The relationship between two different measures of osteoarthritis bone pathology, bone marrow lesions and 3D bone shape: data from the osteoarthritis initiative

Abstract

Purpose: Magnetic resonance imaging (MRI) has provided great insights into the development of OA, and helped highlight the importance of subchondral bone pathology. Bone shape and bone marrow lesions (BMLs) represent different features of MRI-detected subchondral pathology in osteoarthritis (OA) and while BMLs are well studied the relationship between these two remains poorly understood. It is important to understand if they represent a single construct or different parts of the OA process, and to further explore their use as imaging biomarkers. The aim of this study was to determine how these features are related and how they change in OA progression. Methods: 600 participants from the FNIH Biomarkers Initiative of the OAI were included, having Kellgren–Lawrence (KL) 1, 2 or 3 at baseline and MRI data at baseline and 24 months. MRI images obtained from the OAI were scored for BMLs using the semi-quantitative MOAKS system that scores 3 features using an ordinal scale for size, number of BMLs and percentage of lesion that is a BML as opposed to a cyst. Quantitative 3D bone shape data was provided by Imorphics (Manchester, UK) using active appearance models (AAMs) applied separately for femur and tibia from 3T DESS-we images. The shape vector for each bone was calculated by taking the principal components of the mean non-OA shape and the mean OA shape and the vector was normalised by setting the mean OA shape to +1 and mean non-OA shape as −1, with each unit increase of 1 representing 1 standard deviation (SD) calculated in non-OA knees. Four BML scores were computed: “BML total size”, “BML total number”, “BML total sub regions” and BML maximum size”. At baseline the correlation between the BML scores and bone shape measures were assessed using Spearman`s correlation coefficients. The association between 3D quantitative bone shape vectors and BMLs at baseline was analysed using linear regression. Presence of a BML was defined as BML total size ≥ 1. Responsiveness was calculated for both features in 4 pre-defined progression groups and reported as standardised response means (SRMs).Due to nesting of repeated measurements within individuals, multilevel linear modelling was used to assess the longitudinal relationship between change in BML size and change in bone shape vector. Results: Mean age was 61.5, 59% were female and mean BMI was 30.7. Correlation between baseline femur shape vector and femur BML total size was r = 0.28, P < 0.001 and similar for the tibia. Linear models revealed an association between presence of a femur BML at baseline and baseline 3D femur vector in both univariable and multivariable models (adjusted coefficient 0.49, 95% CI 0.30, 0.68) indicating a more positive femur vector (indicative of “increased OA”) in individuals with BMLs at baseline, with a difference equivalent to 0.5 × SD of non-OA knees. Longitudinally bone shape demonstrated more responsiveness to change than all BML measures (SRM 0.89 vs 0.13) for femur bone shape vector vs BML total size respectively (Table 1). Univariable growth models revealed that bone shape vector tended to be more positive over time (indicating worsening) while BML total size reduced over time. Multilevel models also showed that an increase in BML size was related to a more positive bone shape vector (representing worsening OA). Conclusions: There is a relationship between bone shape and BMLs, with increasing OA bone shape vector associated with higher prevalence of BMLs. Bone shape vector demonstrated greater responsiveness than semi-quantitative BMLs over time periods typical of a clinical trial.Table 1Responsiveness of bone shape and BML measures over 24 monthsRadiographic and pain progression N = 194Radiographic progression only N = 103Pain progression only N = 103No progression N = 2002 year responsiveness, SRM (95%CI)Bone shapeFemur0.89 (0.72,1.02)1.02 (0.85,1.20)0.46 (0.31,0.61)0.61 (0.49,0.72)Tibia0.84 (0.70,0.97)0.76 (0.56,0.96)0.26 (0.07,0.43)0.47 (0.33,0.69)BMLsFemur BML total size−0.13 (−0.26,0.02)−0.15 (−0.35,0.07)−0.31 (−0.51,−0.13)−0.24 (−0.37,0.13)Femur BML total number0.38 (0.26,0.50)0.20 (−0.02,0.41)0.17 (−0.04,0.35)0.27 (0.14,0.38)Tibia BML total size0.11 (−0.02,0.26)0.14 (−0.04,0.31)−0.04 (−0.23,0.15)−0.01(−0.16,0.11)Tibia BML total number0.37 (0.24,0.51)0.31 (0.12,0.51)0.19 (0.00,0.33)0.16 (0.02,0.29)Femur BML maximum size−0.05 (−0.19,−0.09)−0.01 (−0.19,0.21)−0.20 (−0.38,0.01)−0.11 (−0.25,0.02)BML total sub regions−0.02 (−0.15,0.13)−0.03 (−0.23,0.15)−0.13 (−0.32,0.07)−0.06 (−0.20,0.08) Open table in a new tab