Effects of repeated intra-articular hyaluronic acid on cartilage degeneration evaluated by T1ρ mapping in knee osteoarthritis.

OBJECTIVES: Intra-articular injection of hyaluronic acid (IAHA) has been used for the treatment of knee osteoarthritis (OA), but its effectiveness remains controversial. This study analyzed knee OA over time by magnetic resonance imaging (MRI) T1ρ mapping to objectively evaluate whether long-term repeated administration of IAHA influences cartilage degeneration. METHODS: Sixty knees of 60 patients [58.3 ± 12.5 years (mean ± standard deviation)] who had multiple T1ρ mapping images were retrospectively analyzed. We calculated the T1ρ values of the medial femorotibial cartilage and classified changes in degenerative areas over time into 3 groups: Improvement, No Change, and Deterioration. RESULTS: Average time between 2 MRI scans was 7.6 ± 1.2 months. The number of IAHA administrations was 15.5 ± 21.3, 8.39 ± 7.19, and 5.80 ± 7.49 in the Improvement, No Change, and Deterioration groups, respectively. Body mass index and number of IAHA administrations were significant factors causing change in the area of degeneration (p < .05) independent of age, sex, Kellgren-Lawrence grade, and posterior horn meniscus tears. CONCLUSION: Cartilage degeneration may be improved with a higher number of administrations of IAHA, based on T1ρ mapping results. This highlights the possibility of increased treatment effectiveness of IAHA for knee OA with repeated administrations.

Effect of physical therapy on early knee osteoarthritis with medial meniscal posterior tear assessed by MRI T2 mapping and 3D-to-2D registration technique: A prospective intervention study.

Objectives: The purpose of this study was to verify that exercise aimed at improving knee kinematics in early-stage knee osteoarthritis (OA) patients with medial meniscus posterior root tears (MMPRTs) reduces knee adduction angle during gait and prevents rapid cartilage degeneration in the medial compartment of the knee.Methods: Subjects were randomly assigned to an adapting alignment exercise (AAE) group, with the goal of improving knee kinematics, and a muscle training and exercise (MTE) group. Before the start of the six-month intervention and following its completion, we performed an analysis of knee kinematics during gait using a 3D-to-2D registration technique and identified the area of cartilage degeneration using MRI T2 mapping.Results: The amount of change between pre- and post-intervention measurements of the maximum angle of adduction was 0.48° (95% CI: -0.14, 1.09) in the MTE group and -0.40° (-0.84, 0.04) in the AAE group (p = .039). The amount of change in the area of cartilage degeneration according to MRI T2 mapping expressed as MTE/AAE group was 7.7 mm2 (-0.4, 15.8)/-2.7 mm2 (-10.8, 5.3) at the posterior knee (p = .043).Conclusion: AAE could be a potential treatment method that improves the natural course of knee OA with MMRPTs.

The most common classification in the mechanical diagnosis and therapy for patients with a primary complaint of non-acute knee pain was Spinal Derangement: a retrospective chart review.

Objectives: To preliminarily investigate in patients with a primary complaint of non-acute knee pain for ≥ 1 month: 1) the proportion of patients with non-acute knee pain classified by Mechanical Diagnosis and Therapy (MDT) as Spinal Derangements, 2) the number of sessions taken to identify the concluding classification, and 3) the ability of MDT classifications, demographics, and symptomatic baselines to predict pain reduction at 1-month follow-up.Methods: This study reviewed data from outpatients managed with MDT. For modeling knee pain reduction at the 1-month follow-up, 3 MDT provisional or concluding classifications (Spinal Derangement, Knee Derangement, and Non-Derangement) and the following variables were included: 1) gender, 2) symptom duration, 3) presence of low back pain (LBP), 4) the Japanese Knee Osteoarthritis Measure, 5) average pain intensity at the initial session using a 0-10 numerical rating scale, and 6) the Kellgren-Lawrence grade.Results: Data from 101 patients were extracted. The percentage of patients with the concluding classification of Spinal Derangement was 44.6%. This was greater in those patient's reporting concomitant LBP (p = .002) and without radiographic findings of knee osteoarthritis (p < .001). A concluding classification was determined by the fourth session in 80% of patients. Multiple regression modeling demonstrated that only the concluding classification significantly predicted the knee pain reduction at the 1-month follow-up.Discussion: These findings suggest the importance of careful screening assessments of the lumbar spine and the importance of detecting Derangements throughout the follow-up sessions for patients with a primary complaint of knee pain.

Volume change in infrapatellar fat pad is associated not with obesity but with cartilage degeneration.

Infrapatellar fat pad has been implicated in knee osteoarthritis. We examined whether infrapatellar fat pad volume is associated with quantitative cartilage changes using magnetic resonance imaging T1ρ mapping. Fifty-eight knees of knee pain patients (19 men, 39 women, mean age 57.0 [range 29-85] years) who were conservatively managed and had >1 T1ρ mapping images taken over time were evaluated. We used three slices from the medial femoral and tibial cartilage; areas showing T1ρ values <130 ms and >50 ms were designated as having cartilage degeneration. Cases were categorized into three groups: Improvement, No Change, and Deterioration. Fat-suppressed T2-weighted sagittal magnetic resonance images were used for measuring infrapatellar fat pad volume. Percent change in infrapatellar fat pad volume was -5.01 ± 5.66%, -2.06 ± 4.92%, and 0.05 ± 6.09% in the Improvement (n = 22), No Change (n = 22), and Deterioration (n = 14) groups, respectively, demonstrating significantly reduced infrapatellar fat pad volume in the Improvement group (p < 0.05). Multivariate regression analyses revealed that the percent change in infrapatellar fat pad volume significantly affected T1ρ change category independent of age, sex, follow-up period, baseline infrapatellar fat pad volume, and Kellgren-Lawrence grade. Infrapatellar fat pad volume and obesity or body weight change showed no correlation. Infrapatellar fat pad volume was reduced in patients with improved quantitative cartilage assessment on magnetic resonance imaging T1ρ mapping. This is the first study demonstrating associations between quantitative cartilage changes and infrapatellar fat pad morphological changes, suggesting a detrimental role of infrapatellar fat pad volume in articular cartilage degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Bone morphological factors influencing cartilage degeneration in the knee.

OBJECTIVES: Morphological features of the distal femur and proximal tibia associated with cartilage degeneration are unknown. This study aimed to elucidate local anatomical parameters of the knee which correlate with articular cartilage degeneration using MRI T1ρ mapping. METHODS: This study involved 200 subjects with knee pain (mean age, 48.7 years; range, 14-80 years) with no severe osteoarthritic changes on plain X-ray. T1ρ values were measured in the regions of interest on the surface layer of the cartilage on mid-coronal images of the femorotibial joint. Assessment of medial and lateral posterior tibial slope (MTS, LTS) and medial and lateral femoral condylar offset ratio (MFCOR, LFCOR) was performed using sagittal proton density-weighted imaging. Morphological assessment of posterior root and horn of menisci was also performed according to a modified Whole Organ Magnetic Resonance Imaging Score (WORMS) of the knee. RESULTS: Multiple regression analysis revealed that a decrease in MTS was associated with increased T1ρ values in the medial tibia, independent of age, osteoarthritic changes on plain X-ray, femur-tibia angle (FTA), and posterior medial meniscal lesions. CONCLUSIONS: Shallow MTS correlates with cartilage degeneration in symptomatic patients. This parameter could help in understanding the etiology of osteoarthritis in the early stage. Future kinematic studies will be needed to confirm our findings.

Effectiveness of Radiofrequency Hyperthermia for Treating Cartilage in Guinea Pigs with Primary Osteoarthritis.

Objective Autophagy was reported to be essential for maintaining chondrocyte function, and reduced autophagy leads to osteoarthritis (OA). Previous studies showed involvement of heat shock stress in the control of autophagy in cells. This study sought to investigate the effect of hyperthermia on the expression of autophagy-related proteins in articular cartilage and the progression of naturally occurring OA in Hartley guinea pigs. Design Radiofrequency pulses of 13.56 MHz were applied to the animals' knees for 20 minutes to induce hyperthermia. The knee joints were resected at 8 hours, 24 hours, 72 hours, 7 days, and 6 months after hyperthermia. Serial sections of knees were examined for histopathological changes. The expression levels of Unc-51-like kinase 1 (ULK1) and Beclin1 were analyzed by immunohistochemistry. Results Analysis of the distribution of positive cells showed that, in cases of moderate OA, ULK1 and Beclin1 expression levels were significantly decreased in the superficial zone (SZ) and middle zone (MZ) ( P < 0.01) compared with normal cartilage. Seven days after exposure to radiofrequency waves, expression levels of ULK1 and Beclin1 were augmented in the SZ in animals with mild OA. The severity of cartilage degradation was significantly reduced ( P < 0.01) in the radiofrequency-treated knees versus the untreated knees. Conclusions This study showed that heat stimulation enhanced autophagy in healthy knee chondrocytes and chondrocytes in knees with mild OA. The study also showed that long-term periodic application of hyperthermia suppresses aging-related progression of OA. The activation of autophagy by radiofrequency hyperthermia may be an effective therapeutic approach for osteoarthritis.

A pilot study comparing the efficacy of radiofrequency and microwave diathermy in combination with intra-articular injection of hyaluronic acid in knee osteoarthritis.

[Purpose] This study aimed to compare the efficacy of radiofrequency diathermy with that of microwave diathermy in combination with intra-articular injection of hyaluronic acid into the knee of patients with osteoarthritis (OA). [Subjects] A total of 17 patients with knee OA were enrolled. The participants were randomly divided into two groups: a radiofrequency diathermy group (RF group, 9 subjects), and a microwave diathermy group (MW group, 8 subjects). [Methods] Subjects received radiofrequency or microwave thermal therapy 3 times at 1-week intervals. Intra-articular injection of hyaluronic acid was administered 10 min before every thermal therapy session. The outcome was evaluated using the Japan Orthopaedic Association (JOA) and the Lequesne Index (LI) at baseline, at weeks 1 (1 week after the first thermal therapy) and 3 (1 week after the last thermal therapy). [Results] The JOA scale increased significantly after three sessions of thermal therapy in the RF group, while no significant increase was observed in the MW group. LI decreased significantly after 3 weeks in the RF group. In the MW group, there was no significant difference in LI between the two time points. [Conclusion] This study revealed that symptom relief in patients with knee OA was greater with radiofrequency diathermy than with microwave diathermy with concurrent use of hyaluronic acid injection, presumably due to the different heating characteristics of the two methods.

Medial meniscal posterior root/horn radial tears correlate with cartilage degeneration detected by T1ρ relaxation mapping.

OBJECTIVE: This study aimed to identify factors on routine pulse sequence MRI associated with cartilage degeneration observed on T1ρ relaxation mapping. MATERIALS AND METHODS: This study included 137 subjects with knee pain. T1ρ values were measured in the regions of interest on the surface layer of the cartilage on mid-coronal images of the femorotibial joint. Assessment of cartilage, subchondral bone, meniscus and ligaments was performed using routine pulse sequence MRI. Radiographic evaluation for osteoarthritis was also performed. RESULTS: Multiple regression analysis revealed posterior root/horn tears to be independent factors increasing the T1ρ values of the cartilage in the medial compartment of the femorotibial joint. Even when adjusted for radiographically defined early-stage osteoarthritis, medial posterior meniscal radial tears significantly increased the T1ρ values. CONCLUSIONS: This study showed that posterior root/horn radial tears in the medial meniscus are particularly important MRI findings associated with cartilage degeneration observed on T1ρ relaxation mapping. Morphological factors of the medial meniscus on MRI provide findings useful for screening early-stage osteoarthritis.

A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis.

Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA.

The effects of radiofrequency hyperthermia on pain and function in patients with knee osteoarthritis: a preliminary report.

BACKGROUND: The clinical evidence of the efficacy of hyperthermia on osteoarthritis (OA) has not yet been clearly established. In addition, the application of a modality that can control the temperature inside the joints has not been reported. The purpose of this study was to investigate the effect of percutaneous radiofrequency hyperthermia, which could safely raise the temperature of the body core, in patients with OA knees. METHODS: Temperature changes inside the knee joint without OA were measured during exposure to radiofrequency. Radiofrequency hyperthermia was performed on 12 OA knees by exposure to 8 MHz and 200 W for 20 min, 3 times, at 1-week intervals. The clinical outcome was evaluated by use of the Lequesne index (LI) and the Japan Orthopaedic Association (JOA) scale. The osteoarthritis research society international (OARSI) responder criteria were also analyzed. RESULTS: Radiofrequency hyperthermia of 8 MHz and 200 W for 20 min increased the temperature inside the joint from 34.4 to 39.4°C. The LI decreased by 3.55 points from baseline during the 3 weeks. The JOA scale improved significantly during the period, reaching 86.25 points at the final examination from baseline of 67.5 points. 67% of patients had a response to the therapy according to OARSI criteria. No side effects were observed. CONCLUSIONS: Radiofrequency hyperthermia can safely increase the temperature inside the knee joint. Radiofrequency hyperthermia on OA knees provides a remarkable pain relief effect and can improve the patients' daily life. In the future, clinical studies should be performed with a protocol containing more cases, with appropriate control groups.

Caspase inhibitors reduce severity of cartilage lesions in experimental osteoarthritis.

OBJECTIVE: To examine the therapeutic efficacy of caspase inhibitors in experimental osteoarthritis (OA). METHODS: Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). Rabbits were treated with intraarticular (i.a.) injections of caspase inhibitors 3 times per week starting 1 week postoperatively. Animals were killed 9 weeks after ACLT, for macroscopic, histologic, and immunohistochemical assessment of the knee joints. RESULTS: I.a. administration of the pan-caspase inhibitor Z-VAD-FMK significantly reduced cartilage degradation, as assessed by macroscopic and microscopic criteria. Untreated knees showed large numbers of chondrocytes with active caspase 3 and the p85 fragment of poly(ADP-ribose) polymerase (PARP p85) that is generated during apoptosis. The frequency of cells positive for PARP p85 and active caspase 3 was reduced in Z-VAD-FMK-treated knees. Inhibitors specific for caspase 3 or caspase 8 showed no significant efficacy. Caspase 1 inhibitor and the combination of caspase 3 and caspase 8 inhibitors reduced OA pathology. CONCLUSION: These results provide direct support for a role of cell death in OA pathogenesis. Caspase inhibitors reduced the severity of cartilage lesions in experimental OA, suggesting that they may have disease-modifying activity in human OA.