Hip and groin pain in male field hockey players: Prevalence, incidence and associations with patient reported outcome scores and hip muscle strength.

OBJECTIVES: Investigate point prevalence (second half season 2018-2019) and incidence (season 2017-2018 and first half season 2018-2019) of non-time-loss and time-loss hip/groin pain in male field hockey players. Secondary aims were to study associations between: current/previous hip/groin pain and hip muscle strength, patient reported outcome measures (PROM) and hip muscle strength, and previous hip/groin pain and PROMs. Additionally we studied normal values for the PROMs (Hip and Groin Outcome Score (HAGOS)). DESIGN: Cross-sectional study. SETTING: Testing at field hockey clubs. PARTICIPANTS: 100 male field hockey players (elite, sub-elite and amateur). MAIN OUTCOME MEASURES: Point prevalence and incidence of hip/groin pain, strength: eccentric adduction and abduction, adductor squeeze, HAGOS. RESULTS: Hip/groin pain point prevalence was 17% (time-loss: 6%) and incidence was 36% (time-loss: 12%). Presence of current or previous hip/groin and lower HAGOS-values were not associated with lower hip muscle strength. Previous hip/groin pain was associated with a significant lower HAGOS-values in all domains, except for the 'participation in physical activities' domain. CONCLUSIONS: Hip/groin pain is common in field hockey. One fifth of players have hip/groin pain and one third had pain in the previous season. Previous hip/groin pain was associated with worse ongoing patient reported outcomes in most domains.

The association between statistical shape modeling-defined hip morphology and features of early hip osteoarthritis in young adult football players: Data from the femoroacetabular impingement and hip osteoarthritis cohort (FORCe) study.

Objective: To explore the relationship between radiographic hip shape and features of early hip osteoarthritis (OA) on magnetic resonance imaging (MRI) in young male and female football players without radiographic hip OA. Design: We used baseline data from a cohort of symptomatic and asymptomatic football players aged 18-50 years. Hip shape was assessed on anteroposterior radiographs with statistical shape modeling (SSM) for men and women separately. Cartilage defects and labral tears were graded using the Scoring Hip Osteoarthritis with MRI (SHOMRI) system. We used logistic regression with generalized estimating equations to estimate associations between each hip shape variant, called shape modes, and cartilage defects or labral tears. Results: We included 229 participants (446 hips, 77.4% male). For each sex, 15 shape modes were analyzed. In men, three shape modes were associated with cartilage defects: adjusted odds ratios (aOR) 0.75 (95%CI 0.58-0.97) per standard deviation (SD) for mode 1; 1.34 (95%CI 1.05-1.69) per SD for mode 12; and 0.61 (95%CI 0.48-0.78) per SD for mode 15; and one also with labral tears: aOR 1.30 (95%CI 1.01-1.69) per SD for mode 12. These modes generally represented variations in the femoral neck and subtypes of cam morphology, with and without pincer morphology. For women, there was no evidence for associations with the outcomes. Conclusions: Several hip shape variants were associated with cartilage defects on MRI in young male football players. Specifically, one subtype of cam morphology was associated with both cartilage defects and labral tears. Hip shape was not associated with early OA features in women.

Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review.

OBJECTIVE: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. DESIGN: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle-Ottawa Scale (NOS) for risk of bias assessment. RESULTS: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). CONCLUSIONS: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations.

Clinical and radiological hip parameters do not precede, but develop simultaneously with cam morphology: a 5-year follow-up study.

PURPOSE: The aim of this study was to (1) investigate whether radiographic and clinical parameters, which influence how stresses during sporting activities act on the proximal femur, are associated with cam morphology or (2) precede cam morphology development. METHODS: Young male football players participated at baseline (n = 89, 12-19 years of age), 2.5-year (n = 63) and 5-year follow-up (n = 49). Standardized anteroposterior pelvic and frog-leg lateral radiographs were obtained at each time-point. Cam morphology was quantified by an alpha angle ≥ 60°, and large cam morphology ≥ 78°. The neck-shaft angle (NSA), epiphyseal extension (EE), lateral center-edge angle (LCEA) and hip internal rotation (IR) were also measured. Cross-sectional associations between NSA, EE, LCEA and IR and (large) cam morphology were studied at all time-points. To study whether these variables preceded cam morphology development, hips without cam morphology at baseline were studied prospectively. RESULTS: A lower NSA, a higher EE and limited IR were consistently associated with cam morphology at all three time-points. These differences were more pronounced in hips with large cam morphology. No association between cam morphology and the LCEA was found. None of the parameters studied preceded cam morphology development. CONCLUSION: Cam morphology developed simultaneously with a varus orientation, growth plate extension towards the femoral neck and limited hip internal rotation. These parameters did not precede cam morphology development. The hip parameters studied cannot be used to identify individuals at risk of developing cam morphology. LEVEL OF EVIDENCE: Level II.

No added value for Computer-Assisted surgery to improve femoral component positioning and Patient Reported Outcomes in Hip Resurfacing Arthroplasty; a multi-center randomized controlled trial.

BACKGROUND: Computer Assisted Surgery (CAS) has proven to improve the accuracy in several orthopedic procedures. Therefore we used this technique to evaluate femoral component positioning in Hip Resurfacing Arthroplasty (HRA). The aim of this study was to evaluate imageless CAS compared to manually implanted femoral components and subsequently evaluates Patient Related Outcome Measures (PROMs). We hypothesized that the use of CAS optimizes the position of the femoral component and improves PROMs. METHODS: This is a multicenter, single-blinded, randomized, controlled trial of two groups. In the CAS group guiding of the femoral component was done with imageless navigation. In the Conventional (control) group the femoral component was placed manually according to the preplanned position. The primary outcome measure consists of a maximum of 3 degrees difference between the postoperative Stem Shaft Angle (SSA) and preplanned SSA. Secondary outcome measures consist of the Hip disability and Osteoarthritis Outcome Scale (HOOS), the Harris Hip Score (HHS) and Visual Analogue Scale (VAS) pain score. RESULTS: A total of 122 patients were randomized, 61 in the CAS group and 61 in the conventional group. There was no significant differences in accuracy of femoral implant position. The mean difference between the postoperative- and preplanned SSA was - 2.26 and - 1.75 degrees (more varus) respectively in the CAS and Conventional group. After surgery both groups show significant improvement in all PROMs compared to the baseline measurements, with no significant differences between the groups. CONCLUSION: Our cohort indicates no benefit for the use of CAS in accuracy of placement of the femoral component in HRA compared to manual implantation. There are no clinical differences in PROMs after 1 year follow up. This study showed no added value and no justification for the use of CAS in femoral component positioning in HRA. TRIAL REGISTRATION: This trial is registered at ClinicalTrails.gov ( https://clinicaltrials.gov/ ) on the 25th of October 2006: NCT00391937. LEVEL OF INCIDENCE: Level IIb, multicenter randomized controlled trial.

Cell-surface markers identify tissue resident multipotential stem/stromal cell subsets in synovial intimal and sub-intimal compartments with distinct chondrogenic properties.

OBJECTIVE: Synovium contains multipotent progenitor/stromal cells (MPCs) with potential to participate in cartilage repair. Understanding the identity of these MPCs will allow their therapeutic potential to be fully exploited. Hence this study aimed to identify primary synovial MPCs and characterize them in the context of cartilage regeneration. METHODS: Primary MPC/MPC-subset specific markers in synovium were identified by FACS analysis of uncultured cells. MPC-subsets from human synovium obtained from patients undergoing total knee arthroplasty were FACS sorted, cultured, immunophenotyped and chondrogenically differentiated. The anatomical localization of MPCs in synovium was examined using immunohistochemistry. Finally, the presence of these MPC subsets in healthy synovium obtained from human organ donors was examined. RESULTS: A combination of CD45, CD31, CD73 and CD90 can isolate two distinct MPC-subsets in synovium. These MPC-subsets, freshly isolated from synovium, did not express CD45 or CD31, but expressed CD73. Additionally, a sub-population of CD73+ cells also expressed CD90. CD45-CD31-CD73+CD90- cells were significantly more chondrogenic than CD45-CD31-CD73+CD90+ cells in the presence of TGFß1. Interestingly, reduced chondrogenic ability of CD73+CD90+ cells could be reversed by the addition of BMP2, showing discrete chondrogenic factor requirements by distinct cell-subsets. In addition, these MPCs had distinct anatomical localization; CD73 was expressed both in intimal and sub-intimal region while CD90 was enriched in the sub-intimal region. We further demonstrated that these subsets are also present in healthy synovium. CONCLUSIONS: We provide indications that primary MPCs in synovial intima and sub-intima are phenotypically and functionally distinct with different chondrogenic properties.

Mesenchymal stem cell secretome reduces pain and prevents cartilage damage in a murine osteoarthritis model.

Mesenchymal stem cells (MSCs) represent a promising biological therapeutic option as an osteoarthritis (OA)-modifying treatment. MSCs secrete factors that can counteract inflammatory and catabolic processes and attract endogenous repair cells. The effects of intra-articular injection of MSC secretome on OA-related pain, cartilage damage, subchondral bone alterations and synovial inflammation were studied in a mouse collagenase-induced OA model. The MSC secretome was generated by stimulating human bone-marrow-derived MSCs with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). 54 mice were randomly assigned to injections with i) MSC secretome from 20,000 MSCs, ii) 20,000 MSCs or iii) medium (control). Pain was assessed by hind limb weight distribution. Cartilage damage, subchondral bone volume and synovial inflammation were evaluated by histology. MSC-secretome- and MSC-injected mice showed pain reduction at day 7 when compared to control mice. Cartilage damage was more abundant in the control group as compared to healthy knees, a difference which was not found in knees treated with MSC secretome or MSCs. No effects were observed regarding synovial inflammation, subchondral bone volume or the presence of different macrophage subtypes. Injection of MSC secretome, similarly to injection of MSCs, resulted in early pain reduction and had a protective effect on the development of cartilage damage in a murine OA model. By using the regenerative capacities of the MSC-secreted factors, it will be possible to greatly enhance the standardisation, affordability and clinical translatability of the approach. This way, this biological therapy could evolve towards a true disease-modifying anti-osteoarthritic drug.

Is a high tibial osteotomy (HTO) superior to non-surgical treatment in patients with varus malaligned medial knee osteoarthritis (OA)? A propensity matched study using 2 randomized controlled trial (RCT) datasets.

OBJECTIVE: No randomized controlled trial (RCT) has compared the high tibial osteotomy (HTO) with non-surgical treatment in patients with medial knee osteoarthritis (OA) and varus malalignment. The aim was to compare the effectiveness of an unloader brace treatment or a usual care program to the HTO regarding pain severity and knee function. DESIGN: Surgical treatment (HTO) to two non-surgical options was compared by combining the data of two RCTs. One RCT (n = 117) compared an unloader brace to usual care treatment; the other RCT (n = 92) compared closing to opening wedge HTO. One-to-many propensity score matching was used to equalize patient characteristics. We compared clinical outcome at 1 year follow-up (VAS pain (0-10) and knee function (HSS, 0-100)) with mixed model analysis. RESULTS: Propensity score matching resulted in a comparison of 30 brace patient with 83 HTO patients, and of 28 usual care patients with 71 HTO patients. Pain at 1 year after HTO (VAS 3.8) was lower than after valgus bracing (VAS 5.0) with a mean difference of -1.1 (95% CI -2.2; -0.1). Function showed a nonsignificant mean difference of 2.1 [95% CI -3.1; 7.3]. Comparing HTO to usual care a difference was seen in pain (-1.7 [95% CI -2.8; -0.6]) and function (6.6 [95% CI 0.2; 13.1]), in favor of the HTO. CONCLUSIONS: Our data suggest that HTO was more effective in pain reduction compared to both non-surgical treatments. Function improved only when HTO was compared to usual care treatment. These small differences question the benefits of surgical treatment over the brace treatment.

Factors determining outcome of corrective osteotomy for malunited paediatric forearm fractures: a systematic review and meta-analysis.

The aim of this study was to identify predictors of a superior functional outcome after corrective osteotomy for paediatric malunited radius and both-bone forearm fractures. We performed a systematic review and meta-analysis of individual participant data, searching databases up to 1 October 2016. Our primary outcome was the gain in pronosupination seen after corrective osteotomy. Individual participant data of 11 cohort studies were included, concerning 71 participants with a median age of 11 years at trauma. Corrective osteotomy was performed after a median of 12 months after trauma, leading to a mean gain of 77° in pronosupination after a median follow-up of 29 months. Analysis of variance and multiple regression analysis revealed that predictors of superior functional outcome after corrective osteotomy are: an interval between trauma and corrective osteotomy of less than 1 year, an angular deformity of greater than 20° and the use of three-dimensional computer-assisted techniques. LEVEL OF EVIDENCE: II.

Influence of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) protocol on T2-mapping: is it possible to comprehensively assess knee cartilage composition in one post-contrast MR examination at 3 Tesla?

OBJECTIVE: To evaluate the possibility of assessing knee cartilage with T2-mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T). DESIGN: T2 mapping was performed in 10 healthy volunteers at baseline; directly after baseline; after 10 min of cycling; and after 90 min delay, and in 16 osteoarthritis patients before and after intravenous administration of a double dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol elements. Differences in T2 relaxation times between each timepoint and baseline were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed-rank tests and the smallest detectable change (SDC). RESULTS: After cycling, a significant change in T2 relaxation times was found in the lateral weight-bearing tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of interests (ROIs), absolute differences were small and lower than the corresponding SDCs. T2-mapping after contrast administration only showed statistically significantly lower T2 relaxation times in the medial posterior femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC. CONCLUSION: Because dGEMRIC protocol elements resulted in only small differences in T2 relaxation times that were not consistent and lower than the SDC in the majority of regions, our results suggest that T2-mapping and dGEMRIC can be performed reliably in a single imaging session to assess cartilage biochemical composition in knee osteoarthritis (OA) at 3 T.

[Metal-on-metal hip implant continues to be a source of concern]. / Metaal-op-metaal heupprothese blijft bron van zorg.

It has recently been suggested that patients with metal-on-metal (MOM) hip implants have an increased chance of mortality. These observations come from a meta-analysis including many small randomised controlled trials (RCTs) and cohort studies. Because of the high risk of bias there is no reason for great concern. In the Netherlands, the Dutch Orthopaedic Association (NOV) advised against the use of MOM implants in 2012, and that all patients with MOM implants should be followed up every year. There are good arguments to continue this policy because of the high risk of revision associated with MOM implants and the potential toxic effects of metal ions. There are also good reasons to follow up patients after a total hip procedure in which a large metal head (> 36 mm) has been used, because they also have increased metal ion release. The tragic story of MOM hip implants stresses that a minimum of 10 years of good clinical data should be required before widespread use of new hip implants is implemented.

Encapsulation of allogeneic mesenchymal stem cells in alginate extends local presence and therapeutic function.

Bone marrow derived mesenchymal stem cells (MSCs) have immunomodulatory and trophic capacities. For therapeutic application in local chronic inflammatory diseases, MSCs, preferably of allogeneic origin, have to retain immunomodulatory properties. This might be achieved by encapsulation of MSCs in a biomaterial that protects them from the host immune system. Most studies investigating the properties of MSCs for therapeutic application use short term cultures of cells in monolayer. Since the physical environment of MSCs can influence their functionality, we evaluated the feasibility of preserving the immunomodulatory properties of MSCs encapsulated in a three-dimensional alginate construct. After 5 weeks of implantation in immunocompetent rats, active allogeneic MSCs encapsulated in alginate were still detectable by Bio Luminescence Imaging and Magnetic Resonance Imaging of luciferase transduced and superparamagnetic iron oxide labelled MSCs. MSCs injected in saline were only detectable up to 1 week after injection. Moreover, the MSCs encapsulated in alginate responded to inflammatory stimuli similarly to MSCs in monolayer culture. In addition, MSC-alginate beads secreted immunomodulatory and trophic factors and inhibited T-cell proliferation after 30 d of in vitro culture. Our data indicate that allogeneic MSCs encapsulated in alginate persist locally and could act as an interactive immunomodulatory or trophic factor release system for several weeks, making this an interesting system to investigate for application in inflammatory disease conditions.

Value of quantitative MRI parameters in predicting and evaluating clinical outcome in conservatively treated patients with chronic midportion Achilles tendinopathy: A prospective study.

OBJECTIVES: To evaluate whether baseline MRI parameters provide prognostic value for clinical outcome, and to study correlation between MRI parameters and clinical outcome. DESIGN: Observational prospective cohort study. METHODS: Patients with chronic midportion Achilles tendinopathy were included and performed a 16-week eccentric calf-muscle exercise program. Outcome measurements were the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire and MRI parameters at baseline and after 24 weeks. The following MRI parameters were assessed: tendon volume (Volume), tendon maximum cross-sectional area (CSA), tendon maximum anterior-posterior diameter (AP), and signal intensity (SI). Intra-class correlation coefficients (ICCs) and minimum detectable changes (MDCs) for each parameter were established in a reliability analysis. RESULTS: Twenty-five patients were included and complete follow-up was achieved in 20 patients. The average VISA-A scores increased significantly with 12.3 points (27.6%). The reliability was fair-good for all MRI-parameters with ICCs>0.50. Average tendon volume and CSA decreased significantly with 0.28cm3 (5.2%) and 4.52mm2 (4.6%) respectively. Other MRI parameters did not change significantly. None of the baseline MRI parameters were univariately associated with VISA-A change after 24 weeks. MRI SI increase over 24 weeks was positively correlated with the VISA-A score improvement (B=0.7, R2=0.490, p=0.02). CONCLUSIONS: Tendon volume and CSA decreased significantly after 24 weeks of conservative treatment. As these differences were within the MDC limits, they could be a result of a measurement error. Furthermore, MRI parameters at baseline did not predict the change in symptoms, and therefore have no added value in providing a prognosis in daily clinical practice.

[Patient expectations and satisfaction concerning total knee arthroplasty]. / Verwachtingen en tevredenheid bij totale knieprothese.

BACKGROUND: Approximately 5-10% of patients is dissatisfied after a total knee arthroplasty. Several studies suggest that unrealistic expectations contribute to this; however, a systematic overview of the literature is missing. DESIGN: Systematic literature review METHOD: Using a systematic search strategy, prospective and retrospective studies with a follow-up of a minimum of six months, were obtained from PubMed publisher, MEDLINE, Embase, Cochrane, PsycINFO, CINAHL, and Web-of-Science. The search terms included 'total knee arthroplasty', 'preoperative expectations' and 'patient satisfaction'. Two reviewers independently selected the studies. Two reviewers independently conducted the quality assessment. Finally, a best evidence synthesis was performed. RESULTS: The search yielded 6802 studies, of which eight met the inclusion criteria. Limited evidence was found that there is no significant relation between expectations and satisfaction regarding limitations in recreation, walking distance, use of a walking aid and expected time to full recovery. Conflicting evidence was found that high expectations regarding general improvement, pain reduction and limitations in activities of daily living are associated with more dissatisfaction. Moderate evidence was found that patients with unfulfilled expectations were more often dissatisfied. CONCLUSION: Limited prospective research has been published on the relationship between expectations and patient satisfaction concerning total knee arthroplasty. The outcomes are very heterogenous and conclusions from these outcomes should be treated carefully. Future research needs to be more standardised and should utilise validated questionnaires.

Adverse events and survival after closing- and opening-wedge high tibial osteotomy: a comparative study of 412 patients.

PURPOSE: Varus medial knee osteoarthritis (OA) can be treated with a closing-wedge (CW) or opening-wedge (OW) high tibial osteotomy (HTO). Little is known about the adverse event (AE) rate of these techniques. The purpose of this study was to examine the AE rate and survival rate of a consecutive series of 412 patients undergoing CW- or OW-HTO. METHODS: Medical records were retrospectively screened, and all patients who underwent HTO from 1993 to 2012 at the Erasmus University Medical Centre were assessed with a self-administered questionnaire. Patients filled in the intermittent and constant osteoarthritis pain score, knee injury and osteoarthritis outcome score, and a general questionnaire focusing on AE. RESULTS: Medical records of 412 patients (354 CW- and 112 OW-HTOs) were screened. Of the 358 eligible patients, 291 (81 %) returned their questionnaire. A total of 80 AE (17 %) were found in 466 osteotomies. In the CW-group, 47 (13 %) serious adverse events (SAE) and 2 (0.6 %) AE were found. In the OW-group, 17 (15 %) SAE and 14 (13 %) AE were found. The most common AE was in 14 (4 %) patients of the CW-group sensory palsy of the common peroneal nerve. The most common AE in the OW-group was persistent pain at the iliac crest [11 (9.8 %) patients]. Hardware was removed in 48 % of the CW-osteotomies and 71 % of the OW-osteotomies (p < 0.05). The probability of survival was 75 % after 10 years in the CW-group versus 90 % in the OW-group (p < 0.05). In both groups, an equal number of patients were "in need for prosthesis" according to OARSI criteria. CONCLUSION: OW-HTO was associated with more AE than CW-HTO. OW-HTO resulted in better survival than CW-HTO. However, in both groups an equal number of patients were in need for prosthesis. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Incidence, prevalence, natural course and prognosis of patellofemoral osteoarthritis: the Cohort Hip and Cohort Knee study.

OBJECTIVE: To examine the proportion of isolated patellofemoral osteoarthritis (PFOA) compared to tibiofemoral osteoarthritis (TFOA) in middle-aged participants with early osteoarthritis (OA) symptoms of the knee; to describe the natural course of PFOA compared with that of TFOA and to identify whether patients with PFOA have a different phenotype compared to patients with TFOA, or with combined PFOA and TFOA (combined osteoarthritis (COA)). DESIGN: Participants with early OA symptoms of the knee were selected, completed questionnaires, underwent physical examination, and had knee radiographs at baseline, and at 2 and 5 years follow-up. Based on radiographs, participants were classified as having isolated TFOA, isolated PFOA, COA, or no radiographic OA. Multivariate logistic regression was used to identify participant characteristics associated with a specific group of OA at 2 years follow-up. RESULTS: The cohort comprised 845 participants (mean age 55.9 years). At baseline, 116 had PFOA, none had TFOA or COA. Of these 116 participants, 66.3% had developed COA at 5 years follow-up. At 2 years follow-up, PFOA, TFOA and COA were present in 77 (10.8%), 39 (5.5%) and 83 (11.6%) participants, respectively. Multivariate regression analyses at 2 years follow-up showed that participants with radiographic PFOA or TFOA were not significantly different from each other with respect to signs and symptoms. CONCLUSIONS: These results suggest that OA is more likely to start in the patellofemoral joint and then progress to COA in individuals with symptoms of early knee OA. No differences in TFOA and PFOA phenotypes were determined with respect to signs and symptoms.

Cartilage inflammation and degeneration is enhanced by pro-inflammatory (M1) macrophages in vitro, but not inhibited directly by anti-inflammatory (M2) macrophages.

OBJECTIVE: Macrophages play a crucial role in the progression of osteoarthritis (OA). Their phenotype may range from pro-inflammatory to anti-inflammatory. The aim of this study was to evaluate the direct effects of macrophage subtypes on cartilage by culturing macrophage conditioned medium (MCM) on human articular cartilage. DESIGN: Human OA cartilage explants were cultured with MCM of pro-inflammatory M(IFNγ+TNFα), or anti-inflammatory M(IL-4) or M(IL-10) human monocyte-derived macrophages. To assess effects of anti-inflammatory macrophages, the cartilage was cultured with a combination of MCM phenotypes as well as pre-stimulated with IFNγ+TNFα cartilage before culture with MCM. The reactions of the explants were assessed by gene expression, nitric oxide (NO) production and release of glycosaminoglycans (GAGs). RESULTS: M(IFNγ+TNFα) MCM affected OA cartilage by upregulation of IL1B (Interleukin 1ß), IL6, MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-5), while inhibiting ACAN (aggrecan) and COL2A1 (collagen type II). M(IL-10) upregulated IL1B and Suppressor of cytokine signaling 1 (SOCS1). NO production and GAG release by the cartilage was increased when cultured with M(IFNγ+TNFα) MCM. M(IL-4) and M(IL-10) did not inhibit the effects of M(IFNγ+TNFα) MCM of neither phenotype affected IFNγ+TNFα pre-stimulated cartilage, in which an inflammatory gene response was deliberately induced. CONCLUSION: M(IFNγ+TNFα) macrophages have a prominent direct effect on OA cartilage, while M(IL-4) and M(IL-10) do not inhibit the effects of M(IFNγ+TNFα), or IFNγ+TNFα induced inflammation of the cartilage. Therapies aiming at inhibiting cartilage degeneration may take this into account by directing suppression of pro-inflammatory macrophages or stimulation of anti-inflammatory macrophages.

Effectiveness of exercise therapy for meniscal lesions in adults: A systematic review and meta-analysis.

OBJECTIVES: This study evaluated the effectiveness of exercise therapy in patients with meniscal lesions. DESIGN: Systematic review and meta-analysis. METHODS: Nine databases were searched up to July 2015, including EMBASE and Medline OvidSP. Randomized and controlled clinical trials in adults with traumatic or degenerative meniscal lesions were considered for inclusion. Interventions had to consist of exercise therapy in non-surgical patients or after meniscectomy, and had to be compared with meniscectomy, no exercise therapy, or to a different type of exercise therapy. Primary outcomes were pain and function on short term (≤3 months) and long term (>3 months). Two researchers independently selected the studies, assessed the risk of bias, and extracted data. RESULTS: Of the 1415 identified articles 14 articles describing 12 studies were included; all had some concerns about the risk of bias. There was no significant difference between exercise therapy and meniscectomy for pain (MD 0.27 [-4.30,4.83]) and function (SMD -0.32 [-0.68,0.03]). After meniscectomy, there was conflicting evidence for the effectiveness of exercise therapy when compared to no exercise therapy for pain and function. There was no significant difference between various types of exercise therapy for pain (MD 19.30 [-6.60,45.20]) and function (SMD 0.01 [-0.27,0.28]). CONCLUSIONS: Exercise therapy and meniscectomy yielded comparable results on pain and function. Exercise therapy compared to no exercise therapy after meniscectomy showed conflicting evidence at short term, but was more effective on function at long term. The preferable type/frequency/intensity of exercise therapy remains unclear. The strength of the evidence was low to very low.