The economics of a national anterior cruciate ligament injury prevention program for amateur football players: a Markov model analysis.

OBJECTIVES: To estimate the long term cost savings, return on investment, and gain in quality-adjusted life years (QALYs) that could be achieved by a national anterior cruciate ligament (ACL) injury prevention program for amateur football (soccer) players in Australia. STUDY DESIGN: Markov model decision analysis. SETTING, PARTICIPANTS: Two hypothetical scenarios including all amateur football players in Australia (340 253 players): no intervention, and a national ACL injury prevention program. Transitions between health states, including ACL rupture, meniscal injury, knee osteoarthritis, and total knee replacement were made in one-year cycles over 35 years from a societal perspective. MAIN OUTCOME MEASURES: Cost savings, return on investment, and QALY gain achieved in the prevention program scenario relative to control scenario, by age group (10-17, 18-34, 35 years or older) and gender. SECONDARY OUTCOMES: incidence of ACL rupture, knee osteoarthritis, total knee replacement, and total knee replacement revision. RESULTS: The total mean cost of an ACL injury was estimated to be $30 665. The national injury prevention program was projected to save $52 539 751 in medical and societal costs caused by ACL ruptures in amateur footballers over 35 years; the estimated return on each dollar invested in the program was $3.51. Over this period, the number of players with ruptured ACLs could be reduced by 4385 (9%), the number of knee osteoarthritis cases by 780 (8.1%), and the number of total knee replacements by 121 (8.1%); 445 QALYs were gained. CONCLUSION: Our findings support investing in a national, evidence-based program for the primary prevention of ACL injuries in amateur football players.

Polygonatum sibiricum polysaccharides protect against knee osteoarthritis by inhibiting the TLR2/NF-κB signaling pathway in vivo and in vitro.

Polygonatum sibiricum polysaccharides (PSP), the primary constituent of Polygonatum sibiricum, have been shown to exhibit a wide range of pharmacological effects, but their impact on osteoarthritis (OA) remains unclear. The objective of this study was to investigate the protective effects of PSP against OA and to elucidate its underlying molecular mechanism. In our in vitro experiments, PSP not only inhibited the IL-1ß-induced inflammatory responses and the nuclear factor kappa-B (NF-κB) signaling pathway in chondrocytes but also regulated the cartilage matrix metabolism. In addition, we detected 394 significantly differentially expressed genes through RNA-seq analysis on PSP-intervened chondrocytes, and the toll-like receptor 2 (TLR2) was identified as the most important feature by functional network analysis and qRT-PCR. It was also revealed that PSP treatment significantly reversed the IL-1-induced up-regulation of TLR2 expression in chondrocytes, while TLR2 overexpression partially inhibited the regulatory effects of PSP on inflammation, NF-κB signaling pathway and matrix metabolism. In our in vivo experiments, PSP treatment alleviated the development of destabilization of medial meniscus (DMM)-induced OA in mouse knee joints, inhibited the DMM-induced activation of the TLR2/NF-κB signaling pathway in mouse knee joint cartilage, and reduced the serum levels of inflammatory cytokines. In conclusion, PSP exerts its anti-inflammatory, matrix synthesis-promoting and matrix catabolism-suppressing effects in knee OA by inhibiting the TLR2/NF-κB signaling pathway, suggesting that PSP may be potentially targeted as a novel all-natural, low-toxicity drug for OA prevention and treatment.

Molecular biomarker approaches to prevention of post-traumatic osteoarthritis.

Up to 50% of individuals develop post-traumatic osteoarthritis (PTOA) within 10 years following knee-joint injuries such as anterior cruciate ligament rupture or acute meniscal tear. Lower-extremity PTOA prevalence is estimated to account for ≥12% of all symptomatic osteoarthritis (OA), or approximately 5.6 million cases in the USA. With knowledge of the inciting event, it might be possible to 'catch PTOA in the act' with sensitive imaging and soluble biomarkers and thereby prevent OA sequelae by early intervention. Existing biomarker data in the joint-injury literature can provide insights into the pathogenesis and early risk trajectory related to PTOA and can help to elucidate a research agenda for preventing or slowing the onset of PTOA. Non-traumatic OA and PTOA have many clinical, radiological and genetic similarities, and efforts to understand early risk trajectories in PTOA might therefore contribute to the identification and classification of early non-traumatic OA, which is the most prevalent form of OA.

Potential Benefits of Statin Therapy in Reducing Osteoarthritis Risk: A Mendelian Randomization Study.

OBJECTIVE: The purpose of this study was to determine the causal effect of statins on osteoarthritis (OA) risk using Mendelian randomization (MR). METHODS: Single nucleotide polymorphism-based genome-wide association analyses of statins were collected from the UK Biobank and FinnGen dataset, and OA data were collected from the UK Biobank and Arthritis Research UK Osteoarthritis Genetics (arcOGEN) study. Two-sample MR analyses were performed using the inverse-variance weighted (IVW) technique. MR-Egger, weighted median, and weighted mode served as supplementary analyses. MR-Egger regression, Cochran's Q test, and Mendelian Randomization Pleiotropy Residual Sum and Outlier analysis were performed as sensitivity analyses. Hydroxymethylglutaryl-coenzyme A reductase (HMGCR) expression and OA risk were evaluated using summary data-based MR (SMR). RESULTS: MR analyses consistently supported a causal connection between statin use and OA risk. A causal effect was observed for atorvastatin (IVW: ß = -2.989, P = 0.003) and rosuvastatin (IVW: ß = -14.141, P = 0.006) treatment on hip OA. Meta-analysis showed the association between atorvastatin and knee OA was statistically significant (odds ratio 0.15; P = 0.004). Simvastatin use exhibited a protective effect against knee (IVW: ß = -1.056, P = 0.004) and hip OA (IVW: ß = -1.405, P = 0.001). Statin medication showed a protective effect on hip OA (IVW: ß = -0.054, P = 0.013). HMGCR correlated significantly with a reduced risk of knee OA (ß = -0.193, PSMR = 0.017), rather than hip OA (ß = 0.067, PSMR = 0.502), which suggested that statins' protective effect on OA may not be related to its lipid-lowering effect. CONCLUSION: This MR study provides compelling evidence that statin treatment may be a protective factor for OA. Further research is required to clarify its underlying mechanism.

Preventing Osteoarthritis After an Anterior Cruciate Ligament Injury: An Osteoarthritis Action Alliance Consensus Statement.

After an anterior cruciate ligament (ACL) injury, people need secondary prevention strategies to identify osteoarthritis at its earliest stages so that interventions can be implemented to halt or slow the progression toward its long-term burden. The Osteoarthritis Action Alliance formed an interdisciplinary Secondary Prevention Task Group to develop a consensus on recommendations to provide clinicians with secondary prevention strategies that are intended to reduce the risk of osteoarthritis after a person has an ACL injury. The group achieved consensus on 15 out of 16 recommendations that address patient education, exercise and rehabilitation, psychological skills training, graded-exposure therapy, cognitive-behavioral counseling (lacked consensus), outcomes to monitor, secondary injury prevention, system-level social support, leveraging technology, and coordinated care models. We hope this statement raises awareness among clinicians and researchers on the importance of taking steps to mitigate the risk of osteoarthritis after an ACL injury.

Study protocol for a randomised placebo controlled trial of platelet-rich plasma injection to prevent post-traumatic knee osteoarthritis after anterior cruciate ligament reconstruction.

INTRODUCTION: The elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction. METHODS AND ANALYSIS: This will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20-49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass index<35 and Kellgren Lawrence osteoarthritis grade<2. The primary outcome will include MRI-T2 values of knee cartilage at 6 months. The secondary outcomes will include pain assessment by Visual Analogue Scale, Knee injury and Osteoarthritis Outcome Score, blood and urine test, physical findings, measurements for muscle strength and joint stability. ETHICS AND DISSEMINATION: The study was approved by The Independent Ethics Committee for Clinical Trials of the Japanese Association for the Promotion of State-of-the-Art Medicine. Results of the trial and each of the outcomes will be shared via conferences and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTb030200391.

OPTIKNEE 2022: consensus recommendations to optimise knee health after traumatic knee injury to prevent osteoarthritis.

The goal of the OPTIKNEE consensus is to improve knee and overall health, to prevent osteoarthritis (OA) after a traumatic knee injury. The consensus followed a seven-step hybrid process. Expert groups conducted 7 systematic reviews to synthesise the current evidence and inform recommendations on the burden of knee injuries; risk factors for post-traumatic knee OA; rehabilitation to prevent post-traumatic knee OA; and patient-reported outcomes, muscle function and functional performance tests to monitor people at risk of post-traumatic knee OA. Draft consensus definitions, and clinical and research recommendations were generated, iteratively refined, and discussed at 6, tri-weekly, 2-hour videoconferencing meetings. After each meeting, items were finalised before the expert group (n=36) rated the level of appropriateness for each using a 9-point Likert scale, and recorded dissenting viewpoints through an anonymous online survey. Seven definitions, and 8 clinical recommendations (who to target, what to target and when, rehabilitation approach and interventions, what outcomes to monitor and how) and 6 research recommendations (research priorities, study design considerations, what outcomes to monitor and how) were voted on. All definitions and recommendations were rated appropriate (median appropriateness scores of 7-9) except for two subcomponents of one clinical recommendation, which were rated uncertain (median appropriateness score of 4.5-5.5). Varying levels of evidence supported each recommendation. Clinicians, patients, researchers and other stakeholders may use the definitions and recommendations to advocate for, guide, develop, test and implement person-centred evidence-based rehabilitation programmes following traumatic knee injury, and facilitate data synthesis to reduce the burden of knee post-traumatic knee OA.

Deconstruction of the Prevention of Knee Osteoarthritis by Swimming Based on Data Mining Technology.

With the continuous development of big data and the continuous improvement of people's living standards, increasingly attention is paid to physical health. Swimming in this sport is effective in preventing the occurrence of arthritis. This paper analyzes the prevention and exploration of arthritis and relies on the traditional method of retrieving clinical literature on the treatment of knee osteoarthritis with traditional Chinese medicine and internal medicine, which requires a lot of manpower and material resources. At this time, the role of data mining technology is brought into play. This article analyzes the prevention of arthritis by swimming. If you rely on the traditional retrieval of clinical literature on the treatment of knee osteoarthritis with traditional Chinese medicine and internal medicine, you will find a lot of disordered data. It takes a lot of manpower and material resources to sort out the summary, and at this time, the role of data mining (DM) technology is brought into play. In this paper, the relevant information of the literature that meets the requirements is established in an Excel database, and the data of the relevant information is entered. Through sorting and analysis, the TCM syndrome types of knee osteoarthritis are summarized. Then, DM technology was used to carry out statistical analysis of frequency and prescription, to summarize the distribution characteristics of the corresponding knee osteoarthritis, TCM syndrome types, and the weight of each syndrome type, and to make a preliminary discussion at the same time. Finally, it is concluded that there are better prevention methods for arthritis in the research methods of traditional Chinese medicine. DM technology has been increasingly applied to all aspects of traditional Chinese medicine. DM technology has improved its research efficiency by 38% and achieved great results, which will play a greater role in promoting the research process of TCM syndrome.

Apple polyphenols exhibits chondroprotective changes of synovium and prevents knee osteoarthritis.

Apple polyphenols (AP) have strong antioxidant and anti-inflammatory properties. We examined the effects of AP on the progression of osteoarthritis (OA) AP was administered to surgically-induced OA model rats for 4 or 8 weeks. This treatment suppressed inflammation and oxidative stress in the synovium, resulting in a decrease in the OA severity score, and the expression of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-13 in the synovium. It was suggested that long-term administration of AP may be effective for the treatment of OA. In addition, superoxide dismutase (SOD) activity was enhanced in serum samples by AP. AP or its constituent procyanidin B2 (PC) were added to HIG-82 synoviocytes. The results showed that AP enhanced cell proliferation and hyaluronan production. This indicates that AP may improve synovial conditions in OA and suppress OA progression. These effects may be attributed to the antioxidant and anti-inflammatory properties of AP.

The preventive and therapeutic role of physical activity in knee osteoarthritis.

The aim of this narrative review is to discuss the results of studies investigating the role of physical activity in knee osteoarthritis (OA). We also formulated two evidence-based exercise programs that could be prescribed to patients with symptomatic knee OA or after joint replacement. The PubMed and Google Scholar databases were searched for articles related to knee OA and physical activity. A total of 86 papers written in English and published from 1957 to 2021 were selected. Adapted physical activity, even at high intensity, does not appear to trigger or exacerbate knee OA; on the contrary, it may prevent obesity or lower limb muscle weakness, both of which are considered predisposing factors for the disease. In patients already diagnosed with knee OA, scientific evidence suggests that both land-based and aquatic activities combining aerobics, strength, and endurance programs are safe and effective. Physical interventions tailored to the patient may also accelerate recovery time after knee arthroplasty. Knee OA is a painful and disabling rheumatic disease that is very common in the elderly population. Pharmacotherapy has a modest effect in controlling disease progression, possibly due to the still limited understanding of OA pathogenesis. Non-pharmacologic interventions, including dietary and lifestyle changes and physical activity, may be more effective and safer than drugs in preventing or treating knee OA.

A comparison of three strategies to reduce the burden of osteoarthritis: A population-based microsimulation study.

OBJECTIVES: The purpose of this study was to compare three strategies for reducing population health burden of osteoarthritis (OA): improved pharmacological treatment of OA-related pain, improved access to joint replacement surgery, and prevention of OA by reducing obesity and overweight. METHODS: We applied a validated computer microsimulation model of OA in Canada. The model simulated a Canadian-representative open population aged 20 years and older. Variables in the model included demographics, body mass index, OA diagnosis, OA treatment, mortality, and health-related quality of life. Model parameters were derived from analyses of national surveys, population-based administrative data, a hospital-based cohort study, and the literature. We compared 8 what-if intervention scenarios in terms of disability-adjusted life years (DALYs) relative to base-case, over a wide range of time horizons. RESULTS: Reductions in DALYs depended on the type of intervention, magnitude of the intervention, and the time horizon. Medical interventions (a targeted increase in the use of painkillers) tended to produce effects quickly and were, therefore, most effective over a short time horizon (a decade). Surgical interventions (increased access to joint replacement) were most effective over a medium time horizon (two decades or longer). Preventive interventions required a substantial change in BMI to generate a significant impact, but produced more reduction in DALYs than treatment strategies over a very long time horizon (several decades). CONCLUSIONS: In this population-based modeling study we assessed the potential impact of three different burden reduction strategies in OA. Data generated by our model may help inform the implementation of strategies to reduce the burden of OA in Canada and elsewhere.

The Role of Vitamin D in Early Knee Osteoarthritis and Its Relationship with Their Physical and Psychological Status.

Osteoarthritis (OA) is a common joint condition and one of the greatest causes of disability worldwide. The role of vitamin D in the origin and development of the disease is not clear, although it could have important implications for diagnosis and treatment. For this proposal, a cross-sectional study with a non-probabilistic sample was performed. In total, 48 with early osteoarthritis (EOA) and 48 matched controls were selected, and serum 25(OH)D and parathyroid hormone (PTH) levels were analyzed. In addition, physical and psychological variables were measured to establish their relationship with vitamin D levels. Patients with EOA showed lower levels (22.3 ± 7.3 ng/mL) in comparison to matched controls (29.31 ± 9.2 ng/mL). A statistically significant higher number (Chi-squared = 8.525; p = 0.004) of patients with EOA had deficiency levels (<20 ng/mL) compared to the control group. Patients with lower vitamin D levels showed higher levels of pain intensity, disability, and anxiety, as well as poorer values for sit-to-stand, walking speed, and social participation. Correlation analysis showed a relationship between serum 25(OH)D, PTH and pain intensity, and social participation. These results highlight the relevance of vitamin D in the early diagnosis and prevention of EOA.

Post-traumatic osteoarthritis progression is diminished by early mechanical unloading and anti-inflammatory treatment in mice.

OBJECTIVE: Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease initiated by injury. Early phase (0-7 days) treatments often include rest (unloading) and anti-inflammatory medications, but how those early interventions impact PTOA progression is unknown. We hypothesized that early unloading and anti-inflammatory treatment would diminish joint inflammation and slow PTOA progression. DESIGN: Mice were injured with non-invasive ACL rupture followed by hindlimb unloading (HLU) or normal cage activity (ground control: GC) for 7 days, after which all mice were allowed normal cage activity. HLU and GC mice were treated with daily celecoxib (CXB; 10 mg/kg IP) or vehicle. Protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone were quantified using micro-computed tomography, and synovitis and articular cartilage were evaluated using whole-joint histology at 7, 14, 21, and 28 days post-injury. RESULTS: HLU significantly reduced protease activity (-22-30% compared to GC) and synovitis (-24-50% relative to GC) at day 7 post-injury (during unloading), but these differences were not maintained at later timepoints. Similarly, trabecular bone volume was partially preserved in HLU mice at during unloading (-14-15% BV/TV for HLU mice, -21-22% for GC mice relative to uninjured), but these differences were not maintained during reloading. Osteophyte volume was reduced by both HLU and CXB, but there was not an additive effect of these treatments (HLU: -46%, CXB: -30%, HLU + CXB: -35% relative to vehicle GC at day 28). CONCLUSIONS: These data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.

Development of an intervention to manage knee osteoarthritis risk and symptoms following anterior cruciate ligament injury.

INTRODUCTION: Anterior cruciate ligament (ACL) injury is a risk factor for developing knee osteoarthritis (OA). We developed an intervention to support people manage risk factors for OA. METHODS: We conducted one-on-one interviews with 20 individuals with OA symptoms 6-15 years post ACL injury and used a nominal group process during a workshop with 40 patients and healthcare professionals (HCPs) to elicit information on the intervention content and delivery characteristics (timing, HCPs, and methods). Interview data were analyzed using content analysis. Nominal group ideas with importance ratings ≥5 of 7 met criteria for inclusion. Results were integrated, considering similarities and differences. RESULTS: Eight content categories were identified: 1. understanding knee injury and expectations about recovery; 2. understanding OA risk; 3. understanding OA signs and symptoms; 4. managing OA risk; 5. managing knee OA symptoms; 6. information for influencers; 7. credible sources; and, 8. updates on new evidence and treatments. Delivery timing reflected a lifespan approach from time of injury through symptomatic knee OA management. Although multiple media for delivery were identified, introductory face-to-face discussions and opportunity for re-accessing HCPs were critical. All HCPs who treat people with ACL should be familiar with and able to deliver the intervention. CONCLUSIONS: This co-development approach identified that an intervention to support people with ACL injury to limit and manage knee OA requires content embedded within an easily accessible, multi-media delivery model with capacity for check-back with HCPs that is appealing to different age groups and personal preferences over the lifespan post injury.

Microbial chondroitin sulfate in experimental knee osteoarthritis model investigation of chondroprotective effect.

OBJECTIVE: Chondroitin sulfate (CS) is a glycosaminoglycan with proven anti-inflammatory, anti-apoptotic, anti-oxidant properties. CS increases type II collagen and proteoglycan synthesis in human joint chondrocytes. CS can reduce the production of pro-inflammatory mediators and proteases to improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM). Due to these characteristics, it is a natural compound that is considered to be Symptomatic Slow-Acting Drugs for Osteoarthritis (SYSADOA). Microbial chondroitin sulfate (MCS) was produced from two different bacterial sources using biotechnological methods by our team. In this study, we aimed to apply microbially produced CS and bovine-derived commercial CS forms to rabbit knees with osteoarthritis experimentally and to evaluate the results. MATERIALS AND METHODS: In this study, a cruciate ligament cutting model was applied to 40 New Zealand rabbits to induce experimental osteoarthritis. Four weeks after the surgical procedure, rabbits were divided into 4 groups as control, animal-derived MCS, E coli-derived MCS and PaJC-derived MCS group. The standard rabbit diet was fed to the control group, and the other groups were additionally fed 17 mg/kg/day CS/MCS for 12 weeks. The rabbits were sacrificed at the 12th week after surgery and the preparations obtained were evaluated histopathologically. RESULTS: As a result, it was observed that regeneration tissue was statistically significant in histopathological cartilage tissue compared to the control group of CS developed from different sources given to rabbits with osteoarthritis. It was determined that among the CS groups produced from different sources, the group with the highest chondroprotective effect was MCS originating from E.coli. CONCLUSIONS: This vegan product (MCS), which we obtained as a result of our study, was produced by our team from a microbial source. According to our analysis, it has the potential to be an effective alternative therapy agent in the treatment of osteoarthritis.

Degenerative Joint Disease After Meniscectomy.

The meniscus has an important role in stabilizing the knee joint and protecting the articular cartilage from shear forces. Meniscus tears are common injuries and can disrupt these protective properties, leading to an increased risk of articular cartilage damage and eventual osteoarthritis. Certain tear patterns are often treated with arthroscopic partial meniscectomy, which can effectively relieve symptoms. However, removal of meniscal tissue can also diminish the ability of the meniscus to dissipate hoop stresses, resulting in altered biomechanics of the knee joint including increased contact pressures. This makes meniscal repair an important treatment consideration whenever possible. Understanding the incidence and mechanism of osteoarthritis development after arthroscopic partial meniscectomy as it relates to different tear morphologies and other treatment alternatives (ie, meniscus repair) is important to appropriately treat meniscus tears.