Association between factors in early life and knee structures in young adults
thesisposted on 2023-05-28, 01:14 authored by Meng, T
Osteoarthritis (OA) is the most common form of arthritis worldwide, and mostly affects knee joint. The patients with knee OA usually suffer from severe knee symptoms and may even live with disability. There is no approved disease-modifying treatment available for knee OA, and existing management may only have limited effects or even have a range of side-effects. Thus, developing the preventive strategies of knee OA may be an effective way in reducing the disease burden. Magnetic resonance imaging (MRI) is an advanced technique which can detect early knee osteoarthritic changes. Several studies reported the associations between modifiable risk factors and MRI-based biomarkers in middle-aged or older adults, but few studies identified the relationships in young adults, who are the ideal target population for knee OA prevention. Therefore, this thesis aimed to describe associations between factors in early life and knee structures in young adults. This thesis used data from an Australian-based cohort study. In 1985, the Australian Schools Health and Fitness Survey (ASHFS) was conducted to provide benchmark data on the health and fitness of Australian school children using a nationally representative sample. A total of 8498 children (aged 7-15 years) participated in ASHFS with childhood measurements collected. During 2004-2006, the Childhood Determinants of Adult Health (CDAH) study were conducted as a 20-year follow-up of ASHFS. 2410 participants (aged 26-36 years) completed a clinic visit with adult measurements collected. During 2008-2010, the participants residing in metropolitan Melbourne and Sydney were invited to participated in the CDAH Knee Cartilage study, which is a sub-study of the CDAH study. 330 participants (aged 31-41 years) completed the knee MRI scans and their knee structures were measured using MRI. Chapter 3 described the associations between childhood adiposity measures and adult knee cartilage defects and bone marrow lesions (BMLs). Childhood adiposity measures, including weight, body mass index (BMI), overweight status and fat mass, were associated with the higher risk of adult patellar cartilage defects. Childhood overweight status was associated with the higher risk of adult patellar BMLs. These associations persisted after further adjusting for corresponding adiposity measure in adulthood. No associations identified in femorotibial compartment. These findings suggested adiposity in childhood may have long-term and independent effects on patellar structural abnormalities in young adults. Chapter 4 described the associations of adiposity measures in childhood and adulthood with knee cartilage thickness, volume and bone area in young adults. Childhood weight and BMI were negatively associated with adult patellar bone area, suggesting the long-term detrimental effects of childhood adiposity on adult patellar morphology. Adult weight was positively associated with bone area in femorotibial compartments, which may be the response to mechanical stress from excess adiposity. Adult waist-hip ratio (WHR) and the change ofWHR from childhood to adulthood were negatively associated with cartilage thickness, volume, and bone area, suggesting central obesity during early life could be detrimental to knee cartilage and bone morphology in young adults. Chapter 5 described associations of body composition, physical activity and physical performance with knee cartilage thickness and subchondral bone area in young adults. Lean mass was positively associated with knee cartilage thickness and subchondral bone area, whereas no significant associations were found for fat mass. Physical activity, including walking, moderate activity, vigorous activity, and total physical activity, were not associated with cartilage thickness or bone area. Long jump, hand grip strength, and physical work capacity, but not leg strength, were positively associated with cartilage thickness. All the physical performance measures (Long jump, hand grip strength, physical work capacity, and leg strength) were positively associated with subchondral bone area. The significant associations for physical performance were largely disappeared after further adjusting for lean mass, and the mediation analysis confirmed the mediating effects of lean mass. These findings suggest that lean mass may play an important role in maintaining knee joint health in young adults. Chapter 6 described the associations of glucose homeostasis and metabolic syndrome (MetS) measures with knee cartilage defects and cartilage volume in young adults. Most glucose homeostasis measures, including fasting insulin, homeostatic model assessment 2 (HOMA2)-insulin resistance, HOMA2-beta cell function, HOMA2-insulin sensitivity, but not fasting glucose, were associated with tibiofemoral cartilage defects. No associations were identified between glucose homeostasis measures and knee cartilage volume. MetS was not associated with knee cartilage defects or cartilage volume. However, two MetS components (high waist circumference and low high-density lipoprotein cholesterol) were associated with the higher risk of tibiofemoral cartilage defects. These results suggested glucose homeostasis and some MetS components may affect early cartilage damage in young adults. In conclusion, this thesis indicates that early life factors may affect knee joint health in young adults. Our findings may be useful in developing preventive strategies for knee OA, though further confirmatory studies are needed.
Rights statementCopyright 2020 the author Chapter 3 appears to be the equivalent of a post-print version of an article published as: Meng, T., Thayer, S., Venn, A., Wu, F., Cicuttini, F., March, L., Dwyer, T., Halliday, A., Cross, M., Laslett, L. L., Jones, G., Ding, C., Antony, B., 2018. Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study, Osteoarthritis and cartilage, 26(8), 1055-1062. The published version is included in the thesis appendices. Chapter 4 appears to be the equivalent of a post-print version of an article published as: Meng, T., Venn, A., Eckstein. F., Wirth, W., Cicuttini, F., March, L., Dwyer, T., Cross, M., Laslett, L. L., Jones, G., Ding, C., Antony, B., Association of adiposity measures in childhood and adulthood with knee cartilage thickness, volume and bone area in young adults, International journal of obesity, 2019, 43(7), 1411-1421, Springer Nature. The published version is included in the thesis appendices. Chapter 5 appears to be the equivalent of a pre-copyedited, author-produced version of an article accepted for publication in Rheumatology following peer review. The version of record, Meng, T., Antony, B., Venn, A., Eckstein, F., Cicuttini, F., March, L. Cross, M., Dwyer, T., Blizzard, L., Jones, G., Laslett, L. L., Ding, C., 2020. Association of body composition, physical activity and physical performance with knee cartilage thickness and bone area in young adults, Rheumatology, 59(7), 1607-1616, is available online (from 25/9/2019) at:https://doi.org/10.1093/rheumatology/kez498 The published version is included in the thesis appendices. Chapter 6 appears to be the equivalent of a post-print version of an article published as: Meng, T., Antony, B., Venn, A., Fraser, B., Cicuttini, F., March, L. Cross, M., Dwyer, T., Jones, G., Laslett, L. L., Ding, C., 2020. Association of glucose homeostasis and metabolic syndrome with knee cartilage defects and cartilage volume in young adults, Seminars in arthritis and rheumatism, 50(2), 192-197. The published version is included in the thesis appendices.