s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S59 89 SPATIAL VARIATION IN THE OCCURRENCE OF OSTEOARTHRITIC LESIONS ON THE BABOON DISTAL FEMUR IS DEPENDENT ON AGE AND SEX T.L. Bredbenner y, S.M. Levine z, J.A. Harris z, T.E. Macrini x, H.B. Coan k, L.M. Havill z, D.P. Nicolella y. y Southwest Res. Inst., San Antonio, TX, USA; z Texas BioMed. Res. Inst., San Antonio, TX, USA; x St. Mary’s Univ., San Antonio, TX, USA; kWestern Carolina Univ., Cullowhee, NC, USA Purpose: Osteoarthritis (OA) is the most common form of arthritis and the major cause of activity limitation and physical disability in older people. It is widely believed that OA results from the local mechanical environment of the joint and, particularly, the cartilage, in combination with systemic susceptibility to the disease. Preliminary study of knee OA in the baboon demonstrated that knee OA occurs commonly and naturally in male and female adults and the frequency of OA in older baboons is comparable to that in older humans. The objective of this study was to determine whether the patterns of occurrence of osteoarthritic lesions in the distal femur were related to age and sex. Methods: The right femur was collected from baboons at routine necropsy (Southwest National Primate Research Center/Texas Biomedical Research Institute; cause of death was unrelated to this study). The study sample included 123 males (16.53 5.13 years) and 300 females (18.94 5.95 years). Animals were categorized as young for age 21.7 years (w65 human years), and the remainder were categorized as middle-aged. For each animal, the distal right femur was macroscopically examined following established methods and the presence and location of any existing lesions were graded (1-4, ranging from normal to severe) and recorded on normalized maps of the articular cartilage surface. This process resulted in a total of 423 cartilage defect maps which were examined on a pointwise basis using multinomial logistic regressions to determine whether variation in cartilage grades were related to age, sex or age x sex interaction. The probability of correlation was color coded at each surface point as the statistical p-map of differences for each test variable. Correlation p-maps were corrected for multiple comparisons using the false discovery rate (FDR) method with a false discovery rate of 0.05. Additionally, a statistical trait model, based on a principal component analysis, was used to describe the spatial variation of defect grades by reducing the w490,000 highly correlated variables for each defect map to a set of 422 uncorrelated and independent principal components (e.g. composite defect traits) without loss of information. Two-way unbalanced analyses of variance were used to test the principal component weighting factors for dependence on age, sex, and age x sex. Results: Uncorrected correlation p-maps demonstrated substantial pointwise variation in the strength of correlations between cartilage grade and age, sex, and age x sex (Figure 1). FDR correction of p-values for multiple comparisons yielded a critical p-value of 0.013 for the pmap showing correlation with age, resulting in 26.1% of the tests being significant (primarily those in the medial femoral condyle). After correction, none of the pointwise tests were significant for correlation between grade and sex or age x sex. Of the 422 principal components generated, 65 were significantly dependent on age, 13 on sex, and 21 on age x sex interaction. Conclusions: Statistical p-maps demonstrated significant correlations with age, particularly in the medial femoral condyle; whereas no significant correlations were demonstrated with sex and age x sex after correction for multiple comparisons. However, it appears that statistical trait modeling may offer a promising pathway towards understanding Figure 1. Perlecan Expression as a Function of Bovine Donor Age Figure 2. Perlecan Expression as a Function of Bovine Donor Age in 2 Year
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