M-P. Hellio Le Graverand

One year change of knee cartilage morphology in the first release of participants from the Osteoarthritis Initiative progression subcohort: association with sex, body mass index, symptoms and radiographic osteoarthritis status

Objective: The Osteoarthritis Initiative (OAI) is a multicentre study targeted at identifying biomarkers for evaluating the progression and risk factors of symptomatic knee OA. Here cartilage loss using 3 Tesla (3 T) MRI is analysed over 1 year in a subset of the OAI, together with its association with various risk factors. Methods: An age- and gender-stratified subsample of the OAI progression subcohort (79 women and 77 men, mean (SD) age 60.9 (9.9) years, body mass index (BMI) 30.3 (4.7)) with both frequent symptoms and radiographic OA in at least one knee was studied. Coronal FLASHwe (fast low angle shot with water excitation) MRIs of the right knee were acquired at 3 T. Seven readers segmented tibial and femoral cartilages blinded to order of acquisition. Segmentations were quality controlled by one expert. Results: The reduction in mean cartilage thickness (ThC) was greater (p = 0.004) in the medial than in the lateral compartment, greater (p = 0.001) in the medial femur (−1.9%) than in the medial tibia (−0.5%) and greater (p = 0.011) in the lateral tibia (−0.7%) than in the lateral femur (0.1%). Multifactorial analysis of variance did not reveal significant differences in the rate of change in ThC by sex, BMI, symptoms and radiographic knee OA status. Knees with Kellgren–Lawrence grade 2 or 3 and with a BMI >30 tended to display greater changes. Conclusions: In this sample of the OAI progression subcohort, the greatest, but overall very modest, rate of cartilage loss was observed in the weight-bearing medial femoral condyle. Knees with radiographic OA in obese participants showed trends towards higher rates of change than those of other participants, but these trends did not reach statistical significance.

Urinary CTX-II levels are associated with radiographic subtypes of osteoarthritis in hip, knee, hand, and facet joints in subject with familial osteoarthritis at multiple sites: the GARP study

Objective: To assess the relation between the urinary concentrations of type II collagen C-telopeptide (UCTX-II) and radiographic signs of osteoarthritis (ROA) in the GARP (Genetics, Arthrosis and Progression) study. Methods: UCTX-II levels were measured in GARP study participants, who are sibling pairs predominantly with symptomatic osteoarthritis at multiple sites. Kellgren and Lawrence scores were used to assess ROA in the knees, hips, hands, and vertebral facet joints, and spinal disc degeneration. A proportionate score was made for each joint location, based on the number of joints with ROA. The sum total ROA score represents a measure of cartilage abnormalities within each patient. By using linear mixed models the total ROA score and the joint site specific ROA scores were correlated with the UCTX-II level. Results: In 302 subjects the mean (SD) and median (range) for UCTX-II were 265 (168) and 219 (1346) ng/mmol creatine, respectively. There was a significant association between the total ROA score and UCTX-II levels. Subsequent multivariate analysis showed that the joint site specific ROA score at all joint sites, except for spinal disc degeneration, contributed independently to this association. Conclusions: The total ROA score of GARP patients, representing cartilage abnormalities at the most prevalent ROA joint locations, showed an excellent correlation with UCTX-II levels. The specific ROA scores at the hip, hand, facet, and knee joints additively and independently explained this association. Even in patients with osteoarthritis at multiple sites, UCTX-II may be a sensitive quantitative marker of ROA.

Progressive increase in body mass index is not associated with a progressive increase in joint space narrowing in obese women with osteoarthritis of the knee

Objective: Given that obesity is a risk factor for osteoarthritis (OA) of the knee, a study was undertaken to determine whether progressively higher body mass index (BMI) among obese women is associated with progressive increases in joint space narrowing (JSN). Methods: Medial compartment JSN over 12 months in Lyon Schuss radiographs of 60 obese women (BMI 30.0–50.5 kg/m2) with radiographic and symptomatic OA was compared with that in 81 non-obese women (BMI <28 kg/m2) with normal radiographs and minimal or no symptoms of knee OA. Results: Among the patients with OA, higher BMI tended to be associated with a higher Kellgren and Lawrence (KL) grade of OA severity. JSN in the non-obese controls was negligible, but in the 30 patients with KL grade 2 and KL grade 3 knees, mean (SD) JSN was 0.12 (0.31) mm and 0.32 (0.50) mm, respectively (p<0.005 and p<0.001). No association was seen between baseline BMI and 12-month JSN in patients with OA; indeed, the regression plot suggested a slight inverse relationship between the two. Conclusions: In obese patients with OA, progressively higher BMI values were not accompanied by a progressively increasing rate of JSN. Joint loading was not evaluated, but it is possible that marked obesity limited the functional capacity of some subjects with OA, protecting their knees from loading. For investigators considering eligibility criteria for a trial of a structure-modifying OA drug, these data suggest that recruitment of patients with a BMI much higher than 30 kg/m2 will not enrich the sample of subjects who will have more rapid JSN than those with a BMI of only 30 kg/m2.

427 DEPTH AS WELL AS SIZE OF BONE MARROW LESIONS MAY PREDICT ADJACENT CARTILAGE LOSS

and the 3D volumes of BMEL were calculated. The signal intensity (SI) increase of BMEL versus normal bone marrow (NBM) was calculated as: (SIBMEL-SINBM)/SINBM×100%. Cartilage degeneration was graded using modified Whole-Organ MRI Score (WORMS) in each compartment as well as in cartilage overlying BMELs in the FSE images. Cartilage was segmented semi-automatically in SPGR images. Five compartments were defined: patellar, lateral/medial femoral condyle (LFC/MFC), lateral/medial tibia (LT/MT). 3D cartilage contour was overlaid to aligned T1ø maps. T1ø values were calculated from each defined compartments, as well as from cartilage overlying BMEL. A Student’s t-test was used to compare the overall cartilage T1ø values between patients with and without BMEL. A paired t-test was used to compare the T1ø and clinical grading between BMEL-overlying cartilage and surrounding cartilage, respectively. The Pearson correlation coefficients were calculated between BMEL-overlying cartilage T1ø and BMEL volume, and between BMELoverlying cartilage T1ø and BMEL SI increase, respectively. Results: Twenty-five BMELs were found in 16 patients (volume 2.88±3.21 cm3; SI increase 265%±110%): 11 in patella, 8 in LFC, 3 in MFC, 2 in MT and one in LT. The overall T1ø values were significantly increased in patients with BMEL compared with those without BMEL (42.5±3.8ms vs 39.6±1.1ms, P=0.012). In patients with BMEL, both T1ø values and WORMS grading were significantly elevated in BMELoverlying cartilage compared to surrounding cartilage (49.5±4.3ms vs 43.3±4.0ms, P< 0.001 for T1ø, and 4.7±1.7 vs 1.2±1.6, P< 0.001 for WORMS grading). Increased T1ø values in BMEL-overlying cartilage were correlated with increased SI of BMEL (R=0.54, P=0.005), but not correlated with BMEL volume (R=0.1, P = 0.63). No significant differences were found in KL and WOMAC gradings between patients with and without BMELs in this population. Conclusions: Patients with BMEL showed overall higher T1ø values in cartilage compared with those who had no BMEL, suggesting BMEL may be correlated with disease severity of OA. Furthermore, in patients with BMEL, both T1ø values and WORMS grading were elevated in BMELoverlying cartilage, suggesting a local spatial correlation between BMEL and more advanced cartilage degeneration. Interestingly, we found the degree of T1ø elevation in BMEL-overlying cartilage is correlated with signal intensity increase of BMEL, but not with the volume of BMEL.

P269 THE RELATIONSHIP BETWEEN RADIOGRAPHIC MEASUREMENT OF JOINT SPACE WIDTH AND MRI MEASUREMENTS OF CARTILAGE THICKNESS AND VOLUME IN OSTEOARTHRITIC AND CONTROL KNEES

M-P. Hellio Le Graverand1, M. Kloppenburg2, S. Botha-Scheepers3, P. Kornaat4, N. Riyazi3, F. Breedveld2, R. Buck1, S. Totterman5, J. Tamez5, E. Vignon6 1Pfizer Global Research and Development, Ann Arbor, MI, 2Rheumatology, Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands, 3Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands, 4Radiology, Leiden University Medical Centre, Leiden, The Netherlands, 5VirtualScopics Inc, Rochester, NY, 6Universite Claude Bernard, Lyon, France