Celecoxib: considerations regarding its potential disease-modifying properties in osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive loss of articular cartilage, subchondral bone sclerosis, osteophyte formation, and synovial inflammation, causing substantial physical disability, impaired quality of life, and significant health care utilization. Traditionally, non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase (COX)-2 inhibitors, have been used to treat pain and inflammation in OA. Besides its anti-inflammatory properties, evidence is accumulating that celecoxib, one of the selective COX-2 inhibitors, has additional disease-modifying effects. Celecoxib was shown to affect all structures involved in OA pathogenesis: cartilage, bone, and synovium. As well as COX-2 inhibition, evidence indicates that celecoxib also modulates COX-2-independent signal transduction pathways. These findings raise the question of whether celecoxib, and potentially other coxibs, is more than just an anti-inflammatory and analgesic drug. Can celecoxib be considered a disease-modifying osteoarthritic drug? In this review, these direct effects of celecoxib on cartilage, bone, and synoviocytes in OA treatment are discussed

User-friendliness of a dedicated orthopedic device for knee joint distraction: Experiences from clinical practice

Introduction: Knee joint distraction (KJD) is a surgical technique for treatment of severe knee osteoarthritis at a relatively young age. In the absence of devices intended for KJD, this procedure has only been performed with devices with another intended use. In collaboration with patients, clinicians and medical device experts, a dedicated distraction (DD) device intended for KJD was developed. Objectives: To compare user-friendliness between the new DD device and a previously used concept distraction (CD) device. Methods: Patients were treated with either of the devices (n = 22 versus n = 22). The intervention duration and treatment complications were registered. After treatment, patients filled out a questionnaire about user-friendliness of the device during treatment, containing questions on difficulties performing activities regarding clothing, sleeping, pin care, daily activities, mobility, and complications. Results were compared between the 2 groups. Results: Intervention duration was on average 56 versus 44 minutes (P .1). Conclusions: The DD device intended for KJD reduces surgery time and improves user-friendliness compared to the CD device. As such, the DD device contributes to implementation of KJD treatment in regular care

Knee joint distraction results in MRI cartilage thickness increase up to 10 years after treatment

OBJECTIVES: Knee joint distraction (KJD) has been shown to result in long-term clinical improvement and short-term cartilage restoration in young OA patients. The objective of the current study was to evaluate MRI cartilage thickness up to 10 years after KJD treatment, using a 3D surface-based approach. METHODS: Twenty end-stage knee OA patients were treated with KJD. MRI scans (1.5 T) were performed before and at 1, 2, 5, 7, and 10 years after treatment. Tibia and femur cartilage segmentation and registration to a canonical surface were performed semi-automatically. Statistical parametric mapping with linear mixed models was used to analyse whole-joint changes. The influence of baseline patient characteristics was analysed with statistical parametric mapping using linear regression. Relevant weight-bearing parts of the femur were selected to obtain the average cartilage thickness in the femur and tibia of the most- (MAC) and least-affected compartment. These compartmental changes over time were analysed using repeated measures ANOVA; missing data was imputed. In all cases, P 0.05). Compartmental analyses showed significant short- and long-term thickness increase in the tibia and femur MAC (all P <0.05). CONCLUSION: KJD results in significant short- and long-term cartilage regeneration, up to 10 years post-treatment. TRIAL REGISTRATION: Netherlands Trial Register, https://www.trialregister.nl, NL419

Reduction of pin tract infections during external fixation using cadexomer iodine

Purpose: Knee joint distraction (KJD) is a joint-preserving treatment for younger osteoarthritis patients. KJD has shown positive results in regular care, but the external fixation frame often caused pin tract skin infections. Therefore, the use of cadexomer iodine was included in the wound care protocol. The goal of this cross-sectional study was to evaluate whether use of this ointment reduced the number of patients with infections during KJD treatment. Methods: Patients treated with KJD in regular care were included if they gave consent for use of their data and completed treatment with the newest distraction device before 2020. All patients followed a wound care protocol, which since March 2019 included using cadexomer iodine ointment. The number of patients experiencing pin tract infections was compared between patients who did (March 2019–December 2019) and did not (November 2017–March 2019) use the ointment. Results: Sixty-seven patients were included; 34 patients used cadexomer iodine and 33 patients did not. Patient who did not use cadexomer iodine experienced twice as many infections (64% vs 32%;p = 0.010). There was a significant difference in the number of patients with serious infections, requiring more antibiotics than the standard 7-day oral antibiotics (30% without vs 6% with cadexomer iodine; p = 0.009). Conclusions: The use of cadexomer iodine ointment during KJD results in a significant reduction of the number of patients experiencing pin tract infections during treatment. Use of this ointment should be considered standard protocol during KJD treatment and could be of value in general external fixator usage as well

Comparison between 2D radiographic weight-bearing joint space width and 3D MRI non-weight-bearing cartilage thickness measures in the knee using non-weight-bearing 2D and 3D CT as an intermediary

Background: In knee osteoarthritis, radiographic joint space width (JSW) is frequently used as a surrogate marker for cartilage thickness; however, longitudinal changes in radiographic JSW have shown poor correlations with those of magnetic resonance imaging (MRI) cartilage thickness. There are fundamental differences between the techniques: radiographic JSW represents two-dimensional (2D), weight-bearing, bone-to-bone distance, while on MRI three-dimensional (3D) non-weight-bearing cartilage thickness is measured. In this exploratory study, computed tomography (CT) was included as a third technique, as it can measure bone-to-bone under non-weight-bearing conditions. The objective was to use CT to compare the impact of weight-bearing versus non-weight-bearing, as well as bone-to-bone JSW versus actual cartilage thickness, in the knee. Methods: Osteoarthritis patients (n = 20) who were treated with knee joint distraction were included. Weight-bearing radiographs, non-weight-bearing MRIs and CTs were acquired before and 2 years after treatment. The mean radiographic JSW and cartilage thickness of the most affected compartment were measured. From CT, the 3D median JSW was calculated and a 2D projectional image was rendered, positioned similarly and measured identically to the radiograph. Pearson correlations between the techniques were derived, both cross-sectionally and longitudinally. Results: Fourteen patients could be analyzed. Cross-sectionally, all comparisons showed moderate to strong significant correlations (R = 0.43–0.81; all p < 0.05). Longitudinal changes over time were small; only the correlations between 2D CT and 3D CT (R = 0.65; p = 0.01) and 3D CT and MRI (R = 0.62; p = 0.02) were statistically significant. Conclusion: The poor correlation between changes in radiographic JSW and MRI cartilage thickness appears primarily to result from the difference in weight-bearing, and less so from measuring bone-to-bone distance versus cartilage thickness

Changes in cartilage thickness and denuded bone area after knee joint distraction and high tibial osteotomy—post‐hoc analyses of two randomized controlled trials

High tibial osteotomy (HTO) and knee joint distraction (KJD) are joint‐preserving treat-ments that unload the more affected compartment (MAC) in knee osteoarthritis. This post‐hoc study compares two‐year cartilage‐thickness changes after treatment with KJD vs. HTO, and identifies factors predicting cartilage restoration. Patients indicated for HTO were randomized to KJD (KJDHTO) or HTO treatment. Patients indicated for total knee arthroplasty received KJD (KJDTKA). Outcomes were the MRI mean MAC cartilage thickness and percentage of denuded bone area (dABp) change two years after treatment, using radiographic joint space width (JSW) as the refer-ence. Cohen’s d was used for between‐group effect sizes. Post‐treatment, KJDHTO patients (n = 18) did not show significant changes. HTO patients (n = 33) displayed a decrease in MAC cartilage thickness and an increase in dABp, but an increase in JSW. KJDTKA (n = 18) showed an increase in MAC cartilage thickness and JSW, and a decrease in dABp. Osteoarthritis severity was the strongest predictor of cartilage restoration. Kellgren–Lawrence grade ≥3 showed significant restoration (p < 0.01) after KJD; grade ≤2 did not. Effect sizes between severe KJD and HTO patients were large for MAC MRI cartilage thickness (d = 1.09; p = 0.005) and dABp (d = 1.13; p = 0.003), but not radiographic JSW (d = 0.28; p = 0.521). This suggests that in knee osteoarthritis patients with high disease severity, KJD may be more efficient in restoring cartilage thickness

Exploring the differences between radiographic joint space width and MRI cartilage thickness changes using data from the IMI-APPROACH cohort

[Abstract] Objective: Longitudinal weight-bearing radiographic joint space width (JSW) and non-weight-bearing MRI-based cartilage thickness changes often show weak correlations. The current objective was to investigate these correlations, and to explore the influence of different factors that could contribute to longitudinal differences between the two methods. Methods: The current study included 178 participants with medial osteoarthritis (OA) out of the 297 knee OA participants enrolled in the IMI-APPROACH cohort. Changes over 2 years in medial JSW (ΔJSWmed), minimum JSW (ΔJSWmin), and medial femorotibial cartilage thickness (ΔMFTC) were assessed using linear regression, using measurements from radiographs and MRI acquired at baseline, 6 months, and 1 and 2 years. Pearson R correlations were calculated. The influence of cartilage quality (T2 mapping), meniscal extrusion (MOAKS scoring), potential pain-induced unloading (difference in knee-specific pain scores), and increased loading (BMI) on the correlations was analyzed by dividing participants in groups based on each factor separately, and comparing correlations (slope and strength) between groups using linear regression models. Result: Correlations between ΔMFTC and ΔJSWmed and ΔJSWmin were statistically significant (p < 0.004) but weak (R < 0.35). Correlations were significantly different between groups based on cartilage quality and on meniscal extrusion: only patients with the lowest T2 values and with meniscal extrusion showed significant moderate correlations. Pain-induced unloading or BMI-induced loading did not influence correlations. Conclusions: While the amount of loading does not seem to make a difference, weight-bearing radiographic JSW changes are a better reflection of non-weight-bearing MRI cartilage thickness changes in knees with higher quality cartilage and with meniscal extrusion

Relationship Between Motion, Using the GaitSmartTM System, and Radiographic Knee Osteoarthritis: An Explorative Analysis in the IMI-APPROACH Cohort

Multicenter study[Abstract] Objectives: To assess underlying domains measured by GaitSmartTMparameters and whether these are additional to established OA markers including patient reported outcome measures (PROMs) and radiographic parameters, and to evaluate if GaitSmart analysis is related to the presence and severity of radiographic knee OA. Methods: GaitSmart analysis was performed during baseline visits of participants of the APPROACH cohort (n = 297). Principal component analyses (PCA) were performed to explore structure in relationships between GaitSmart parameters alone and in addition to radiographic parameters and PROMs. Logistic and linear regression analyses were performed to analyse the relationship of GaitSmart with the presence (Kellgren and Lawrence grade ≥2 in at least one knee) and severity of radiographic OA (ROA). Results: Two hundred and eighty-four successful GaitSmart analyses were performed. The PCA identified five underlying GaitSmart domains. Radiographic parameters and PROMs formed additional domains indicating that GaitSmart largely measures separate concepts. Several GaitSmart domains were related to the presence of ROA as well as the severity of joint damage in addition to demographics and PROMs with an area under the receiver operating characteristic curve of 0.724 and explained variances (adjusted R2) of 0.107, 0.132 and 0.147 for minimum joint space width, osteophyte area and mean subchondral bone density, respectively. Conclusions: GaitSmart analysis provides additional information over established OA outcomes. GaitSmart parameters are also associated with the presence of ROA and extent of radiographic severity over demographics and PROMS. These results indicate that GaitsmartTM may be an additional outcome measure for the evaluation of OA