Childhood and adulthood determinants of knee joint health in young adults

Osteoarthritis (OA) is the most common joint disorder in adults around the world. Knee OA is the most common form of OA and results in deterioration of knee structure and function for which there is no cure. The risk factors for OA include age, female sex obesity and injury, but the effect of physical activity on knee joint health is still controversial. Identifying modifiable risk factors early in life has the potential to prevent the development of knee OA in later life; however, there is sparse evidence relating childhood factors such as physical fitness and fatness to adult joint health. Knee magnetic resonance imaging (MRI) has revolutionised the knee OA research with its ability to quantify the different knee structures and to grade the abnormalities of these structures. Some of these quantified structures such as tibial bone area and tibial cartilage volume and the structural abnormalities such as subchondral bone marrow lesions (BMLs), cartilage defects and meniscal lesions are known to be associated with the development and progression of OA in later life. The aims of this thesis are to determine whether physical activity, physical performance measures and fatness in childhood measured 25 years prior are associated with knee joint structure and symptoms in young adults, and to explore the correlates of knee structural and functional measures in young adults. Participants broadly representative of the Australian population were selected from the Australian Schools Health and Fitness Survey (ASHFS) of 1985. Participants of ASHFS underwent anthropometric and physical performance measurements during childhood (age 7-15 years). They were followed up and these measurements were repeated 20 years later in Childhood Determinants of Adult Health (CDAH) study. Physical performance measures included physical fitness measures such as physical work capacity at 170 beats/min (`PWC_170`), running times, sit-ups, long jump and leg muscle strength. Physical activity, smoking and alcohol history were recorded using questionnaires. Body mass index (BMI), lean mass, fat mass and waist hip ratio were calculated from the anthropometric measurements. A representative sub-sample (n=330, aged 31-41 years, female 47%) underwent magnetic resonance imaging (MRI) of their knees as well as questionnaires on knee pain five years later in CDAH Knee Cartilage study. MRI scans were processed to determine the structural measures such as tibial bone size and cartilage volume and structural abnormalities such as BML, cartilage defects, and meniscal abnormalities. The associations of childhood factors with adult knee structures and symptoms were determined. The associations of adulthood factors such as physical activity, cholesterol levels, sex hormones and systemic inflammatory markers with adult knee structures were also determined. Childhood physical performance measures including cardiorespiratory fitness measures were beneficially associated with adulthood knee bone size and cartilage volume, independent of the adult-attained fitness level. Cartilage volume accrual was partially mediated by bone size, indicating the importance of subchondral bone in the development of cartilage in adulthood. Childhood overweight measures were associated with higher knee pain in adulthood independent of adulthood overweight status. The trajectory of overweight status from childhood to adulthood indicated that participants who were overweight at both childhood and adulthood have the highest prevalence and risk of knee pain in adulthood. Knee cartilage volume measured in young adults was associated with body composition, physical activity, physical performance measures, sex hormones and fibrinogen measured five years prior. The association of physical activity and fitness with cartilage volume was independent of each other suggesting the influence of environmental factors and the potential for intervention to increase knee cartilage volume. Subchondral bone abnormalities such as BMLs in young adults were positively associated with knee symptoms and other knee structural abnormalities such as cartilage defects and meniscal lesions. Moderate physical activity and higher high-density lipoprotein (HDL) cholesterol may be protective while vigorous physical activity may weakly increase the risk of medial tibiofemoral BMLs in young adults. In conclusion, physical performance measures and/or physical activity in childhood and adulthood are beneficially associated with tibial cartilage volume and tibial bone size measured in adulthood. Obesity measures in childhood and adulthood are detrimentally associated with knee pain and/or structural abnormalities measured through MRI. These findings suggest the importance of increasing physical activity/fitness and reducing overweight in childhood and adulthood to have a healthy knee joint which may prevent the development of OA in later life. The positive association of sex hormone binding globulin and the negative association of inflammatory markers with knee cartilage volume indicate the possibility of intervention in modifying knee joint health