18F-FDG Uptake of Knee Joints in Age-Related OA
ACR criteria for diagnosis of OA require more than three of the clinical-, radiological-, and laboratory criteria. In this study, symptomatic knees that met the ACR requirement for OA showed a significant increase of F-FDG uptake, and metabolic alteration represented by the change of SUVmean was consistent with a history of knee OA and clinical-, radiological knee OA. The intra-articular SUVmax showed positive correlation with the joint-SUVmean and showed a significant increase in association with joint symptoms indicating OA. The joint-SUVmean showed a significant increase according to the grades of radiological bony changes, and the values were higher in clinical-, laboratory, and radiological OA than those in non-OA.
PET provides molecular imagery of biochemical and metabolic changes and is supposed to overcome the limitations of anatomical imaging studies. Because it is able to illuminate whole body, PET has been widely used for detection and staging of malignancies. For PET imaging, F-FDG is one of the most commonly used radioisotopes. Because malignant tissues are active in metabolism, increased glucose uptake can be reflected by F-FDG uptake as a glucose analog. Glucose taken up by cells is metabolized to glucose-6-phosphate and then to fructose-6-phosphate and fructose 1,6-biphosphonate; however, F-FDG-6-phosphate accumulates in the cell, which creates the images seen on the PET scan. Increased metabolism associated with infection or inflammation can also be detected by PET using F-FDG; this allows for assessment for inflammatory bone and joint diseases, such as rheumatoid arthritis, psoriatic arthritis, and osteomyelitis. OA accompanies metabolic alterations and inflammatory changes; therefore, increasing F-FDG uptake could be predicted in OA. Wandler et al., who evaluated the pattern and value of F-FDG uptake in shoulder joints, reported that the uptake pattern was diffuse, including the whole joint in patients with OA. Nakamura et al. reported that F-FDG uptake was up-regulated in OA and generally accumulated in periarticular lesions.
Females are particularly prone to OA, with a risk twice as high as that of males. This has been thought to be associated with estrogen deficiency after menopause, which down-regulates the estrogen receptor on the surface of chondrocytes, resulting in decreased synthesis of proteoglycan. In this study, the SUVmean of knee joints was higher in males than in females, however, the changes of the values increased in strong correlation with aging in females, but not in males. This finding might indicate that although metabolic rate is higher in males than in females, the metabolic alteration by aging may be remarkable in females, which is consistent with OA. The differences according to age and gender showed agreement with the higher incidence of OA in aging females than in males.
The glycolysis and pentose phosphate pathways are major pathways of glucose metabolism, and the uronic acid pathway and hexosamine biosynthetic pathways are important for excretion of metabolites as glucuronides and for synthesis of amino-sugars such as glycosaminoglycans (GAGs) and proteoglycans (PGs). In addition to the metabolic pathways, glucose uptake and metabolism can be influenced by the oxygen tension of tissues, thus, decreased tissue perfusion and hypoxia could affect glucose uptake and metabolism by anaerobic glycolysis.
Intra-articular and peri-articular structures, including synovium, subchondral bone, ligaments, and synovial fluid, as well as cartilage, may be affected by and generate mechanical loads and soluble mediators directing chondrocytes to activation, cartilage to breakdown, and joints to degeneration. Intra-articular reactions are very important in joint degeneration and pathogenesis of OA; therefore, because discrimination of the respective structures is difficult using PET and CT images, this study adopted intra-articular SUVmax for evaluation of the impact of focal intra-articular reactions on OA. In the current study, the SUVmean of knee joints for global joint metabolism might contain SUVs from peri-articular and intra-articular structures, including subchondral bones, and the intra-articular SUVmax for focal intra-articular reactions irrespective to the structures might involve uptake by synoviums, ligaments, and menisci as well as cartilage.
This study has a specific limitation related to assessment of bony changes of the knee. The K/L grading system of knee joints was originally based on X-ray images, however, in this study, K/L grades were used for the reconstructed CT images of the knee joints. Despite the limitation, the images discriminated bony changes in association with OA and its severity. Even though the increase of joint-SUVmean can be related to direct damage/pathology of articular structures and it is not only related to aging, the change of joint-SUVmean as an indicator for metabolic alteration of knee joints is clearly correlated with presence and severity of primary OA and aging in OA, especially in females.
Discussion
ACR criteria for diagnosis of OA require more than three of the clinical-, radiological-, and laboratory criteria. In this study, symptomatic knees that met the ACR requirement for OA showed a significant increase of F-FDG uptake, and metabolic alteration represented by the change of SUVmean was consistent with a history of knee OA and clinical-, radiological knee OA. The intra-articular SUVmax showed positive correlation with the joint-SUVmean and showed a significant increase in association with joint symptoms indicating OA. The joint-SUVmean showed a significant increase according to the grades of radiological bony changes, and the values were higher in clinical-, laboratory, and radiological OA than those in non-OA.
PET provides molecular imagery of biochemical and metabolic changes and is supposed to overcome the limitations of anatomical imaging studies. Because it is able to illuminate whole body, PET has been widely used for detection and staging of malignancies. For PET imaging, F-FDG is one of the most commonly used radioisotopes. Because malignant tissues are active in metabolism, increased glucose uptake can be reflected by F-FDG uptake as a glucose analog. Glucose taken up by cells is metabolized to glucose-6-phosphate and then to fructose-6-phosphate and fructose 1,6-biphosphonate; however, F-FDG-6-phosphate accumulates in the cell, which creates the images seen on the PET scan. Increased metabolism associated with infection or inflammation can also be detected by PET using F-FDG; this allows for assessment for inflammatory bone and joint diseases, such as rheumatoid arthritis, psoriatic arthritis, and osteomyelitis. OA accompanies metabolic alterations and inflammatory changes; therefore, increasing F-FDG uptake could be predicted in OA. Wandler et al., who evaluated the pattern and value of F-FDG uptake in shoulder joints, reported that the uptake pattern was diffuse, including the whole joint in patients with OA. Nakamura et al. reported that F-FDG uptake was up-regulated in OA and generally accumulated in periarticular lesions.
Females are particularly prone to OA, with a risk twice as high as that of males. This has been thought to be associated with estrogen deficiency after menopause, which down-regulates the estrogen receptor on the surface of chondrocytes, resulting in decreased synthesis of proteoglycan. In this study, the SUVmean of knee joints was higher in males than in females, however, the changes of the values increased in strong correlation with aging in females, but not in males. This finding might indicate that although metabolic rate is higher in males than in females, the metabolic alteration by aging may be remarkable in females, which is consistent with OA. The differences according to age and gender showed agreement with the higher incidence of OA in aging females than in males.
The glycolysis and pentose phosphate pathways are major pathways of glucose metabolism, and the uronic acid pathway and hexosamine biosynthetic pathways are important for excretion of metabolites as glucuronides and for synthesis of amino-sugars such as glycosaminoglycans (GAGs) and proteoglycans (PGs). In addition to the metabolic pathways, glucose uptake and metabolism can be influenced by the oxygen tension of tissues, thus, decreased tissue perfusion and hypoxia could affect glucose uptake and metabolism by anaerobic glycolysis.
Intra-articular and peri-articular structures, including synovium, subchondral bone, ligaments, and synovial fluid, as well as cartilage, may be affected by and generate mechanical loads and soluble mediators directing chondrocytes to activation, cartilage to breakdown, and joints to degeneration. Intra-articular reactions are very important in joint degeneration and pathogenesis of OA; therefore, because discrimination of the respective structures is difficult using PET and CT images, this study adopted intra-articular SUVmax for evaluation of the impact of focal intra-articular reactions on OA. In the current study, the SUVmean of knee joints for global joint metabolism might contain SUVs from peri-articular and intra-articular structures, including subchondral bones, and the intra-articular SUVmax for focal intra-articular reactions irrespective to the structures might involve uptake by synoviums, ligaments, and menisci as well as cartilage.
This study has a specific limitation related to assessment of bony changes of the knee. The K/L grading system of knee joints was originally based on X-ray images, however, in this study, K/L grades were used for the reconstructed CT images of the knee joints. Despite the limitation, the images discriminated bony changes in association with OA and its severity. Even though the increase of joint-SUVmean can be related to direct damage/pathology of articular structures and it is not only related to aging, the change of joint-SUVmean as an indicator for metabolic alteration of knee joints is clearly correlated with presence and severity of primary OA and aging in OA, especially in females.
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