Determinants and management of the progression of osteoarthritis in older adults

Osteoarthritis (OA) is one of the most common musculoskeletal disorders, of which knee and hip OA account for the biggest burden of disease. It is a multifactorial disease with many risk factors and determinants such as age, sex and lifestyle factors including obesity, physical activity and diet being associated with both the onset and progression of the disease. Owing to the complex nature of the disease, no definitive treatment is available for OA. In order to better manage and treat this condition, it is important to improve the understanding of the lifestyle and structural factors related to the progression of the disease as well as the management of these factors. Therefore, the overall aims of this thesis were to identify determinants, risk factors and potential management strategies for the progression of OA in older adults. In this thesis, data from two studies were utilised. The first study was a prospective population-based cohort study of older adults who were between 50 and 80 years of age named the Tasmanian Older Adults Cohort Study (TASOAC). The participants for the study were selected from sex-stratified random sampling from the electoral role in Southern Tasmania (population 229,000). Data was collected at baseline and at 2.5, 5 and 10 years after the initial clinic assessment. At baseline, information on objective measures of body composition using body mass index (BMI) obtained by weight and height measures and fat and lean mass using dual-energy x-ray absorptiometry (DXA) were obtained. Pedometer measured ambulatory activity (AA) was recorded at baseline and socioeconomic status (SES) of the participants was collected by matching each participant's residential address to the corresponding Australian Bureau of Statistics (ABS) Census Collection District to determine the Socio-Economic Indexes for Areas (SEIFA) value from the 2001 census. Knee pain of the participants at baseline and the 10-year follow-up was collected using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). In addition, various imaging modalities such as radiography of the knee and hip at baseline and Magnetic Resonance Imaging (MRI) of the knee at baseline and the 10-year follow-up were conducted. Based on the radiographs, the status of radiographic OA (ROA) was defined. Utilising the knee MRI of the participants, several structural features such as Tibial cartilage volume and bone-marrow lesions (BMLs) were measured. The incidence of primary (first-time) total knee replacements (TKR) and total hip replacements (THR) were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). The second study was a single-blind, single-center, 18-month, randomized controlled trial of older adults aged over 55 years named the Intensive Diet and Exercise for Arthritis trial (IDEA). The study was designed to evaluate the effects of weight loss obtained by diet and/or exercise on OA outcomes of the knee. Participants were eligible for the study if they had Kellgren-Lawrence grade (KLG) 2-3 tibiofemoral or tibiofemoral with patellofemoral OA of at least one knee, pain on most days due to knee OA, a BMI between 27 and 41 kg/m\\(^2\\) and a sedentary lifestyle, i.e. <30 min/week of formal exercise over the past 6 months. The participants were randomized to one of three 18-month interventions: exercise only, diet only or diet+exercise. MRI was obtained in a random subsample (n=105) of the IDEA participants at baseline and the 18-month follow-up. Using these MRIs, the medial and lateral menisci were segmented, and position and size parameters were measured quantitatively, along with semiquantitative extrusion measures. In the first study of this thesis, we assessed the association between SES and time to THR and TKR due to OA in older adults. The results showed that less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR) in comparison to the most disadvantaged participants; however, this association was attenuated adjustments for hip pain and hip ROA. This suggests that time to joint replacements is determined according to the symptoms/need of the participants rather than their SES, indicating reductions in expected disparity between SES and time to joint replacement. This further confirms the usefulness of using joint replacement as a marker of end-stage OA in the knee and hip. The second study evaluated the association between AA and body composition measures such as BMI, fat mass, lean mass and waist circumference with the risk of TKR and THR due to OA in a population of community-dwelling older adults. The results showed that AA was related to a higher risk of TKR and a lower risk of THR. BMI, total fat, trunk fat mass and waist circumference were associated with a higher risk of TKR although body composition measures were not related to THR. These finding suggest that habitual activity and obesity may have different causal pathways for OA progression in knee and hip joints. In the third study, we investigated the prospective associations between baseline hip morphology defined as hip shape modes using Statistical Shape Modelling (SSM) and the progression of several clinical and MRI-based knee OA outcomes in older adults. The results showed that longer, wider femoral neck and larger femoral head (mode 1) was associated with increased risk of worsening knee pain, whereas wider femoral neck (mode 9) was related to reduced risk of worsening knee pain. Larger greater trochanter (mode 7) and greater acetabular coverage (mode 10) were linked to lower cartilage volume loss, while shorter, wider femoral neck (mode 9) was associated with increased cartilage volume loss. Smaller femoral head (mode 4) was related to increased risk of worsening BMLs. Greater acetabular coverage (mode 10) was associated with a reduced risk of TKR. Overall these findings may imply that hip shape variations are important in the long-term progression of knee OA in older adults. The fourth study assessed whether weight loss achieved by diet and/or exercise is related to meniscus extrusion parameters in the medial and lateral meniscus over 18 months. The results showed that weight loss was related to less progression of medial meniscus extrusion as measured by the maximum and mean extrusion distances. Weight loss was not associated with lateral meniscus position, medial or lateral meniscus size or with semiquantitative measures. These findings suggest that weight loss is related to beneficial modifications of medial meniscus extrusion in older adults. In conclusion, this sequence of studies first established the importance of TKR and THR as a marker of end-stage OA and showed that habitual activity and obesity act differently on end-stage OA of the hip and knee joints. Additionally, variations in hip shape may be an important structural feature that is associated with the progression of knee OA. Lastly, weight loss was related to less progression of meniscus extrusion in older adults with knee OA. Overall, the findings of this thesis suggest the importance of certain lifestyle factors. Better management of these factors may help to reduce OA progression in older adults.