scholarly journals Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 854
Author(s):  
Dragan Primorac ◽  
Vilim Molnar ◽  
Eduard Rod ◽  
Željko Jeleč ◽  
Fabijan Čukelj ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Platelet Rich Plasma ◽  
Treatment Options ◽  
Stromal Vascular Fraction ◽  
Disease Stage ◽  
Knee Oa ◽  
Marrow Mesenchymal Stem Cells ◽  
The Moment ◽  
And Function ◽  
Orthopedic Patients

Being the most common musculoskeletal progressive condition, osteoarthritis is an interesting target for research. It is estimated that the prevalence of knee osteoarthritis (OA) among adults 60 years of age or older is approximately 10% in men and 13% in women, making knee OA one of the leading causes of disability in elderly population. Today, we know that osteoarthritis is not a disease characterized by loss of cartilage due to mechanical loading only, but a condition that affects all of the tissues in the joint, causing detectable changes in tissue architecture, its metabolism and function. All of these changes are mediated by a complex and not yet fully researched interplay of proinflammatory and anti-inflammatory cytokines, chemokines, growth factors and adipokines, all of which can be measured in the serum, synovium and histological samples, potentially serving as biomarkers of disease stage and progression. Another key aspect of disease progression is the epigenome that regulates all the genetic expression through DNA methylation, histone modifications, and mRNA interference. A lot of work has been put into developing non-surgical treatment options to slow down the natural course of osteoarthritis to postpone, or maybe even replace extensive surgeries such as total knee arthroplasty. At the moment, biological treatments such as platelet-rich plasma, bone marrow mesenchymal stem cells and autologous microfragmented adipose tissue containing stromal vascular fraction are ordinarily used. Furthermore, the latter two mentioned cell-based treatment options seem to be the only methods so far that increase the quality of cartilage in osteoarthritis patients. Yet, in the future, gene therapy could potentially become an option for orthopedic patients. In the following review, we summarized all of the latest and most important research in basic sciences, pathogenesis, and non-operative treatment.

A single intraarticular platelet-rich plasma improves pain and function for patients with early knee osteoarthritis: Analyses by radiographic severity and age

2021 ◽  
pp. 1-10
Author(s):  
Shu-Fen Sun ◽  
Chien-Wei Hsu ◽  
Huey-Shyan Lin ◽  
I-Hsiu Liou ◽  
Yi-Chun Chou ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Platelet Rich Plasma ◽  
Age Group ◽  
Radiographic Severity ◽  
Knee Oa ◽  
Patients Satisfaction ◽  
Younger Age ◽  
Subgroup Analyses ◽  
The Mean ◽  
And Function

BACKGROUND: Most studies use platelet-rich plasma (PRP) requiring multiple intraarticular injections for knee osteoarthritis (OA). OBJECTIVE: To investigate the efficacy of a single intraarticular PRP injection for patients with early knee OA and consider subgroup analyses of radiographic severity and age, respectively. METHODS: Forty-one patients with knee OA (Kellgren-Lawrence grade 1–2) received a single PRP injection into the target knee and were assessed at baseline and 1, 3, and 6 months postinjection. The primary outcome was the mean change from baseline in the visual analog scale (VAS) pain (0–100 mm) at 6 months postinjection. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne index, single leg stance test (SLS), use of rescue analgesics and patients’ satisfaction. RESULTS: Thirty-eight patients completed the study. The mean pain VAS decreased significantly from 45.6 ± 13.0 mm at baseline to 16.9 ± 13.4 mm, 14.0 ± 13.1 mm and 15.5 ± 14.0 mm at 1, 3 and 6-month follow-ups (p< 0.001 for all). Significant improvements in WOMAC, Lequesne index, SLS and consumption of analgesics from baseline (p< 0.001 for all) were noted at each follow-up. Patients’ satisfaction was high. No serious adverse events occurred. Subgroup analyses revealed that patients with grade 1 OA showed significantly greater VAS pain reduction at 3 months (p= 0.006) and 6 months (p= 0.005) than patients with grade 2 OA. The older-age group (age > 60) showed significantly greater improvements in VAS pain, WOMAC function subscale scores and total scores at 6-month postinjection, compared with the younger age-group (age ≤ 60). The younger-age group reported better satisfaction at 1 and 3-month postinjection. CONCLUSIONS: One injection of PRP improved pain and function for 6 months for patients with early knee OA. This study supports putting the one-injection regimen into clinical practice. Further research is needed for more definite conclusions.

scholarly journals Effect of Dextrose Prolotherapy, Platelet Rich Plasma and Autologous Conditioned Serum on Knee Osteoarthritis: A Randomized Clinical Trial

2020 ◽  
Author(s):  
Alireza Pishgahi ◽  
Rozita Abolhasan ◽  
Seyed Kazem Shakouri ◽  
Mohammad Sadegh Soltani-Zangbar ◽  
Shahla Dareshiri ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Knee Osteoarthritis ◽  
Randomized Clinical Trial ◽  
Platelet Rich Plasma ◽  
Womac Score ◽  
Knee Function ◽  
Post Intervention ◽  
Knee Oa ◽  
Autologous Conditioned Serum ◽  
And Function

Knee osteoarthritis (OA) is one of the common degenerative articular disorders that are related to decreased quality of life. Currently, novel biologic therapeutic approaches are introduced in the literature for OA management. In this study, the clinical efficiency of Dextrose prolotherapy, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) injection on the level of pain and function in Knee OA were compared. A randomized clinical trial was directed on 92 knee OA patients. Patients were randomly divided into three groups: 30 were received dextrose prolotherapy once in a week for three weeks, 30 received autologous PRP for two times with seven days interval, and in the remaining 32 patients 2ml of ACS were injected two times every seven days. Study participants were measured through the Western Ontario and McMaster Universities (WOMAC) score, the visual analogue scale (VAS), at baseline, 1 and 6 months post-intervention. Both ACS and PRP treated patients showed improvement in pain intensity and knee function during 1 and 6 months pursue; however, this progress was more significant in the ACS group. Dextrose prolotherapy showed no substantial changes in pain and function of the affected knee in treated patients. Treatment of Knee OA with ACS and PRP injections are associated with pain reduction and knee function improvement. Not only, ACS therapy is more effective than that of PRP, but also due to its less variability in processing and less reported side effects, it could be considered as a safe and effective non-surgical alternative for OA management.  

scholarly journals In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Habib Zahir ◽  
Bijan Dehghani ◽  
Xiaoning Yuan ◽  
Yurii Chinenov ◽  
Christine Kim ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Clinical Outcomes ◽  
Inflammatory Responses ◽  
Platelet Rich Plasma ◽  
Autologous Blood ◽  
Limited Information ◽  
Knee Oa ◽  
Patient Reported ◽  
Treatment Comparisons

AbstractAutologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

scholarly journals The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis

2021 ◽  
Vol 22 (11) ◽  
pp. 5492
Author(s):  
Dawid Szwedowski ◽  
Joanna Szczepanek ◽  
Łukasz Paczesny ◽  
Jan Zabrzyński ◽  
Maciej Gagat ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Operative Treatment ◽  
Animal Studies ◽  
Platelet Rich Plasma ◽  
Treatment Options ◽  
Treatment Protocols ◽  
Metabolic Functions ◽  
Inflammatory Drugs ◽  
Positive Effect

Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.

The Relationship Between Early-Stage Knee Osteoarthritis and Lower-Extremity Alignment, Joint Laxity, and Subjective Scores of Pain, Stiffness, and Function

2016 ◽  
Vol 25 (3) ◽  
pp. 213-218
Author(s):  
Charlie A. Hicks-Little ◽  
Richard D. Peindl ◽  
Tricia J. Hubbard-Turner ◽  
Mitchell L. Cordova
Keyword(s):  
Knee Joint ◽  
Lower Extremity ◽  
Knee Osteoarthritis ◽  
Outcome Measures ◽  
Early Stage ◽  
Joint Laxity ◽  
Knee Oa ◽  
Lower Extremity Alignment ◽  
Knee Joint Laxity ◽  
And Function

Context:Knee osteoarthritis (OA) is a debilitating disease that affects an estimated 27 million Americans. Changes in lowerextremity alignment and joint laxity have been found to redistribute the medial and/or lateral loads at the joint. However, the effect that changes in anteroposterior knee-joint laxity have on lower-extremity alignment and function in individuals with knee OA remains unclear.Objective:To examine anteroposterior knee-joint laxity, lower-extremity alignment, and subjective pain, stiffness, and function scores in individuals with early-stage knee OA and matched controls and to determine if a relationship exists among these measures.Design:Case control.Setting:Sports-medicine research laboratory.Participants:18 participants with knee OA and 18 healthy matched controls.Intervention:Participants completed the Western Ontario McMaster (WOMAC) osteoarthritis questionnaire and were tested for total anteroposterior knee-joint laxity (A-P) and knee-joint alignment (ALIGN).Main Outcome Measures:WOMAC scores, A-P (mm), and ALIGN (°).Results:A significant multivariate main effect for group (Wilks’ Λ = 0.30, F7,26 = 8.58, P < .0001) was found. Knee-OA participants differed in WOMAC scores (P < .0001) but did not differ from healthy controls on ALIGN (P = .49) or total A-P (P = .66). No significant relationships were identified among main outcome measures.Conclusion:These data demonstrate that participants with early-stage knee OA had worse pain, stiffness, and functional outcome scores than the matched controls; however, ALIGN and A-P were no different. There was no association identified among participants’ subjective scores, ALIGN, or A-P measures in this study.

What Is the Price and Claimed Efficacy of Platelet-Rich Plasma Injections for the Treatment of Knee Osteoarthritis in the United States?

2018 ◽  
Vol 32 (09) ◽  
pp. 879-885 ◽  
Author(s):  
Nicolas S. Piuzzi ◽  
Mitchell Ng ◽  
Ariel Kantor ◽  
Kenneth Ng ◽  
Stephanie Kha ◽  
...  
Keyword(s):  
United States ◽  
Standard Deviation ◽  
Knee Osteoarthritis ◽  
Clinical Efficacy ◽  
Health Care Providers ◽  
Platelet Rich Plasma ◽  
The United States ◽  
Care Providers ◽  
Knee Oa ◽  
The Mean

AbstractPlatelet-rich plasma (PRP) injections are often used for the treatment of knee osteoarthritis (OA), despite clinical value and cost-effectiveness not being definitely established. PRP injections are considered as a potential means of reducing pain and improving function in patients with knee OA, in the hope of delaying or avoiding the need for surgical intervention. Centers that offer PRP injections usually charge patients out of pocket and directly market services. Therefore, the purpose of this study was to quantify the current (1) prices and (2) marketed clinical efficacy of autologous PRP injections for knee OA. A prospective cross-sectional study was performed based on 286 centers identified in the United States offering PRP injections for knee OA. A total of 179 (73.4%) centers were successfully contacted via e-mail or phone, using a simulated 52-year-old male patient with knee OA. Scripted questions were asked by the simulated patient to determine the current marketed prices and clinical efficacy, either reported as “good results” or “symptomatic improvement,” claimed by each treating center. The mean price for a single unilateral knee same-day PRP injection was $714 with a standard deviation of $144 (95% confidence interval [CI]: $691–737, n = 153). The mean claim of clinical efficacy was 76% with a standard deviation of 11% (95% CI: 73.5–78.3%, n = 84). Out of the 84 clinics, 10 claimed “90 to 100% efficacy,” 27 claimed “80 to 90%,” 29 claimed “70 to 80%,” 9 claimed “60 to 70%,” 8 claimed “50 to 60%,” and 1 claimed “40 to 60%.” These findings provide a unique perspective on the PRP market for the treatment of knee OA that is valuable to physicians and health care providers in providing better education to patients on the associated costs and purported clinical benefits of PRP injections.

scholarly journals Does the Conservative Non-pharmacological Management of Knee Osteoarthritis in Switzerland Reflect the Clinical Guidelines? A Survey Among General Practitioners, Rheumatologists, and Orthopaedic Surgeons

2021 ◽  
Vol 2 ◽  
Author(s):  
Lea Ettlin ◽  
Irina Nast ◽  
Erika O. Huber ◽  
Karin Niedermann
Keyword(s):  
Knee Osteoarthritis ◽  
General Practitioners ◽  
Treatment Options ◽  
Barriers And Facilitators ◽  
First Line ◽  
Pharmacological Management ◽  
Physically Active ◽  
Knee Oa ◽  
Diagnostic Measures ◽  
Active Patient

Introduction: The International Guidelines recommend exercise, education and weight management (if appropriate) as the first-line conservative treatment for patients with knee osteoarthritis (OA) to enhance their self-management. The aim of this study was to investigate the current state of conservative non-pharmacological management of patients with knee OA in Switzerland and to explore the perceived barriers and facilitators to the application of the guideline recommendations.Materials and methods: Eleven semi-structured interviews with selected general practitioners (GPs), rheumatologists and orthopaedic surgeons were performed. Based on these results, an online survey was developed and sent to the members of three scientific medical societies. Questions addressed the frequency of diagnostic measures, treatment options, reasons for referral to exercise and also barriers and facilitators.Results: A total of 234 members responded. They indicated that patients normally present due to pain (n = 222, 98.2%) and functional limitations of the knee (n = 151, 66.8%). In addition to clinical assessment, X-ray (n = 214, 95.5%) and MRI (n = 70, 31.3%) were the most frequently used diagnostic measures. Treatment options usually involved patient education for diagnosis (n = 223, 98.6%) and suitable activities (n = 217, 96%), pharmacological treatment (n = 203, 89.8%) and referral to physiotherapy (n = 188, 83.2%). The participants estimated that they had referred 54% of their patients with knee OA for a specific exercise. The referral to exercise was driven by “patient expectation/high level of suffering” (n = 73, 37.1%) and their “own clinical experience” (n = 49, 24.9%). The specialists rated the most important barriers to referral to exercise as “disinterest of patient” (n = 88, 46.3%) and “physically active patient” (n = 59, 31.1%). As the most important facilitators, they rated “importance to mention exercise despite the short time of consultation” (n = 170, 89.4%) and “insufficiently physically active patient” (n = 165, 86.9%).Discussion: A substantial evidence–performance gap in the management of patients with knee OA appears to exist in Switzerland. For the systematic referral to exercise as the first-line intervention, it might be useful for medical doctors to suggest a structured exercise programme to patients with knee OA, rather than just advising general exercise.

scholarly journals Injections in the osteoarthritic knee: a review of current treatment options

2021 ◽  
Vol 6 (6) ◽  
pp. 501-509
Author(s):  
Gerardo Fusco ◽  
Francesco M. Gambaro ◽  
Berardo Di Matteo ◽  
Elizaveta Kon
Keyword(s):  
Platelet Rich Plasma ◽  
Symptomatic Relief ◽  
Treatment Options ◽  
Cartilage Degradation ◽  
Current Treatment ◽  
Biologic Agents ◽  
Knee Oa ◽  
Molecular Approaches

Knee osteoarthritis is a degenerative condition characterized by progressive cartilage degradation, subchondral damage, and bone remodelling. Among the approaches implemented to achieve symptomatic and functional improvements, injection treatments have gained increasing attention due to the possibility of intra-articular delivery with reduced side effects compared to systemic therapies. In addition to well-established treatment options such as hyaluronic acid (HA), cortico-steroids (CS) and oxygen-ozone therapy, many other promising products have been employed in the last decades such as polydeoxyribonucleotide (PDRN) and biologic agents such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Moreover, ultrasound-guided intra-meniscal injection and X-ray-guided subchondral injection techniques have been introduced into clinical practice. Even when not supported by high evidence consensus, intra-articular CS and HA injections have gained precise indications for symptomatic relief and clinical improvement in OA. Biological products are strongly supported by in vitro evidence but there is still a lack of robust clinical evidence. PRP and MSCs seem to relieve OA symptoms through a regulation of the joint homeostasis, even if their capability to restore articular cartilage is still to be proved in vivo. Due to increasing interest in the subchondral bone pathology, subchondral injections have been developed with promising results in delaying joint replacement. Nevertheless, due to their recent development and the heterogeneity of the injected products (biologic agents or calcium phosphate), this approach still lacks strong enough evidence to be fully endorsed. Combined biological treatments, nano-molecular approaches, monoclonal antibodies and ‘personalized’ target therapies are currently under development or under investigation with the aim of expanding our armamentarium against knee OA. Cite this article: EFORT Open Rev 2021;6:501-509. DOI: 10.1302/2058-5241.6.210026

scholarly journals Efficacy of Platelet-Rich Plasma and Plasma for Symptomatic Treatment of Knee Osteoarthritis: A Double-Blinded Placebo-Controlled Randomized Clinical Trial.

2021 ◽  
Author(s):  
Murillo Dório ◽  
Rosa Maria Rodrigues Pereira ◽  
Alexandre Galeno Branco Luz ◽  
Leticia Alle Deveza ◽  
Ricardo Manoel Oliveira ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Primary Outcome ◽  
Platelet Rich Plasma ◽  
Controlled Trial ◽  
Symptomatic Treatment ◽  
Treatment Alternative ◽  
Double Blind ◽  
Secondary Outcomes ◽  
Double Blinded ◽  
And Function

Abstract Background: Platelet-rich plasma (PRP) has a still conflicting efficacy for knee osteoarthritis (KOA) and might be a minimally invasive and safe treatment alternative. The potential benefit of only plasma (non-enriched) has never been investigated. Our aim was to evaluate the efficacy of intra-articular platelet-rich plasma (PRP) and plasma to improve pain and function in participants with KOA over 24 weeks. Methods: Randomized, double-blind, placebo-controlled trial with 3 groups (n = 62): PRP (n = 20), plasma (n = 21) and saline (n = 21). Two ultrasound-guided knee injections were performed with a 2-week interval. The primary outcome was visual analog scale 0-10 cm (VAS) for overall pain at week 24, with intermediate assessments at weeks 6 and 12. Main secondary outcomes were: KOOS, OMERACT-OARSI criteria and TUGT. Results: At baseline, 92% of participants were female, with a mean age of 65 years, mean BMI of 28.0 Kg/m2and mean VAS pain of 6.2 cm. Change in pain from baseline at week 24 were -2.9 (SD 2.5), -2.4 (SD 2.5) and -3.5 cm (SD 3.3) for PRP, plasma and saline, respectively (p intergroup = 0.499). There were no differences between the three groups at weeks 6 and 12. Similarly, there were no differences between groups regarding secondary outcomes. The PRP group showed higher frequency of adverse events (65% versus 24% and 33% for plasma and saline, respectively, p = 0.02), mostly mild transitory increase in pain.Conclusions: PRP and plasma were not superior to placebo for pain and function improvement in KOA over 24 weeks. The PRP group had a higher frequency of mild transitory increase in pain.Trial registration: ClinicalTrials.gov, NCT03138317, 03/05/2017.

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