A structural approach to skeletal fragility in chronic kidney disease

Abstract

Renal osteodystrophy is a multifactorial disorder of bone metabolism in chronic kidney disease (CKD). As CKD progresses, ensuing abnormalities in mineral metabolism result in distortions in trabecular microarchitecture, thinning of the cortical shell, and increased cortical porosity. Recent studies have shown significantly increased hip fracture rates in CKD stages 3 and 4, in dialysis patients, and in transplant recipients. The majority of studies of bone loss in CKD relied on dual-energy x-ray absorptiometry (DXA) measures of bone mineral density. However, DXA summarizes the total bone mass within the projected bone area, concealing distinct structural alterations in trabecular and cortical bone. Recent data have confirmed that peripheral quantitative computed tomography (pQCT) measures of cortical density and thickness provide substantially better fracture discrimination in dialysis patients, compared with hip or spine DXA. This review summarizes the growing evidence for bone fragility in CKD stages 3 through 5, considers the effects of CKD on trabecular and cortical bone structure as it relates to fracture risk, and details the potential advantages and disadvantages of DXA and alternative measures of bone density, geometry, and microarchitecture, including pQCT, high-resolution pQCT, and micro-magnetic resonance imaging for fracture risk assessment in CKD.

Figure 1. PQCT Scans in the Mid-shaft of the Tibia in (A) a 64 year old male with stage 4 CKD, and (B) a 62 year old male with normal renal function

This figure illustrates the bone loss on the endosteal surface and the reduced endocortical volumetric BMD. (From Nickolas TL, Leonard MB, Shane E 2008 Chronic kidney disease and bone fracture: a growing concern. Kidney Int 74(6):721-31)

Figure 2. ROC Curves for DXA areal BMD in the Hip and pQCT cortical vBMD in the midshaft of the radius in Dialysis Patients

(From Jamal SA, Gilbert J, Gordon C, Bauer DC 2006 Cortical pQCT measures are associated with fractures in dialysis patients. J Bone Miner Res 21(4):543-8.)

Figure 3. Axial μCT images (8.2 micron resolution) in the femoral neck illustrate the effects of renal osteodystrophy on trabecular microarchitecture in rats

(adapted from Hopper TA, et al. 2007 Quantitative microcomputed tomography assessment of intratrabecular, intertrabecular, and cortical bone architecture in a rat model of severe renal osteodystrophy. J Comput Assist Tomogr 31(2):320-8.)

Figure 4. Tibia 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 FW, Leonard MB, Saha PK, Gomberg BR 2004 Quantitative high-resolution magnetic resonance imaging reveals structural implications of renal osteodystrophy on trabecular and cortical bone. J Magn Reson Imaging 20(1):83-9)