438 MACROSCOPIC AND HISTOPATHOLOGIC ANALYSIS OF HUMAN KNEE MENISCI IN AGING AND OSTEOARTHRITIS

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438 MACROSCOPIC AND HISTOPATHOLOGIC ANALYSIS OF HUMAN KNEE MENISCI IN AGING AND OSTEOARTHRITIS
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  S202  Poster Presentations/Osteoarthritis and Cartilage 19S1 (2011) S53 – S236 437SIDE DIFFERENCES OF THIGH MUSCLE CROSS SECTIONAL AREASIN KNEES WITH THE SAME RADIOGRAPHIC OA (KL) GRADE, BUT UNILATERAL FREQUENT PAIN T. Dannhauer 1,2 , M. Sattler 1,2 , M. Hudelmaier 1,2 , A.M. S¨anger 3 ,D.J. Hunter 4 , K. Kwoh 5 , F. Eckstein 1,2 .  1 Paracelsus Med. Univ., Salzburg, Austria;  2 Chondrometrics GmbH, Ainring, Germany;  3 Salzburg Univ.,Salzburg, Austria;  4 Univ. of Sydney, Sydney, Australia;  5 Univ. of Pittsburghand Pittsburgh VAHS, Pittsburgh, PA, USA Purpose:  It has been reported that thigh muscle status, specificallyanatomical cross sectional areas (ACSAs) and maximal force, may play arole in the onset and progression of knee OA. It is, however, less clearwhether changes in ACSAs and muscle force are associated with OA “perse”, or with knee pain (that is associated with knee OA). As many, butnot all knees with radiographic OA (rOA) are painful, we aim to take afirst step in disentangling the above relationships by studying whetherthe pain status in knees with OA is associated with differences in thighmuscle status.Our objectives therefore are (1) to determine whether ACSAs of thethigh extensors, flexor, and adductors display significant side-differences(same person) between the knee with frequent pain (i.e. painful knees)vs. those without pain (i.e. painless knees) with the same rOA grade (i.e.calculated KLG2 or 3, from OARSI atlas graded osteophyte and JSN status);(2) to analyze whether extensor and flexor muscle forces show significantside-differences in painful vs. painless rOA knees, and (3) to examine thecorrelation between force and ACSAs in painful vs. painless rOA knees. Methods:  A between-knee, within-person design was used to studyknees with frequent pain (most days of the month within the past12 months; P01SxKOA = 2) versus knees without pain P01SxKOA =0 ),in participants with the same rOA grade (P01OAGRD: KLG2 or 3) inboth knees. All cases satisfying these criteria (that did not show achange in pain frequency  > 1 grade within the next 12 months) weredrawn from the 4796 Osteoarthritis Initiative (OAI) participants (public-use data sets 0/1.2.2): 31 women, 17 men (n=48; age 45–78 years).Public use MRI data (0.E.1.: T1-weighted SE sequence) and customsoftware were used to determine the ACSAs of the extensors, flexorsand adductors in the axial image that was located at 35% of the femorallength (from distal to proximal; estimated based on body height) and inthe two adjacent images (0.5cm proximal and 0.5cm distal). The vastusmedialis (VMO) MSCA was determined in a slice located at 31% (distalto proximal). Maximal isometric extensor (V00_R/L_EmaxF) and flexorforces (V00_R/L_FmaxF) were taken from the OAI data base. These weremeasured using an isometric chair (Metitur Oy, Jyvaskyla, Finland). Apaired t-test was used to compare between painful and contra-lateralpainless knees within participants. Results:  Painful knees showed significantly lower extensor ACSAs (49.6vs. 52.6cm2; −6.2%; p=0.00003), VMO ACSAs (16.5 vs. 17.6cm2; −7.8%;p=0.0007) and maximal extensor muscle forces (331 vs. 364 N; −15.4%;p=0.003) compared with contra-lateral painless knees. In contrast, therewere no significant differences in flexor and adductor ACSAs or flexorforces (all p > 0.39). Results were similar in men and women, and inKLG2 and KLG3 knees. The maximal force per unit ACSA tended to belower in painful vs. painless knees (6.55 vs. 6.87 N/cm2, p=0.058 forthe extensors, and 4.39 vs. 4.48 N/cm2, p=0.57 for the flexors) butthe differences did not reach statistical significance. The correlationsbetween extensor force vs. extensor ACSA were r=0.64 in painful andr=0.66 in painless knees, those between flexor force vs. flexor ACSAr=0.44 in painful and r=0.52 in painless knees, and those betweenextensor and flexor force 0.69 in painful and 0.79 in painless knees.Again, the correlations were similar in men and women and in KLG2and KLG3 knees. Conclusions:  Knees with rOA and frequent knee pain demonstratereduced extensor muscle ACSAs and force compared to contra-lateralrOA knees without knee pain, but no differences in flexor ACSAs andforce, or adductor ACSAs. Further longitudinal studies are needed todetermine whether muscle status is “cause or consequence” of kneepain. Nevertheless, the current findings provide support to quadricepsstrengthening programs for knee pain in rOA. 438MACROSCOPIC AND HISTOPATHOLOGIC ANALYSIS OF HUMAN KNEEMENISCI IN AGING AND OSTEOARTHRITIS C. Pauli 1 , S.P. Grogan 2 , S. Patil 2 , S. Akihiko 1 , J. Koziol 1 , M.K. Lotz 1 ,D.D. D’Lima 2 .  1 The Scripps Res. Inst., La Jolla, CA, USA;  2 Scripps Hlth., La Jolla, CA, USA Purpose:  Meniscus lesions following trauma or associated withosteoarthritis (OA) have been described, yet meniscus aging has not beensystematically analyzed. The objectives of this study were to (i) establishstandardized protocols for representative macroscopic and microscopicanalysis, (ii) improve existing scoring systems, and (iii) apply thesetechniques to a large number of human menisci. Methods:  Medial and lateral menisci from 107 human knees wereobtained and cut in two different planes (triangle/cross-section andtransverse/horizontal) in three separate locations (mid portion, anteriorand posterior horns). All sections included vascular and avascular regionsand were graded for i) surface integrity, ii) cellularity, iii) matrix/fiberorganization and collagen alignment, and iv) Safranin-O stainingintensity. The cartilage in all knee compartments was also scored. Results:  The new macroscopic and microscopic grading systems showedhigh inter-reader and intra-reader intra-class correlation coefficients. Themajor age-related changes in menisci in joints with no or minimal OAincluded increased Safranin-O staining intensity, decreased cell density,the appearance of acellular zones, and evidence of mucoid degenerationwith some loss of collagen fiber organization. The earliest meniscuschanges occurred predominantly along the inner rim. Menisci fromOA joints showed severe fibrocartilaginous separation of the matrix,extensive fraying, tears and calcification. Abnormal cell arrangementsincluded decreased cellularity, diffuse hypercellularity along with cellularhypertrophy and abnormal cell clusters. In general, the anterior horns of both medial and lateral menisci were less affected by age and OA. Conclusions:  New standardized protocols and new validated gradingsystems allowed us to conduct a more systematic evaluation of changesin aging and OA menisci at a macroscopic and microscopic level.Several meniscus abnormalities appear to be specific to aging in theabsence of significant OA. With aging the meniscal surface can be intactbut abnormal matrix organization and cellularity was observed withinthe meniscal substance. The increased Safranin-O staining appears torepresent a shift from fibroblastic to chondrocytic phenotype duringaging and early degeneration. 439MOLECULAR ANALYSIS OF AGE- AND SEX-RELATED GENE EXPRESSIONIN HUMAN MENISCAL TEARS WITH AND WITHOUT CONCOMITANT  ANTERIOR CRUCIATE LIGAMENT TEAR  M.F. Rai, R.H. Brophy, Z. Zhang, A. Torgomyan, L.J. Sandell.  Dept. of Orthopaedic Surgery, Washington Univ. Sch. of Med., St. Louis, MO, USA Purpose:  The meniscus plays a critical protective role for the knee jointby contributing to load transmission, shock absorption and joint stability.Little is known about gene expression in meniscal tears, particularly asit relates to injury pattern and patient age and sex. The purpose of this study was to test the hypothesis that gene expression in meniscaltears varies depending on patient age and sex and whether the anteriorcruciate ligament (ACL) is also torn. Methods:  Meniscal tissue explants (n=28) were removed at the time of clinically indicated partial meniscectomy in patients with meniscal tear(MT) alone or combined with ACL tear (MT+ACL tear). mRNA expressionwas examined by quantitative real-time PCR for several molecularmarkers of osteoarthritis (OA) including pro-inflammatory cytokines(IL-1 a , IL-1 b , IL-6, TNF a ), chemokines (IL-8, CCL3, CCL3L1, CXCL1,CXCL3, CXCL6, CCL20), aggrecanases (ADAMTS-4, -5), metalloproteinases(MMP-1, -3, -9, -13), transcription factors (NF 󰃺  B2, NF 󰃺  BIA, I 󰃺  BA) andmatrix components (BMP-2, Col1a1, Col2a1, aggrecan). Results:  Expression of ADAMTS-4 (p=0.003), -5 (p=0.001), MMP-1(p=0.007), -9 (p=0.002), -13 (p=0.01) and NF 󰃺  B2 (p=0.01) wassignificantly higher in MT patients under 40 (Fig. 1A). Similarly, theexpression of ADAMTS-4 (p=0.002) and -5 (p=0.02), and MMP-1(p=0.02) and -13 (p=0.002) was higher in MT+ACL patients  < 40(Fig. 1B). In MT+ACL tear patients, the expression of IL-1 b  (p=0.01), TNF a (p=0.02), MMP-13 (p=0.004), CCL3 (p=0.03), and CCL3L1 (p=0.03) wassignificantly higher while that of aggrecan (p=0.03) was lower than inpatients with only meniscal tears (Fig. 1C). The only sex-based difference
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