Analysis of Clinical Efficacy of Clearing Heat and Dispelling Paralysis Soup in the Treatment of Osteoarthritis of the Knee Joint and Its Effect on Patients' Motor Function.

OBJECTIVE: To investigate the effects of clearing heat and dispelling paralysis soup for osteoarthritis of the knee joint on the motor function of the knee joint and the level of inflammation of the organism in patients. METHODS: One hundred and sixteen patients with knee osteoarthritis admitted from January 2020 to May 2021 were selected and randomly divided into 2 groups, 58 cases in the control group were treated with loxoprofen sodium dispersible tablets, and 58 cases in the experimental group were treated with Qinghe dispel paralysis soup on the basis of the control group and the patients' balance ability analysis, gait parameter change analysis, VAS, JOA, AIMS2-SF scale assessment, and serum index. The treatment effects of the two treatment regimens were analyzed by testing. RESULTS: The anterior-posterior axis, left-right axis, A2-A6, A4-A8, and circumferential axis of the experimental group were lower than those of the control group after treatment (P < 0.05); the step length of the experimental group was higher than that of the control group after treatment (P < 0.05), and there were no significant differences in step speed, double-support phase, and step width (P > 0.05), but both groups improved significantly compared with those before treatment (P < 0.05); the VAS score of the experimental group was lower than that of the control group after treatment. The VAS scores of the experimental group were lower than those of the control group, and the scores of JOA and AIMS2-SF were higher than those of the control group (P < 0.05); the levels of TIMP-1 in the experimental group were higher than those in the control group, and the levels of TNF-α, TLR4, MMP-3, and IL-1 were lower than those in the control group after treatment (P < 0.05); there was no significant difference in the incidence of adverse reactions between the two groups during treatment (P > 0.05), and the efficiency of the experimental group was higher than that of the control group (P < 0.05). CONCLUSION: Combined treatment with Qinghe dispel paralysis soup can better promote the recovery of balance, improve motor ability, and reduce the development of inflammation in the organism, with high safety and effectiveness.

Effect of Resveratrol on Serum Levels of Type II Collagen and Aggrecan in Patients with Knee Osteoarthritis: A Pilot Clinical Study.

Treatment of knee osteoarthritis (OA) remains a challenging concern. Preclinical studies provided accumulating evidence on resveratrol efficacy in ameliorating degenerative articular damage. The present study was conducted to evaluate the effects of resveratrol as monotherapy on the serum level of type II collagen (Coll 2-1) and aggrecan in patients with knee osteoarthritis. The study was an open-labeled noncontrolled clinical trial. Resveratrol 500 mg/day in a single oral dose was given to the patients with knee osteoarthritis for 90 days. The serum levels of Coll-2-1, aggrecan, and biomarkers of inflammation were measured pre- and posttreatment. Hematological profiles and both hepatic and renal function markers were investigated at the baseline and at the end of the treatment for evaluating the tolerability and safety of resveratrol. Visual Analog Scale (VAS) for pain and Knee injury and Osteoarthritis Outcome Score (KOOS) for disease activity were clinically assessed monthly. Administration of 500 mg resveratrol for three months led to a nonsignificant decrease in the serum level of Coll 2-1 while a significant increase in aggrecan serum level. Resveratrol significantly improves pain score measured by VAS and KOOS after 30 days. Improvements in patients' activity and functional status were also evident at day 30 and kept on for three months which was reflected by KOOS subscale scores and with a significant improvement in all KOOS areas. In conclusion, oral administration of resveratrol as a monotherapy provides a remarkable improvement in the clinical status of the patients but has no significant effect on serum levels of Coll 2-1.

Effects of photobiomodulation and a physical exercise program on the expression of inflammatory and cartilage degradation biomarkers and functional capacity in women with knee osteoarthritis: a randomized blinded study.

BACKGROUND: The knee osteoarthritis (OA) is a joint disease characterized by degradation of articular cartilage that leads to chronic inflammation. Exercise programs and photobiomodulation (PBM) are capable of modulating the inflammatory process of minimizing functional disability related to knee OA. However, their association on the concentration of biomarkers related to OA development has not been studied yet. The aim of the present study is to investigate the effects of PBM (via cluster) with a physical exercise program in functional capacity, serum inflammatory and cartilage degradation biomarkers in patients with knee OA. METHODS: Forty-two patients were randomly allocated in 3 groups: ESP: exercise + sham PBM; EAP: exercise + PBM and CG: control group. Six patients were excluded before finished the experimental period. The analyzed outcomes in baseline and 8-week were: the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and the evaluation of serum biomarkers concentration (IL-1ß, IL-6, IL-8, IL-10 e TNF-α, and CTX-II). RESULTS: An increase in the functional capacity was observed in the WOMAC total score for both treated groups (p < 0.001) and ESP presents a lower value compared to CG (p < 0.05) the 8-week post-treatment. In addition, there was a significant increase in IL-10 concentration of EAP (p < 0.05) and higher value compared to CG (p < 0.001) the 8-week post-treatment. Moreover, an increase in IL-1ß concentration was observed for CG (p < 0.05). No other difference was observed comparing the other groups. CONCLUSION: Our data suggest that the physical exercise therapy could be a strategy for increasing functional capacity and in association with PBM for increasing IL-10 levels in OA knee individuals. TRIAL REGISTRATION: ReBEC (RBR-7t6nzr).

Evaluation of electroacupuncture for symptom modification in a rodent model of spontaneous osteoarthritis.

OBJECTIVE: Faced with the frustration of chronic discomfort and restricted mobility due to osteoarthritis (OA), many individuals have turned to acupuncture for relief. However, the efficacy of acupuncture for OA is uncertain, as much of the evidence is inconclusive. The purpose of this study was to evaluate electroacupuncture (EA) in a rodent model of OA such that conclusions regarding its effectiveness for symptom or disease modification could be drawn. METHODS: Ten 12-month-old male Hartley guinea pigs-which characteristically have moderate to advanced OA at this age-were randomly assigned to receive EA for knee OA (n = 5) or anesthesia only (control group, n = 5). Treatments were performed three times weekly for 3 weeks, followed by euthanasia 2 weeks later. Gait analysis and enclosure monitoring were performed weekly to evaluate changes in movement. Serum was collected for inflammatory biomarker testing. Knee joints were collected for histology and gene expression. RESULTS: Animals receiving EA had significantly greater changes in movement parameters compared to those receiving anesthesia only. There was a tendency toward decreased serum protein concentrations of complement component 3 (C3) in the EA group compared to the control group. Structural and antioxidant gene transcripts in articular cartilage were increased by EA. There was no significant difference in total joint histology scores between groups. CONCLUSION: This study provides evidence that EA has a positive effect on symptom, but not disease, modification in a rodent model of OA. Further investigations into mechanistic pathways that may explain the efficacy of EA in this animal model are needed.

Association of Serum Vitamin D with Serum Cytokine Profile in Patients with Knee Osteoarthritis.

OBJECTIVE: The role of vitamin D in the pathogenesis of osteoarthritis (OA) is not well understood. In this study, we aimed to investigate the association of serum vitamin D with the serum cytokine profile in patients with primary knee OA. DESIGN: In a cross-sectional study, 116 patients with radiologic diagnosis of grade I to III knee OA were included. The study population included 79 (75.9%) females and 25 (24.1%) males with a mean age of 55.1 ± 9.6 years. The serum concentration of IL-6, IL-8, TNF-α, IL-4, IL-10, IL-13, and vitamin D were assessed using an enzyme-linked immunosorbent assay. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used for the assessment of patient's reported disability associated with knee OA. RESULTS: Serum vitamin D status was deficient, insufficient, and sufficient in 18 (15.5%), 63 (54.3%), 35 (30.2%) patients, respectively. Higher levels of serum IL-6 were observed in patients with vitamin D deficiency (P = 0.022). The mean serum vitamin D level was not associated with OA grade (P = 0.88) and WOMAC scores of the patients (P = 0.67). Serum IL-6 level was significantly associated with both OA grade and WOMAC scores of the patients (P < 0.001 and P = 0.001, respectively). The vitamin D status was not significantly associated with the serum levels of other evaluated cytokines. CONCLUSION: Vitamin D deficiency in knee OA seems to be associated with a higher release of IL-6. Therefore, vitamin D supplementation could reduce the disease burden by controlling the IL-6 release.

The efficacy of jade moxibustion in knee osteoarthritis.

INTRODUCTION: This study aims to compare clinical effect between Jade moxibustion and traditional moxibustion, and to determine the clinical effect of Jade moxibustion on knee osteoarthritis (KOA). METHODS/DESIGN: This is a 2-parallel-group, randomized controlled trial. A total of 148 subjects with KOA (Kellgren-Lawrence grade II or III) will be recruited and randomized to receive Jade moxibustion treatment or a traditional moxibustion treatment in a 1:1 ratio. Jade moxibustion group: The affected knee of the subjects will be covered with jade kneepad. Traditional moxibustion group: Chosen the ST35, ST34, EX-LE4, SP10 and Ashi points at the affected knee. The subjects will receive treatment three times a week, altogether 12 times in 4 weeks. The main outcomes are WOMAC knee pain score, knee function score and SF-36 quality of life questionnaire changes at the 4th week. Secondary outcomes include WOMAC knee pain score and knee function score, overall clinical efficacy evaluation, medication, safety evaluation at the 2nd, 12th, and 24th week, and cytokines related to osteoarthritis in serum. DISCUSSION: This randomized controlled trial used traditional moxibustion as a control group to provide rigorous evidence for the clinical efficacy and safety of Jade moxibustion in treatment of KOA. TRIAL REGISTRATION: ISRCTN registry, No 21174552. Registered on 28 February 2020.

A clinical pilot study to evaluate the efficacy of oral intake of phellinus linteus (sanghuang) extract on knee joint and articular cartilage: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of degenerative arthritis. We used Phellinus linteus (PL), which has been well-known anti-inflammatory function. In this study, we will evaluate if PL extract improves symptoms with KOA. METHODS: This study will be an 8-week single-center randomized controlled double-blind clinical trial. Total of 24 subjects with KOA will be enrolled and they will be divided into 3 groups, PL 1,000 mg, PL 1,500 mg and placebo. Subjects will be followed up every 4 weeks with efficacy and safety at the 2nd and 3rd visits. All subjects should maintain a dosage schedule for this protocol. The primary outcome will be assessed with the Korean version of the Western Ontario and McMasters Universities. And the secondary outcomes will be measured using the visual analog scale, quality of life scale (EQ-5D-3L), ESR, C-reactive protein, and C-telopeptide of type-II collagen. Statistical analysis will be performed on the principle of full analysis set. DISCUSSION: This study has inclusion and exclusion criteria and a well-controlled intervention. This clinical trial is the first step to assess the efficacy and safety of PL in patients with KOA. This study will make an important contribution to the literature and aid follow-up research into the use of PL in KOA.

The Oxidative Stress in Knee Osteoarthritis Patients. An Attempt of Evaluation of Possible Compensatory Effects Occurring in the Disease Development.

Background and Objective: Osteoarthritis (OA) is a disorder of the musculoskeletal system resulting in worsening of life condition. The research revealed the involvement of oxidative stress into both OA pathogenesis and the effects of therapeutic agents applied in OA cases. The activities of the most important antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant status (TAS), in blood of the knee OA patients were studied, with the aim of clarifying which enzymatic antioxidants are involved into osteoarthritis (OA)-related oxidative stress and whether any compensatory effects occur. The results were additionally analyzed with regard to gender. Methods: Whole blood SOD (U/mL), plasma GPx (U/L) and CAT (U/mL) activities as well as plasma TAS (mmol/L)) in knee OA patients were investigated. Sixty-seven patients (49 females and 18 males) with primary knee OA were enrolled. The control comprised 21 subjects (10 females and 11 males) free of osteoarthritis or inflammation. Results: TAS was decreased in OA subjects (4.39 0.53 vs. 4.70 0.60), with this effect being more significant in OA females (4.31 0.51 vs. 5.02 0.54). GPx was depressed in all OA patients (518 176 vs. 675 149). In both genders, GPx was decreased, significantly in males (482 185 vs. 715 105). SOD was decreased in all OA patients (109 32 vs. 127 42). CAT showed no difference in all OA subjects vs. control, while in OA females it was depleted (20.2 (11.6-31.6) vs. 38.5 (27.9-46.6)) and in OA men it increased (26.9 (23.3-46.5) vs. 14.0 (7.0-18.6)). Conclusions: The obtained results suggest that in men some compensatory mechanisms towards OA-related oxidative stress occurred. Based on the obtained data, the introduction of antioxidant supplements into OA therapy could be suggested with further research concerning the choice of agents.

Dietary magnesium intake, serum high sensitivity C-reactive protein and the risk of incident knee osteoarthritis leading to hospitalization-A cohort study of 4,953 Finns.

OBJECTIVES: To study whether low dietary magnesium (Mg) intake and serum high sensitivity C-reactive protein (hs-CRP) predict the development of clinical knee osteoarthritis (OA). METHODS: The cohort consisted of 4,953 participants of a national health examination survey who were free of knee and hip OA at baseline. Information on the incidence of knee OA leading to hospitalization was drawn from the National Care Register for Health Care. During the follow-up of 10 years, 123 participants developed incident knee OA. Dietary magnesium intake was assessed on the basis of a food frequency questionnaire from the preceding year. We used Cox's proportional hazards model to estimate the strength of the association between the tertiles of dietary Mg intake and incident knee OA, adjusted for baseline age, gender, energy intake, BMI, history of physical workload, leisure time physical activity, injuries, knee complaints, the use of Mg supplements, and serum hs-CRP levels. RESULTS: At baseline, dietary Mg intake was inversely associated with serum hs-CRP even after adjustment for all the potential confounding factors. During the follow-up, the adjusted hazard ratios (with their 95% confidence intervals) for incident knee OA in dietary Mg intake tertiles were 1.00, 1.28 (0.78-2.10), and 1.38 (0.73-2.62); the p value for trend was 0.31. Serum hs-CRP level at baseline did not predict incident knee OA. CONCLUSIONS: The results do not support the hypothesis that low dietary Mg intake contributes to the development of clinical knee OA, although Mg intake is inversely associated with serum hs-CRP level.

Vitamin D supplementation and inflammatory and metabolic biomarkers in patients with knee osteoarthritis: post hoc analysis of a randomised controlled trial.

The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.

Effect of Auriculotherapy on the Plasma Concentration of Biomarkers in Individuals with Knee Osteoarthritis.

Knee osteoarthritis (KOA) is one of the most frequent noncommunicable diseases with pain associated symptoms and affects the musculoskeletal system. Various forms of treatment can be indicated, and nonpharmacological treatment is also an available option for the management of KOA individuals. For instance, auriculotherapy (AT) is one possible procedure associated with the Traditional Chinese Medicine for dealing with KOA. It is believed that the concentration of certain biomarkers could be altered in individuals with KOA after AT. The aim of this study was to evaluate the effect of AT on plasma concentration of biomarkers in KOA individuals. This intervention is a controlled trial. Twenty-one subjects were grouped in two groups and submitted to AT with the stimulation of the Shen Men, kidney, and knee points in the treatment group or different points in the control group, once a week for 5 weeks. Blood was collected before the beginning of protocols and a week after the last session. Kolmogorov-Smirnov and Wilcoxon tests were performed, and a p ≤ 0.05 was considered statistically significant. Hematological parameters did not show any significant variation between the control group and treated group. Concerning the biochemical parameters, a significant reduction of direct bilirubin (from 43.31 ± 22.10 to 21.21 ± 5.30 µmol/L, p = 0.003), aspartate aminotransferase (from 0.48 ± 0.16 to 0.38 ± 0.09 µKat/L, p = 0.010), and triglycerides (from 7.04 ± 2.90 to 5.45 ± 2.57 mmol/L, p = 0.008) in the treated group was obtained. In conclusion, the analysis of results suggests that AT might be a useful intervention for the management of KOA individuals.

Evaluation of serum beta-endorphin and substance P in knee osteoarthritis patients treated by laser acupuncture.

Background Laser acupuncture is one of the complementary modalities used for treating osteoarthritis. The study was performed to evaluate the effectiveness of laser acupuncture in the treatment of grade 2 knee osteoarthritis. Patients and methods Forty patients having bilateral knee osteoarthritis were divided into two groups (20 patients in each group). The patients of the first group were subjected to 12 laser sessions at the following acupoints (St 35, St36, Sp9, Sp10 and Gb 34). During each session, laser of 90 mw was directed to each acupoint for 1 min giving energy of 5.4 joules. Energy of 21.6 joules was directed to ashi points. The laser had a wavelength of 808 nm, beam diameter 2 mm and was applied with a continuous wave. The cases of the second group were used as controls. Each patient is exposed to sham laser (laser probe is directed to the same acupoints while the device is off). Results The 20 patients receiving laser showed significant improvement in pain on (VAS), increase in serum beta-endorphin and a decrease in substance P more than those exposed to sham laser. Conclusions Laser acupuncture is a safe and cheap tool for management of grade 2 knee osteoarthritis.

Efficacy of Chondroitin Sulfate for Painful Knee Osteoarthritis: A One-Year, Randomized, Double-Blind, Multicenter Clinical Study in Japan.

We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, double-blind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or <8) in 73 patients. Serum level of cartilage oligomeric matrix protein and hyaluronic acid were also determined. In the subgroup with severe symptoms (Lequesne's index ≥8), the chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months' therapy. However, no dose-related effects were found on cartilage oligomeric matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good tolerability. We conclude that chondroitin sulfate is useful for pain control in knee osteoarthritis.

Association of Vitamin K Status Combined With Vitamin D Status and Lower-Extremity Function: A Prospective Analysis of Two Knee Osteoarthritis Cohorts.

OBJECTIVE: Vitamins K and D are important for the function of vitamin K-dependent proteins in joint tissues. It is unclear whether these nutrients are mutually important to functional outcomes related to knee osteoarthritis (OA). We evaluated the association of vitamin K and D sufficiency with lower-extremity function in the Health, Aging and Body Composition knee OA substudy (Health ABC) and conducted a replication analysis in an independent cohort, the Osteoarthritis Initiative (OAI). METHODS: In Health ABC (60% female, mean ± SD age 75 ± 3 years) baseline nutrient status was measured using circulating vitamin K and 25-hydroxyvitamin D (25[OH]D). Lower-extremity function was assessed using the Short Physical Performance Battery (SPPB) and usual 20-meter gait speed. In the OAI (58% female, mean ± SD age 61 ± 9 years), baseline nutrient intake was estimated by food frequency questionnaire. Lower-extremity function was assessed using usual 20-meter gait speed and chair stand completion time. Multivariate mixed models were used to evaluate the association of vitamin K and D status and intake with lower-extremity function over 4-5 years. RESULTS: Health ABC participants with sufficient plasma vitamin K (≥1.0 nmoles/liter) and serum 25(OH)D (≥50 nmoles/liter) generally had better SPPB scores and faster usual gait speed over followup (P ≤ 0.002). In the OAI, sufficient vitamin K and vitamin D intake combined was associated with overall faster usual gait speed and chair stand completion time over followup (P ≤ 0.029). CONCLUSION: Sufficient vitamin K status combined with sufficient vitamin D status was associated with better lower-extremity function in 2 knee OA cohorts. These findings merit confirmation in vitamin K and D co-supplementation trials.

Omega-6: Omega-3 PUFA Ratio, Pain, Functioning, and Distress in Adults With Knee Pain.

OBJECTIVES: Osteoarthritis (OA) is associated with inflammation, chronic pain, functional limitations, and psychosocial distress. High omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are associated with lower levels of inflammatory mediators, anti-nociception, and adaptive cognitive/emotional functioning. High omega-6 (n-6) PUFAs are associated with inflammation, nociception, and psychological distress. While findings related to n-3 supplementation in knee OA are mixed, consideration of the n-6:n-3 ratio and additional outcome measures may provide improved understanding of the potential relevance of these fatty acids in OA. On the basis of recommended and typical ranges of the n-6:n-3 ratio, we hypothesized that in adults with knee pain, those with a high n-6:n-3 ratio would have greater pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared with those with a low n-6:n-3 ratio. MATERIALS AND METHODS: A cross-sectional investigation of clinical and experimental pain and physical and psychosocial functioning was completed in 167 adults ages 45 to 85 meeting knee OA screening criteria. Blood samples were collected and the plasma n-6:n-3 PUFA ratio determined. Quartile splits were computed and low (n=42) and high (n=41) ratio groups were compared. RESULTS: The high ratio group reported greater pain and functional limitations, (all Ps<0.04), mechanical temporal summation (hand and knee, P<0.05), and perceived stress (P=0.008) but not depressive symptoms. DISCUSSION: In adults with knee pain, a high n-6:n-3 ratio is associated with greater clinical pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared with a low ratio group. Findings support consideration of the n-6:n-3 PUFA ratio and additional clinical endpoints in future research efforts.

Effect of vitamin D supplementation on knee osteoarthritis: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: To provide evidence regarding the effect of vitamin D supplementation on symptomatic knee osteoarthritis (OA). METHODS: A systematic review and meta-analysis was performed to quantitatively pool the results from randomized clinical trials. Studies were identified from a search of the Embase, MEDLINE and Web of Science databases up to January 22, 2017, and also from conference abstracts, ClinicalTrials.gov and the reference lists of identified studies. A standardized mean difference (SMD) was used to assess effect sizes, as outcomes were reported on different scales. Depending on the degree of heterogeneity, random-effects or fixed-effects models were used to pool outcomes. RESULTS: Up to January 22, 2017, four clinical trials containing 570 subjects in the vitamin D supplementation group and 560 subjects in the placebo group were identified. All of the included studies were of high quality and had a low risk of bias for each domain. The results indicated that vitamin D supplementation had a statistically significant but small-to-moderate effect on pain control in patients with knee OA (SMD=-0.32, 95% CI: -0.63 to -0.02). However, no effects were observed for the change in tibial cartilage volume (SMD=0.12, 95% CI: -0.05 to 0.29) or joint space width (SMD=0.07, 95% CI: -0.08 to 0.23). The subgroup analysis indicated that vitamin D supplementation had no significant effect regardless of whether patients had sufficient or insufficient serum 25(OH)D levels at baseline. CONCLUSIONS: The results of this study indicate that vitamin D supplementation may not have a clinically significant effect on pain control or structure progression among patients with knee OA. Longer-term clinical trials with rigorous measurement of symptom and radiologic changes are required to further clarify the effect of vitamin D supplementation in patients with symptomatic knee OA and low serum 25(OH)D levels.

Effects of single or combined administration of salmon calcitonin and omega-3 fatty acids vs. diclofenac sodium in sodium monoiodoacetate-induced knee osteoarthritis in male Wistar rats.

BACKGROUND: There is a continuous search for a better therapy in osteoarthritis (OA) management. Therefore, this study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3) relative to diclofenac sodium (DF) in induced knee osteoarthritic male Wistar rats. METHODS: The 40 rats that were used in this study were divided into 8 groups (n=5 rats), viz: Normal control; OA control; OA+N-3; OA+Low dose of Sct (Sct.Lw); OA+High dose of Sct (Sct.Hi); OA+N-3+SCt.Lw; OA+N-3+Sct.Hi; and, OA+DF. OA was induced with 4 mg of sodium monoiodoacetate in 40 µL of saline. The solution was injected into the left knee joint space of anaesthetised rats. Sct was administered at 2.5 and 5.0 IU/kg b.w. (im), whereas N-3 and DF were administered at 200 and 1 mg/kg b.w. (p.o.), respectively. Treatments commenced 9 days after the induction of OA, and they lasted for 28 days. RESULTS: Sct and/or N-3 significantly reduced c-telopeptide of type 1 collagen (CTX-1), collagen type 2 α-1 (C2M), malondialdehyde (MDA), uric acid (UA), and interleukin-6 (IL-6), but, significantly increased superoxide dismutase (SOD) after OA induction. Both therapies had additive effects on C2M, MDA, SOD, and catalase (CAT), but, non-additive actions on UA, IL-6, and CTX-1. Like the Sct and N-3, DF significantly reduced CTX-1, C2M, UA, and IL-6. However, it had no significant effect on SOD and MDA, even though it significantly reduced CAT activity. None of the therapies had significant effect on total alkaline phosphatase activity, except N-3+Sct.Lw. CONCLUSIONS: The combined, and sometimes the single administration of Sct and N-3 proved to be better therapies in OA management than DF.

The effect of vitamin D supplementation on knee osteoarthritis: A meta-analysis of randomized controlled trials.

OBJECTIVE: We conducted a meta-analysis of RCTs to evaluate the effects of vitamin D supplementation in the prevention of symptom and structural progression of knee OA. METHODS: PubMed, Embase, and Web of Science databases were searched to identify relevant studies. Outcomes included Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, function, stiffness, tibial cartilage volume, and serum vitamin D3 levels, and adverse events. Results were expressed as weight mean difference (WMD) with 95% confidence interval (CI), and risk ratio (RR) with 95%CI. RESULTS: Four RCTs involving 1136 patients were included in this study. Pooled estimates suggested that vitamin D supplementation was associated with a significant reduction in WOMAC pain, and WOMAC function, but not in WOMAC stiffness. Vitamin D supplementation increased the serum vitamin D3 level, but had no effect on tibial cartilage volume. Subgroup analysis showed that, a daily supplement of more than 2000 IU vitamin D significantly decreased the WOMAC pain and WOMAC function. There was no significant difference in incidence of adverse events between the vitamin D and placebo groups. CONCLUSION: Vitamin D supplementation was effective in improving the WOMAC pain and function in patients with knee OA. However, it had no beneficial effect on the prevention of tibial cartilage loss. Therefore, there is currently a lack of evidence to support the use of vitamin D supplementation in preventing the progression of knee OA.

Can balneotherapy modify microRNA expression levels in osteoarthritis? A comparative study in patients with knee osteoarthritis.

The aim of this study was to evaluate the whole-blood levels of miR-155, miR-223, miR-181a, miR-146a, and miR-let-7e in patients with bilateral knee osteoarthritis (OA) after a cycle of mud-bath therapy (MBT). Thirty-two patients with knee OA defined by the ACR criteria were included. Twenty-one patients (MBT group) were daily treated with a combination of local mud-packs at 42 °C and baths in mineral water, at 37 °C for 15 min, for 12 applications over a period of 2 weeks, in addition to standard therapy; 11 patients (control group) continued their conventional treatment alone. Global pain score evaluated by visual analog scale (VAS), WOMAC subscores, and microRNA expression were evaluated at baseline and after 2 weeks. Peripheral whole blood was collected into PAXgene™ Blood RNA tubes, stored at - 80 °C, and total RNA was extracted. The expression of miR-155, miR-223, miR-181a, miR-146a, and miR-let-7e was determined by qRT-PCR. After MBT, we observed a statistically significant improvement of clinical parameters and a significant decrease of miR-155, miR-181a, miR-146a (p < 0.001), and miR-223 (p < 0.01) expression levels. No clinical and biochemical modifications were detected in the control group. No significant variations of miR-let-7e were shown in both groups after 2 weeks. In conclusion, MBT can modify the expression of miR-155, miR-181a, miR-146a, and miR-223, which are upregulated in OA. It could be due to the heat stress and the hydrostatic pressure, since some miRNAs were found to be temperature- and mechano-responsive. Further studies are needed to better explain the mechanism of action of MBT and the role of miRNAs in OA.