A structural approach to the assessment of fracture risk in children and adolescents with chronic kidney disease

Abstract

Children with chronic kidney disease (CKD) have multiple risk factors for impaired accretion of trabecular and cortical bone. CKD during childhood poses an immediate fracture risk and compromises adult bone mass, resulting in significantly greater skeletal fragility throughout life. High-turnover disease initially results in thickened trabeculae, with greater bone volume. As disease progresses, resorption cavities dissect trabeculae, connectivity degrades, and bone volume decreases. Increased bone turnover also results in increased cortical porosity and decreased cortical thickness. Dual-energy X-ray absorptiometry (DXA)-based measures of bone mineral density (BMD) are derived from the total bone mass within the projected bone area (g/cm(2)), concealing distinct disease effects in trabecular and cortical bone. In contrast, peripheral quantitative computed tomography (pQCT) estimates volumetric BMD (vBMD, g/cm(3)), distinguishes between cortical and trabecular bone, and provides accurate estimates of cortical dimensions. Recent data have confirmed that pQCT measures of cortical vBMD and thickness provide substantially greater fracture discrimination in adult dialysis patients compared with hip or spine DXA. The following review considers the structural effects of renal osteodystrophy as it relates to fracture risk and the potential advantages and disadvantages of DXA and alternative measures of bone density, geometry, and microarchitecture, such as pQCT, micro-CT (microCT), and micro magnetic resonance imaging (microMRI) for fracture risk assessment.

Fig. 1

Differential effects of primary hyperparathyroidism on posterior–anterior and lateral dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) in the spine in adults (data derived from Duan et al. [47]

Fig. 2

Peripheral skeleton quantitative computed tomography (pQCT) scans in the midshaft of the tibia in a pediatric renal transplant recipient (a) and healthy control (b). This figure illustrates the bone loss on the endosteal surface and the reduced endocortical volumetric bone mineral density (vBMD)

Fig. 3

Receiver operating characteristic (ROC) curves for dual-energy X-ray absorptiometry (DXA) areal bone mineral density (BMD) in the hip and peripheral skeleton quantitative computed tomography (pQCT) cortical volumetric BMD (vBMD) in the midshaft of the radius in dialysis patients (From Jamal et al. [59])

Fig. 4

Axial micro computed tomography (μCT) images (8.2-μm resolution) in the femoral neck illustrate the effects of renal osteodystrophy on trabecular microarchitecture in growing rats. (Adapted from Hopper et al. [60])

Fig. 5

Tibia micro magnetic resonance imaging (μMRI) illustrates severe cortical thinning and loss of trabecular connectivity and bone volume in a hemodialysis patient compared with a healthy age- and gender-matched control (Adapted from Wehrli et al. [65])