scholarly journals Clinically Relevant Molecular Biomarkers for Use in Human Knee Osteoarthritis: A Systematic Review

Cartilage ◽  
2020 ◽  
pp. 194760352094123
Author(s):  
James G. Convill ◽  
Gwenllian F. Tawy ◽  
Anthony J. Freemont ◽  
Leela C. Biant

Objective Biomarkers in osteoarthritis (OA) could serve as objective clinical indicators for various disease parameters, and act as surrogate endpoints in clinical trials for disease-modifying drugs. The aim of this systematic review was to produce a comprehensive list of candidate molecular biomarkers for knee OA after the 2013 ESCEO review and discern whether any have been studied in sufficient detail for use in clinical settings. Design MEDLINE and Embase databases were searched between August 2013 and May 2018 using the keywords “knee osteoarthritis,” “osteoarthritis,” and “biomarker.” Studies were screened by title, abstract, and full text. Human studies on knee OA that were published in the English language were included. Excluded were studies on genetic/imaging/cellular markers, studies on participants with secondary OA, and publications that were review/abstract-only. Study quality and bias were assessed. Statistically significant data regarding the relationship between a biomarker and a disease parameter were extracted. Results A total of 80 studies were included in the final review and 89 statistically significant individual molecular biomarkers were identified. C-telopeptide of type II collagen (CTXII) was shown to predict progression of knee OA in urine and serum in multiple studies. Synovial fluid vascular endothelial growth factor concentration was reported by 2 studies to be predictive of knee OA progression. Conclusion Despite the clear need for biomarkers of OA, the lack of coordination in current research has led to incompatible results. As such, there is yet to be a suitable biomarker to be used in a clinical setting.

2015 ◽  
Vol 28 (3) ◽  
pp. 605-616
Author(s):  
Andressa Silva ◽  
Marco Túlio de Mello ◽  
Sebastião Augusto Gávea Junior ◽  
Sandra Souza de Queiroz ◽  
Sergio Tufik ◽  
...  

AbstractObjective The objective of this review was to evaluate the evidence of the influence of therapeutic modalities on postural balance in patients with knee osteoarthritis (OA).Methods A search for published papers on therapeutic modalities was conducted using the Pubmed, Medline, Lilacs and SciELO databases. The keywords “knee” and “balance” in combination with “osteoarthritis” were used as the search strategy. Randomized controlled clinical trials published in the last 10 years in either English or Portuguese were selected. The PEDro scale was applied to assess the quality of the selected clinical trials.Results A total of 46 studies of patients with knee OA were found, of which seven were analyzed in full and 39 were excluded because they did not meet the inclusion criteria. Of the seven studies reviewed, six were considered to have a high methodological quality on the PEDro scale. Several therapeutic modalities were found (physical exercise, hydrotherapy, electrotherapy and manual therapy), and postural balance improved in only three studies.Conclusion The studies included in this systematic review had a high methodological quality, so it can be concluded that the therapeutic modalities used in those studies improved postural balance in patients with knee OA.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043026
Author(s):  
Erin M Macri ◽  
Michael Callaghan ◽  
Marienke van Middelkoop ◽  
Miriam Hattle ◽  
Sita M A Bierma-Zeinstra

IntroductionKnee osteoarthritis (OA) is a prevalent and disabling musculoskeletal condition. Biomechanical factors may play a key role in the aetiology of knee OA, therefore, a broad class of interventions involves the application or wear of devices designed to mechanically support knees with OA. These include gait aids, bracing, taping, orthotics and footwear. The literature regarding efficacy of mechanical interventions has been conflicting or inconclusive, and this may be because certain subgroups with knee OA respond better to mechanical interventions. Our primary aim is to identify subgroups with knee OA who respond favourably to mechanical interventions.Methods and analysisWe will conduct a systematic review to identify randomised clinical trials of any mechanical intervention for the treatment of knee OA. We will invite lead authors of eligible studies to share individual participant data (IPD). We will perform an IPD meta-analysis for each type of mechanical intervention to evaluate efficacy, with our main outcome being pain. Where IPD are not available, this will be achieved using aggregate data. We will then evaluate five potential treatment effect modifiers using a two-stage approach. If data permit, we will also evaluate whether biomechanics mediate the effects of mechanical interventions on pain in knee OA.Ethics and disseminationNo new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publication in peer-reviewed journals and summaries posted on websites serving the public and clinicians.PROSPERO registration numberCRD42020155466.


2019 ◽  
Vol 53 (18) ◽  
pp. 1162-1167 ◽  
Author(s):  
Marthe Mehus Lie ◽  
May Arna Risberg ◽  
Kjersti Storheim ◽  
Lars Engebretsen ◽  
Britt Elin Øiestad

BackgroundThis updated systematic review reports data from 2009 on the prevalence, and risk factors, for knee osteoarthritis (OA) more than 10 years after anterior cruciate ligament (ACL) tear.MethodsWe systematically searched five databases (PubMed, EMBASE, AMED, Cinahl and SPORTDiscus) for prospective and retrospective studies published after 1 August 2008. Studies were included if they investigated participants with ACL tear (isolated or in combination with medial collateral ligament and/or meniscal injuries) and reported symptomatic and/or radiographic OA at a minimum of 10 years postinjury. We used a modified version of the Downs and Black checklist for methodological quality assessment and narrative synthesis to report results. The study protocol was registered in PROSPERO.ResultsForty-one studies were included. Low methodological quality was revealed in over half of the studies. At inclusion, age ranged from 23 to 38 years, and at follow-up from 31 to 51 years. Sample sizes ranged from 18 to 780 participants. The reported radiographic OA prevalence varied between 0% and 100% >10 years after injury, regardless of follow-up time. The studies with low and high methodological quality reported a prevalence of radiographic OA between 0%–100% and 1%–80%, respectively. One study reported symptomatic knee OA for the tibiofemoral (TF) joint (35%), and one study reported symptomatic knee OA for the patellofemoral (PF) joint (15%). Meniscectomy was the only consistent risk factor determined from the data synthesis.ConclusionRadiographic knee OA varied between 0% and 100% in line with our previous systematic review from 2009. Symptomatic and radiographic knee OA was differentiated in two studies only, with a reported symptomatic OA prevalence of 35% for the TF joint and 15% for PF joint. Future cohort studies need to include measurement of symptomatic knee OA in this patient group.PROSPERO registration numberCRD42016042693.


2019 ◽  
Vol 32 (11) ◽  
pp. 1046-1057 ◽  
Author(s):  
Kavin Sundaram ◽  
Juan S. Vargas-Hernández ◽  
Tomas Roca Sanchez ◽  
Nestor Moreno Moreu ◽  
Michael A. Mont ◽  
...  

AbstractKnee osteoarthritis (OA) is a highly prevalent disease and treatment options for early stages of OA are needed. Intraosseous injections of bone substitute and biologic materials have been proposed to expand the therapeutic arsenal by potentially halting OA progression and delaying the need for knee arthroplasty in patients with early/moderate-stage disease. Therefore, the goal of this study was assessed the efficacy and safety of subchondral intraosseous injection for the treatment of knee OA. A systematic review was performed on PubMed-Medline, and the Cochrane Database of systematic reviews. English and Spanish retrospective and prospective studies assessing the results of subchondral intraosseous injection of bone substitute materials and/or biologicals in human patients with knee OA, with a minimum of 6 months of follow-up were collected. A total of 1,081 potential articles were identified through our search. Six studies were included with a total of 163 patients. The mean follow-up was 18 months (range: 6–24 months). Patient reported outcomes measures (PROMs), complications, and conversion to total knee arthroplasty (TKA) were collected. All six studies showed PROMs improvement relative to baseline. Overall, the five studies reporting visual-analog scale (VAS) pain outcomes improved from a baseline mean score of 6.68 to 2.74. Also, knee injury and osteoarthritis score (KOOS), Tegner-Lysholm, and/or international knee documentation committee (IKDC) scores rose compared with baseline scores in all studies. Overall, 2.5% (4/163) of patients had a complication attributed to study-related treatment. Most patients (81%, 86/106) remained TKA-free at a 1-year follow-up. Subchondral intraosseous injections of bone substitute materials and platelet-rich plasma (PRP) suggest (1) improved PROMs of pain and functional status, (2) low complication rate, and (3) relatively low rates of conversion to TKA. However, the current studies investigating these treatments exhibited high degree of heterogeneity in both measurement of outcomes and delivery of treatment, with a high risk of bias. This procedure should not be utilized in advanced knee OA. In light of the limitations of the current literature, advising in favor or against this therapy for early to moderate knee OA is challenging.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Regina WS Sit ◽  
Vincent CH Chung ◽  
Kenneth D. Reeves ◽  
David Rabago ◽  
Keith KW Chan ◽  
...  

Abstract Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi–randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.


2017 ◽  
Vol 52 (6) ◽  
pp. 497-506 ◽  
Author(s):  
Jeffrey B. Driban ◽  
Jennifer M. Hootman ◽  
Michael R. Sitler ◽  
Kyle P. Harris ◽  
Nicole M. Cattano

Objective:  Information regarding the relative risks of developing knee osteoarthritis (OA) as a result of sport participation is critical for shaping public health messages and for informing knee-OA prevention strategies. The purpose of this systematic review was to investigate the association between participation in specific sports and knee OA. Data Sources:  We completed a systematic literature search in September 2012 using 6 bibliographic databases (PubMed; Ovid MEDLINE; Journals@Ovid; American College of Physicians Journal Club; Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Review, Database of Abstracts of Reviews of Effects; and Ovid HealthStar), manual searches (4 journals), and reference lists (56 articles). Study Selection:  Studies were included if they met the following 4 criteria: (1) an aim was to investigate an association between sport participation and knee OA; (2) the outcome measure was radiographic knee OA, clinical knee OA, total knee replacement, self-reported diagnosis of knee OA, or placement on a waiting list for a total knee replacement; (3) the study design was case control or cohort; and (4) the study was written in English. Articles were excluded if the study population had an underlying condition other than knee OA. Data Extraction:  One investigator extracted data (eg, group descriptions, knee OA prevalence, source of nonexposed controls). Data Synthesis:  The overall knee-OA prevalence in sport participants (n = 3759) was 7.7%, compared with 7.3% among nonexposed controls (referent group n = 4730, odds ratio [OR] = 1.1). Specific sports with a significantly higher prevalence of knee OA were soccer (OR = 3.5), elite-level long-distance running (OR = 3.3), competitive weight lifting (OR = 6.9), and wrestling (OR = 3.8). Elite-sport (soccer or orienteering) and nonelite-sport (soccer or American football) participants without a history of knee injury had a greater prevalence of knee OA than nonexposed participants. Conclusions:  Participants in soccer (elite and nonelite), elite-level long-distance running, competitive weight lifting, and wrestling had an increased prevalence of knee OA and should be targeted for risk-reduction strategies.


Cartilage ◽  
2019 ◽  
pp. 194760351988878
Author(s):  
Larry E. Miller ◽  
Samir Bhattacharyya ◽  
William R. Parrish ◽  
Michael Fredericson ◽  
Brad Bisson ◽  
...  

Objective The objective of this systematic review and meta-analysis was to report the safety of intra-articular hyaluronic acid (IAHA) in patients with symptomatic knee osteoarthritis (OA). Methods We identified randomized controlled trials reporting the safety of IAHA versus IA saline in adults with symptomatic knee OA. Main safety outcomes were adverse events (AEs), local AEs, serious adverse events (SAEs), study withdrawals, and AE-related study withdrawals. Results A total of 35 randomized controlled trials with 38 group comparisons comprising 8,078 unique patients (IAHA: 4,295, IA saline: 3,783) were included in the meta-analysis. Comparing IAHA with IA saline over a median of 6 months follow-up, there were no differences in the risk of AEs (42.4% vs. 39.7%, risk ratio [RR] = 1.01, 95% CI = 0.96-1.07, P = 0.61), SAEs (1.8% vs. 1.2%, RR = 1.44, 95% CI = 0.91-2.26, P=0.12), study withdrawals (12.3% vs. 12.7%, RR = 0.99, 95% CI = 0.87-1.12, P = 0.83), or AE-related study withdrawals (2.7% vs. 2.1%, RR = 1.37, 95% CI = 0.97-1.93, P = 0.08). Local AEs, all of which were nonserious, were more common with IAHA vs. IA saline (14.5% vs. 11.7%, RR = 1.21, 95% CI = 1.07-1.36, P = 0.003) and typically resolved within days. Conclusion IAHA was shown to be safe for use in patients with symptomatic knee OA. Compared with IA saline, IAHA is associated with an increased risk of nonserious, transient local reactions. There was no evidence to suggest any additional safety risks of IAHA.


Cartilage ◽  
2020 ◽  
pp. 194760352094294
Author(s):  
Angelo Boffa ◽  
Giulia Merli ◽  
Luca Andriolo ◽  
Christian Lattermann ◽  
Gian M. Salzmann ◽  
...  

Objective The aim of this systematic review was to analyze the evidence about the efficacy of the several synovial fluid (SF) biomarkers proposed for knee osteoarthritis (OA), categorizing them by both molecular characteristics and clinical use according to the BIPEDs criteria, to provide a comprehensive and structured overview of the current literature. Design A systematic review was performed in May 2020 on PubMed, Cochrane Library, and Embase databases about SF biomarkers in patients with knee OA. The search was limited to articles in the last 20 years on human studies, involving patients with knee OA, reporting SF biomarkers. The evidence for each selected SF biomarker was quantified according to the 6 categories of BIPEDs classification. Results A total of 159 articles were included in the qualitative data synthesis and 201 different SF biomarkers were identified. Among these, several were investigated multiple times in different articles, for a total of 373 analyses. The studies included 13,557 patients with knee OA. The most promising SF biomarkers were C4S, IL-6, IL-8, Leptin, MMP-1/3, TIMP-1, TNF-α, and VEGF. The “burden of disease” and “diagnostic” categories were the most represented with 132 and 106 different biomarkers, respectively. Conclusions The systematic review identified numerous SF biomarkers. However, despite the high number of studies on the plethora of identified molecules, the evidence about the efficacy of each biomarker is supported by limited and often conflicting findings. Further research efforts are needed to improve the understanding of SF biomarkers for a better management of patients with knee OA.


Author(s):  
Shih-Hsiang Chou ◽  
Po-Chih Shen ◽  
Cheng-Chang Lu ◽  
Zi-Miao Liu ◽  
Yin-Chun Tien ◽  
...  

Radiofrequency ablation (RFA) was first introduced for treating knee osteoarthritis (OA) in 2010 and has emerged as a minimally invasive treatment option. Three RFA techniques have been adopted for treating knee OA, including conventional, pulsed, and cooled RFA. However, the efficacy among different RFA techniques in the treatment of knee OA is still unclear. Three electronic databases were systematically searched for relevant articles, including PubMed, Embase, and Cochrane Library. A meta-analysis of articles that investigated the use of RFA techniques in the treatment of knee OA was conducted to pool the effect size in pain before and after treatment. A total of 20 eligible articles (including 605 patients) were included for our meta-analysis. After treatment, the patients had significant improvements in pain for all three RFA techniques when compared with the baseline level for the 1, 3-, and 6-month follow-ups (p < 0.00001). However, there were no significant differences in the efficacy among the three RFA techniques for all follow-up visits (p > 0.05). The three RFA techniques demonstrated a significant improvement in pain for up to 6 months after treatment. Comparing the efficacy of the three RFA techniques in the treatment of knee OA, our results showed that no significant differences in pain relief among the three RFA techniques were observed at the 1-, 3-, 6, and 12-month follow-up visits.


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