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Indian Journal of Orthopaedics Jul 2024Osteoarthritis (OA) is a common degenerative disorder of the synovial joints and is usually an age-related disease that occurs due to continuous wear and tear of the... (Review)
Review
INTRODUCTION
Osteoarthritis (OA) is a common degenerative disorder of the synovial joints and is usually an age-related disease that occurs due to continuous wear and tear of the cartilage in the joints. Presently, there is no proven medical management to halt the progression of the disease in the early stages. The purpose of our systematic review is to analyze the possible metabolites and metabolic pathways that are specifically involved in OA pathogenesis and early treatment of the disease.
MATERIALS AND METHODS
The articles were collected from PubMed, Cochrane, Google Scholar, Embase, and Scopus databases. "Knee", "Osteoarthritis", "Proteomics", "Lipidomics", "Metabolomics", "Metabolic Methods", and metabolic* were employed for finding the articles. Only original articles with human or animal OA models with healthy controls were included.
RESULTS
From the initial screening, a total of 458 articles were identified from the 5 research databases. From these, 297 articles were selected in the end for screening, of which 53 papers were selected for full-text screening. Finally, 50 articles were taken for the review based on body fluid: 6 urine studies, 15 plasma studies, 16 synovial fluid studies, 11 serum studies, 4 joint tissue studies, and 1 fecal study. Many metabolites were found to be elevated in OA. Some of these metabolites can be used to stage the OA Three pathways that were found to be commonly involved are the TCA cycle, the glycolytic pathway, and the lipid metabolism.
CONCLUSION
All these studies showed a vast array of metabolites and metabolic pathways associated with OA. Metabolites like lysophospholipids, phospholipids, arginine, BCCA, and histidine were identified as potential biomarkers of OA but a definite association was not identified, Three pathways (glycolytic pathway, TCA cycle, and lipid metabolic pathways) have been found as highly significant in OA pathogenesis. These metabolic pathways could provide novel therapeutic targets for the prevention and progression of the disease.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s43465-024-01169-5.
PubMed: 38948380
DOI: 10.1007/s43465-024-01169-5 -
Indian Journal of Orthopaedics Jul 2024Exosomes are the smallest extracellular vesicles (30-150 nm) secreted by all cell types, including synovial fluid. However, because biological fluids are complex,... (Review)
Review
BACKGROUND
Exosomes are the smallest extracellular vesicles (30-150 nm) secreted by all cell types, including synovial fluid. However, because biological fluids are complex, heterogeneous, and contain contaminants, their isolation is difficult and time-consuming. Furthermore, the pathophysiology of osteoarthritis (OA) involves exosomes carrying complex components that cause macrophages to release chemokines and proinflammatory cytokines. This narrative review aims to provide in-depth insights into exosome biology, isolation techniques, role in OA pathophysiology, and potential role in future OA therapeutics.
METHODS
A literature search was conducted using PubMed, Scopus, and Web of Science databases for studies involving exosomes in the osteoarthritis using keywords "Exosomes" and "Osteoarthritis". Relevant articles in the last 15 years involving both human and animal models were included. Studies involving exosomes in other inflammatory diseases were excluded.
RESULTS
Despite some progress, conventional techniques for isolating exosomes remain laborious and difficult, requiring intricate and time-consuming procedures across various body fluids and sample origins. Moreover, exosomes are involved in various physiological processes associated with OA, like cartilage calcification, degradation of osteoarthritic joints, and inflammation.
CONCLUSION
The process of achieving standardization, integration, and high throughput of exosome isolation equipment is challenging and time-consuming. The integration of various methodologies can be employed to effectively address specific issues by leveraging their complementary benefits. Exosomes have the potential to effectively repair damaged cartilage OA, reduce inflammation, and maintain a balance between the formation and breakdown of cartilage matrix, therefore showing promise as a therapeutic option for OA.
PubMed: 38948378
DOI: 10.1007/s43465-024-01175-7 -
Indian Journal of Orthopaedics Jul 2024Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years.... (Review)
Review
INTRODUCTION
Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years. Conventional treatment modalities have limitations and side-effects. To overcome these limitations, over the last decade, there has been an increased interest in the use of orthobiologics derived from autologous sources including platelet-rich plasma (PRP), bone-marrow aspirate concentrate (BMAC) and adipose tissue derived formulations. This review qualitatively presents the in-vitro, pre-clinical, clinical and on-going clinical studies exploring the safety and efficacy of BMAC for management of hip OA.
MATERIALS AND METHODS
The electronic database search was done through PubMed, Embase, Web of Science, Scopus, ProQuest and Google Scholar till February 2024. The search terms used were "osteoarthritis" OR "hip osteoarthritis" OR "orthobiologics" OR "efficacy or use of orthobiologic treatment" OR "bone-marrow concentrate" OR "bone-marrow aspirate concentrate", AND "BMAC". The inclusion criteria were clinical studies of any level of evidence written in the English language, published till February 2024, evaluating the safety and efficacy of intra-articular administration of BMAC for the management of hip OA.
RESULTS
A total of 5 studies were included in this review for qualitative data synthesis. The total number of patients who participated in the study was 182, ranging from 4 to 112 in a single study. No adverse events were reported throughout the duration of the study. In addition, intra-articular administration of BMAC led to reduced pain, and improved function and overall quality of life (QoL).
CONCLUSION
The results from this review demonstrated that administration of BMAC is safe and potentially efficacious in terms of reducing pain, improving function and overall QoL of patients with hip OA in short- and mid-term average follow-up based on the included studies. Nonetheless, more adequately powered, multi-center, prospective, double-blind, non-randomized and randomized controlled trials with long-term follow-up are warranted to establish long-term safety and efficacy of BMAC for management of hip OA and justify its routine clinical use.
PubMed: 38948376
DOI: 10.1007/s43465-024-01183-7 -
Indian Journal of Orthopaedics Jul 2024The knee is the most commonly affected joint in osteoarthritis (OA), affecting millions of people worldwide. Knee OA significantly impacts the activities of daily living... (Review)
Review
INTRODUCTION
The knee is the most commonly affected joint in osteoarthritis (OA), affecting millions of people worldwide. Knee OA significantly impacts the activities of daily living (ADL) along with affecting overall quality of life of patients (QoL), thereby leading to substantial socio-economic burden. Conservative therapies are prioritized, resorting to surgery only when needed. However, these traditional approaches have limitations. Regenerative medicine, involving the use of orthobiologics, including autologous peripheral blood-derived orthobiologics such as growth factor concentrate (GFC), has evolved and shown potential for managing knee OA. The primary goal of this review is to summarize the results of in vitro, preclinical and clinical studies involving GFC for the management of knee OA.
METHODS
Multiple databases (PubMed, Scopus, Google Scholar, Web of Science and Embase) were searched applying terms for the intervention 'GFC' and treatment 'knee OA' for the studies published in the English language to March 10, 2024.
RESULTS
Only three clinical studies met our pre-defined criteria and were included in this review.
CONCLUSION
Intra-articular administration of GFC is safe and potentially efficacious to manage OA of the knee. More, adequately powered, multi-center, prospective, RCTs are warranted to demonstrate the long-term effectiveness of GFC in patients suffering from mild-to-moderate knee OA and to justify its routine clinical use. Further studies evaluating the efficacy of GFC compared to other orthobiologics are also required to allow physicians/surgeons to choose the optimal orthobiologic for the treatment of OA of the knee.
PubMed: 38948375
DOI: 10.1007/s43465-024-01172-w -
Indian Journal of Orthopaedics Jul 2024The evaluation of anti-apoptotic and chondroprotective properties of a single injection of PRP using immunohistochemistry (IHC).
PURPOSE OF THE STUDY
The evaluation of anti-apoptotic and chondroprotective properties of a single injection of PRP using immunohistochemistry (IHC).
METHODS
This was a placebo-controlled blinded experimental study. Ten healthy Dunkin Hartley guinea pigs were selected. One knee of each animal was injected with a single injection of PRP (Group A); the contralateral knee acted as a control and was injected with a single injection of normal saline (Group B). These groups were further divided into A3 and B3 based on the timeline of animal sacrifice (3 months) and A6 and B6 (6 months). The formalin-preserved articular cartilage blocks were subjected to IHC to stain Aggrecan, Caspase-3, and Collagen-2.
RESULTS
The mean IHC score was significantly low for Caspase-3 (-0.029) in intervention group (A3) in comparison to placebo control group (B3) pointing towards decreased apoptosis. The mean IHC values were significantly higher for Collagen II (-0.011) for intervention group (A6) in contrast to control group (B6); values were also significantly low for Caspase-3 (-0.029) in A6 as compared to B6. The mean Caspase-3 values were significantly higher in A6 as compared to A3 (-0.029).
CONCLUSION
The impact of a solitary injection of PRP on upregulation of anabolic pathways inside cartilage is relatively slower as compared to its effect on downregulation of apoptotic pathways. Even a single PRP injection holds the potential to change cartilage microenvironment, but the effects are not long lasting.
PubMed: 38948372
DOI: 10.1007/s43465-024-01145-z -
Indian Journal of Orthopaedics Jul 2024Knee osteoarthritis (OA) is a widespread, disabling condition with no intervention to fully restore cartilage or halt progression. Bone marrow aspirate concentrate...
INTRODUCTION
Knee osteoarthritis (OA) is a widespread, disabling condition with no intervention to fully restore cartilage or halt progression. Bone marrow aspirate concentrate (BMAC), an autologous product from bone marrow aspiration, has shown promise as a regenerative therapy due to its cell composition and chondrogenic effects. Our study aims to assess the functional outcomes, including pain, function, satisfaction, and complications post-BMAC injection in knee OA patients.
MATERIALS AND METHODS
In this prospective, single-center study, 63 patients with grade II-III knee OA (Kellgren-Lawrence (K-L) scale) unresponsive to conservative management underwent BMAC injection. The procedure involved bone marrow aspiration from the anterior iliac crest, processing to obtain a concentrate, followed by intra-articular injection. Patients were followed for 24 months, assessing outcomes using the Visual Analog Scale (VAS), International Knee Documentation Committee (IKDC) score, and MOCART 2.0 score.
RESULTS
The cohort, with a slight female predominance and predominantly aged 41-50 years, majorly comprised K-L grade III OA patients. BMAC treatment resulted in significant improvements in VAS pain scores, IKDC functional scores, and MOCART 2.0 scores over the 24-month follow-up.
CONCLUSION
BMAC injection provides significant improvement in both pain and functional outcomes at mid-term follow-up in patients with mild-to-moderate OA of the knee. Further high-quality, adequately powered, multi-center, prospective, double-blinded, randomized controlled trials with longer follow-up are necessary to justify the routine clinical use of BMAC for treatment of patients suffering with knee OA.
PubMed: 38948370
DOI: 10.1007/s43465-024-01168-6 -
Indian Journal of Orthopaedics Jul 2024In addition to other variables associated with PRP injections for Knee Osteoarthritis (OA), some confusion exists about the role of exogenous activators. The current...
BACKGROUND
In addition to other variables associated with PRP injections for Knee Osteoarthritis (OA), some confusion exists about the role of exogenous activators. The current study looks at matched groups getting PRP injections with or without activator (Calcium gluconate) in early knee OA patients.
METHODS
Patients of early OA knee meeting inclusion criteria were randomly divided into 2 groups; Group A (43 patients) received 8 ml PRP injection alone, and Group B (48 patients) received 8 ml PRP along with 2 ml Calcium gluconate as activator. The patients were evaluated at baseline, 6 weeks, 3 months and 6 months for WOMAC Pain and Total WOMAC scores; secondary variables assessed were VAS score and patient satisfaction.
RESULTS
The baseline characteristics of both groups were comparable. Leucocyte-depleted PRP with 5 times concentration and average absolute platelet numbers of 7.144 billion per knee was injected. Mean Pain WOMAC scores decreased in both groups from baseline (group A-8.68, group B-9.09) to final follow-up (group A-4.67, group B-5.11). Similarly, Mean Total WOMAC scores decreased from baseline (group A-37.81, group B-37.41) to (group A-21, group B-21.36) at the final follow-up in both groups. There was no significant difference between both groups, and both showed similar trends. Similar findings were noted for VAS scores. Patient satisfaction was also not different (group A, 90.69%, group B, 89.58%) at the end of 6 months.
CONCLUSION
Our study concluded doubtful role of adding exogenous activator to PRP preparation.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s43465-024-01159-7.
PubMed: 38948365
DOI: 10.1007/s43465-024-01159-7 -
Osteoarthritis Imaging Sep 2023The aim of this literature review is to yield a comprehensive and exhaustive overview of the existing evidence and up-to-date applications of artificial intelligence for...
OBJECTIVE
The aim of this literature review is to yield a comprehensive and exhaustive overview of the existing evidence and up-to-date applications of artificial intelligence for knee osteoarthritis.
METHODS
A literature review was performed by using PubMed, Google Scholar, and IEEE databases for articles published in peer-reviewed journals in 2022. The articles focusing on the use of artificial intelligence in diagnosis and prognosis of knee osteoarthritis and accelerating the image acquisition were selected. For each selected study, the code availability, considered number of patients and knees, imaging type, covariates, grading type of osteoarthritis, models, validation approaches, objectives, and results were reviewed.
RESULTS
395 articles were screened, and 35 of them were reviewed. Eight articles were based on diagnosis, six on prognosis prediction, three on classification, three on accelerated image acquisition, and 15 on segmentation of knee osteoarthritis. 57% of the articles used MRI, 26% radiography, 6% MRI together with radiography, 6% ultrasonography, and 6% only clinical data. 23% of the articles made the computer codes available for their study, and 26% used clinical data. External validation and nested cross-validation were used in 17% and 14% of articles, respectively.
CONCLUSIONS
The use of artificial intelligence provided a promising potential to enhance the detection and management of knee osteoarthritis. Translating the developed models into clinics is still in the early stages of development. The translation of artificial intelligence models is expected to be further examined in prospective studies to support clinicians in improving routine healthcare practice.
PubMed: 38948116
DOI: 10.1016/j.ostima.2023.100161 -
ACS Omega Jun 2024Osteoarthritis (OA) is a kind of arthritis that impairs movement and causes joint discomfort. Recent research has demonstrated a connection between cellular senescence...
Osteoarthritis (OA) is a kind of arthritis that impairs movement and causes joint discomfort. Recent research has demonstrated a connection between cellular senescence and the degenerative processes of OA chondrocytes. In yeast and human cells, protein tyrosine phosphatase 1B (PTP1B) knockdown prolongs longevity; however, the function of PTP1B in chondrocyte senescence has not been investigated. The goal of the current investigation was to evaluate PTP1B's contribution to human OA chondrocyte senescence. The function of PTP1B and cellular senescence in the onset of OA was investigated and confirmed by using a combination of bioinformatics techniques, clinical samples, and experimental procedures. The RNA sequencing data pertinent to the OA were obtained using the Gene Expression Omnibus database. Function enrichment analysis, protein-protein correlation analysis, the construction of the correlation regulatory network, and an investigation into possible connections between PTP1B and cellular senescence in OA were all carried out using various bioinformatic techniques. Compared with healthy cartilage, PTP1B expression was increased in OA cartilage. According to a Pearson correlation study, cellular senescence-related genes, including MAP2K1 and ABL1, were highly correlated with PTP1B expression levels in senescent chondrocytes. Furthermore, tests confirmed that PTP1B knockdown slowed cartilage degradation and prevented chondrocyte senescence in OA. In conclusion, we showed that PTP1B knockdown prevented the senescence of chondrocytes and prevented cartilage degradation in OA. These findings offer a fresh perspective on the pathophysiology of OA, opening up new avenues for OA clinical diagnosis and targeted treatment.
PubMed: 38947824
DOI: 10.1021/acsomega.3c10313 -
World Journal of Orthopedics Jun 2024Meniscal sparing surgery is a widely utilised treatment option for unstable meniscal tears with the aim of minimising the risk of progression towards osteoarthritis....
BACKGROUND
Meniscal sparing surgery is a widely utilised treatment option for unstable meniscal tears with the aim of minimising the risk of progression towards osteoarthritis. However, there is limited data in the literature on meniscal repair outcomes in skeletally immature patients.
AIM
To evaluate the re-operation rate and functional outcomes of meniscal repairs in children and adolescents.
METHODS
We performed a retrospective review of all patients who underwent arthroscopic meniscal repair surgery between January 2007 and January 2018. All patients were under the age of 18 at the time of surgery. Procedures were all performed by a single surgeon. Information was gathered from our hospital Electronic Patient Records system. The primary outcome measure was re-operation rate (need for further surgery on the same meniscus). Secondary outcome measures were surgical complications and patient reported outcome measures that were International Knee Documentation Committee (IKDC), Tegner and Lysholm scores.
RESULTS
We identified 59 patients who underwent 66 All-inside meniscal repairs (32 medial meniscus and 34 Lateral meniscus). Meniscal repairs were performed utilizing FasT-Fix (Smith and Nephew) implants. There were 37 males and 22 females with an average age of 14 years (range 6-16). The average follow-up time was 53 months (range 26-140). Six patients had concomitant anterior cruciate ligament reconstruction surgery along with the meniscal repair. There were no intra-operative complications. The re-operation rate for meniscal repairs was 16.6% (11 cases) with 2 patients requiring further meniscal repairs and 9 patients underwent partial meniscectomies. The mean postoperative IKDC score was 88 (44-100), Tegner score was 7(2-10) and Lysholm score was 94 (57-100).
CONCLUSION
Our results showed that arthroscopic repair of meniscal tears in the paediatric population is an effective treatment option that has a low failure rate and good postoperative clinical with the advantage of preserving meniscal tissues.
PubMed: 38947260
DOI: 10.5312/wjo.v15.i6.547