Study protocol for a randomised placebo controlled trial of platelet-rich plasma injection to prevent post-traumatic knee osteoarthritis after anterior cruciate ligament reconstruction.

INTRODUCTION: The elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction. METHODS AND ANALYSIS: This will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20-49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass index<35 and Kellgren Lawrence osteoarthritis grade<2. The primary outcome will include MRI-T2 values of knee cartilage at 6 months. The secondary outcomes will include pain assessment by Visual Analogue Scale, Knee injury and Osteoarthritis Outcome Score, blood and urine test, physical findings, measurements for muscle strength and joint stability. ETHICS AND DISSEMINATION: The study was approved by The Independent Ethics Committee for Clinical Trials of the Japanese Association for the Promotion of State-of-the-Art Medicine. Results of the trial and each of the outcomes will be shared via conferences and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTb030200391.

Apple polyphenols exhibits chondroprotective changes of synovium and prevents knee osteoarthritis.

Apple polyphenols (AP) have strong antioxidant and anti-inflammatory properties. We examined the effects of AP on the progression of osteoarthritis (OA) AP was administered to surgically-induced OA model rats for 4 or 8 weeks. This treatment suppressed inflammation and oxidative stress in the synovium, resulting in a decrease in the OA severity score, and the expression of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-13 in the synovium. It was suggested that long-term administration of AP may be effective for the treatment of OA. In addition, superoxide dismutase (SOD) activity was enhanced in serum samples by AP. AP or its constituent procyanidin B2 (PC) were added to HIG-82 synoviocytes. The results showed that AP enhanced cell proliferation and hyaluronan production. This indicates that AP may improve synovial conditions in OA and suppress OA progression. These effects may be attributed to the antioxidant and anti-inflammatory properties of AP.

A comparison of three strategies to reduce the burden of osteoarthritis: A population-based microsimulation study.

OBJECTIVES: The purpose of this study was to compare three strategies for reducing population health burden of osteoarthritis (OA): improved pharmacological treatment of OA-related pain, improved access to joint replacement surgery, and prevention of OA by reducing obesity and overweight. METHODS: We applied a validated computer microsimulation model of OA in Canada. The model simulated a Canadian-representative open population aged 20 years and older. Variables in the model included demographics, body mass index, OA diagnosis, OA treatment, mortality, and health-related quality of life. Model parameters were derived from analyses of national surveys, population-based administrative data, a hospital-based cohort study, and the literature. We compared 8 what-if intervention scenarios in terms of disability-adjusted life years (DALYs) relative to base-case, over a wide range of time horizons. RESULTS: Reductions in DALYs depended on the type of intervention, magnitude of the intervention, and the time horizon. Medical interventions (a targeted increase in the use of painkillers) tended to produce effects quickly and were, therefore, most effective over a short time horizon (a decade). Surgical interventions (increased access to joint replacement) were most effective over a medium time horizon (two decades or longer). Preventive interventions required a substantial change in BMI to generate a significant impact, but produced more reduction in DALYs than treatment strategies over a very long time horizon (several decades). CONCLUSIONS: In this population-based modeling study we assessed the potential impact of three different burden reduction strategies in OA. Data generated by our model may help inform the implementation of strategies to reduce the burden of OA in Canada and elsewhere.

Microbial chondroitin sulfate in experimental knee osteoarthritis model investigation of chondroprotective effect.

OBJECTIVE: Chondroitin sulfate (CS) is a glycosaminoglycan with proven anti-inflammatory, anti-apoptotic, anti-oxidant properties. CS increases type II collagen and proteoglycan synthesis in human joint chondrocytes. CS can reduce the production of pro-inflammatory mediators and proteases to improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM). Due to these characteristics, it is a natural compound that is considered to be Symptomatic Slow-Acting Drugs for Osteoarthritis (SYSADOA). Microbial chondroitin sulfate (MCS) was produced from two different bacterial sources using biotechnological methods by our team. In this study, we aimed to apply microbially produced CS and bovine-derived commercial CS forms to rabbit knees with osteoarthritis experimentally and to evaluate the results. MATERIALS AND METHODS: In this study, a cruciate ligament cutting model was applied to 40 New Zealand rabbits to induce experimental osteoarthritis. Four weeks after the surgical procedure, rabbits were divided into 4 groups as control, animal-derived MCS, E coli-derived MCS and PaJC-derived MCS group. The standard rabbit diet was fed to the control group, and the other groups were additionally fed 17 mg/kg/day CS/MCS for 12 weeks. The rabbits were sacrificed at the 12th week after surgery and the preparations obtained were evaluated histopathologically. RESULTS: As a result, it was observed that regeneration tissue was statistically significant in histopathological cartilage tissue compared to the control group of CS developed from different sources given to rabbits with osteoarthritis. It was determined that among the CS groups produced from different sources, the group with the highest chondroprotective effect was MCS originating from E.coli. CONCLUSIONS: This vegan product (MCS), which we obtained as a result of our study, was produced by our team from a microbial source. According to our analysis, it has the potential to be an effective alternative therapy agent in the treatment of osteoarthritis.

The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair.

Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using a Gli1 reporter line, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1-lineage cells. Normally, meniscal tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh agonist right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.

Conditioned medium of IGF1-induced synovial membrane mesenchymal stem cells increases chondrogenic and chondroprotective markers in chondrocyte inflammation.

Recently, mesenchymal stem cells (MSCs) have been the most explored cells for cell therapy for osteoarthritis (OA) that can be obtained from various sources. Synovial membrane MSCs (SMMSCs) provide best potential for OA therapy, however they are not widely explored. Conditioned medium of SMMSCs (SMMSCs-CM) rich in growth factors and cytokines can inhibit apoptosis and increase chondrocytes cell proliferation. The aim of the present study was to determine growth factors content in SMMSCs-CM as well as the chondrogenic and chondroprotective markers expression in OA model after insulin-like growth factor (IGF)1-induced and non-induced SMMSCs-CM treatments. Chondrocyte cell line (CHON002) was induced by IL1ß as OA model (CHON002 with IL1ß (IL1ß-CHON002)) and treated with SMMSCs-CM with or without IGF1 induction to determine its effectiveness in repairing OA cells model. ELISA was used to assay BMP2, fibroblast growth factor 18 (FGF18) and transforming growth factor (TGF) ß1 (TGFß1) levels in SMMSCs-CM, matrix metalloproteinase (MMP) 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4) levels in OA cells model treated with SMMSCs-CM. RT-qPCR analyses were used to investigate the gene expression of SOX9, COL2, and COL10. CM from SMMSCs cultured and induced by IGF1 150 ng/mL was the most effective concentration for increasing the content of growth factor markers of SMMSCs-CM, which had successfully increased negative cartilage hypertrophy markers (SOX9 and COL2) and reduced hypertrophy markers (COL10, MMP13, and ADAMTS4). Preconditioning with IGF1 has better and very significant results in lowering MMP13 and ADAMTS4 levels. The present study supports IGF1 pre-conditioned SMMSCs-CM to develop a new therapeutic approach in OA improvement through its chondrogenic and chondroprotective roles.

Remodified Mason-Allen suture technique concomitant with high tibial osteotomy for medial meniscus posterior root tears improved the healing of the repaired root and suppressed osteoarthritis progression.

PURPOSE: To evaluate the results of the remodified Mason-Allen suture technique concomitant with high tibial osteotomy (HTO) for medial meniscal posterior root tears (MMPRTs). The hypothesis was that this procedure would improve clinical results, prevent progression of knee osteoarthritis and increase the healing rate of the repaired root. METHODS: Total 17 patients of mean 51.5 ± 4.4 years who were underwent this combined procedure for MMPRT completed this study. Lysholm and Hospital for Special Surgery (HSS) scores, Kellgren-Lawrence (KL) grade reflecting osteoarthritis progression were evaluated preoperatively and at the last follow-up. Medial meniscus extrusion (MME) was measured on magnetic resonance imaging preoperatively and at mean 26.1 ± 2.3 months postoperatively. Second-look arthroscopy was performed at mean 25.1 ± 5.3 months postoperatively. The healing status of the repaired root was classified as complete, partial and failed healing. The Outerbridge (OB) grade of the medial femoral condyle (MFC) was compared between index surgery and second-look arthroscopy. RESULTS: Mean follow-up duration was 66.4 ± 6.5 months. Mean Lysholm and HSS mean scores improved significantly from preoperatively to the last follow-up: Lysholm: 56.9 ± 5.4 to 83.5 ± 6.0 (P < 0.001); HSS: 56.1 ± 6.0 to 81.7 ± 7.7 (P < 0.001). The mean mechanical alignment of the lower extremity was corrected from varus to the neutral range at the last follow-up. The preoperative KL grade was not significantly different from the KL grade at the last follow-up (P = 0.071). On MRI, mean MME increased from 3.0 ± 0.7 mm to 3.1 ± 0.7 mm (P = 0.046). Second-look arthroscopy showed 64.7% complete, 29.4% partial and 5.9% failed healing of the repaired root. The initial OB grade of the MFC showed no progression (P = 0.103). CONCLUSIONS: The remodified Mason-Allen suture technique concomitant with HTO for MMPRTs significantly improved clinical outcomes and suppressed OA progression at 66.4 months. However, this procedure produced limited complete healing of the repaired roots in 64.7% of patients. LEVEL OF EVIDENCE: IV.

Arthroscopic partial meniscectomy for a degenerative meniscus tear: a 5 year follow-up of the placebo-surgery controlled FIDELITY (Finnish Degenerative Meniscus Lesion Study) trial.

OBJECTIVES: To assess the long-term effects of arthroscopic partial meniscectomy (APM) on the development of radiographic knee osteoarthritis, and on knee symptoms and function, at 5 years follow-up. DESIGN: Multicentre, randomised, participant- and outcome assessor-blinded, placebo-surgery controlled trial. SETTING: Orthopaedic departments in five public hospitals in Finland. PARTICIPANTS: 146 adults, mean age 52 years (range 35-65 years), with knee symptoms consistent with degenerative medial meniscus tear verified by MRI scan and arthroscopically, and no clinical signs of knee osteoarthritis were randomised. INTERVENTIONS: APM or placebo surgery (diagnostic knee arthroscopy). MAIN OUTCOME MEASURES: We used two indices of radiographic knee osteoarthritis (increase in Kellgren and Lawrence grade ≥1, and increase in Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing and osteophyte sum score, respectively), and three validated patient-relevant measures of knee symptoms and function (Western Ontario Meniscal Evaluation Tool (WOMET), Lysholm, and knee pain after exercise using a numerical rating scale). RESULTS: There was a consistent, slightly greater risk for progression of radiographic knee osteoarthritis in the APM group as compared with the placebo surgery group (adjusted absolute risk difference in increase in Kellgren-Lawrence grade ≥1 of 13%, 95% CI -2% to 28%; adjusted absolute mean difference in OARSI sum score 0.7, 95% CI 0.1 to 1.3). There were no relevant between-group differences in the three patient-reported outcomes: adjusted absolute mean differences (APM vs placebo surgery), -1.7 (95% CI -7.7 to 4.3) in WOMET, -2.1 (95% CI -6.8 to 2.6) in Lysholm knee score, and -0.04 (95% CI -0.81 to 0.72) in knee pain after exercise, respectively. The corresponding adjusted absolute risk difference in the presence of mechanical symptoms was 18% (95% CI 5% to 31%); there were more symptoms reported in the APM group. All other secondary outcomes comparisons were similar. CONCLUSIONS: APM was associated with a slightly increased risk of developing radiographic knee osteoarthritis and no concomitant benefit in patient-relevant outcomes, at 5 years after surgery. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01052233 and NCT00549172).

Assessment of Free-Living Cadence Using ActiGraph Accelerometers Between Individuals With and Without Anterior Cruciate Ligament Reconstruction.

CONTEXT: Anterior cruciate ligament reconstruction (ACLR) and gait speed are risk factors for developing knee osteoarthritis (OA). Measuring minute-level cadence during free-living activities may aid in identifying individuals at elevated risk of developing slow habitual gait speed and, in the long term, OA. OBJECTIVE: To assess differences in peak 1-minute cadence and weekly time in different cadence intensities between individuals with and without ACLR. DESIGN: Cross-sectional study. SETTING: Short-term, free-living conditions. PATIENTS OR OTHER PARTICIPANTS: A total of 57 participants with ACLR (34 women, 23 men; age = 20.9 ± 3.2 years, time since surgery = 28.7 ± 17.7 months) and 42 healthy control participants (22 women, 20 men; age = 20.7 ± 1.7 years). MAIN OUTCOME MEASURE(S): Each participant wore a physical activity monitor for 7 days. Data were collected at 30 Hz, processed in 60-second epochs, and included in the analyses if the activity monitor was worn for at least 10 hours per day over 4 days. Mean daily steps, peak 1-minute cadence, and weekly minutes spent at 60 to 79 (slow walking), 80 to 99 (medium walking), 100 to 119 (brisk walking), ≥100 (moderate- to vigorous-intensity ambulation), and ≥130 (vigorous-intensity ambulation) steps per minute were calculated. One-way analyses of covariance were conducted to determine differences between groups, controlling for height and activity-monitor wear time. RESULTS: Those with ACLR took fewer daily steps (8422 ± 2663 versus 10 033 ± 3046 steps; P = .005) and spent fewer weekly minutes in moderate- to vigorous-intensity cadence (175.8 ± 116.5 minutes versus 218.5 ± 137.1 minutes; P = .048) than participants without ACLR. We observed no differences in minutes spent at slow (ACLR = 77.4 ± 40.5 minutes versus control = 83.9 ± 34.3 minutes; P = .88), medium (ACLR = 71.6 ± 40.2 minutes versus control = 82.9 ± 46.8 minutes; P = .56), brisk (ACLR = 115.3 ± 70.3 minutes versus control = 138.3 ± 73.3 minutes; P = .18), or vigorous-intensity (ACLR = 24.3 ± 36.5 minutes versus control = 38.1 ± 60.9 minutes; P = .10) cadences per week. CONCLUSIONS: Participants with ACLR walked approximately 40 fewer minutes per week in moderate- to vigorous-intensity cadence than participants without ACLR. Increasing the time spent at cadence ≥100 steps per minute and overall volume of physical activity may be useful as interventional targets to help reduce the risk of early development of OA after ACLR.

Huoxuezhitong capsule ameliorates MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway.

Huoxuezhitong capsule (HXZT, activating blood circulation and relieving pain capsule), has been applied for osteoarthritis since 1974. It consists of Angelica sinensis (Oliv.) Diels, Panax notoginseng (Burkill) F. H. Chen ex C. H., Boswellia sacra, Borneol, Eupolyphaga sinensis Walker, Pyritum. However, the direct effects of HXZT on osteoarthritis and the underlying mechanisms were poorly understood. In this study, we aimed to explore the analgesia effect of HXZT on MIA-induced osteoarthritis rat and the underlying mechanisms. The analgesia and anti-inflammatory effect of HXZT on osteoarthritis in vivo were tested by the arthritis model rats induced by monosodium iodoacetate (MIA).. Mechanistic studies confirmed that HXZT could inhibit the activation of NF-κB and down-regulate the mRNA expression of related inflammatory factors in LPS-induced RAW264.7 and ATDC5 cells. Furtherly, in LPS-induced RAW264.7 cells, HXZT could suppress NF-κB via inhibiting PI3K/Akt pathway. Taken together, HXZT capsule could ameliorate MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway.

L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study.

The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)ß-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1ß (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1ß-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1ß-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.

Investigation of the efficacy of daidzein in experimental knee osteoarthritis-induced with monosodium iodoacetate in rats.

BACKGROUND: Osteoarthritis (OA) is a degenerative chronic illness that most frequently occurs in the knee joint. Daidzein (DZ) an isoflavone has anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effectiveness of DZ as a treatment for experimental knee OA (KOA) in rats. METHOD: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. Thereafter, 49 Wistar albino male rats (250-300 g, 12-16 weeks old) were randomly divided into 7 groups: C (healthy control); DC (KOA + saline); hyaluronic acid (HA); HA+ intraarticular (ia) DZ; oral (po) DZ; ia DZ; HA + po DZ groups. DZ and/or HA were administered intraarticularly to the rats as 50 µL on days 1, 7, 14, and 21. Alternatively, the DZ was administered orally as 0.5 mL twice daily for 21 days. After the treatment, rats were sacrificed by decapitation under general anesthesia. Serum samples were analyzed to determine the total oxidant status (TOS) and total antioxidant status (TAS) and the levels of TNF-α, IL-1ß, MMP-13, and DZ. Knee joint samples underwent histopathological examination, and TNF-α, IL-1ß, NOS2, and MMP-13 were analyzed with immunohistochemical methods. RESULTS: HA, DZ, and DZ + HA effectively reduced the levels of TNF-α, IL-1ß, and MMP-13 in the serum of the DC group (p < 0.001). In groups that received HA, DZ, or DZ + HA, the serum TAS increased compared with the DC group (p < 0.05). When the DZ + HA combination was used, a more pronounced reduction in the levels of TNFα, NOS2, IL-1ß, and MMP-13 was observed in knee joints. In addition, the cracks on the cartilage surface and fibrillation were completely improved in the groups that received HA, DZ, or DZ + HA compared with the DC group. CONCLUSION: DZ had anti-inflammatory and antioxidant effects in a rat OA model. Therefore, DZ, as monotherapy or especially in combination with HA, may be a promising and beneficial therapy for OA. Key Points •DZ has been shown to reduce TNF-α, IL-1ß, and MMP-13 both in serum and in tissue samples taken from the knee-joints. •The cracks on the cartilage surface and fibrillation in KOA were completely improved by using DZ and DZ + HA combination. •DZ may be useful to eliminate/reduce/ameliorate inflammation and oxidative damage in the pathogenesis of KOA. •DZ, alone or in combination with HA, may be a promising natural compound with beneficial effects in the treatment of KOA.

Lateral meniscal cysts: long-term clinical and radiological results of a partial meniscectomy and percutaneous decompressive needling.

INTRODUCTION: The aim of this study was to describe clinical and radiological long-term results of an arthroscopic partial meniscectomy associated with an outside-in decompressive needling of the cyst for lateral parameniscal cyst. METHODS: Eighteen patients with symptomatic parameniscal cysts treated between April 2002 and September 2009 were retrospectively included in the study. All patients underwent arthroscopic partial meniscectomy (preserving peripheral rim) and needling of the cyst using a 20-gauge needle. Pre- and post-operative IKDC, Tegner, and Lysholm scores were used to evaluate clinical results. Radiological results were obtained from pre- and post-operative radiographies and post-operative MRI scans. Both supine and weight bearing MRI examinations were performed. Kellgren-Lawrence and WORMS scales were used to evaluate osteoarthritis development of the knee. RESULTS: The mean follow-up period was 11.6 ± 2.6 years (range 7-15). Horizontal lesions were found in 56% of patients. All patients fully recovered. Mean Lysholm scores passed from mean pre-operative value 52 ± 16.9 to post-operative 85 ± 11.9 (P < 0.01) and mean IKDC scale score changed from 49.5 ± 14.7 to 67 ± 23.5 (P < 0.01). Mean Tegner scores did not change significantly. Post-operative radiographies showed a Kellgren-Lawrence scale grade 0 in six patients (33%), a grade I in eight (44%), a grade II in three (17%), and a grade III in one patient (6%). No patients were found with a Kellgren-Lawrence scale grade IV. No significant differences with pre-operative radiographies were found (chi-square = 1.867; df = 3; P = 0.60) in osteoarthritis development of the knee. Reported WORMS scores had an average of 12.4 ± 5.1. No recurrence of any cysts was observed. DISCUSSION: Different treatments for lateral meniscal cysts have been proposed, but proper management of the cyst is still controversial. The results of this study suggest that the outside-in needling of the cyst associated with partial meniscectomy is a highly effective, simple, and repeatable technique. Excellent clinical outcomes were reported at a mean follow-up of 11.6 ± 2.6 years (range 7-15). Imaging evaluation showed no significant evolution to osteoarthritis of the knee. CONCLUSIONS: Partial arthroscopic meniscectomy associated with percutaneous decompressive needling of the cyst wall under arthroscopic visualization showed positive clinical and radiological long-term results. Neither traditional radiographies nor innovative standing MRIs showed findings of osteoarthritis.

Patellar Bone-Tendon-Bone Autografts versus Quadriceps Tendon Allograft with Synthetic Augmentation in a Canine Model.

Patellar bone-tendon-bone (pBTB) autografts are often considered the "gold standard" for complete anterior cruciate ligament (ACL) reconstruction and are also associated with significant complications and early-onset knee osteoarthritis (OA). A novel quadriceps tendon allograft with synthetic augmentation, or "internal brace" (QTIB), has been reported to have potential advantages for ACL reconstruction based on animal model data. In this preclinical canine comparison study, we hypothesized that QTIB allograft compared with pBTB autograft would provide superior durability for knee stability, function, and prevention of OA. Under approval from our Institutional Animal Care and Use Committee, adult purpose-bred research hounds (n = 10) underwent arthroscopic complete transection of the ACL followed by either an arthroscopic-assisted all-inside ACL reconstruction using the QTIB allograft (n = 5) or pBTB autograft (n = 5). Contralateral knees were used as nonoperated controls (n = 10). Radiographic and arthroscopic assessments were performed at 2 and 6 months, respectively, after surgery. Anterior drawer, internal rotation, lameness, kinetics, pain, effusion, and comfortable range of knee motion were measured at 2, 3, and 6 months. Biomechanical and histologic assessments were performed at 6 months. All reconstructed knees were stable and had intact ACL grafts 6 months after surgery. At 6 months, QTIB reconstructed knees had significantly less lameness, lower pain, less effusion, and increased range of motion when compared with BTB knees (p < 0.05). BTB knees had significantly higher radiographic OA scores than QTIB knees at 6 months (p < 0.05). Superior outcomes associated with QTIB allograft may be due to the lack of donor site morbidity, the use of a robust tendon graft, and/or protection of the graft from the synthetic augmentation. Robust tendon grafts combined with a synthetic internal brace and platelet-rich plasma (PRP) may allow for more rapid and robust tendon-bone healing and graft "ligamentization," which protects the graft from early failure and rapid OA development that can plague commonly-used allografts.

Does surgery reduce knee osteoarthritis, meniscal injury and subsequent complications compared with non-surgery after ACL rupture with at least 10 years follow-up? A systematic review and meta-analysis.

OBJECTIVE: We compared long-term follow-up from surgical versus non-surgical treatment of ACL rupture regarding radiographic knee osteoarthritis (OA), secondary surgery, laxity and patient-reported outcome measures (PROMs). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, MEDLINE, CINAHL and the Cochrane Library databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies directly comparing the minimally invasive surgical (arthroscopy or miniarthrotomy) and non-surgical treatment of ACL rupture with at least 10 years of follow-up in adult patients were included. RESULTS: Five studies met the eligibility criteria. A meta-analysis revealed a higher risk of radiographic knee OA and a lower risk of secondary meniscal surgery for patients in the surgical group. The risk of graft rupture/secondary ACL revision and secondary ACL reconstruction was equal in the surgical and non-surgical groups. Knee laxity was lower among patients in the surgical group in four studies. No difference was found in the PROMs (ie, International Knee Documentation Committee, Tegner, Knee Injury and Osteoarthritis Outcome, and Lysholm scores). CONCLUSION: The risk of radiographic knee OA was higher, but the risk of secondary meniscal injury was lower 10 years after surgical treatment of ACL rupture. The risk of graft rupture/secondary ACL revision or secondary reconstruction was unrelated to treatment type. The degree of knee laxity was reduced after surgical treatment in comparison with non-surgical treatment, while PROMs were similar. However, due to the methodological challenges highlighted in this systematic review, these findings must be interpreted with caution. PROSPERO REGISTRATION NUMBER: CRD42019119468.

Injury of the Meniscus Root.

Meniscus root tears biomechanically disrupt normal joint loading and lead to joint overload with the possible development of spontaneous osteonecrosis of the knee and early-onset osteoarthritis. Proper identification and treatment of meniscal root tears has been proven to restore joint loading and improve patient outcomes.

Meniscal Allograft Transplants.

Meniscus allograft transplantation is an established surgical treatment indicated in symptomatic meniscus-deficient patients with minimal to no arthritis. Treatment decision making should be individualized after a thorough history and physical examination, with diagnostic imaging and arthroscopy to assess the status of the meniscus. The senior author prefers to use a bridge-in-slot technique, where osseous fixation of the allograft is completed through passage of a bone bridge to a tibial slot. Outcomes in meniscus allograft transplantation are favorable, with reported significant improvements in clinical outcome and low failures in short- and midterm follow-up studies.

Meniscus Scaffolds for Partial Meniscus Defects.

The meniscus is a crucial player in knee joint homeostasis. Loss of meniscus tissue can result in early onset of clinical symptoms like pain and loss of function, and structural degeneration of the articular cartilage. In case of a symptomatic segmental defect of the medial or lateral meniscus, different innovative options using biological or synthetic scaffolds are now available to regenerate meniscuslike tissue, with the aim of allowing a satisfactory clinical improvement to patients. However, the role of any of these procedures in terms of chondroprotection is questionable, and the overall outcomes in the long term still can be improved.

Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model.

The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.

Effects of a valgus unloader brace in the medial meniscectomized knee joint: a biomechanical study.

BACKGROUND: Patients undergoing total or partial arthroscopic meniscectomy for treating traumatic meniscal tears are at greater risk of developing knee osteoarthritis (OA) due to increased mechanical load. The purpose of this study was to evaluate the effects of a valgus unloader brace in the medial meniscectomized knee joint during the gait cycle. METHODS: A three-dimensional finite element model of the knee joint was developed using the substructures segmented from magnetic resonance images. Experimentally measured forces and moments for one complete gait cycle, without brace and with brace at three different alignment angles (0°, 4°, and 8°), were applied to the finite element model, and the changes in the tibiofemoral contact mechanics were estimated. RESULTS: The brace in 0°/4°/8° valgus alignment modes reduced the total contact force in the medial compartment by 16%/46%/82% at opposite toe off and 18%/17%/29% at opposite initial contact events, while it increased the total contact force in the lateral compartment by 31%/81%/110% at opposite toe off and 30%/38%/45% at opposite initial contact events, respectively, when compared to the unbraced meniscectomized knee. CONCLUSIONS: Increasing the valgus alignment from 0° to 4° and 8° resulted in a greater reduction of contact conditions (total contact force, total contact area, peak contact pressure) in the medial compartment and vice versa in the lateral compartment. This decrease in contact conditions in the medial compartment infers enhanced knee joint function due to a valgus unloader brace, which translates to increased knee-related confidence. Results suggest choosing a higher valgus alignment angle could potentially increase the risk for the onset of osteoarthritis in the lateral compartment, and this computational model could be used in validating the effectiveness of braces on joint health.