Novel approaches to musculoskeletal disease

Osteoarthritis (OA) is the most common musculoskeletal disease, affecting not only articular cartilage but also the subchondral bone and surrounding soft tissues. OA affects ~8% of the Australian population. It is a major cause of disability and poor quality of life. Importantly, there is currently no cure for OA. Radiography has long been considered the gold standard for measuring OA. However, the use of magnetic resonance imaging (MRI) is increasingly common, given its non-invasive nature, ability to directly visualise articular cartilage in vivo, and lack of exposure to radiation. MRI has enabled the study of OA along the disease continuum, from its asymptomatic stages through to established and end-stage disease. A number of the risk factors that influence OA as well as the underlying pathogenesis of disease are still unclear. Thus this thesis aims to contribute to current knowledge by examining novel relationships in musculoskeletal disease. This thesis includes community-based populations as well as osteoarthritic populations to allow examination of structural changes not only in the presence of disease but also before disease development or at early stages of disease. Papers 1 and 2 examined the relationship between bone marrow lesions (BMLs) and subchondral bone cysts, and how they influence progression of disease in tibiofemoral OA. BMLs and cysts were found to commonly co-exist, with 98% of participants who had a cyst also having a BML. Importantly, those with both a BML and cyst had worse structural outcomes than those with a BML only, or those with neither BML nor cyst. Paper 3 examined the patellofemoral compartment to determine how patellofemoral geometry is associated with knee pain and patella cartilage volume. A more medially inclined patella was associated with reduced pain and increased medial patella cartilage volume. On the other hand, a higher riding patella was associated with detrimental effects on medial patella cartilage. Paper 4 aimed to better understand the role of obesity in musculoskeletal disease. Gaining ≥ 5% of body weight over ~2 years was associated with incident knee symptoms (pain, stiffness and functional difficulties) compared to remaining stable in weight, whilst losing ≥ 5% of body weight was associated with improved knee symptoms. Similar effects were seen in relation to knee structure, whereby those who gained weight had increased cartilage loss whilst those who lost weight had reduced cartilage loss. Paper 5 examined the role of obesity in the foot, and describes the differential contributions of different components of body composition. Whilst fat mass was positively associated with foot pain, there was no association between muscle mass and foot pain. Moreover, a gynoid fat distribution was favourable over an android distribution as gynoid fat was associated with reduced foot pain. Taken together, this thesis attempted to fill some of the gaps in the literature in relation to some more novel risk factors and their relationship with musculoskeletal disease. Further research is still required to build on the findings in this thesis, with the potential to contribute to the development of more effective prevention strategies.