Can One Evaluate Bone Disease in CKD Without a Biopsy?
Can One Evaluate Bone Disease in CKD Without a Biopsy?
DXA, quantitative computed tomography (QCT), and high resolution peripheral computed tomography (HR-pQCT) are imaging methods that quantify bone mass and structural aspects of bone quality. They do not measure turnover or mineralization. Therefore, they cannot be used alone to determine ROD type or assess completely disease severity. Furthermore, monitoring disease activity with imaging methods may be difficult because there are no data correlating changes in the parameters measured by these tools with changes in fracture risk.
DXA is widely available and is the clinical standard for measuring fracture risk in patients with healthy kidney function. However, fracture risk screening by DXA in CKD has been controversial. DXA does not have sufficient resolution to discriminate between cortical and trabecular bone, it provides a composite measure of cortical and trabecular compartments, and is unable to determine turnover or mineralization. Furthermore, as a result of study limitations, the results of cross-sectional and prospective studies on fracture discrimination and prediction were inconsistent. However, recent prospective trials in patients with predialysis CKD, ESRD on hemodialysis, and after kidney transplantation strongly suggest that low areal bone mineral density (BMD) measured by DXA at the total hip and femoral neck predicts future fracture (Table 1). Indeed, these prospective trials have begun to clarify and validate the use of DXA in CKD and help clinicians use and interpret DXA imaging. They indicate that in CKD, fracture risk screening is possible by imaging the forearm, total hip or femoral neck and that the World Health Organization definition of osteoporosis (T-score ≤2.5) is clinically relevant.
High-resolution imaging methods measure and quantify cortical and trabecular three-dimensional (volumetric) BMD, geometry, microarchitecture, and strength. Currently, these tools are used for research. QCT has a resolution of 300 μm and measures volumetric BMD and the geometry of cortical and trabecular compartments. Peripheral QCT has been used to assess the skeletal effects of CKD in patients predialysis, on hemodialysis, and after kidney transplantation. Studies reported that in CKD patients, cortical deficits predominated and cortical abnormalities both discriminated and predicted fracture. Similarly, HR-pQCT separately measures cortical and trabecular volumetric BMD and geometry, but its higher nominal resolution of 82 μm permits quantification of trabecular number, thickness, and separation. Finite element analysis, a computational method to quantify bone strength, can be applied to three-dimensional HR-pQCT datasets to measure strength either of whole bone or of individual cortical and trabecular compartments. Recently, advanced HR-pQCT processing methods have been developed to characterize cortical porosity and trabecular plate and rod structure. In patients from across the CKD spectrum, our group and others have demonstrated in cross-sectional and prospective studies that measurement of bone mass, geometry, and microarchitecture by HR-pQCT at the distal radius and tibia discriminated fracture status, detected abnormalities in bone quality that negatively impact bone strength, and elucidated underlying microstructural defects that result in BMD abnormalities measured by DXA. For example, in a prospective study of 54 patients with moderate-to-end-stage renal disease, we found that mean annualized losses of areal BMD at the forearm were 2.9%. With HR-pQCT, we identified microstructural mechanisms of forearm bone loss detected by DXA; there was significant loss of cortical area (–2.9%), density (–1.3%), and thickness (–2.8%) and significant increases in cortical porosity (+4.2%). Prospective studies are needed to determine whether the measurement of bone mass and microarchitecture by HR-pQCT predicts fracture, and whether therapies that mitigate microarchitectural abnormalities detected by HR-pQCT protect against fracture.
The value of combining measures of areal BMD by DXA with measures of bone geometry and microarchitecture by HR-pQCT to enhance fracture prediction above that of either imaging test alone is not established. In a cross-sectional study of CKD patients with and without fracture, Jamal et al. studied the value of combing measures from DXA with measures from HR-pQCT. Areal BMD was measured by DXA at the mainly trabecular ultradistal radius, and total volumetric BMD and cortical thickness were measured by HR-pQCT at the distal radius. When HR-pQCT measures were added to areal BMD by DXA, the area under the curve (AUC) was 0.81 [95% confidence interval (CI) 0.74–0.88]. This was not significantly different from the areal BMD obtained by DXA at the radius alone (AUC 0.80; 95% CI 0.74–0.87; P = 0.4). The reasons for this negative finding are likely owing to redundancies in parameters measured by these imaging methods. Both DXA and HR-pQCT measure structural aspects of bone quality. Thus, an enhancement of assessing bone disease severity in CKD-MBD will most likely be obtained by combining structural with dynamic measures of bone quality.
Imaging Bone Disease in Chronic Kidney Disease
DXA, quantitative computed tomography (QCT), and high resolution peripheral computed tomography (HR-pQCT) are imaging methods that quantify bone mass and structural aspects of bone quality. They do not measure turnover or mineralization. Therefore, they cannot be used alone to determine ROD type or assess completely disease severity. Furthermore, monitoring disease activity with imaging methods may be difficult because there are no data correlating changes in the parameters measured by these tools with changes in fracture risk.
DXA is widely available and is the clinical standard for measuring fracture risk in patients with healthy kidney function. However, fracture risk screening by DXA in CKD has been controversial. DXA does not have sufficient resolution to discriminate between cortical and trabecular bone, it provides a composite measure of cortical and trabecular compartments, and is unable to determine turnover or mineralization. Furthermore, as a result of study limitations, the results of cross-sectional and prospective studies on fracture discrimination and prediction were inconsistent. However, recent prospective trials in patients with predialysis CKD, ESRD on hemodialysis, and after kidney transplantation strongly suggest that low areal bone mineral density (BMD) measured by DXA at the total hip and femoral neck predicts future fracture (Table 1). Indeed, these prospective trials have begun to clarify and validate the use of DXA in CKD and help clinicians use and interpret DXA imaging. They indicate that in CKD, fracture risk screening is possible by imaging the forearm, total hip or femoral neck and that the World Health Organization definition of osteoporosis (T-score ≤2.5) is clinically relevant.
High-resolution imaging methods measure and quantify cortical and trabecular three-dimensional (volumetric) BMD, geometry, microarchitecture, and strength. Currently, these tools are used for research. QCT has a resolution of 300 μm and measures volumetric BMD and the geometry of cortical and trabecular compartments. Peripheral QCT has been used to assess the skeletal effects of CKD in patients predialysis, on hemodialysis, and after kidney transplantation. Studies reported that in CKD patients, cortical deficits predominated and cortical abnormalities both discriminated and predicted fracture. Similarly, HR-pQCT separately measures cortical and trabecular volumetric BMD and geometry, but its higher nominal resolution of 82 μm permits quantification of trabecular number, thickness, and separation. Finite element analysis, a computational method to quantify bone strength, can be applied to three-dimensional HR-pQCT datasets to measure strength either of whole bone or of individual cortical and trabecular compartments. Recently, advanced HR-pQCT processing methods have been developed to characterize cortical porosity and trabecular plate and rod structure. In patients from across the CKD spectrum, our group and others have demonstrated in cross-sectional and prospective studies that measurement of bone mass, geometry, and microarchitecture by HR-pQCT at the distal radius and tibia discriminated fracture status, detected abnormalities in bone quality that negatively impact bone strength, and elucidated underlying microstructural defects that result in BMD abnormalities measured by DXA. For example, in a prospective study of 54 patients with moderate-to-end-stage renal disease, we found that mean annualized losses of areal BMD at the forearm were 2.9%. With HR-pQCT, we identified microstructural mechanisms of forearm bone loss detected by DXA; there was significant loss of cortical area (–2.9%), density (–1.3%), and thickness (–2.8%) and significant increases in cortical porosity (+4.2%). Prospective studies are needed to determine whether the measurement of bone mass and microarchitecture by HR-pQCT predicts fracture, and whether therapies that mitigate microarchitectural abnormalities detected by HR-pQCT protect against fracture.
The value of combining measures of areal BMD by DXA with measures of bone geometry and microarchitecture by HR-pQCT to enhance fracture prediction above that of either imaging test alone is not established. In a cross-sectional study of CKD patients with and without fracture, Jamal et al. studied the value of combing measures from DXA with measures from HR-pQCT. Areal BMD was measured by DXA at the mainly trabecular ultradistal radius, and total volumetric BMD and cortical thickness were measured by HR-pQCT at the distal radius. When HR-pQCT measures were added to areal BMD by DXA, the area under the curve (AUC) was 0.81 [95% confidence interval (CI) 0.74–0.88]. This was not significantly different from the areal BMD obtained by DXA at the radius alone (AUC 0.80; 95% CI 0.74–0.87; P = 0.4). The reasons for this negative finding are likely owing to redundancies in parameters measured by these imaging methods. Both DXA and HR-pQCT measure structural aspects of bone quality. Thus, an enhancement of assessing bone disease severity in CKD-MBD will most likely be obtained by combining structural with dynamic measures of bone quality.
