Genetic Mechanisms of Knee Osteoarthritis
Genetic Mechanisms of Knee Osteoarthritis
To describe the differences in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis and age- and sex-matched controls with no family history of knee osteoarthritis, a population-based longitudinal study of 163 matched pairs (mean age 45 years, range 26 to 61) was performed at baseline and about 2 years later. Knee cartilage defect score (0 to 4), cartilage volume and bone size were determined with T1-weighted fat saturation magnetic resonance imaging. Body mass index (BMI), lower-limb muscle strength, knee pain, physical work capacity at 170 beats/minute (PWC170) and radiographic osteoarthritis were measured by standard protocols. In comparison with controls, offspring had higher annual knee cartilage loss (-3.1% versus -2.0% at medial tibial site, -1.9% versus -1.1% at lateral tibial site and -4.7% versus -3.7% at patellar site, all P < 0.05), a greater increase in medial cartilage defect score (+0.15 versus -0.01, P < 0.05) and a greater decline in PWC170 (-0.7 watts/kg versus -0.4 watts/kg, P < 0.01). There were no significant differences in change in BMI, lower-limb muscle strength, knee pain or tibial bone area between these two groups; however, the differences in knee cartilage loss and cartilage defect change decreased in magnitude and became non-significant after adjustment for baseline cartilage volume, tibial bone area, BMI and knee pain. This longitudinal study suggests that knee cartilage loss, change in cartilage defects and decrease in physical fitness all have roles in the development of knee osteoarthritis, which is most probably polygenic but may reflect a shared environment. Importantly, the cartilage changes are largely dependent on baseline differences in cartilage volume, tibial bone area, BMI and knee pain, suggesting that these factors might have a role in their initiation.
Knee osteoarthritis (OA) is a slowly developing chronic disease that has a multifactorial origin. Although several environmental factors including obesity, acute joint injury and occupational factors are important in its pathogenesis, a modest but significant genetic effect for knee radiographic osteoarthritis (ROA) has been reported in most studies although the actual genes and mechanisms underlying this association are uncertain. A limitation of these studies is that radiographic measurement used in most of them provides only a broad-brush view of joint pathology because of its two-dimensional nature, semi-quantitative scoring system and/or inherent measurement error. Magnetic resonance imaging (MRI) can visualize knee joint structure directly and is recognised as a valid, accurate and reproducible tool for measuring knee cartilage volume, tibial bone surface area and cartilage defects and therefore has the potential to delineate early structural change in the knee. Recent data from our case control study suggested greater medial tibial bone area and both more prevalent and more severe knee cartilage defects but no difference in knee cartilage volume in the offspring of individuals with severe knee OA in later life compared with controls, whereas tibial bone surface area, knee cartilage defects and cartilage volume have significant heritability in twin and sibling-pair studies. These results suggest that increases in tibial bone area and cartilage defects may be under genetic control. In contrast, cartilage volume is not an initiating factor even given cartilage loss is a key factor in established OA.
Non-knee structural components such as higher body mass index (BMI) and lower-limb muscle strength might also have a role in the genetics of knee OA, although Manek and colleagues have suggested that obesity and OA are under separate genetic control. It is unclear what the role of physical fitness is. The aim of this population-based longitudinal study was therefore to describe the two-year change in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee OA, and age- and sex-matched controls with no family history of knee OA.
To describe the differences in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis and age- and sex-matched controls with no family history of knee osteoarthritis, a population-based longitudinal study of 163 matched pairs (mean age 45 years, range 26 to 61) was performed at baseline and about 2 years later. Knee cartilage defect score (0 to 4), cartilage volume and bone size were determined with T1-weighted fat saturation magnetic resonance imaging. Body mass index (BMI), lower-limb muscle strength, knee pain, physical work capacity at 170 beats/minute (PWC170) and radiographic osteoarthritis were measured by standard protocols. In comparison with controls, offspring had higher annual knee cartilage loss (-3.1% versus -2.0% at medial tibial site, -1.9% versus -1.1% at lateral tibial site and -4.7% versus -3.7% at patellar site, all P < 0.05), a greater increase in medial cartilage defect score (+0.15 versus -0.01, P < 0.05) and a greater decline in PWC170 (-0.7 watts/kg versus -0.4 watts/kg, P < 0.01). There were no significant differences in change in BMI, lower-limb muscle strength, knee pain or tibial bone area between these two groups; however, the differences in knee cartilage loss and cartilage defect change decreased in magnitude and became non-significant after adjustment for baseline cartilage volume, tibial bone area, BMI and knee pain. This longitudinal study suggests that knee cartilage loss, change in cartilage defects and decrease in physical fitness all have roles in the development of knee osteoarthritis, which is most probably polygenic but may reflect a shared environment. Importantly, the cartilage changes are largely dependent on baseline differences in cartilage volume, tibial bone area, BMI and knee pain, suggesting that these factors might have a role in their initiation.
Knee osteoarthritis (OA) is a slowly developing chronic disease that has a multifactorial origin. Although several environmental factors including obesity, acute joint injury and occupational factors are important in its pathogenesis, a modest but significant genetic effect for knee radiographic osteoarthritis (ROA) has been reported in most studies although the actual genes and mechanisms underlying this association are uncertain. A limitation of these studies is that radiographic measurement used in most of them provides only a broad-brush view of joint pathology because of its two-dimensional nature, semi-quantitative scoring system and/or inherent measurement error. Magnetic resonance imaging (MRI) can visualize knee joint structure directly and is recognised as a valid, accurate and reproducible tool for measuring knee cartilage volume, tibial bone surface area and cartilage defects and therefore has the potential to delineate early structural change in the knee. Recent data from our case control study suggested greater medial tibial bone area and both more prevalent and more severe knee cartilage defects but no difference in knee cartilage volume in the offspring of individuals with severe knee OA in later life compared with controls, whereas tibial bone surface area, knee cartilage defects and cartilage volume have significant heritability in twin and sibling-pair studies. These results suggest that increases in tibial bone area and cartilage defects may be under genetic control. In contrast, cartilage volume is not an initiating factor even given cartilage loss is a key factor in established OA.
Non-knee structural components such as higher body mass index (BMI) and lower-limb muscle strength might also have a role in the genetics of knee OA, although Manek and colleagues have suggested that obesity and OA are under separate genetic control. It is unclear what the role of physical fitness is. The aim of this population-based longitudinal study was therefore to describe the two-year change in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee OA, and age- and sex-matched controls with no family history of knee OA.
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