An important development in osteoarthritis imaging has been the ability to assess joint space width (JSW) from weight bearing CT (WBCT). The value of combining JSW with subchondral bone parameters in disease assessment is less well understood, particularly with respect to disease phenotype. To investigate associations of worsening medial and lateral tibiofemoral compartment structural disease over 2 years with a multivariate combination of baseline 3-D JSW and bony parameters from WBCT. WBCT knee imaging was acquired at the 144-month visit of the Multicenter Osteoarthritis Study along with same-visit and 2-year follow-up medial and lateral OARSI joint space narrowing (JSN) grade. After semi-automatic segmentation of 663 available knees, joint space mapping delivered 3-D JSW maps. Cortical bone mapping was performed to measure trabecular attenuation (TA), endocortical thickness (ET), and subchondral thickness (ST) at the femoral (f) and tibial (t) surfaces. A template was registered to each individual joint surface, a 3-D statistical shape model created, and all 7 spatially co-located parameters transferred to the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of JSW plus each bone parameter in turn on the experimental variables of 2-year medial and lateral OARSI JSN worsening. One knee per participant was used, selecting the side with greater JSN worsening, randomly if equal. 10 knees did not have radiographic grading, so the analysis used single knees from 394 individuals. 218 were female, mean ± SD age was 63.5 ± 9.6 years, mass 82.7 ± 17.7 kg, height 170 ± 9 cm, and BMI 28.5 ± 5.0 kg/m2. SPM results (figs 1-4 below) revealed significant parameter ROIs in the lateral tibiofemoral compartment that were associated with worsening of medial and lateral OARSI JSN grade at 2 years. Baseline lateral compartment JSW was significantly wider by up to ∼1 mm (unmasked lateral compartment blue zone in fig. 1) in combination with lower baseline tTA by up to ∼25 attenuation units (AU) (unmasked lateral compartment red zone in fig. 2) for each increment in future medial JSN over 2 years. The reverse was demonstrated for future lateral JSN with narrower baseline lateral JSW by up to ∼1 mm (unmasked lateral compartment red zone in fig. 3) in combination with higher baseline tTA by up to ∼25 AU (unmasked lateral compartment blue zone in fig. 4) for each grade of future lateral JSN over 2 years. Baseline JSW was significantly narrower at the lateral margin of the lateral compartment by up to ∼1 mm in combination with thicker tST and fST by up to ∼0.2 mm for each grade of future lateral JSN (not shown). Baseline medial 3-D JSW did not relate to any substantial significant future narrowing for any JSW-bone parameter combination for future medial or lateral JSN. ET results (with JSW) were very similar to those for ST at both sides of the joint. 3-D JSW analysed in combination with bone parameters at the lateral (but not medial) tibiofemoral compartment are significantly related to future medial and lateral OARSI JSN grade. Lower lateral compartment tTA (with higher JSW) is related to future medial JSN and may be an effect of trabecular remodelling from reduced lateral loading, while greater thickness of subchondral and endocortical bone in the lateral compartment (alongside lower JSW) can be explained by subchondral sclerosis. These results suggest the lateral compartment warrants closer attention for following both medial and lateral compartmental progression. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: [email protected].
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