Clinical controlled study of Zhongyi Ointment() in the treatment of Kellgren-Lawrence gradeⅡknee osteoarthritis with moderate-to-severe pain

In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy of deer bone extract (DBE) in participants with knee osteoarthritis (OA). We enrolled 50 participants aged 50-70 years, having knee OA with a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score ≥5.0. The participants were assigned to the placebo or DBE group (550 mg/day) for 12 weeks. The outcome measures were as follows: pain score on the visual analog scale (VAS); WOMAC score; and blood and urine biomarkers. In the DBE group, VAS scores, WOMAC total scores, and WOMAC subscores (for pain, stiffness, and physical function) improved significantly compared with the baseline values. However, there was no significant difference in outcomes between the DBE and placebo groups. The present findings suggest that DBE may mildly reduce joint pain and stiffness and improve joint function in patients with painful knee OA.

Background: Knee osteoarthritis (OA) is a chronic degenerative joint disease and inflammatory pain which decreases daily activities. Objective: The aim of the present investigation was to examine skin permeation and skin irritation test of Phyllanthus Amarus (PA) cream including the effects of four weeks of treatment with PA cream in patients with osteoarthritis (OA) of the knee. Methods: The permeation study of PA cream was determined by Franz diffusion cells using a stillborn piglet skin. The primary irritation test was evaluated in rabbits and human volunteers following the Draize test. The study included sixty respondents diagnosed with symptomatic knee OA (12 males, 48 females). All the respondents volunteered to participate and randomly allocated into 3 groups including (n =20 in each group), followed by the placebo group and Phyllanthus Amarus (PA) cream group and NSAIDs cream group. They used a cream twice per day for four weeks. The patients were tested on 3 occasions; before two weeks and four weeks for the treatment period. The respondents were completely assessed for pain and function assessment by the visual analog scale (VAS) and the Western Ontario and McMaster Universities O-osteoarthritis Index questionnaire (WOMAC), respectively. Results: The PA cream showed good skin permeation after 10 hours. It had a high accumulative amount in the dermis and the receiving chamber more than the stratum corneum. Therefore, it could help to relieve pain and prolong the effect. The PA cream did not irritate the skin of rabbits and human volunteers. It is safe to be used in clinical treatment. The VAS and total WOMAC scores significantly decreased after 2 weeks (P < 0.001) and 4 weeks (P < 0.001) of intervention compared with before treatment in both the PA cream and NSAIDs groups in OA knee. However, the VAS and total WOMAC score of PA cream were not significantly compared with the NSAIDs groups. Conclusion: The Phyllanthus amarus cream is a new choice, and effective method for OA of the knee treatment. These data indicate that the treatment through Phyllanthus amarus cream improves pain relief and function.

The objective of this study was to investigate the safety and efficacy of a dietary supplement, Arthrem, containing an extract from the medicinal plant Artemisia annua, on pain, stiffness, and functional limitation in osteoarthritis (OA) of the hip or knee. Forty-two patients were randomized to one of three groups (n = 14 in each group): 150-mg Artemisia annua extract (ART) twice daily (BD) (ART low dose), 300-mg ART BD (ART high dose), or placebo BD administered over 12weeks. Efficacy was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) and visual analog scale (VAS) for pain. Participants treated with ART low dose demonstrated significant improvement in WOMAC total scores from baseline to 12weeks (mean change, -12.2; standard deviation, [SD] 13.84; p = 0.0159); improvement was not shown in the placebo group (mean change, -7.8; SD, 19.80; p = 0.1029). Statistically significant reductions were seen from baseline in the ART low-dose group for individual WOMAC components stiffness and physical function. VAS pain scores were statistically significantly reduced from baseline to 12weeks in the ART low-dose group (mean change, -21.4mm; SD, 23.48mm; p = 0.0082) but not the placebo group (mean change, -11.5mm; SD, 28.97mm, p = 0.1757). No statistically significant changes occurred from baseline in the placebo or ART high-dose groups for any parameter. ART low dose was well tolerated. ART has potential as an anti-inflammatory/analgesic in OA. Treatment with ART 150mg BD is associated with clinically relevant reductions in pain over 12weeks. Further studies are warranted.

The effects of topical and oral Nigella sativa oil on clinical findings in knee osteoarthritis: A double-blind, randomized controlled trial

Efficacy and safety of oral Nigella sativa oil for symptomatic treatment of knee osteoarthritis: A double-blind, randomized, placebo-controlled clinical trial

The aim of this study is to compare the clinical efficacy and safety of platelet-rich plasma (PRP) and hyaluronic acid in the treatment of hip osteoarthritis. Data were collected from the PubMed, Embase, Cochrane Library, and Web of Science databases. The outcomes selected included the Visual Analog Scale (VAS) score, the Harris Hip Score (HHS), the Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) and its relevant subscores. A standardized mean difference (SMD) was used as the combined effect size, and a random-effects model was applied for analysis. The magnitude of the effect size was interpreted according to Jacob Cohen's criteria. A total of seven studies involving 465 patients were included. The meta-analysis results indicated that in terms of pain relief, the PRP group showed a statistically significant advantage in VAS scores at 6 months (SMD = -0.38 and p = 0.01). Subgroup analysis revealed that LP-PRP yielded significant improvement (SMD = -0.32 and p = 0.02), whereas LR-PRP did not (SMD = -0.46 and p = 0.18). Similarly, multiple injections (SMD = -0.43 and p = 0.02) demonstrated superiority compared to a single injection (SMD = -0.12 and p = 0.63).Regarding WOMAC-pain scores, the PRP group exhibited statistical differences at 6 months (SMD = -0.45 and p = 0.0006) and 12 months (SMD = -0.36 and p = 0.03). In terms of functional impairment, no significant differences were found in the HHS (SMD = 0.13 and p = 0.64) or WOMAC subscores (WOMAC-stiffness: SMD = 0.01 and p = 0.97 and WOMAC-function: SMD = -0.24 and p = 0.06) at any follow-up time point. However, the WOMAC total score indicated that the overall health status of patients in the PRP group was superior to that in the HA group after treatment (SMD = -0.42 and p = 0.009). The findings of this study indicate that compared with HA, PRP demonstrates a statistically significant advantage in alleviating pain (VAS and WOMAC-pain) and improving overall symptoms (WOMAC total score) in patients with hip osteoarthritis (HOA) although the effect size was found to be moderate. However, regarding the improvement of joint function (HHS and WOMAC-function), no significant differences were observed between the two groups. In summary, while PRP presents a statistical benefit over HA in the treatment of HOA, the effect size is limited; therefore, further high-quality studies are warranted to definitively confirm its clinical superiority.

Spa therapy is a potential treatment for knee osteoarthritis (KOA). The primary objective of this randomized controlled trial (RCT) was to investigate the effectiveness of a 3-week spa therapy intervention on the 6-month change in function (mobility and functional ability) of KOA patients. Secondary objectives examined the effectiveness of the intervention on KOA-related pain, stiffness, overall symptoms severity, and patient’s quality of life. Community-dwelling adults, aged 50–80 years-old with KOA were randomized to spa therapy intervention or control (usual care) group. The primary outcome measure was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) function subscale. Other outcome measures were the WOMAC pain subscale and a pain visual analog scale, the WOMAC stiffness subscale, the WOMAC total scores, the EQ-5D-3 L for quality-of-life, and patient reported outcomes. Among the 173 individuals randomized, 145 (n = 74 in spa therapy, mean age 67.5 ± 6.4, 67.6% women; n = 71 in controls, mean age 68.3 ± 6.7, 64.8% women) were analyzed. A significant between-group mean difference of 11.7 points in the WOMAC function subscale, favoring the spa therapy group, was found at six months follow-up (primary outcome measure). The intervention was effective in significantly improving most secondary outcomes, including the WOMAC stiffness, pain (and pain visual analog scale) and total scores, as well as the minimum clinically meaningful changes in KOA symptoms, and patient’s quality of life. Improvements were achieved during the intervention period and remained significant over the 6-month follow-up. This work demonstrated the effectiveness of spa therapy in KOA treatment.

Background/AimsNonsteroidal anti-inflammatory drugs relieve osteoarthritis (OA) symptoms but cause adverse effects. D-002, a mixture of beeswax alcohols, is effective against experimental OA. A pilot study found that D-002 (50 mg/day) for 8 weeks improves OA symptoms. The aim of this study was to investigate the effects of D-002 (50 to 100 mg/day) administered for 6 weeks on OA symptoms.MethodsPatients with OA symptoms were double-blindly randomized to D-002 (50 mg) or placebo for 6 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the visual analog scale (VAS) scores. Patients without symptom improvement at week 3 were titrated to two daily tablets. The primary outcome was the total WOMAC score. WOMAC pain, joint stiffness and physical function scores, VAS score, and use of rescue medications were secondary outcomes.ResultsAll randomized patients (n = 60) completed the study, and 23 experienced dose titration (two in the D-002 and 21 in the placebo groups). At study completion, D-002 reduced total WOMAC (65.4%), pain (54.9%), joint stiffness (76.8%), and physical function (66.9%) WOMAC scores, and the VAS score (46.8%) versus placebo. These reductions were significant beginning in the second week, and became enhanced during the trial. The use of rescue medication by the D-002 (6/30) group was lower than that in the placebo (17/30) group. The treatment was well tolerated. Seven patients (two in the D-002 and five in the placebo group) reported adverse events.ConclusionsThese results indicate that D-002 (50 to 100 mg/day) for 6 weeks ameliorated arthritic symptoms and was well tolerated.

A prospective randomized controlled study was conducted to investigate the early postoperative analgesic effectiveness of using liposomal bupivacaine (LB) for local infiltration anesthesia (LIA) in unicompartmental knee arthroplasty (UKA). Between January 2024 and July 2024, a total of 80 patients with knee osteoarthritis (KOA) who met the selection criteria were enrolled in the study. Patients were randomly assigned to either the LB group or the "cocktail" group in a 1∶1 ratio using a random number table, with 40 patients in each group. Baseline characteristics, including gender, age, body mass index, operated side, Kellgren-Lawrence grade, and preoperative American Society of Anesthesiologists (ASA) classification, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee joint range of motion, showed no significant difference between the two groups ( P>0.05). Both groups received LIA and comprehensive pain management. The surgical duration, incision length, pain-related indicators [resting and activity visual analogue scale (VAS) scores, total dosage of oral morphine, WOMAC scores], knee joint range of motion, first ambulation time after operation, length of hospital stay, and postoperative adverse events. There was no significant difference between the two groups in surgical duration, incision length, first ambulation time after operation, length of hospital stay, total dosage of oral morphine, and pre-discharge satisfaction with surgery and WOMAC scores ( P>0.05). At 4, 12, and 24 hours after operation, the resting and activity VAS scores in the "cocktail" group were lower than those in the LB group; at 60 and 72 hours postoperatively, the resting VAS scores in the LB group were lower than those in the "cocktail" group, with the activity VAS scores also being lower at 60 hours; all showing significant differences ( P<0.05). There was no significant difference in the above indicators between the two groups at other time points ( P>0.05). On the second postoperative day, the sleep scores of the LB group were significantly higher than those of the "cocktail" group ( P<0.05), while there was no significant difference in sleep scores on the day of surgery and the first postoperative day ( P>0.05). Additionally, the incidence of complications showed no significant difference between the two groups ( P>0.05). The use of LB for LIA in UKA can provide prolonged postoperative pain relief; however, it does not demonstrate a significant advantage over the "cocktail" method in terms of short-term analgesic effects or reducing opioid consumption and early functional recovery after UKA. Nevertheless, LB may help reduce postoperative sleep disturbances, making it a recommended option for UKA patients with cardiovascular diseases and insomnia or other mental health issues.

The association between baseline laboratory parameters and experienced well-being in healthy individuals remains uncertain. This study explored the relationship between clinical laboratory profiles and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical functional limitation in healthy individuals in Qatar. Clinical laboratory data were collected from 1,764 Qatar Biobank participants who also completed the WOMAC questionnaire: lipid profiles (high-density lipoprotein, low-density lipoprotein, cholesterol, and triglycerides), endocrine markers (TSH, T3, T4, estradiol, and testosterone), and two inflammatory markers (CRP and fibrinogen). Multiple linear regression was used with 11 clinical indicators as independent variables and the subscale and total WOMAC scores as dependent variables. Multivariate effects of each indicator on the outcomes were assessed, and univariate effects were examined when significant. Testosterone had a significant impact on all WOMAC subscales (pain, stiffness, and functional limitation) and the total WOMAC score. Higher testosterone levels were associated with a reduction in pain (β = -0.03, t = -3.505, p < 0.001, 95% CI = -0.052, -0.015), stiffness (β = -0.01, t = -2.265, p = 0.024, 95% CI = -0.018, -0.001), physical dysfunction (β = -0.08, t = -3.265, p = 0.001, 95% CI = -0.135, -0.034), and total WOMAC scores (β = -0.127, t = -3.444, p < 0.001, 95% CI = -0.199, -0.055). Elevated fibrinogen levels were associated with an increase in stiffness (β = 0.155, t = 2.241, p = 0.025, 95% CI = 0.019, 0.290), physical dysfunction (β = 1.17, t = 2.808, p = 0.005, 95% CI = 0.354, 1.997), and total WOMAC scores (β = 1.610, t = 2.691, p = 0.007, 95% CI = 0.437, 2.784). Testosterone may protect against pain, stiffness, and physical dysfunction, while high fibrinogen levels might be a surrogate of systemic inflammation that enhances stiffness and limits physical function. Measuring multiple clinical and laboratory markers in healthy individuals may enhance our understanding of the molecular mechanisms underlying pain.

Background:Intra-articular injection therapies offer attractive treatment options to improve symptoms and potentially modify osteoarthritis (OA) disease progression. However, it remains unclear whether the observed effects of these injections are attributable...

BackgroundTo compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA).MethodsIn 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.ResultsSeventy-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%).ConclusionThe 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 registrationClinical Trials Registry – India CTRI/2017/02/007962. Registered on 27 February 2017

This study aimed to determine whether there was a relationship between preoperative patient-reported outcome measures (PROMs) and satisfaction after total knee arthroplasty (TKA), and whether there was a relationship between the amount of improvement in PROM or final PROM and satisfaction and whether that relationship differed 1 and 2 years after TKA. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and satisfaction of 267 limbs who underwent TKA were analyzed. Logistic regression analysis was performed to determine whether there was a relationship between preoperative WOMAC or improvement in WOMAC or final WOMAC and satisfaction at 1 and 2 years after TKA. Pearson and Filon's z test was performed to determine whether there was a difference in evaluating satisfaction between the amount of improvement in WOMAC and final WOMAC. There was no significant relationship between preoperative WOMAC and satisfaction. A higher improvement in WOMAC total score and better final WOMAC total scores at 1 and 2 years after TKA were related to greater satisfaction. At 1 year after TKA, there was no significant difference in evaluating satisfaction between the amount of improvement in WOMAC and final WOMAC. However, 2 years after TKA, the final WOMAC function and total score were more related to satisfaction than the amount of improvement in WOMAC function and total score. In the early postoperative period, there was no difference in evaluating satisfaction between the amount of improvement in WOMAC and final WOMAC, whereas over time, the final WOMAC was more related to satisfaction.

ObjectivesWe evaluated the effects of digital home-based transcranial direct current stimulation (tDCS) paired with audio-delivered mindfulness-based meditation (MBM) on knee-specific clinical pain and symptoms in patients with symptomatic knee osteoarthritis, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). As sex is a major source of variability in responses to tDCS and MBM, we examined treatment effects by sex.MethodsParticipants (N = 200) from a double-blind, randomized, sham-controlled parent trial were allocated to one of four parallel groups: (1) active tDCS + active MBM, (2) active tDCS + sham MBM, (3) sham tDCS + active MBM, or (4) sham tDCS + sham MBM. They underwent 10 20-minute sessions of anodal tDCS (active or sham) simultaneously with MBM (active or sham). WOMAC measures were secondary outcomes in the parent trial. Linear mixed-effects models, adjusted for baseline demographic and clinical characteristics, compared changes in WOMAC total and subscores (pain, stiffness, and physical function) across groups immediately (10 days) and three months post-intervention.ResultsThe sample was predominantly female (69.0%). Among females, only the active tDCS + active MBM group showed significantly greater reductions in WOMAC total scores—particularly in physical function—compared to the sham tDCS + sham MBM group immediately post-intervention (p = .049). No significant immediate effects were observed among males across WOMAC outcomes. No persistent effects of active tDCS + active MBM were observed at three months in either sex.ConclusionsAlthough digital home-based tDCS paired with MBM may improve knee-specific symptoms, this effect was observed only among females and was short-term. Furthermore, findings should be interpreted cautiously given the sex imbalance.

To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis (OA) in a randomized, double-blind, placebo-controlled trial. Fifty-two patients with symptomatic hip OA were randomly allocated to receive placebo (10 mg bipuvicaine, 2 ml saline) (n = 21) or corticosteroid treatment (10 mg bipuvicaine, 40 mg triamcinolone hexacetonide) (n = 31). Patients were followed up for 1, 2, 3, and 6 months. The primary outcome measure was the pain improvement response, defined as a 20% decrease in the Western Ontario and McMaster Universities OA Index (WOMAC) pain score (on 5 100-mm visual analog scales [VAS]) (WOMAC20) from baseline to 2 months postinjection. Secondary outcomes were a 50% decrease in the WOMAC pain score (WOMAC50), changes in other WOMAC subscale scores, patient's global assessment of health (on a 100-mm VAS), and Short Form 36 (SF-36) quality of life indices. Analyses were based on the intent-to-treat principle. The mean WOMAC pain score fell 49.2% (decreasing from 310.1 mm to 157.4 mm) at 2 months postinjection in patients receiving corticosteroid, compared with a decrease of 2.5% (from 314.3 mm to 306.5 mm) in the placebo group (P < 0.0001). The proportion of WOMAC20 responders at 2 months' followup was significantly higher in the corticosteroid group (67.7%) compared with the placebo group (23.8%) (P = 0.004); similar proportions of WOMAC50 responders were observed between groups (61.3% in the corticosteroid group versus 14.3% in the placebo group; P = 0.001). Response differences were maintained at 3 months' followup (58.1% responders in the corticosteroid group versus 9.5% responders in the placebo group; P = 0.004). Significant differences in the WOMAC stiffness and physical function scores (P < 0.0001), patient's global health scores (P = 0.005), and SF-36 physical component scores (P = 0.04) were observed, with patients in the corticosteroid group showing greater improvements. There were no differences in the frequency of adverse events between groups. This placebo-controlled trial confirms that corticosteroid injection can be an effective treatment of pain in hip OA, with benefits lasting up to 3 months in many cases. Future studies should address questions related to the benefits of repeated steroid injection and the effects of this treatment on disease modification.