Changes in bone area discriminated people with OA from controls and was more responsive than the current and impending standards for assessing OA progression. The shape change in OA bone provides a new window on OA pathogenesis and a focus for clinical trials.

s u m m a r yBackground: To investigate changes in knee 3D bone shape over the first 5 years after acute anterior cruciate ligament (ACL) injury in participants of the randomized controlled KANON-trial. Methods: Serial MR images over 5 years from 121 young (32 women, mean age 26.1 years) adults with an acute ACL tear in a previously un-injured knee were analyzed using statistical shape models for bone. A matched reference cohort of 176 individuals was selected from the Osteoarthritis Initiative (OAI). Primary endpoint was change in bone area of the medial femoral condyle; exploratory analyses compared results by treatment and examined other knee regions. Comparisons were made using repeated measures mixed model ANOVA with adjustment for age, sex and body mass index (BMI). Results: Mean medial femur bone area increased 3.2% (78.0 [95% CI 70.2 to 86.4] mm 2 ) over 5 years after ACL injury and most prominently in knees treated with ACL reconstruction (ACLR). A higher rate of increase occurred over the first 2 years compared to the latter 3-years (66.2 [59.3 to 73.2] vs 17.6 [12.2 to 23.0] mm 2 ) and was 6.7 times faster than in the reference cohort. The pattern and location of shape change in the extrapolated KANON data was very similar to that observed in another knee-osteoarthritis cohort. Conclusion: 3D shape modelling after acute ACL injury revealed rapid bone shape changes, already evident at 3 months. The bone-change pattern after ACL injury demonstrated flattening and bone growth on the outer margins of the condyles similar to that reported in established knee osteoarthritis.

Objective.Accurate automated segmentation of cartilage should provide rapid reliable outcomes for both epidemiological studies and clinical trials. We aimed to assess the precision and responsiveness of cartilage thickness measured with careful manual segmentation or a novel automated technique.Methods.Agreement of automated segmentation was assessed against 2 manual segmentation datasets: 379 magnetic resonance images manually segmented in-house (training set), and 582 from the Osteoarthritis Initiative with data available at 0, 1, and 2 years (biomarkers set). Agreement of mean thickness was assessed using Bland-Altman plots, and change with pairwise Student t test in the central medial femur (cMF) and tibia regions (cMT). Repeatability was assessed on a set of 19 knees imaged twice on the same day. Responsiveness was assessed using standardized response means (SRM).Results.Agreement of manual versus automated methods was excellent with no meaningful systematic bias (training set: cMF bias 0.1 mm, 95% CI ± 0.35; biomarkers set: bias 0.1 mm ± 0.4). The smallest detectable difference for cMF was 0.13 mm (coefficient of variation 3.1%), and for cMT 0.16 mm(2.65%). Reported change using manual segmentations in the cMF region at 1 year was −0.031 mm (95% CI −0.022, −0.039), p < 10−4, SRM −0.31 (−0.23, −0.38); and at 2 years was −0.071 (−0.058, −0.085), p < 10−4, SRM −0.43 (−0.36, −0.49). Reported change using automated segmentations in the cMF at 1 year was −0.059 (−0.047, −0.071), p < 10−4, SRM −0.41 (−0.34, −0.48); and at 2 years was −0.14 (−0.123, −0.157, p < 10−4, SRM −0.67 (−0.6, −0.72).Conclusion.A novel cartilage segmentation method provides highly accurate and repeatable measures with cartilage thickness measurements comparable to those of careful manual segmentation, but with improved responsiveness.

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