONOS study).

BACKGROUND: Osteoarthritis (OA) represents a leading cause of disability with limited data available for the Greek patients. OBJECTIVES: To evaluate the impact of moderate to severe symptomatic hip/knee OA under treatment on physical performance and quality of life. METHODS: A non-interventional, cross-sectional, epidemiological study of patients with moderate/severe OA, recruited in a single visit from 9 expert sites in Athens, Greece. Assessments were based on commonly used outcome scales: the Hip disability and Osteoarthritis Outcome Score (HOOS), the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the EuroQol-5-Dimensions 3-levels questionnaire (EQ-5D-3L). RESULTS: One hundred sixty-four patients were included in the analysis. Most of the patients were females (78.7%), with a mean age of 70.5 ± 10.2 years. Comorbidities were reported by 87.2% of patients with hypertension being the most frequently reported (53.7%), followed by dyslipidemia (31.1%), obesity (24.4%) and diabetes mellitus (23.2%). Paracetamol was the most common treatment (96%), followed by NSAIDs (75%), opioids (50%) and locally applied medications (42.7%). Both hip and knee OA patients showed substantial deterioration in health-related quality of life (QoL) and health status as reflected by the HOOS/KOOS (Function in sport and recreation was the most impaired subscale, followed by Hip- or Knee-related QoL). The mean EQ-5D-3L index score was 0.396 ± 0.319 and the mean EQ-VAS score was 52.1 ± 1.9. When compared indirectly to the local population norms our OA population had worse QoL indices. CONCLUSION: Our findings suggest the functional disability and impaired QoL of Greek patients with moderate/severe hip/knee OA under treatment emphasizing the need for novel treatments that will reduce the burden of the disease.

Recommendations for the management of hip and knee osteoarthritis: A systematic review of clinical practice guidelines.

OBJECTIVES: Guideline adherence for hip and knee osteoarthritis management is often poor, possibly related to the quality and/or inconsistent recommendations. This systematic review of hip and knee osteoarthritis guidelines aimed to appraise the quality and consistency in recommendations across higher-quality guidelines. METHODS: Eight databases, guideline repositories, and professional associations websites were searched on 27/10/2022. Guideline quality was appraised using the Appraisal of Guidelines for Research and Evaluation II (AGREE II tool) (six domains). Higher quality was defined as scoring ≥60% for domains 3 (rigour of development), 6 (editorial independence), plus one other. Consistency in recommendations across higher-quality guidelines was reported descriptively. This review was registered prospectively (CRD42021216154). RESULTS: Seven higher-quality and 18 lesser-quality guidelines were included. AGREE II domain scores for higher-quality guidelines were > 60% except for applicability (average 46%). Higher-quality guidelines consistently recommended in favour of education, exercise, and weight management and non-steroidal anti-inflammatory drugs (hip and knee), and intra-articular corticosteroid injections (knee). Higher quality guidelines consistently recommended against hyaluronic acid (hip) and stem cell (hip and knee) injections. Other pharmacological recommendations in higher-quality guidelines (e.g., paracetamol, intra-articular corticosteroid (hip), hyaluronic acid (knee)) and adjunctive treatments (e.g., acupuncture) were less consistent. Arthroscopy was consistently recommended against in higher-quality guidelines. No higher-quality guidelines considered arthroplasty. CONCLUSION: Higher-quality guidelines for hip and knee osteoarthritis consistently recommend clinicians implement exercise, education, and weight management, alongside consideration of Non-Steroidal Anti-Inflammatory Drugs and intra-articular corticosteroid injections (knee). Lack of consensus on some pharmacological options and adjunctive treatments creates challenges for guideline adherence. Future guidelines must prioritise providing implementation guidance, considering consistently low applicability scores.