Assessment of hip structure and musculature using MRI and DXA images from TASOAC cohort

Introduction Osteoarthritis (OA) is a multifactorial musculoskeletal disorder and its aetiology is under investigation. Current research and therapeutic interventions for hip OA are limited. In early or advanced stages of hip OA, imaging techniques can be used to scrutinize overall structural and muscular changes in the joint such as bone marrow lesions (BMLs), hip cartilage defects, hip effusion-synovitis, bone shape and muscle health. Investigating these factors can provide information on interactive pathways vital for understanding the aetiology of OA. This thesis reports the results of six such investigations. Materials and Methods The Tasmanian Older Adult Cohort (TASOAC) is a large population based cohort study initiated in 2002. Older adults aged 50-80 years (51% female, mean age 62yrs) were enrolled into the study at baseline (Phase 1) with a first follow-up approximately 3 years later (Phase 2), a second follow up (Phase 3) approximately 5 years from baseline and a third follow up (Phase 4) approximately 10 years from baseline. Hip and knee pain was assessed using the WOMAC (Western Ontario and McMaster Universities Osteoarthritis). Pedometers and a dynamometer were used to measure physical activity and muscle strength respectively. Hip structural abnormalities and hip muscle cross-sectional area (CSA) were assessed from MRI scans. Bone mineral density (BMD) was estimated by dual-energy x-ray absorptiometry (DXA). Morphological shape of the hip was assessed by Active Shape Modelling (ASM) imaging software and radiographic hip OA (ROA) was determined from X-rays. Results The first two studies focus on hip BMLs and their cross-sectional and longitudinal associations with hip and knee pain, high cartilage signal and BMD. Overall, the proportion of hip BMLs at the femoral and/or acetabular site was 28%. About 8% of the population had a large hip BML. In the first study, those with large hip BMLs had greater hip pain. Incidence of larger hip BMLs (femoral and acetabular) was associated with an increase in hip pain. On the other hand, resolution of femoral BMLs was associated with a decrease in knee pain. Additionally, 1 S.D increase in hip BML size was associated with worsening hip pain. High cartilage signal intensity was strongly associated with hip BMLs but not with hip pain. This study identified that hip BMLs associate not only with hip and knee pain but also with early changes in the hip cartilage. In the second study, irrespective of size, hip BMLs were found to be associated with local (total hip and femoral neck) BMD but not with distant (spine) BMD. Femoral BMLs were associated with higher femoral neck BMD while acetabular BMLs were associated with lower hip and femoral neck BMD. This novel study suggests that hip BMLs located in two different compartments might represent bone areas undergoing different pathological changes. In the third study, correlates of hip cartilage defects were examined. About 76% of the subjects had a hip cartilage defect. Any and grade 2 hip cartilage defects were associated with higher prevalence of hip pain. Any hip cartilage defects associated with lower muscle strength, particularly among men. The associations of grade 1 defect with high cartilage signal were stronger for men than for women. However, associations between grade 1 defects and BMLs were equivalent in both sexes. Grade 2 defects were linked with several outcomes such as hip BML, larger hip effusion-synovitis and hip ROA (in men), and lower steps per day. This study indicates that cartilage defects/damage, especially grade 2 hip cartilage defects are associated with major clinical and structural risk factors relevant to hip OA even in the general population. The fourth study describes the cross-sectional and longitudinal correlates of hip effusion-synovitis. Cross-sectionally, presence of hip effusion-synovitis at multiple sites was associated with presence of hip pain, and hip cartilage defects were associated with greater hip effusion-synovitis CSA. No other associations were found. Longitudinally, independently of each other, persistent hip BMLs and incident hip cartilage defects predicted larger hip effusion-synovitis size. However, change in hip pain from baseline to follow up and baseline hip ROA were not associated with hip effusion-synovitis. Additionally, baseline hip cartilage defects were associated with worsening hip BMLs at follow up. Similarly, baseline hip BMLs were associated with hip cartilage defects at follow-up. Overall, these results suggest that hip cartilage defects, hip BMLs and hip effusion-synovitis share possible causal pathways and the extent of hip effusion-synovitis might influence hip pain. The fifth study explored the link between hip musculature (hip muscle CSA), muscle strength and bone mass (BMD). Among older adults, hip flexor CSA had the strongest association with BMD of the hip. The associations for pectineus and sartorius hip muscles CSA with BMD were stronger for women in comparison to men. Most of hip muscles CSA were associated with muscle strength and muscle strength was weakly associated with BMD. These findings suggest that for older adults, muscle bulk contributes to hip bone mass more so than muscle strength and maintaining muscle mass would aid in preservation of bone health. The sixth and the final study focused on hip morphology (shape) and its associations with various outcomes. Using Active shape modelling (ASM) imaging software and SHAPE software, hip shape was assessed and the first six principal components (modes) describing the variations in measurements of hip shape were extracted. These modes explained 68% of total hip shape variations in the sample population. At baseline, modes 1, 2, 4 and 6 were associated with hip ROA, modes 1, 3, 4 and 6 correlated with hip cartilage volume and all except mode 2 with muscle strength. Higher mode 1, and lower mode 3 and 6 scores at baseline predicted greater hip pain at follow-up and higher mode 1 and mode 2 scores were associated with hip effusion-synovitis. Greater scores for modes 2 (decreasing acetabular coverage) and 4 (non-spherical femoral head) at baseline predicted 10-year total hip replacement (THR); while mode 4 alone correlated with bone marrow lesions (BMLs), effusion-synovitis, and increased cartilage signal. Conclusions Overall, structural changes are slow and relatively uncommon in the preclinical stages of hip OA. Nevertheless, hip BMLs, hip cartilage defects, high cartilage signal and hip effusion-synovitis are inter-related and contribute to changes in the subchondral bone; with a probable role in the pathogenesis of hip OA. Additionally, muscle bulk and strength could aid in preservation of bone density and assessing bone shape using ASM could benefit in improving assessment and monitoring of disease progression and identifying those at higher risk of OA.

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