J.A.N. Verhaar

Platelet-rich plasma injection for chronic Achilles tendinopathy: A randomized controlled trial

CONTEXT Tendon disorders comprise 30% to 50% of all activity-related injuries; chronic degenerative tendon disorders (tendinopathy) occur frequently and are difficult to treat. Tendon regeneration might be improved by injecting platelet-rich plasma (PRP), an increasingly used treatment for releasing growth factors into the degenerative tendon. OBJECTIVE To examine whether a PRP injection would improve outcome in chronic midportion Achilles tendinopathy. DESIGN, SETTING, AND PATIENTS A stratified, block-randomized, double-blind, placebo-controlled trial at a single center (The Hague Medical Center, Leidschendam, The Netherlands) of 54 randomized patients aged 18 to 70 years with chronic tendinopathy 2 to 7 cm above the Achilles tendon insertion. The trial was conducted between August 28, 2008, and January 29, 2009, with follow-up until July 16, 2009. INTERVENTION Eccentric exercises (usual care) with either a PRP injection (PRP group) or saline injection (placebo group). Randomization was stratified by activity level. MAIN OUTCOME MEASURES The validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire, which evaluated pain score and activity level, was completed at baseline and 6, 12, and 24 weeks. The VISA-A score ranged from 0 to 100, with higher scores corresponding with less pain and increased activity. Treatment group effects were evaluated using general linear models on the basis of intention-to-treat. RESULTS After randomization into the PRP group (n = 27) or placebo group (n = 27), there was complete follow-up of all patients. The mean VISA-A score improved significantly after 24 weeks in the PRP group by 21.7 points (95% confidence interval [CI], 13.0-30.5) and in the placebo group by 20.5 points (95% CI, 11.6-29.4). The increase was not significantly different between both groups (adjusted between-group difference from baseline to 24 weeks, -0.9; 95% CI, -12.4 to 10.6). This CI did not include the predefined relevant difference of 12 points in favor of PRP treatment. CONCLUSION Among patients with chronic Achilles tendinopathy who were treated with eccentric exercises, a PRP injection compared with a saline injection did not result in greater improvement in pain and activity. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00761423.

Prevalence and incidence of shoulder pain in the general population; a systematic review.

Objective: To investigate the incidence and prevalence of shoulder complaints in the general population. Method: A systematic review of the literature was conducted. Medline, Embase, and Cinahl were searched for relevant studies. Results: Eighteen studies on prevalence and one study on incidence met the inclusion criteria. Incidence figures of 0.9–2.5% were found for different age groups. Prevalence figures differed from 6.9 to 26% for point prevalence, 18.6–31% for 1‐month prevalence, 4.7–46.7% for 1‐year prevalence and 6.7–66.7% for lifetime prevalence. Prevalence rates decreased when the case definition was restricted, in terms of duration of pain or the presence of limited movements, and increased when the location for pain was enlarged. Conclusion: The reported prevalence figures on shoulder complaints diverged strongly. Health professionals and policymakers who estimate the amount of medical care needed and related costs should be aware of the variations in prevalence rate and the underlying reasons for these differences.

Effect of Arthritic Synovial Fluids on the Expression of Immunomodulatory Factors by Mesenchymal Stem Cells: An Explorative in vitro Study

Background: In diseased joints, the catabolic environment results in progressive joint damage. Mesenchymal stem cells (MSCs) can have immunomodulatory effects by secreting anti-inflammatory factors. To exert these effects, MSCs need to be triggered by pro-inflammatory cytokines. To explore the potential of MSCs as a treatment for diseased joints, we studied the effect of synovial fluid (SF) from donors with different joint diseases and donors without joint pathology on the immunomodulatory capacities of human MSCs in vitro. We hypothesized that SF of diseased joints influences the immunomodulatory effects of MSCs. Materials and Methods: MSCs were cultured in medium with SF of six osteoarthritis (OA) or six rheumatoid arthritis (RA) donors and three donors without joint pathology were used as control. Gene expressions of IL-6, HGF, TNFa, TGFb1, and indoleamine 2,3-dioxygenase (IDO) were analyzed. l-kynurenine concentration in conditioned medium (CM) by MSCs with SF was determined as a measure of IDO activity by MSCs. Furthermore, the effect of CM with SF on proliferation of activated lymphocytes was analyzed. Results: Addition of SF significantly up-regulated the mRNA expression of IL-6 and IDO in MSCs. SF(OA) induced significantly higher expression of IDO than SF(control), although no difference in IDO activity of the MSCs could be shown with a l-kynurenine assay. Medium conditioned by MSCs with SF(OA or RA) suppressed activated lymphocyte proliferation in vitro more than medium conditioned by MSCs without SF or with SF(control). Discussion: SF can influence the expression of genes involved in immunomodulation by MSCs and the effect on lymphocyte proliferation. We found indications for disease-specific differences between SFs but the variation between donors, even within one disease group was high. These data warrant further research to examine the potential application of MSC therapy in arthritic joints.

Can Platelet-Rich Plasma Enhance Tendon Repair? A Cell Culture Study

Background Autologous platelet-rich plasma (PRP) application appears to improve tendon healing in traumatic tendon injuries, but basic knowledge of how PRP promotes tendon repair is needed. Hypothesis Platelet-rich plasma has a positive effect on cell proliferation and collagen production and induces the production of matrix-degrading enzymes and endogenous growth factors by human tenocytes. Study Design Controlled laboratory study. Methods Human tenocytes were cultured 14 days in 2% fetal calf serum medium complemented with 0%, 10%, or 20% vol/vol platelet-rich clot releasate ([PRCR] the active releasate of PRP) or platelet-poor clot releasate (PPCR). At day 4,7, and 14, cell amount, total collagen, and gene expression of collagen Iα1 (COL1) and Mod (COL3), matrix metalloproteinases ([MMPs] MMP1, MMP3, and MMP13), vascular endothelial-derived growth factor (VEGF)-A, and transforming growth factor (TGF)-β1 were analyzed. Results Platelet numbers in PRP increased to 2.55 times baseline. Growth-factor concentrations of VEGF and platelet-derived growth factor (PDGF)-BB were higher in PRCR than PPCR. Both PRCR and PPCR increased cell number and total collagen, whereas they decreased gene expression of COL1 and COL3 without affecting the COL3/COL1 ratio. PRCR, but not PPCR, showed upregulation of MMP1 and MMP3 expression. Matrix metalloproteinase 13 expression was not altered by either treatment. PRCR increased VEGF-A expression at all time points and TGF-β1 expression at day 4. Conclusion In human tenocyte cultures, PRCR, but also PPCR, stimulates cell proliferation and total collagen production. PRCR, but not PPCR, slightly increases the expression of matrix-degrading enzymes and endogenous growth factors. Clinical Relevance In vivo use of PRP, but also of PPP to a certain extent, in tendon injuries might accelerate the catabolic demarcation of traumatically injured tendon matrices and promote angiogenesis and formation of a fibrovascular callus. Whether this will also be beneficial for degenerative tendinopathies remains to be elucidated.

One-Year Follow-up of Platelet-Rich Plasma Treatment in Chronic Achilles Tendinopathy A Double-Blind Randomized Placebo-Controlled Trial

Background Achilles tendinopathy is a common disease among both athletes and in the general population in which the use of platelet-rich plasma has recently been increasing. Good evidence for the use of this autologous product in tendinopathy is limited, and data on longer-term results are lacking. Purpose To study the effects of a platelet-rich plasma injection in patients with chronic midportion Achilles tendinopathy at 1-year follow-up. Study Design Randomized controlled trial; Level of evidence, 1. Methods Fifty-four patients, aged 18 to 70 years, with chronic tendinopathy 2 to 7 cm proximal to the Achilles tendon insertion were randomized to receive either a blinded injection containing platelet-rich plasma or saline (placebo group) in addition to an eccentric training program. The main outcome was the validated Victorian Institute of Sports Assessment–Achilles score. Patient satisfaction was recorded and ultrasound examination performed at baseline and follow-up. Results The mean Victorian Institute of Sports Assessment–Achilles score improved in both the platelet-rich plasma group and the placebo group after 1 year. There was no significant difference in increase between both groups (adjusted between-group difference, 5.5; 95% confidence interval, –4.9 to 15.8, P = .292). In both groups, 59% of the patients were satisfied with the received treatment. Ultrasonographic tendon structure improved significantly in both groups but was not significantly different between groups (adjusted between-group difference, 1.2%; 95% confidence interval, –4.1 to 6.6, P = .647). Conclusion This randomized controlled trial showed no clinical and ultrasonographic superiority of platelet-rich plasma injection over a placebo injection in chronic Achilles tendinopathy at 1 year combined with an eccentric training program.

The Dutch version of the knee injury and osteoarthritis outcome score: A validation study

BackgroundThe Knee Injury and Osteoarthritis Outcome Score (KOOS) was constructed in Sweden. This questionnaire has proved to be valid for several orthopedic interventions of the knee. It has been formally translated and validated in several languages, but not yet in Dutch. The purpose of the present study was to evaluate the clinimetric properties of the Dutch version of the KOOS questionnaire in knee patients with various stages of osteoarthritis (OA).MethodsThe Swedish version of the KOOS questionnaire was first translated into Dutch according to a standardized procedure and second tested for clinimetric quality. The study population consisted of patients with different stages of OA (mild, moderate and severe) and of patients after primary TKA, and after a revision of the TKA. All patients filled in the Dutch KOOS questionnaire, as well as the SF-36 and a Visual Analogue Scale for pain. The following analyses were performed to evaluate the clinimetric quality of the KOOS: Cronbachs alpha (internal consistency), principal component analyses (factor analysis), intraclass correlation coefficients (reliability), spearmans correlation coefficient (construct validity), and floor and ceiling effects.ResultsFor all patients groups Cronbachs alpha was for all subscales above 0.70. The ICCs, assessed for the patient groups with mild and moderate OA and after revision of the TKA patients, were above 0.70 for all subscales. Of the predefined hypotheses 60% or more could be confirmed for the patients with mild and moderate OA and for the TKA patients. For the other patient groups less than 45% could be confirmed. Ceiling effects were present in the mild OA group for the subscales Pain, Symptoms and ADL and for the subscale Sport/Recreation in the severe OA group. Floor effects were found for the subscales Sport/Recreation and Qol in the severe OA and revision TKA groups.ConclusionBased on these different clinimetric properties within the present study we conclude that the KOOS questionnaire seems to be suitable for patients with mild and moderate OA and for patients with a primary TKA. The Dutch version of the KOOS had a lower construct validity for patients with severe OA on a waiting list for TKA and patients after revision of a TKA. Further validation studies on the Dutch version of the KOOS should also include a knee specific questionnaire for assessing the construct validity.

Lateral extensor release for tennis elbow. A prospective long-term follow-up study.

A prospective study was done of the results of lateral release of the common extensor origin in sixty-three patients who had a tennis elbow. Fifty-seven of these patients were followed for a mean of fifty-nine months (range, fifty to sixty-five months). At the time of the operation, the extensor origin was macroscopically normal in all but six patients. Forty-seven (76 per cent) of the sixty-two patients who were evaluated at one year had no pain or only slight pain, whereas before the operation three patients (5 per cent) had had slight pain and sixty (95 per cent), severe pain. Of the fifty-seven patients who were re-examined after five years, fifty-two (91 per cent) had no pain or only slight pain. At one year, twenty patients (32 per cent) had an excellent over-all result; twenty-three (37 per cent), a good result; twelve (19 per cent), a fair result; and seven (11 per cent), a poor result. At five years, there were thirty-two excellent results (56 per cent), nineteen good results (33 per cent), four fair results (7 per cent), and two poor results (4 per cent). No association between the preoperative findings and the results of the operation was found. It was concluded that lateral extensor release, a relatively simple operation that can be performed in an outpatient setting, may be regarded at this time as the operative procedure with which other operations for tennis elbow should be compared.

Psychological factors affecting the outcome of total hip and knee arthroplasty: a systematic review.

OBJECTIVES Recently, numerous studies have reported that psychological factors can influence the outcome of total knee arthroplasty (TKA) and total hip arthroplasty (THA). However, a systematic overview is missing. The objective of this study was to examine which psychological factors influence the outcome of TKA and THA and to what extent. METHODS Data were obtained from the MEDLINE and EMBASE databases from inception to January 2011. Search terms included TKA and THA, outcome measures, and psychological aspects. Two reviewers independently selected the studies. Studies with a prospective before-after design with a minimum follow-up time of 6 weeks were included. One reviewer extracted the results and 2 reviewers independently conducted quality assessment. We distinguished between follow-up shorter and equal or longer than 1 year. RESULTS Thirty-five of 1837 studies met the inclusion criteria and were included in this systematic review. In follow-ups shorter than 1 year, and for knee patients only, strong evidence was found that patients with pain catastrophizing reported more pain postoperatively. Furthermore, strong evidence was found that preoperative depression had no influence on postoperative functioning. In long-term follow-up, 1 year after TKA, strong evidence was found that lower preoperative mental health (measures with the SF-12 or SF-36) was associated with lower scores on function and pain. For THA, only limited, conflicting, or no evidence was found. CONCLUSIONS Low preoperative mental health and pain catastrophizing have an influence on outcome after TKA. With regard to the influence of other psychological factors and for hip patients, only limited, conflicting, or no evidence was found.

The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review

INTRODUCTION Osteoarthritis (OA) of the knee joint is caused by genetic and hormonal factors and by inflammation, in combination with biomechanical alterations. It is characterized by loss of articular cartilage, synovial inflammation and subchondral bone sclerosis. Considerable evidence indicates that the menisci, ligaments, periarticular muscles and the joint capsule are also involved in the OA process. This paper will outline the theoretical framework for investigating the infrapatellar fat pad (IPFP) as an additional joint tissue involved in the development and progression of knee-OA. METHODS A literature search was performed in Pubmed from 1948 until October 2009 with keywords InFrapatellar fat pad, Hoffa fat pad, intraarticular adipose tissue, knee, cartilage, bone, cytokine, adipokine, inflammation, growth factor, arthritis, and OA. RESULTS The IPFP is situated intracapsularly and extrasynovially in the knee joint. Besides adipocytes, the IPFP from patients with knee-OA contains macrophages, lymphocytes and granulocytes, which are able to contribute to the disease process of knee-OA. Furthermore, the IPFP contains nociceptive nerve fibers that could in part be responsible for anterior pain in knee-OA. These nerve fibers secrete substance P, which is able to induce inflammatory responses and cause vasodilation, which may lead to IPFP edema and extravasation of the immune cells. The IPFP secretes cytokines, interleukins, growth factors and adipokines that influence cartilage by upregulating the production of matrix metalloproteinases (MMPs), stimulating the expression of pro-inflammatory cytokines and inhibiting the production of cartilage matrix proteins. They may also stimulate the production of pro-inflammatory mediators, growth factors and MMPs in synovium. CONCLUSION These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA.

Platelet-Rich Plasma Releasate Inhibits Inflammatory Processes in Osteoarthritic Chondrocytes

Background: Platelet-rich plasma (PRP) has recently been postulated as a treatment for osteoarthritis (OA). Although anabolic effects of PRP on chondrocytes are well documented, no reports are known addressing effects on cartilage degeneration. Since OA is characterized by a catabolic and inflammatory joint environment, the authors investigated whether PRP was able to counteract the effects of such an environment on human osteoarthritic chondrocytes. Hypothesis: Platelet-rich plasma inhibits inflammatory effects of interleukin-1 (IL-1) beta on human osteoarthritic chondrocytes. Study Design: Controlled laboratory study. Methods: Human osteoarthritic chondrocytes were cultured in the presence of IL-1 beta to mimic an osteoarthritic environment. Medium was supplemented with 0%, 1%, or 10% PRP releasate (PRPr, the active releasate of PRP). After 48 hours, gene expression of collagen type II alpha 1 (COL2A1), aggrecan (ACAN), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, matrix metalloproteinase (MMP)13, and prostaglandin-endoperoxide synthase (PTGS)2 was analyzed. Additionally, glycosaminoglycan (GAG) content, nitric oxide (NO) production, and nuclear factor kappa B (NFκB) activation were studied. Results: Platelet-rich plasma releasate diminished IL-1 beta–induced inhibition of COL2A1 and ACAN gene expression. The PRPr also reduced IL-1 beta–induced increase of ADAMTS4 and PTGS2 gene expression. ADAMTS5 gene expression and GAG content were not influenced by IL-1 beta or additional PRPr. Matrix metalloproteinase 13 gene expression and NO production were upregulated by IL-1 beta but not affected by added PRPr. Finally, PRPr reduced IL-1 beta–induced NFκB activation to control levels containing no IL-1 beta. Conclusion: Platelet-rich plasma releasate diminished multiple inflammatory IL-1 beta–mediated effects on human osteoarthritic chondrocytes, including inhibition of NFκB activation. Clinical Relevance: Platelet-rich plasma releasate counteracts effects of an inflammatory environment on genes regulating matrix degradation and formation in human chondrocytes. Platelet-rich plasma releasate decreases NFκB activation, a major pathway involved in the pathogenesis of OA. These results encourage further study of PRP as a treatment for OA.