[Status of outcome measures in randomized controlled trials of kidney-tonifying and blood-activating method in treatment of knee osteoarthritis].

This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.

Revolutionizing Knee Osteoarthritis Treatment: Innovative Self-Nano-Emulsifying Polyethylene Glycol Organogel of Curcumin for Effective Topical Delivery.

In the current study, self-nano-emulsifying (SNE) physically cross-linked polyethylene glycol (PEG) organogel (SNE-POG) as an innovative hybrid system was fabricated for topical delivery of water-insoluble and unstable bioactive compound curcumin (CUR). Response surface methodology (RSM) based on Optimal Design was utilized to evaluate the formulation factors. Solid fiber mechanism with homogenization was used to prepare formulations. Pharmaceutical evaluation including rheological and texture analysis, their mathematical correlations besides physical and chemical stability experiments, DSC study, in vitro release, skin permeation behavior, and clinical evaluation were carried out to characterize and optimize the SNE-OGs. PEG 4000 as the main organogelator, Poloxamer 188 (Plx188) and Ethyl Cellulose (EC) as co-gelator/nanoemulsifier agents, and PEG 400 and glycerin as solvent/co-emulsifier agents could generate SNE-POGs in PS range of 356 to 1410 nm that indicated organic base percentage and PEG 4000 were the most detrimental variables. The optimized OG maintained CUR stable in room and accelerated temperatures and could release CUR sustainably up to 72 h achieving high flux of CUR through guinea pig skin. A double-blind clinical trial confirmed that pain scores, stiffness, and difficulty with physical function were remarkably diminished at the end of 8 weeks compared to the placebo (71.68% vs. 7.03%, 62.40% vs. 21.44%, and 45.54% vs. 8.66%, respectively) indicating very high efficiency of system for treating knee osteoarthritis. SNE-POGs show great potential as a new topical drug delivery system for water-insoluble and unstable drugs like CUR that could offer a safe and effective alternative to conventional topical drug delivery system.

Network pharmacology combined with experimental validation to investigate the effect of Rongjin Niantong Fang on chondrocyte apoptosis in knee osteoarthritis.

Knee osteoarthritis (KOA) is a chronic degenerative disease that affects the quality of life of middle­aged and elderly individuals, and is one of the major factors leading to disability. Rongjin Niantong Fang (RJNTF) can alleviate the clinical symptoms of patients with KOA, but the molecular mechanism underlying its beneficial effects on KOA remains unknown. Using pharmacological analysis and in vitro experiments, the active components of RJNTF were analyzed to explore their potential therapeutic targets and mechanisms in KOA. The potential targets and core signaling pathways by which RJNTF exerts its effects on KOA were obtained from databases such as Gene Expression Omnibus, Traditional Chinese Medicine Systems Pharmacology and Analysis Platform. Subsequently, chondrocyte apoptosis was modeled using hydrogen peroxide (H2O2). Cell Counting Kit­8 assay involving a poly [ADP­ribose] polymerase­1 (PARP1) inhibitor, DAPI staining, reverse transcription­quantitative PCR, Annexin V­FITC/PI staining and flow cytometry, western blotting and co­immunoprecipitation analysis were used to determine the therapeutic efficacy of RJNTF on KOA and to uncover the molecular mechanism. It was found that PARP1­knockdown lentivirus, incubation with PARP1 inhibitor PJ34, medium and high doses of RJNTF significantly reduced H2O2­induced chondrocyte apoptosis. Medium and high doses of RJNTF downregulated the expression of cleaved caspase­3, cleaved PARP1 and PAR total proteins, as well as nucleus proteins of apoptosis­inducing factor (AIF) and migration inhibitory factor (MIF), and upregulated the expression of caspase­3, PARP1 total protein, as well as the cytoplasmic expression of AIF and MIF, suggesting that RJNTF may inhibit chondrocyte apoptosis through the PARP1/AIF signaling pathway.

Effects of alendronate on cartilage lesions and micro-architecture deterioration of subchondral bone in patellofemoral osteoarthritic ovariectomized rats with patella-baja.

BACKGROUND: Patellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks. METHODS: Patella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague-Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 µg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT). RESULTS: Our results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone. CONCLUSION: The early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

Proteome-Wide Mendelian Randomization and Colocalization Analysis Identify Therapeutic Targets for Knee and Hip Osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease. Although some biomarkers and drug targets of OA have been discovered and employed, limitations and challenges still exist in the targeted therapy of OA. Mendelian randomization (MR) analysis has been regarded as a reliable analytic method to identify effective therapeutic targets. Thus, we aimed to identify novel therapeutic targets for OA and investigate their potential side effects based on MR analysis. In this study, two-sample MR, colocalization analysis, summary-data-based Mendelian randomization (SMR) and Mendelian randomization phenome-wide association study (MR-PheWAS) were conducted. We firstly analyzed data from 4907 plasma proteins to identify potential therapeutic targets associated with OA. In addition, blood expression quantitative trait loci (eQTLs) data sources were used to perform additional validation. A protein-protein interaction (PPI) network was also constructed to delve into the interactions among identified proteins. Then, MR-PheWASs were utilized to assess the potential side effects of core therapeutic targets. After MR analysis and FDR correction, we identified twelve proteins as potential therapeutic targets for knee OA or hip OA. Colocalization analysis and additional validation supported our findings, and PPI networks revealed the interactions among identified proteins. Finally, we identified MAPK3 (OR = 0.855, 95% CI: 0.791-0.923, p = 6.88 × 10-5) and GZMK (OR = 1.278, 95% CI: 1.131-1.444, p = 8.58 × 10-5) as the core therapeutic targets for knee OA, and ITIH1 (OR = 0.847, 95% CI: 0.784-0.915, p = 2.44 × 10-5) for hip OA. A further MR phenome-wide association study revealed the potential side effects of treatments targeting MAPK3, GZMK, and ITIH1. This comprehensive study indicates twelve plasma proteins with potential roles in knee and hip OA as therapeutic targets. This advancement holds promise for the progression of OA drug development, and paves the way for more efficacious treatments of OA.

Efficacy and safety of extracorporeal shock wave therapy combined with sodium hyaluronate in treatment of knee osteoarthritis: a systematic review and Meta-analysis.

OBJECTIVE: To assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) combined with sodium hyaluronate (HA) for the treatment of knee osteoarthritis (KOA). METHODS: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, and SinoMed were searched from inception to July 2020. The quality of the randomized controlled trials was evaluated independently by two reviewers according to the criteria in the Cochrane Collaboration for Systematic Reviews. The identified articles were then screened individually using EndnoteX9 for eligibility in this Meta-analysis. The heterogeneity among the articles was evaluated using I2. RESULTS: A total of 17 studies, comprising 2000 individuals, were included in this Meta-analysis. The results showed that a significant improvement was observed in knee pain and function based on the clinical efficacy of ESWT combined with HA. Statistical analysis of clinical efficacy showed that [relative risk (RR) = 1.21, 95% confidence interval (CI) (1.12, 1.30), P < 0.01]. Statistical analysis of visual analog scale showed that [standardized mean difference (SMD) = －2.84, 95%CI (－4.01, －1.66), P < 0.01]. Western Ontario and McMaster University osteoarthritis index statistical analysis showed that [SMD = －1.57, 95% CI (－2.52, －0.61), P < 0.01]. Lysholm score statistical analysis showed that [SMD = 1.71, 95% CI (0.98, 2.44), P < 0.01]. In addition, only minor side effects, such as redness and swelling of the skin, were observed. CONCLUSIONS: Medium to low quality evidence showed that ESWT combined with HA offers an inexpensive, well-tolerated, safe, and effective method to improve pain and functionality in patients with KOA. However, tightly controlled, randomized, large multicenter trials are warranted to validate the current findings.

Miao medicine Gu Yan Xiao tincture inhibits mTOR to stimulate chondrocyte autophagy in a rabbit model of osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Gu Yan Xiao tincture, a blend of traditional Chinese herbs, is traditionally used for osteoarthritis and related pain. This study investigated its mechanism of action in order to rationalize and validate its therapeutic use. AIM OF THE STUDY: This study analyzed, in a rabbit model of knee osteoarthritis, whether and how Gu Yan Xiao tincture exerts therapeutic benefits by modulating chondrocyte autophagy. MATERIALS AND METHODS: The active constituents within the GYX tincture were identified using liquid chromatography-mass spectrometry. The rabbit model was established by injecting animals with type II collagenase intra-articularly, and the effects of topically applied tincture were examined on osteoarthritis lesions of the knee using histopathology, micro-computed tomography and x-ray imaging. Effects of the tincture were also evaluated on levels of inflammatory cytokines, matrix metalloproteases, and autophagy in chondrocytes. As a positive control, animals were treated with sodium diclofenac. RESULTS: The tincture mitigated the reduction in joint space, hyperplasia of the synovium and matrix metalloproteases in serum that occurred after injection of type II collagenase in rabbits. These therapeutic effects were associated with inhibition of mTOR and activation of autophagy in articular chondrocytes. Inhibiting mTOR with rapamycin potentiated the therapeutic effects of the tincture, while inhibiting autophagy with 3-methyladenine antagonized them. CONCLUSIONS: Gu Yan Xiao tincture mitigates tissue injury in a rabbit model of osteoarthritis, at least in part by inhibiting mTOR and thereby promoting autophagy in chondrocytes. These results rationalize the use of the tincture not only against osteoarthritis but also potentially other diseases involving inhibition of autophagy in bones and joints.

Association of long-term use of non-steroidal anti-inflammatory drugs with knee osteoarthritis: a prospective multi-cohort study over 4-to-5 years.

This study examines the long-term impact of non-steroidal anti-inflammatory drugs (NSAIDs) on the progression of symptoms and structural deterioration of the joint in knee osteoarthritis. The study analyzes data from 4197 participants (8394 knees) across the Osteoarthritis Initiative (OAI), Multicenter Osteoarthritis Study (MOST), and Cohort Hip and Cohort Knee (CHECK) over 4-to-5 years. Adjustments were made for major covariates. We focussed on binary outcomes to assess the presence or absence of significant changes. We found that, relative to non-users, individuals using NSAIDs long-term were significantly more likely to experience aggravated symptoms exceeding the minimally clinically important difference, specifically, pain (OR: 2.04, 95% CI: 1.66-2.49), disability (OR: 2.21, 95% CI: 1.74-2.80), and stiffness (OR: 1.58, 95% CI: 1.29-1.93). Long-term users also faced a higher probability than non-users of having total knee replacement (OR: 3.13, 95% CI: 2.08-4.70), although no significant difference between long-term users and non-users was observed for structural deterioration in the knee joint (OR: 1.25, 95% CI: 0.94-1.65). While acknowledging the limitations of this study due to its observational design and the potential for bidirectional causality, these findings suggest that long-term NSAID use could accelerate the progression to total knee replacement by markedly exacerbating symptoms.

Structure-Guided Discovery of Potent and Selective CLK2 Inhibitors for the Treatment of Knee Osteoarthritis.

Osteoarthritis is the most common joint disorder. However, there are no disease-modifying drugs approved for OA treatment. CDC2-like kinase 2 (CLK2) could modulate Wnt signaling via alternative splicing of Wnt target genes and further affect bone differentiation, chondrocyte function, and inflammation, making CLK2 an attractive target for OA therapy. In this study, we designed and synthesized a series of highly potent CLK2 inhibitors based on Indazole 1. Among them, compound LQ23 showed more elevated inhibitory activity against CLK2 than the lead compound (IC50, 1.4 nM) with high CLK2/CLK3 selectivity (>70-fold). Furthermore, LQ23 showed outstanding antiosteoarthritis effects in vitro and in vivo, with the roles specific in decreased inflammatory cytokines, downregulated cartilage degradative enzymes, and increased joint cartilage via suppressing CLK2/Wnt signaling pathway. Overall, these data support LQ23 as a potential candidate for intra-articular knee OA therapy, leveraging its unique mechanism of action for targeted treatment.

Modified Mesenchymal stem cell, platelet-rich plasma, and hyaluronic acid intervention in early stage osteoarthritis: A systematic review, meta-analysis, and meta-regression of arthroscopic-guided intra-articular approaches.

BACKGROUND: Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid (HA). This study aimed to assess the synergy of MSCs, PRP, and varying HA doses, and determine optimal MSC sources to treat early-stage OA in the perspective of Lysholm score, VAS Score, KSS score, and WOMAC score. METHOD: Original articles from 2013 to 2023 were screened from four databases, focusing on clinical trials and randomized controlled trials. The Risk of Bias in Non-randomized Studies-of Interventions (ROB-2) tool evaluated bias, and a PICOS criteria table guided result construction. Revman 5.4 analyzed outcomes such as Lysholm score, VAS score, KSS, WOMAC score, cartilage volume, and defect size using MRI. This systematic review adhered to PRISMA guidelines. RESULT: Nine studies met the final inclusion criteria. Meta-analysis revealed a significant improvement in Lysholm score (MD: 17.89; 95% CI: 16.01, 19.77; I2 = 0%, P = 0.56), a notable reduction in VAS score (MD: -2.62; 95% CI: -2.83, -2.41; I2 = 99%, P < 0.00001), elevated KSS (MD: 29.59; 95% CI: 27.66, 31.52; I2 = 95%, P < 0.0001), and reduced WOMAC score (MD: -12.38; 95% CI: -13.75, -11.01; I2 = 99%, P < 0.0001). CONCLUSIONS: Arthroscopic guided high-dose subchondral application of primary cultured synovial MSCs in popliteal PRP media with HA effectively regenerates cartilage defects and improves clinical outcomes in early-stage osteoarthritis. Clarification of MSC sources and quantities enhances the understanding of this promising treatment modality.

Modulation of gut microbiota by crude mulberry polysaccharide attenuates knee osteoarthritis progression in rats.

Mulberry (Morus alba L.), a kind of common fruits widely cultivated worldwide, has been proven various biological activities. However, its potential role in the progression of knee osteoarthritis (KOA) remains unclear. This study aims to investigate the potential protective effects of crude polysaccharide extracted from mulberry fruit, referred to as a complex blend of polysaccharides and other unidentified extracted impurities, on KOA progression. The KOA rats were established by injection of 1 mg sodium monoiodoacetate into knee, and administrated with crude mulberry polysaccharide (Mup) by gastric gavage for 4 weeks. Furthermore, intestinal bacteria clearance assay (IBCA) and fecal microbiota transplantation were conducted for the evaluation of the effect of gut microbiota (GM) on KOA. Our findings demonstrated that Mup, particularly at a dosage of 200 mg/kg, effectively improved abnormal gait patterns, reduced the level of inflammation, mitigated subchondral bone loss, restored compromised joint surfaces, alleviated cartilage destruction, and positively modulated the dysregulated profile of GM in KOA rats. Moreover, IBCA compromised the protective effects of Mup, while transplantation of fecal bacteria from Mup-treated rats facilitated KOA recovery. Collectively, our study suggested that Mup had the potential to ameliorate the progression of KOA, potentially through its modulation of GM profile.

Intraarticular botulinum toxin type A versus corticosteroid or hyaluronic acid for painful knee osteoarthritis: A meta-analysis of head-to-head randomized controlled trials.

Intraarticular botulinum toxin type A (BTA) has been shown to be effective for painful knee osteoarthritis (KOA), while the efficacy and safety of intraarticular BTA compared to corticosteroid and hyaluronic acid (HA) remains unknown. A meta-analysis was performed to compare. A search was conducted in Medline (PubMed), CENTER (Cochrane Library), Embase (Ovid), Web of Science, Wanfang, and CNKI to find head-to-head randomized controlled trials (RCTs) directly compare the efficacy and safety between intraarticular BTA and intraarticular corticosteroid or HA for patients with painful KOA. The Cochrane Q test and estimation of I2 were used to assess heterogeneity among studies. After incorporating heterogeneity, a random-effects model was employed for data pooling. Overall, six RCTs involving 348 adults with KOA were included. Intraarticular BTA showed similar efficacy with corticosteroid as evidenced by the changes of pain visual analog scale (VAS: -0.35 [-0.97, 0.28]), total Western Ontario McMaster Universities Arthritis Index (WOMAC: 0.28 [-4.13, 4.69]), and WOMAC for pain (0.64 [-0.42, 1.70]), stiffness (-0.02 [-0.54, 0.50]), and function (0.00 [-2.99, 3.00]). Intraarticular BTA was shown to be more effective than HA in improving pain VAS (-1.31 [-1.97, -0.64]) and WOMAC for pain (-4.81 [-8.73, -0.89]), while the influence on WOMAC for knee stiffness (-1.01 [-4.43, 2.41]) and knee function (-1.86 [-6.71, 2.99]) were similar between groups. No serious adverse events were reported. Evidence from pilot RCTs suggests that intraarticular BTA may confer similar efficacy to corticosteroid for KOA, while BTA may be superior to HA for improving knee pain.

Effects of a Combination of Polynucleotide and Hyaluronic Acid for Treating Osteoarthritis.

Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNFα levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade.

Melatonin is a potential novel analgesic agent for osteoarthritis: Evidence from cohort studies in humans and preclinical research in rats.

Melatonin exhibits potential for pain relief and long-term safety profile. We examined the analgesic effects of oral melatonin on osteoarthritis (OA) and investigated the underlying mechanism. Using data from a UK primary care database, we conducted a cohort study in individuals with OA to compare the number of oral analgesic prescriptions and the risk of knee/hip replacement between melatonin initiators and hypnotic benzodiazepines (i.e., active comparator) initiators using quantile regression models and Cox-proportional hazard models, respectively. To elucidate causation, we examined the effects of melatonin on pain behaviors and explored several metabolites that may serve as potential regulatory agents of melatonin in the monoiodoacetate rat model of OA. Using data from another community-based cohort study, that is, the Xiangya OA Study, we verified the association between the key serum metabolite and incident symptomatic knee OA. Compared with the hypnotic benzodiazepines cohort (n = 8135), the melatonin cohort (n = 813) had significantly fewer subsequent prescriptions of oral analgesics (50th percentile: 5 vs. 7, 75th percentile: 19 vs. 29, and 99th percentile: 140 vs. 162) and experienced a lower risk of knee/hip replacement (hazard ratio = 0.47, 95% Cl: 0.30-0.73) during the follow-up period. In rats, oral melatonin alleviated pain behaviors and increased serum levels of glycine. There was an inverse association between baseline serum glycine levels and the risk of incident symptomatic knee OA in humans (n = 760). In conclusion, our findings indicate that oral melatonin shows significant potential to be a novel treatment for OA pain. The potential role of glycine in its analgesic mechanism warrants further investigation.

Association of lipid-lowering drugs with osteoarthritis outcomes from a drug-target Mendelian randomization study.

BACKGROUND: Osteoarthritis (OA), a prevalent musculoskeletal disorder, has been suggested to have a potential association with metabolic syndrome, particularly lipid metabolism. Studies exploring the effects of lipid-lowering drugs on OA have yielded conflicting results. OBJECTIVE: This study employed a drug-targeted Mendelian randomization approach to investigate the association between genetically predicted lipid-modulating effects of commonly targeted lipid-lowering agents and the risk of OA, with the aim of providing a theoretical foundation for the use of lipid-lowering drugs in OA treatment. METHODS: Employing Mendelian randomization (MR) analysis, we examined the potential causal relationship between lipid-lowering drugs and OA. Genetic variants associated with LDL cholesterol levels were selected from the GWAS summary data, and a series of statistical analyses, including inverse-variance weighted (IVW), weighted median (WM), and MR-Egger, were performed to estimate causal effects. RESULTS: We observed significant associations between genetically proxied lipid-lowering drug targets and OA risk. Notably, HMGCR-mediated LDL cholesterol showed an association with overall OA of the hip or knee (OR = 0.865, 95%CI: 0.762 to 0.983, p = 0.026, q = 0.07) and knee osteoarthritis specifically (OR = 0.746, 95%CI: 0.639 to 0.871, p = 2.180×10-4, q = 0.004). PCSK9-mediated LDL cholesterol also demonstrated an association with OA of the hip or knee (OR = 0.915, 95%CI: 0.847 to 0.988, p = 0.023, q = 0.07) and knee osteoarthritis (OR = 0.901, 95%CI: 0.821 to 0.990, p = 0.03, q = 0.07). NPC1L1-mediated LDL cholesterol showed a positive association with OA of the hip or knee (OR = 1.460, 95%CI: 1.127 to 1.890, p = 0.004, q = 0.033). Furthermore, LDLR-mediated LDL cholesterol demonstrated an association with OA of the hip or knee (OR = 0.882, 95%CI: 0.788 to 0.988, p = 0.03, q = 0.07) and hip osteoarthritis (OR = 0.867, 95%CI: 0.769 to 0.978, p = 0.02, q = 0.07). CONCLUSIONS: These findings provide preliminary evidence for the potential therapeutic use of lipid-lowering drugs in OA treatment. Further investigation is needed to validate these findings and explore the precise mechanisms underlying the observed associations.

Effectiveness of Bach Nien Kien Health Supplement in the Treatment of Patients With Symptomatic Knee Osteoarthritis.

BACKGROUND/AIM: Knee osteoarthritis (KOA) is the most common disease in adults. We conducted a clinical study to evaluate the efficacy and safety of Bach Nien Kien (BNK) in supportive therapy for patients with symptomatic KOA. PATIENTS AND METHODS: An open interventional study was performed on 60 patients aged 38 to 70 with the diagnosis of symptomatic KOA. The patients were assigned to a study group (SG) with 30 subjects and a control group (CG) with 30 subjects using a matching method. The patients in SG were treated with electroacupuncture, glucosamine supplement, and BNK, while the patients in CG received the same treatment without BNK. RESULTS: At the end of the 30-day treatment (d30), the SG had a reduction in VAS score compared to a pre-treatment level of 3.03±0.96 points, which was more than the CG of 2.5±0.90 points. The excellent result in the SG was 10%, and the CG had no excellent result. The good result in the SG was 56.7%, and the CG group was only 26.7%. The moderate and poor results in the CG were high, 63.3%, and 10%, respectively; in the SG, only 26.7% and 6.7%. The difference in overall treatment results between the SG and CG was statistically significant (p<0.05). During the 30-day treatment period in both groups, no patient reported any undesirable effects. CONCLUSION: Bach Nien Kien health supplement is effective and safe for controlling KOA symptoms and improving joint motion and quality of life for patients with symptomatic KOA.

Periostial and cartilage morphology in knee osteoarthritis: beneficial effects of supplementation with Pycnogenol® + Centellicum®.

BACKGROUND: The aim of this registry study was to evaluate the progress of osteoarthrosis (OA) symptoms after the intake of a new standardized supplement combination (Pycnogenol® + Centellicum®, both Horphag Research) in a group of subjects with OA. METHODS: Supplemented subjects took daily 150 mg Pycnogenol® + 450 mg Centellicum® for 6 months. Another comparable group of subjects using only standard management (SM) was included as a reference. RESULTS: Forty-five subjects with a mean age of 42 years completed the study, 25 in the supplemented group and 20 in the SM group. There were no safety problems or tolerability issues with the supplements. The two groups, SM and SM + Pycnogenol® + Centellicum® were comparable for age and clinical characteristics at inclusion. The two main ultrasound characteristics of cartilage, its thickness and surface-irregularity were more improved with the supplements. Pain scores, C reactive protein, the level of fitness and the use of extra pain killers (as rescue medication) were all significantly improved at 6 months with the supplement combination compared to SM (P<0.05). Plasma free radicals, pain-free walking distance on treadmill and erythrocyte sedimentation rate (ESR) were significantly improved with the supplements compared to SM. CONCLUSIONS: The morphological improvement - visible with ultrasound - correlates with a decrease in clinical symptoms and with a more efficient ambulation without pain. SM along with the Pycnogenol® Centellicum® combination are useful to avoid drug treatments that may expose patients to some side effects over time.

Open, Observational, Single-Arm, Multicenter Study Assessing the Effectiveness of a Dietary Supplement Containing Hydrolyzed Collagen, Chondroitin Sulfate, and Glucosamine for Osteoarthritis Pain Reduction.

Osteoarthritis (OA) is an age-related degenerative joint disease with a great impact on patients' well-being and quality of life. This is an observational, open, single-arm multicenter study aimed to evaluate the effectiveness of a nutritional supplement in patients with knee and/or hip OA. A total of 186 patients were recruited from Spanish centers and received a supplement containing hydrolyzed collagen (3000 mg), chondroitin sulfate (800 mg), glucosamine sulfate (700 mg), turmeric extract (250 mg) and devil's claw (150 mg), once daily during 6 months. The primary outcome was the patients' self-perceived pain in the affected joints measured with a visual analogue scale (VAS). Secondary outcome was the patient's functioning, measured with the Lequesne Functional Index and the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Participants showed a significant reduction in self-perceived pain after 3 (mean reduction ± standard deviation, 1.99 ± 1.05) and 6 months (3.57 ± 1.39) of treatment (p < 0.0001 in both comparisons). Lequesne Functional Index score was significantly reduced at 3 months (3.86 ± 2.94) and at 6 months (6.73 ± 4.30) of treatment (p < 0.0001 in both comparisons). The WOMAC index was also significantly reduced after 3 (14.24 ± 10.04) and 6 months (26.43 ± 17.35) of treatment (p < 0.0001 in both comparisons). Significant reductions in WOMAC subdomains (p < 0.0001 in all comparisons) were observed. No severe adverse events were reported during the study. The main results arising from this study show that this nutritional supplementation can improve OA-related symptoms and physical function with a good safety profile in patients with hip and/or knee OA.

American Academy of Orthopaedic Surgeons Technology Overview Summary: Platelet-Rich Plasma (PRP) for Knee Osteoarthritis.

The Platelet-Rich Plasma (PRP) for Knee Osteoarthritis Technology Overview is based on a systematic review of current scientific and clinical research. Through analysis of the current best evidence, this technology overview seeks to evaluate the efficacy of PRP for patients with knee osteoarthritis. The systematic literature review resulted in 54 articles: 36 high-quality and 18 moderate-quality. The findings of these studies were summarized to present findings on PRP versus control/placebo, acetaminophen, non-steroidal anti-inflammatory drugs, corticosteroids, exercise, prolotherapy, autologous conditioned serum, bone marrow aspirate concentrate, hyaluronic acid, and ozone therapy. In addition, the work group highlighted areas that needed additional research when evidence proved lacking on the topic and carefully noted the potential harms associated with an intervention, required resource utilization, acceptability, and feasibility.

Confirmation of pain-related neuromodulation mechanism of Bushen Zhuangjin Decoction on knee osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Zhuangjin Decoction (BZD) are an herbal compound commonly used to treat osteoarthritis (OA) in China. AIM OF THE STUDY: This study aimed to verify the mechanism of Bushen Zhuangjin Decoction in relieving the pain of knee osteoarthritis. MATERIALS AND METHODS: Network pharmacology evaluation was used to discover the potential targets of BZD to relieve pain in KOA. The therapeutic effects of BZD treatment on KOA pain using histomorphology, behavioral assessments, suspension chip analysis, and ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) assays. The functional magnetic resonance imaging was used to explore the effects of BZD treatment on brain function associated to KOA. RESULTS: Network pharmacological analysis revealed the association between the analgesic effect of BZD on KOA and the pain signaling neurotransmitter 5-HT. Subsequently, we conducted experiments to verify the therapeutic effect of BZD on pain in KOA animal models. Behavioral tests demonstrated that the pain threshold of knee osteoarthritis rats decreased in PWT and PWL, but BZD was able to increase the pain threshold. Histopathological staining indicated thinning of the cartilage layer and sparse trabeculae in the subchondral bone. Suspension chip analysis revealed a significant increase in pro-inflammatory factors of IL-1α, IL-5, IL-12, IL-17A, RANTES, TNF-α and M-CSF in KOA, along with a significant decrease in anti-inflammatory factor of IL-13. However, BZD treatment decreased the expression of pro-inflammatory factors and increased the content of anti-inflammatory factor. UHPLC-MS/MS analysis showed a significant decrease in the serum levels of GABA, E, GSH, Kyn, Met, and VMA in KOA, which were significantly increased by BZD. Conversely, the serum levels of TrpA, TyrA, Spd, and BALa were significantly increased in KOA and significantly decreased by BZD. ELISA and Western blot analysis showed increased expression of subchondral bone pain-related neuropeptides SP, CGRP, TH, NPY, VEGFA, 5-HT3 in KOA, which were decreased in BZD. Functional magnetic resonance imaging demonstrated that BZD exerts its therapeutic effect on KOA by modulating the activity and functional connections of the cortex, hypothalamus, and hippocampus. CONCLUSIONS: This study confirmed the significant role of pain-related neuromodulation mechanisms in the analgesic therapy of BZD and provides a theoretical foundation for using BZD as a traditional Chinese medical treatment for KOA pain.