Cross-sectional and longitudinal association between types of meniscal pathology and knee pain: Data from the osteoarthritis initiative

s / Osteoarthritis and Cartilage 23 (2015) A82eA416 A277 434 CROSS-SECTIONAL AND LONGITUDINAL ASSOCIATION BETWEEN TYPES OF MENISCAL PATHOLOGY AND KNEE PAIN: DATA FROM THE OSTEOARTHRITIS INITIATIVE B. Eathakkattu Antony yz, J. Driban y, L.L. Price y, G.H. Lo x, R.J. Ward y, C.B. Eaton k, C. Ding z, T.E. McAlindon y. y Tufts Med. Ctr., Boston, MA, USA; zMenzies Res. Inst. Tasmania, Hobart, Australia; xMichael E. DeBakey VA Med. Ctr. and Baylor Coll. of Med., Houston, TX, USA; kBrown Univ. Sch. of Med., Providence, RI, USA Purpose: Meniscal pathology increases the risk for the incidence and progression of knee osteoarthritis but is only weakly related to knee pain. However, the association of meniscal pathology with knee pain has primarily been analyzed based on the presence or absence of meniscal pathology, which does not account for the type of meniscal pathology. We hypothesize that certain types of meniscal pathology may relate to knee pain andmay predict change in knee pain. The aim of this study was to explore the association of different types of knee meniscal pathology with knee pain and change in knee pain over 2 years. Methods: We selected a convenience sample of the Osteoarthritis Initiative (OAI) who had complete data for the OAI Bone Ancillary Project. The right knee was selected as the index knee unless there was a contraindication for magnetic resonance (MR) imaging. A single experienced fellowship trained musculoskeletal radiologist reviewed the 24-month OAI MR images for meniscal pathology by location (i.e., anterior, body, and posterior horn) within the medial and lateral menisci using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) meniscal tear classification system. For analyses, we reclassified the 10 original ISAKOS categories into 5 categories: normal, degenerative signal, morphological deformity, any tear (i.e., horizontal, horizontal flap, vertical-longitudinal, radial, radial-longitudinal, complex tear), and maceration. To replicate prior studies, we explored whether the presence or absence of any meniscal pathology in a knee was associated with pain. Total number of regions affected by meniscal pathology for each knee (0-6) was calculated by counting the number of regions that had pathologic findings. Knee pain was assessed using Western Ontario andMcMaster Osteoarthritis Index (WOMAC) scale at 24 and 48 months. Knee pain at 24 months was categorized into 3 categories: 1) no or little pain (WOMAC pain score 0 or 1), 2) mild pain (WOMAC pain score 2 or 3), 3) moderate-severe pain (WOMAC pain score > 3). Longitudinally, we categorized the change in pain into 3 categories based on the presence or absence of pain and a clinically meaningful change in pain (absolute change of 2 or relative change of 40%): 1) no pain or a meaningful decrease in pain (reference category), 2) pain but no change over time, and 3) meaningful increase in pain. Ordinal logistic regression was performed to determine the association of baseline meniscal pathology with knee pain and change in knee pain over 2 years. All models were adjusted for age, sex, and bodymass index (BMI). Results: 465 participants were included in the analysis with mean age of 63.2 (9.1) years, 53% male, mean BMI 29.5 (4.5) kg/m2, 71% KL grade >1⁄42, and 86% with any type of meniscal pathology. Tables below show the associations of meniscal pathology with knee pain (Table 1) and change in knee pain (Table 2). There was no association between presence of any meniscal pathology with knee pain or change in knee pain. Having all six meniscal regions affected with any pathology was associated with greater pain (OR:2.65) compared to those with normal menisci. However, having more affected meniscal regions was not related to an increase in pain. This pattern persisted when the number of regions affected by maceration was analyzed cross-sectionally and longitudinally. When we assessed the types of meniscal pathology, cross-sectionally, the only significant associationwas betweenmeniscal maceration and greater knee pain (OR:2.89). Longitudinally, there was a significant association between morphological deformity (OR:1.46) and increase in knee pain over 2 years. Removing surgery or injury cases did not change our results. Conclusions: These results suggest that meniscal maceration is associated with higher knee pain that may not change over time. However, we hypothesize that morphological deformity may lead to maceration over time, which may explain why morphologic deformity is associated with an increased pain over time. Further prospective studies are warranted to determine if discrete tear incidence is related to acute knee pain and if a subset of knees can then function without pain. Abstracts / Osteoarthritis and Cartilage 23 (2015) A82eA416 A278s / Osteoarthritis and Cartilage 23 (2015) A82eA416 A278 435 DECREASED NFAT1 EXPRESSION LEVEL PROMOTES THE ONSET AND PROGRESSION OF KNEE OSTEOARTHRITIS FOLLOWING MENISCAL DESTABILIZATION J. Wang, Y. Feng, Q. Hua, W. Kramer, N. Barnthouse. Univ. of Kansas Med. Ctr., Kansas City, KS, USA Purpose: The risk of posttraumatic osteoarthritis (PTOA) after joint injuries ranges from 20% to more than 50% evenwith the best current care of joint injuries. The risk of PTOA increases with age of patients, suggesting thatbiologic factorsmaybe involved in theprogressionof PTOA.However, the key biologic factors responsible for PTOA progression remain unclear. NFAT1 (NFATc2) is a member of the nuclear factor of activated T cells (NFAT) family of transcription factors originally identified as a regulator of the expression of cytokine genes during the immune response. Our recent studies revealed that mice lacking NFAT1 exhibit normal skeletal development but display dysfunction of articular chondrocytes and OA-like changes in adults,withearlyosteoarthritic changes in the knee joints after 6-8months of age. This study aimed to test our hypothesis that the global NFAT1 expression level affects the time of onset and progression of knee PTOAafter surgical destabilizationof themedialmeniscus (DMM) inmice. Methods: We generated bilateral DMM by surgical transection of the medial meniscotibial ligament (MMTL) in 2 to 3-month-old Nfat1 knockout (Nfat1-/-), Nfat1þ/-, and wild-type (WT) mice. All animal procedures were approved by the Institutional Animal Care and Use Committee. Animals were anesthetized by intra-peritoneal injection of ketamine and xylazine. Under a surgical microscope, the knee joint was exposed through a medial parapatellar incision under sterile conditions. The MMTL was transected with micro-surgical scissors to destabilize the medial meniscus. For sham surgery, the MMTL was visualized but not transected. The joint capsule was closed with 8-0 resorbable Vicryl sutures and the skin incision closed with 5-0 non-resorbable sutures. Operated animals were allowed caged mobility after surgery and were monitored to ensure healthy recovery. Animals were euthanized at 4, 8, and 16 weeks after surgery. The knee joints were harvested and processed for histochemical and histomorphometric analyses to evaluate the severity of knee osteoarthritis (OA). Articular cartilage samples harvested from the medial femoral condyle and medial tibial plateau were processed for gene expression analyses by quantitative real-time PCR (qPCR). Statistical analyses were performed with Student t-test and ANOVA. Results: Tissue sections stained with safranin-O and fast green were used for histomorphometric analyses to determine the severity of knee OA. We utilized a semi-quantitative OA grading scale as previously described (Glasson et al. Osteoarthritis Cartilage 2007; 15:1061). After the DMM surgery, Nfat1-/and Nfat1þ/mice displayed earlier onset of OA and significantly more severe OA in the knee joints than WT mice. The osteoarthritic changes such as cartilage lesions and chondroosteophyte formation were more apparent on the medial side than the lateral side of the knee joint in all three groups. Nfat1-/-, Nfat1þ/-, and WT mice receiving the sham surgery displayed focal loss of safranin-O staining in the articular cartilage of the knee joints at 4 and 8 weeks but recovered at 16 weeks without apparent osteoarthritic changes. qPCR analyses demonstrated that expression levels of Col10a1 (a marker of hypertrophic chondrocytes) and specific pro-inflammatory cytokines