Diacerein Versus Chondroitin Sulfate in Treatment of Adult Kashin-Beck Disease: An Intervention Trial in Heilongjiang Province, China

Background: Kashin-Beck disease (KBD) is a special type of osteoarthritis and has disabled and stunted the growth of hundreds of people in China. It also can affect patients' ability to work and live. So, how to conduct effective treatment for adult KBD patients has become a major public health problem in current KBD endemic areas. In this trial, therapeutic effects of diacerein and chondroitin sulfate on adult KBD was to evaluate and compare so that we can screen out more suitable drug. Methods: 308 KBD patients were divided into two groups and received chondroitin sulphate (Group A) and diacerein (Group B) for 24 weeks, respectively. Data were collected at 0 week (baseline), 12 weeks (primary end point) and 24 weeks (secondary end point) to calculate the proportion of patients with effective therapeutic effect and overall improvement rate (primary efficacy parameters), WOMAC pain and stiffness scores (secondary efficacy parameters). Blood sample was collected to measure liver and renal function indexes. All indexes and parameters were analysed with SPSS software and intent-to-treat (ITT) analysis was applied. Results: Two primary efficacy parameters in group B at primary end point were significantly higher than those in group A (P=0.021, P=0.007), but no statistical differences were seen in these two primary efficacy parameters between two groups at secondary end point or between primary and secondary end points in same group (all P>0.05). In both groups, with the prolongation of treatment time, WOMAC pain and stiffness scores decreased significantly (all P<0.001), but no significant differences were seen between primary and secondary end points (all P>0.05). In addition, in both groups, the occurrences of total adverse events were relatively low and no side effect on liver function was seen. Diacerein also had no side effect on renal function. Conclusion: For treatment of adult KBD, both diacerein and chondroitin sulfate were effective, and diacerein might work stronger than chondroitin sulfate. Taking into account both efficacy and safety, the optimal intervention time of diacerein was 12 weeks. Trial registration: The trial was registered complementally on 31/10/2020, and the registration number in the Chinese Clinical Trial Registry is ChiCTR2000039600 (http://www.chictr.org.cn).

Intra Articular Ozone Modulates Inflammation and Has Anabolic Effect on Knee Osteoarthritis: IL-6 and IGF-1 as Pro-Inflammatory and Anabolic Biomarkers

Objectives: (1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world rehabilitation setting; (2) to differentiate Ozone effect in diabetic (DM)/obese and non-DM/non-obese patients; (3) to evaluate clinical effectiveness by visual analog scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study ran from January 2018 to September 2021. Inclusion criteria: (a) patients 18 years or older; (b) with knee OA KL 2° or more; (c) biochemical analysis before-and-after treatment; (d) pain more than 3 on VAS. Exclusion Criteria: (a) previous knee surgery; (b) favism; (c) pregnancy; (d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: (a) IL-6; (b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: (a) CRP, (b) ESR, (c) uric acid, (d) VAS pain, (e) WOMAC pain, function and stiffness. Ozone protocol consisted of four sessions (once a week) of an intra-articular infiltration of 20 mL (20 µg/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-α Plus®). For biochemical evaluation, SNIBE MAGLUMI ™ IL-6 (CLIA) and SNIBE MAGLUMI ™ IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by a Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.70 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only non-DM/non-obese knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p < 0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in a real world rehabilitation setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone tends to downregulate pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.

Comparing Patient-Reported Outcomes From Sham and Saline-Based Placebo Injections for Knee Osteoarthritis: Data From a Randomized Clinical Trial of Lorecivivint

Background: Durable, meaningful symptom responses to intra-articular saline placebo injections are observed in knee osteoarthritis (OA) trials, but it is unclear if these are due to physiological effects. Purpose: To perform a prospective comparison of patient-reported outcome responses among participants with knee OA who underwent intra-articular injection of saline-based placebo or sham (dry needle). Study Design: Randomized controlled trial; Level of evidence, 2. Methods: From a 24-week randomized double-blind trial, participants with moderate to severe knee OA received 2-mL intra-articular injections of saline-based placebo (PBO; 99.45% PBS) or sham (dry needle) to the target knee. Least squares mean differences of changes from baseline to week 24 were compared between the PBO and sham groups for the following: pain Numeric Rating Scale; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function; and patient global assessment. Bang Blinding Index was used to evaluate all-group blinding on day 1 and week 24. Results: In total, 116 and 117 participants were randomized to the PBO and sham groups, respectively. Within the full trial population, the mean ± SD age and body mass index were 59.0 ± 8.5 years and 28.97 ± 4.01, respectively. An overall 406 (58.4%) were female, and 394 (57.3%) had Kellgren-Lawrence grade 3 target knee OA. The PBO and sham groups demonstrated clinically meaningful improvements (≥10%) from baseline in all patient-reported outcomes at all time points (ie, weeks 4-24). Mean differences (95% CI) at week 24 between the PBO and sham groups were as follows: pain Numeric Rating Scale, –0.10 (–0.79 to 0.59; P = .78); WOMAC pain, –2.89 (–9.70 to 3.92; P = .40); WOMAC stiffness, –2.37 (–9.37 to 4.63; P = .51); and WOMAC function, –1.39 (–8.06 to 5.29; P = .68). Bang Blinding Index indicated that blinding was maintained. Conclusion: PBO and sham groups demonstrated equivalent patient-reported outcomes at all time points through week 24, suggesting that responses attributed to saline were contextual (ie, to the procedure) and not physiological. Registration: NCT03122860 (ClinicalTrials.gov identifier).

Study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis of the knee

Background: Osteoarthritis (OA) of the knee is the most common degenerative joint disorder that results in disability and increased morbidity. Conventional treatment of OA with non-steroidal anti-inflammatory drugs (NSAIDs) often leads to serious adverse side effects that may increase morbidity and mortality. Glucosamine and Methylsulfonylmethane (MSM) have anti-inflammatory and analgesic properties which may supplement NSAIDs. Hence this study was aimed to determine the effectiveness and safety of these drugs in the management of knee OAMethods: 76 (63.33%) female and 44 (36.67%) male patients of OA of the knees were divided equally into four groups depending upon the therapy with Glucosamine or MSM or their combination (study groups) or none of them (control group) for 12 weeks. After the written consent, a detail Clinical History& Examination, Biochemical investigations, X-rays of chest and knees and ECG were done. The outcome of the treatment was assessed by Western Ontario and McMaster University Osteoarthritis (WOMAC) Index and for any adverse drug effects.Results: After 12 weeks of study there was significant decrease in mean WOMAC pain scores (27.29-39.13) and total aggregate scores (23.53-37.14%) in study groups (p<0.01-p<0.001) as compared to control group (14.28 % and 8.82% respectively). Besides the relief of pain and improvement in physical functions were superior in patients treated with combination therapy. Conclusions: This study showed Glucosamine & MSM are effective in the management of OA of knee and are safe health supplement to NSAIDs while their combination was more superior and effective.

Increased motor cortex inhibition as a marker of compensation to chronic pain in knee osteoarthritis

This study aims to investigate the associative and multivariate relationship between different sociodemographic and clinical variables with cortical excitability as indexed by transcranial magnetic stimulation (TMS) markers in subjects with chronic pain caused by knee osteoarthritis (OA). This was a cross-sectional study. Sociodemographic and clinical data were extracted from 107 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models per TMS markers: motor threshold (MT), motor evoked potential (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). In our multivariate models, the two markers of intracortical inhibition, SICI and CSP, had a similar signature. SICI was associated with age (β: 0.01), WOMAC pain (β: 0.023), OA severity (as indexed by Kellgren–Lawrence Classification) (β: − 0.07), and anxiety (β: − 0.015). Similarly, CSP was associated with age (β: − 0.929), OA severity (β: 6.755), and cognition (as indexed by the Montreal Cognitive Assessment) (β: − 2.106). ICF and MT showed distinct signatures from SICI and CSP. ICF was associated with pain measured through the Visual Analogue Scale (β: − 0.094) and WOMAC (β: 0.062), and anxiety (β: − 0.039). Likewise, MT was associated with WOMAC (β: 1.029) and VAS (β: − 2.003) pain scales, anxiety (β: − 0.813), and age (β: − 0.306). These associations showed the fundamental role of intracortical inhibition as a marker of adaptation to chronic pain. Subjects with higher intracortical inhibition (likely subjects with more compensation) are younger, have greater cartilage degeneration (as seen by radiographic severity), and have less pain in WOMAC scale. While it does seem that ICF and MT may indicate a more acute marker of adaptation, such as that higher ICF and MT in the motor cortex is associated with lesser pain and anxiety.

A community-centric multi-disciplinary education program with the 8-section brocade Tai Chi therapy for patients with osteoarthritis of the knee – a pilot study

Background Osteoarthritis (OA) of the knee is one of the most common chronic degenerative joint diseases, and a multi-disciplinary approach to educating patients with OA knee are effective in symptoms management. Tai Chi exercise is a novel approach to relieving knee OA symptoms. Combining both educational program and Tai Chi has not yet been explored. Methods Multi-disciplinary education program included a total of 4-week 2-h weekly talks delivered by different health professionals with live demonstrations. This was then followed by a 1-h Tai Chi class (Baduanjin). Results from IPAQ (Physical activity level), WOMAC (evaluate knee OA conditions), and SF-36v2 (quality of life) were collected at the first class of education program, 3 and 6 months after the end of Tai Chi class. CSQ-8 (program effectiveness) was administered on the last day of Tai Chi class. Results One hundred and twelve patients joined the program. The overall attendance was over 90% with close-to-zero dropout rate. Satisfaction scored high in 85% of patients. WOMAC pain scores (p = 0.04) and SF-36v2 emotional role (p = 0.02) were statistically decreasing (improving) at 6 months after the program. SF-36v2 physical role and mental health tended to improve with time. Conclusions Combining both multidisciplinary education program program and Tai Chi exercise for knee OA patients was proven feasible. This program received high satisfaction, high attendance and very low dropout rates without any adverse event. Patients’ pain and emotion were significantly improved. A large-scale randomized trial introducing a control group is recommended. Trial registration Registry: ClinicalTrials.gov Registration number: NCT04204213 Date of registration: 18/12/2019 (Retrospectively registered)

Effect of a Single-Shot of a High-Density Viscoelastic Solution of Hyaluronic Acid in Patients with Symptomatic Primary Knee Osteoarthritis: The No-Dolor Study

Background Pronolis®HD mono 2.5% is a novel, one-shot, high-density sterile viscoelastic solution, recently available in Spain, which contains a high amount of intermediate molecular weight hyaluronic acid (HA), highly concentrated (120 mg in 4.8 mL solution: 2.5%). The objective of the study was to analyze the efficacy and safety of this treatment in symptomatic primary knee osteoarthritis (OA). Methods This observational, prospective, multicenter, single-cohort study involved 166 patients with knee OA treated with a single-shot of Pronolis®HD mono 2.5% and followed up as many as 24 weeks. Results Compared with baseline, the score of the Western Ontario and McMaster Universities Arthritis Osteoarthritis Index (WOMAC) pain subscale significantly reduced at the 12-week visit (primary endpoint, median: 9 interquartile range [IQR]: 7-11 versus median: 4; IQR: 2-6). The percentage of patients achieving >50% improvement in the pain subscale increased progressively from 37.9% (at 2 weeks) to 66.0% (at 24 weeks). Similarly, WOMAC scores for pain on movement, stiffness subscale, and functional capacity subscale showed significant reductions at the 12-week visit which were maintained up to the 24-week visit. The EuroQol visual analog scale score significantly increased after 12 weeks (median: 60 versus 70). The need for rescue medication (analgesics/nonsteroidal anti-inflammatory drugs) also significantly decreased in all post-injection visits. Three patients (1.6%) reported local adverse events (joint swelling) of mild intensity. Conclusions In conclusion, a single intra-articular injection of the high-density viscoelastic gel of HA is effective and safe for the relief of symptoms in patients with knee OA. Trial registration: ClinicalTrial# NCT04196764

Intra Articular Ozone Modulates Inflammation and Has Anabolic Effect on Knee Osteoarthritis: IL-6 and IGF-1 as Pro-Inflammatory and Anabolic Biomarkers

Objectives: 1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world in Rehabilitation Setting; 2) to evaluate clinical effectiveness by Visual Analog Scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study run from January 2018 to September 2021. Inclusion criteria: a) patients 18 years or older; b) with knee OA KL 2&ordm; or more; c) biochemical analysis before-and-after treatment; d) pain more than 3 on VAS. Exclusion Criteria: a) previous knee surgery; b) favism; c) pregnancy; d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: a) IL-6; b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: a) CRP, b) ESR, c) uric acid, d) VAS pain, e) WOMAC pain, function and stiffness. Ozone protocol consisted of 4 sessions (once a week) of an intra-articular infiltration of 20 mL (20&micro;g/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-&alpha; Plus &reg;). For biochemical evaluation, SNIBE MAGLUMI &trade; IL-6 (CLIA) and SNIBE MAGLUMI &trade; IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.7 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p&lt;0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in real world Rehabilitation Setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone downregulates pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.

Efficacy of mud plus bath therapy as compared to bath therapy in osteoarthritis of hands and knees: a pilot single-blinded randomized controlled trial

The primary objective of this study was to assess the efficacy of mud plus bath therapy in comparison to bath therapy alone in hand and knee osteoarthritis (HOA and KOA). We conducted a single-blinded randomized controlled trial (RCT). Patients were randomly assigned to either mud plus bath therapy (group 1) or balneotherapy (group 2). The primary outcome was a change in AUSCAN questionnaire for HOA and in WOMAC for KOA at month 12. Evaluations were performed at baseline (B), immediately after the interventions (week 2, W2) and after 3 (M3), 6 (M6), 9 (M9) and 12 (M12) months. 37 patients with KOA and 52 with HOA were randomized in the study. In HOA patients, AUSCAN pain improved more in group 1 compared to group 2 at M3, M6 and M12 (p<0.001, p=0.001 and p=0.038, respectively). AUSCAN stiffness improved more in group 1 at M3 (p=0.001). AUSCAN function improved more at M3, M6, M9 and M12 (p=0.001, p=0.001, p=0.014 and p=0.018, respectively). Regarding, KOA, WOMAC function decreased more prominently in group 1 compared to group 2 at M9 (p=0.007). The absolute values of WOMAC function at M6 and M9 were lower in group 1 compared to group 2 (p=0.029 and p=0.001, respectively). WOMAC pain absolute values were lower in group 1 at W2 (p=0.044) and at M9 (p=0.08). We conducted a RCT on the efficacy of mud plus balneotherapy over balneotherapy alone in HOA and KOA. We found that mud plus balneotherapy was more effective than balneotherapy alone on clinical outcomes of HOA. Differences in clinical outcomes of KOA were not significant, yet numerically higher.

Pharmacological Use of Gamma-Aminobutyric Acid Derivatives in Osteoarthritis Pain Management: A Systematic Review

Background Pain is the major complication of osteoarthritis (OA) patients and is a decisive symptom for medical intervention. Gamma-aminobutyric acid (GABA) derivatives are optional painkillers but not widely used in pain management of OA patients. We synthesized the efficacy and safety of GABA derivatives for OA pain management. Methods We searched Medline, Cochrane CENTRAL, Embase, and ClinicalTrals.gov from inception to 13 October 2021 and included randomized controlled trials (RCTs) comparing the efficacy and safety of GABA derivatives with placebo or standard control in OA pain management. Two independent reviewers extracted data and assessed these studies for risk of bias using Cochrane Collaboration’s tool for RCT. Results In total, three eligible RCTs (n=3) meeting the eligibility criteria were included. Among these RCTs, one focused on hand OA pain management, while two RCTs focused on knee OA. In hand OA, pregabalin reduced numerical rating scale (NRS) score and the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score significantly compared with placebo, and caused 55 AEs. In knee OA, pregabalin reduced visual analogue scale (VAS) score and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score significantly with no recorded adverse event (AE). Meanwhile, in knee OA, gabapentin reduced both VAS score and WOMAC pain score compared with acetaminophen and caused 9 AEs. Conclusions GABA derivates are effective and safe in OA pain management. However, future researches with large sample size are needed to further prove the efficacy of GABA derivates in OA pain control. Trial registration: CRD42021240225.