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

Processes ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 138
Author(s):  
Marcos E. Fernández-Cuadros ◽  
Olga S. Pérez-Moro ◽  
María J. Albaladejo-Florín ◽  
María M. Tobar-Izquierdo ◽  
Amelia Magaña-Sánchez ◽  
...  

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.

Author(s):  
Marcos E. Fernández-Cuadros ◽  
Olga S. Pérez-Moro ◽  
María J Albaladejo-Florín ◽  
Rubén Algarra-López ◽  
María M. Tobar-Izquierdo ◽  
...  

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.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shubha Singhal ◽  
Nazer Hasan ◽  
Kirti Nirmal ◽  
Rohit Chawla ◽  
Shalini Chawla ◽  
...  

Abstract Background To compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA). Methods In this randomized, non-inferiority, controlled clinical study, patients of knee OA were randomized to receive bioavailable turmeric extract (BCM-95®) 500 mg capsule two times daily or paracetamol 650 mg tablet three times daily for 6 weeks. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The secondary outcome measures were WOMAC total, WOMAC stiffness, and WOMAC physical function scores. Responder analysis of individual patients at different levels (≥ 20%, ≥ 50%, and ≥ 70%) for WOMAC score was calculated. TNF alpha and CRP levels were evaluated and adverse events (AE) were also recorded. Results Seventy-one and seventy-three knee OA patients, respectively in bioavailable turmeric extract and paracetamol groups, completed the study. Non-inferiority (equivalence) test showed that WOMAC scores were equivalent in both the groups (p value < 0.05) in all the domains within the equivalence limit defined by effect size (Cohen’s d) of 0.5 whereas CRP and TNF-α were better reduced with turmeric extract than paracetamol. After 6 weeks of treatment, WOMAC total score, pain, stiffness, and function scores got a significant improvement of 23.59, 32.09, 28.5, and 20.25% respectively with turmeric extract. In the turmeric extract group, 18% of patients got more than 50% improvement and 3% of patients got more than 70% improvement in WOMAC pain and function/stiffness score and none of the patients in the paracetamol group met the criteria. CRP and TNF-α got significantly reduced (37.21 and 74.81% respectively) in the turmeric extract group. Adverse events reported were mild and comparatively less in the turmeric extract group (5.48%) than in the paracetamol group (12.68%). Conclusion The results of the study suggest that bioavailable turmeric extract is as effective as paracetamol in reducing pain and other symptoms of knee osteoarthritis and found to be safe and more effective in reducing CRP and TNF-α. Trial registration Clinical Trials Registry – India CTRI/2017/02/007962. Registered on 27 February 2017


Author(s):  
Masoud Hashemi ◽  
Mehrdad Taheri ◽  
Payman Dadkhah ◽  
Hasti Hassani ◽  
Mohammadhossein Ataie ◽  
...  

Background: The aim of this study was to compare the efficacy of ozone injection at Tibio-femoral joint with Supra-patellar recess on knee osteoarthritis (OA). Methods: In this randomized, controlled clinical trial, 99 patients with symptomatic knee OA were randomized into two groups. 47 patients selected to receive 7-8 ml ozone (20 µg/ml) through Tibio-femoral joint injection, and 49 patients received 10 ml ozone (20 µg/ml) through supra-patellar recess injection by using in-plane ultrasound-guided. The primary outcome was the change from baseline in the visual analogue scale (VAS) (0-100 mm) pain score during 3 months after injection. Secondary outcome measures included the Western Ontario and McMaster universities OA Index (WOMAC), Lequesne index, time “Up and Go” (TUG) test, single-limb stance (SLS) tests, patient satisfaction, and adverse effects. All of these measurements were evaluated at the base time, 48 hours, 2 weeks, 1 month, 2 months, and 3 months after injection. Results: Both groups had significantly improvement in the primary and secondary outcome measures. VAS pain score except at the 3–month follow-up (16.8±13.3 versus 18.1±16.6, 95% CI, -7.33 to 4.73, p =0.6), WOMAC pain score, WOMAC stiffness score at all evaluated times, and WOMAC total score at 48 hours after injection (95% CI, -19.4 to -4.9) were significantly better among Tibio-femoral ozone injection compare to Supra-patellar recess injection (95% CI, -20.68 to -6.51, p<0.001)). In both groups satisfaction, TUG and SLS times were improved, but no significant difference was seen between groups (p>0.05). At the 3-month follow-up, WOMAC pain and total scores for only Tibio-femoral joint injection group as well as WOMAC function, TUG and SLS times for both groups were gradually coming back to the baseline. Conclusion: Ozone injection in both groups was associated with pain relief, functional improvement, and quality of life in patient with knee OA. Pain and stiffness of joint were improved better in Supra-patellar recess ozone injection.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Aleksandra R. Budarick ◽  
Emily L. Bishop ◽  
Marcia L. Clark ◽  
Christopher D. Cowper-Smith

Purpose. Traditional knee osteoarthritis (OA) braces are usually indicated for a minority of patients with knee OA, as they are only suitable for those with unicompartmental disease affecting the tibiofemoral joint. A new assistive brace design is intended for use in a wider range of knee OA patients with heterogeneous symptoms characteristic of patellofemoral, tibiofemoral, or multicompartmental knee OA. The purpose of this case series was to explore whether the use of this novel “tricompartment offloader” (TCO) brace was associated with clinically relevant improvements in pain and function. Materials and Methods. A retrospective analysis of individuals with knee OA ( n = 40 ) was conducted to assess pain, function, physical activity, and use of medication and other treatments before and after brace use. Validated outcome measures including the Visual Analog Scale (VAS) and Lower Extremity Functional Scale (LEFS) were used to assess pain and physical function (primary outcome measures). Exploratory measures were used to quantify physical activity levels and use of medication and other treatments (secondary outcome measures). Results. Average total pain (VAS) scores decreased by 36.6 mm and physical function (LEFS) scores increased by 16.0 points following the use of the TCO brace. Overall, 70% of the participants indicated increased weekly physical activity and 60% reported a decrease in their use of at least one other treatment. Conclusions. Results from this case series suggest that the TCO brace shows strong potential to fill a conservative treatment gap for patients with heterogeneous symptoms of knee OA that are characteristic of patellofemoral or multicompartment disease. Further investigation is warranted.


2011 ◽  
Vol 70 (10) ◽  
pp. 1798-1803 ◽  
Author(s):  
Henning Bliddal ◽  
Anthony R Leeds ◽  
Lise Stigsgaard ◽  
Arne Astrup ◽  
Robin Christensen

ObjectiveTo evaluate 1-year symptomatic improvement in obese patients with knee osteoarthritis (OA) on an intensive low-energy diet (LED) maintained by frequent consultations with a dietician compared to minimal attention.MethodsThe LED programme consisted of group therapy with dietary consultations and two periods of a low-calorie diet of 810 kcal/day during weeks 0–8 and weeks 32–36. The control group only received dietary instruction and attention for 2 h at baseline, and at weeks 8, 32, 36 and 52. The primary end point (total Western Ontario and McMaster Universities (WOMAC) index) was assessed as the mean group difference during and after 1 year.ResultsThe study population consisted of 89 patients, 89% women, average age 63 years. After 1 year, mean weight loss in the LED group was −10.9 kg (11%) versus −3.6 kg (4%) in the control group (p<0.0001). There was no difference between the groups in total WOMAC index (p=0.11), although both groups improved. However, the LED intervention resulted in less WOMAC pain (7.7 mm), with a group mean difference of 7.2 mm (95% CI 1.0 to 13.4, p=0.022). After one year 14 (32.8%) responded to LED versus 7 (15.6%) to control, with an absolute benefit of 16.3% (−1.1& to 33.6%, p=0.066).ConclusionContinuous reinforcement of a weight loss programme can be successful over a year in obese knee OA patients. Weight loss was statistically reflected only by a reduction in pain. However, the overall clinical benefits of the intervention on health should lead to a strong recommendation of weight loss in this group of patients.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 409.2-409
Author(s):  
E. Strebkova ◽  
E. Tchetina ◽  
L. Alekseeva

Background:Currently, a large number of molecular biological and genetic markers are known to be involved in the development of osteoarthritis (OA). The mammalian target of rapamycin (mTOR) signaling pathway is responsible for chondrocyte proliferation, cartilage matrix production, and cell growth. OA is characterized by increased mTOR synthesis, which is accompanied by an increase in proliferative activity and destruction of chondrocytes. Obesity is an important factor in the progression of knee OA. The study of mTOR expression in patients with OA and obesity is an urgent task in the development of personalized OA therapy.Objectives:To determine the expression of mTOR in patients with knee OA in combination with obesity and normal body weight. To evaluate the effect of mTOR on the clinical manifestations of OA in patients with different body mass index (BMI).Methods:The study included 73 female patients aged 45-65 y.o. with Kellgren-Lawrence stage II-III knee OA. The patients were divided into 2 groups: group 1 (n=50) with obesity (BMI > 30 kg / cm2) and group 2 (n=23) with normal or increased body weight (BMI < 30 kg/cm2). The average age of patients with obesity is 56.5 ± 5.87 years, without obesity - 58.7 ± 5.43 years. Clinical manifestations were evaluated by a WOMAС. RNA was isolated from the patients ‘ blood samples, which was used to determine the expression of mTOR.Results:Patients with knee OA with and without obesity did not differ in age. OA develops at an earlier age in obese patients, than in non-obese patients (p < 0.001). Patients from 1 group had a high BMI > 30 kg/m2 at the onset of OA. Obese patients had more severe knee OA is significantly more often detected: Kellgren-Lawrence stage III was determined in 10% of obese patients and in 4.35% - without obesity (p < 0.001). Significantly higher values of the WOMAC index pain, stiffness, joint functional failure, and total WOMAC were observed in obese patients (p = 0.006, p = 0.039, p = 0.037, and p = 0.014, respectively). Obese patients had higher VAS pain scores (p < 0.05) compared to patients with a lower BMI. Obese patients had a higher mTOR expression (p < 0.05) of 8.02±8.62, compared to non-obese patients. High mTOR expression was associated with VAS knee pain (r=0.78; p < 0.05) and WOMAC pain (r=0.89; p<0.05) in obese patients (Table 1).Table 1.Correlation of m-TORParametersmTOR (1 group, n=50)mTOR (2 group, n=23)Body weightр > 0,05р > 0,05Pain (VAS)r=0,78; р<0,05p = 0,07; r = 0,45Pain (WOMAC)r=0,89; р<0,05р > 0,05Total WOMACр > 0,05р > 0,05Conclusion:Our study showed that patients with obesity and knee OA have higher rates of mTOR expression, compared to patients with normal body weight. High mTOR expression correlates with the severity of knee pain in obese patients. Thus, the evaluation of mTOR expression in obese patients and knee OA plays an important role in predicting the severity of clinical manifestations of OA, and may influence the choice of personalized therapy tactics for such patients.Disclosure of Interests:None declared


Author(s):  
Kun Yung Kim ◽  
Gi-Wook Kim

BACKGROUND: Knee osteoarthritis (OA) is accompanied by inflammation and angiogenesis. Modifying angiogenesis through transcatheter arterial embolization (TAE) can be a potential treatment for knee OA. OBJECTIVE: We subjected five OA knees in three patients to TAE and report the results of our post-treatment observations. CASE DESCRIPTION: Three patients that had experienced knee pain for a minimum of one year prior to the study, and whose pain had persisted despite conservative treatment, were included in this study. Patients more often chose conservative treatment over surgical treatment. Pain and functional scales were evaluated before, immediately, and 1 month after TAE using the Numeric Rating Scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). TAE was performed by an experienced interventional radiologist. The average values of NRS evaluated before and after 5 TAEs were 5.2 before TAE, 3 immediately after TAE, and 3.6 after 1 month of TAE, and the average values of WOMAC were 52, 38.4, and 36.4, respectively. There were no major adverse effects. CONCLUSION: The examined cases support the conclusion that TAE is an effective treatment for patients with knee OA. Substantial pain relief and WOMAC improvement were observed both immediately and one month after TAE.


PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Ya. O. Yemchenko ◽  
V. I. Shynkevych ◽  
K. Ye Ishcheikin ◽  
I. P. Kaidashev

Background. Macrophages are of great importance in the development of obesity and psoriasis. Signaling via PPAR-γ in certain macrophage populations is associated with M2-like features and anti-inflammatory profile. In this research, we evaluated the anti-inflammatory action of pioglitazone by the immunohistochemical study of M1 and M2 macrophages in psoriasis-affected skin in obese patients. Methods. We used immunohistochemistry to characterize CD68+ and CD163+ macrophages and pathomorphological description of skin biopsy, obtained from 6 obese psoriatic patients before and after treatment with 15, 30, and 45 mg pioglitazone, once a day during 6 months. Two patients with conventional therapy and without pioglitazone served as control. Results. Generally, CD163+ cell quantities in psoriasis-affected skin significantly dominated over CD68+ before and after all treatment regiments. Among patients who received pioglitazone, some of them clearly responded to treatment from lowest to highest doses by decreasing CD68+ cells. In the group with 30 mg pioglitazone regiment, we detected a significant reduction of CD68+ cells in dermal infiltrates: CI 95% (16–32) before versus CI 95% (2–7) after treatment. Pioglitazone dose escalation led to certain normalization of skin morphology. Conclusion. The immunohistochemical study allows us to show the anti-inflammatory effect of pioglitazone in psoriatic obese patients, which can be mediated by reducing the number of СD68+ macrophages, but not СD163+ macrophages, in the affected dermis.


BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e017652 ◽  
Author(s):  
Christelle Nguyen ◽  
Isabelle Boutron ◽  
Gabriel Baron ◽  
Emmanuel Coudeyre ◽  
Francis Berenbaum ◽  
...  

IntroductionOsteoarthritis (OA) pathophysiology is driven in part by joint inflammation. Resveratrol has in vitro anti-inflammatory properties. We aim to assess the efficacy of oral resveratrol for knee pain at 3 months in people with knee OA.Methods and analysisWe will conduct a randomised double-blind placebo-controlled trial. Overall, 164 individuals with knee OA fulfilling 1986 American College of Rheumatology criteria will be recruited in three tertiary care centres in France and randomised to receive oral resveratrol, 40 mg (two caplets) two times per day for 1 week, then 20 mg (one caplet) two times per day or a matching placebo for a total of 6 months. Randomisation will be centralised and stratified by centre. The allocation ratio of assignments will be 1:1. The primary outcome will be the mean change from baseline in knee pain on a self-administered 11-point pain Numeric Rating Scale at 3 months. Secondary outcomes will be the mean change in knee pain at 6 months, the function subscore of the Western Ontario and McMaster Universities Arthritis Index score, patient global assessment, proportion of responders according to the Osteoarthritis Research Society International–Outcome Measures in Rheumatology criteria at 3 and 6 months, and self-reported number of intra-articular injections of corticosteroids or hyaluronic acid and consumption of analgesics and non-steroidal anti-inflammatory drugs since the last contact. Other interventions will be allowed and self-reported. Adherence will be monitored by capsule counts and a booklet and adverse events recorded at 3 and 6 months. Statisticians, treating physicians and participants will be blinded to the allocated treatment.Ethics and disseminationThe oral resveratrol in knee osteoarthritis (ARTHROL) trial has been authorised by theAgenceNationale de Sécurité du Médicament et des Produits de Santéand ethics were approved by theComité deProtection des Personnes Île-de-FranceIII. The findings of the study will be published in a peer-reviewed journal and disseminated at conferences. The design of ARTHROL will warrant the translation of its findings into clinical practice.Trial registration numberClinicalTrials.gov identifier:NCT02905799. Pre-results. First received: 14 September 2016. Last updated: 16 September 2016. Status: not yet recruiting.


Sign in / Sign up

Export Citation Format

Share Document