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      Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis

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          Abstract

          Background

          Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA.

          Methods

          The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation.

          Results

          Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: − 0.31; 95% confidence interval (CI): − 0.55 to − 0.06; P = 0.01 < 0.05). PRP combined with HA for KOA achieved better improvements in the WOMAC Function Score (SMD: -0.32; 95% CI: − 0.54 to − 0.10; P < 0.05) and WOMAC Total Score (SMD: -0.42; 95% CI: − 0.67 to − 0.17; P < 0.05) at the 12-month follow-up than did the application of PRP alone. In a comparison of Lequesne Index scores at the 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: − 0.67 to − 0.17; P < 0.05). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone ( P > 0.05).

          Conclusions

          Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.

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          Most cited references36

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          Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines.

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            The effect of osteoarthritis definition on prevalence and incidence estimates: a systematic review.

            To understand the differences in prevalence and incidence estimates of osteoarthritis (OA), according to case definition, in knee, hip and hand joints. A systematic review was carried out in PUBMED and SCOPUS databases comprising the date of publication period from January 1995 to February 2011. We attempted to summarise data on the incidence and prevalence of OA according to different methods of assessment: self-reported, radiographic and symptomatic OA (clinical plus radiographic). Prevalence estimates were combined through meta-analysis and between-study heterogeneity was quantified. Seventy-two papers were reviewed (nine on incidence and 63 on prevalence). Higher OA prevalences are seen when radiographic OA definition was used for all age groups. Prevalence meta-analysis showed high heterogeneity between studies even in each specific joint and using the same OA definition. Although the knee is the most studied joint, the highest OA prevalence estimates were found in hand joints. OA of the knee tends to be more prevalent in women than in men independently of the OA definition used, but no gender differences were found in hip and hand OA. Insufficient data for incidence studies didn't allow us to make any comparison according to joint site or OA definition. Radiographic case definition of OA presented the highest prevalences. Within each joint site, self-reported and symptomatic OA definitions appear to present similar estimates. The high heterogeneity found in the studies limited further conclusions. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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              Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis.

              To evaluate the therapeutic trajectory of intra-articular hyaluronic acid (IAHA) vs placebo for knee osteoarthritis (OA). Our data sources include Medline, EMBASE, CINAHL, BIOSIS, Web of Science, Google Scholar, Cochrane database; hand searched reviews, manuscripts, and, supplements; author contacts for unpublished data. Randomized trials that reported effects of IAHA vs placebo on knee OA were selected based on inclusion criteria. We computed effect sizes for change from baseline at 4, 8, 12, 16, 20 and 24 weeks, using Bayesian random effects model. We performed multivariate analyses adjusting for correlation between time points. Meta-regressions were performed adjusting for potential confounders. The 54 eligible trials included 7545 participants. The conduct and quality of these trials varied in number of aspects. The effect size (ES) favored IAHA by week 4 (0.31; 95% CI 0.17, 0.45), reaching peak at week 8 (0.46; 0.28, 0.65), and then trending downwards, with a residual detectable effect at week 24 (0.21; 0.10, 0.31). This therapeutic trajectory was consistent among the subset of high quality trials and on multivariate analysis adjusting for correlation between time points. Our meta-analysis highlights a therapeutic trajectory of IAHA for knee OA pain over 6 months post-intervention. With this additional perspective, we are able to infer that IAHA is efficacious by 4 weeks, reaches its peak effectiveness at 8 weeks and exerts a residual detectable at 24 weeks. On the other hand, the peak effect size (0.46; 0.28, 0.65), is greater than published effects from other OA analgesics [acetaminophen (ES=0.13; 0.04, 0.22); NSAIDs (ES=0.29; 0.22, 0.35); COX-2 inhibitors (ES=0.44; 0.33, 0.55)]. An effect size above 0.20 is considered to be clinically relevant on an individual patient basis in chronic pain conditions such as knee OA. Thus, its properties could have utility for certain clinical situations, or in combination with other therapies. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                zhaojinlong41@163.com
                ynhtsmile@126.com
                liangguihonghe@163.com
                lingfengzeng0202@163.com
                czyangwy@163.com
                liujun.gdtcm@hotmail.com
                Journal
                BMC Musculoskelet Disord
                BMC Musculoskelet Disord
                BMC Musculoskeletal Disorders
                BioMed Central (London )
                1471-2474
                11 April 2020
                11 April 2020
                2020
                : 21
                : 224
                Affiliations
                [1 ]GRID grid.411866.c, ISNI 0000 0000 8848 7685, The Second School of clinical medical Sciences, , Guangzhou University of Chinese Medicine, ; Guagnzhou, 510405 China
                [2 ]GRID grid.411866.c, ISNI 0000 0000 8848 7685, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Traditional Chinese Medicine), ; Guangzhou, 510120 China
                [3 ]Guangdong Academy of Traditional Chinese Medicine, Research Team on Bone and Joint Degeneration and Injury, Guangzhou, 510120 China
                Author information
                https://orcid.org/0000-0001-7079-1336
                https://orcid.org/0000-0002-6197-1375
                https://orcid.org/0000-0002-7599-2628
                https://orcid.org/0000-0003-1311-8641
                https://orcid.org/0000-0001-8657-2269
                https://orcid.org/0000-0002-1943-3880
                Article
                3262
                10.1186/s12891-020-03262-w
                7149899
                32278352
                6c1e03fe-deb2-40a2-aadb-eb856a4cdf73
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 30 January 2020
                : 2 April 2020
                Funding
                Funded by: Project of Guangdong Provincial Department of Finance
                Award ID: No.[2014]157, No.[2018]8
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100010031, Postdoctoral Research Foundation of China;
                Award ID: No. 2018M633036
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100009330, Medical Science and Technology Foundation of Guangdong Province;
                Award ID: No. B2019091
                Award Recipient :
                Funded by: the National Natural Science Foundation of China
                Award ID: No.81873314, No.81974574, No. 81473698
                Award Recipient :
                Funded by: Key scientific research platforms and research projects of universities in Guangdong Province
                Award ID: No. 2018KQNCX041
                Award Recipient :
                Funded by: the Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine
                Award ID: No.YN2019ML08, No. YK2013B2N19, YN2015MS15
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Orthopedics
                platelet-rich plasma,hyaluronic acid,knee osteoarthritis,meta-analysis
                Orthopedics
                platelet-rich plasma, hyaluronic acid, knee osteoarthritis, meta-analysis

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