Chronic kidney disease and bone fracture: a growing concern

Abstract

Susceptibility to fracture is increased across the spectrum of chronic kidney disease (CKD). Moreover, fracture in patients with end-stage kidney disease (ESKD) results in significant excess mortality. The incidence and prevalence of CKD and ESKD are predicted to increase markedly over the coming decades in conjunction with the aging of the population. Given the high prevalence of both osteoporosis and CKD in older adults, it is of the utmost public health relevance to be able to assess fracture risk in this population. Dual-energy X-ray absorptiometry (DXA), which provides an areal measurement of bone mineral density (aBMD), is the clinical standard to predict fracture in individuals with postmenopausal or age-related osteoporosis. Unfortunately, DXA does not discriminate fracture status in patients with ESKD. This may be, in part, because excess parathyroid hormone (PTH) secretion may accompany declining kidney function. Chronic exposure to high PTH levels preferentially causes cortical bone loss, which may be partially offset by periosteal expansion. DXA can neither reliably detect changes in bone volume nor distinguish between trabecular and cortical bone. In addition, DXA measurements may be low, normal, or high in each of the major forms of renal osteodystrophy (ROD). Moreover, postmenopausal or age-related osteoporosis may also affect patients with CKD and ESKD. Currently, transiliac crest bone biopsy is the gold standard to diagnose ROD and osteoporosis in patients with significant kidney dysfunction. However, bone biopsy is an invasive procedure that requires time-consuming analyses. Therefore, there is great interest in developing non-invasive high-resolution imaging techniques that can improve fracture risk prediction for patients with CKD. In this paper, we review studies of fracture risk in the setting of ESKD and CKD, the pathophysiology of increased fracture risk in patients with kidney dysfunction, the utility of various imaging modalities in predicting fracture across the spectrum of CKD, and studies evaluating the use of bisphosphonates in patients with CKD.

Figure 1. Example images from techniques to evaluate bone structure

pQCT scans of the tibia mid-diaphysis in (a) 64-year-old male with CKD Stage 4, and (b) 62-year-old male with normal kidney function. In comparison with the cortex of the healthy control, the cortex of the patient with CKD is noted to have decreased cortical density and cortical thinning.

Figure 2. Example images from techniques to evaluate bone structure

Tibia micro-MRI from a healthy control (left) and a patient with ESKD (right). Increased trabecular disconnectivity of the tibia from the patient with ESKD is noted by decreased trabecular density and loss of horizontal trabecular elements.

Figure 3. Example images from techniques to evaluate bone structure

Representative HR-pQCT images from a healthy patient (a); a patient with ESKD (b); and a DXA image from the same patient with ESRD (c). HR-pQCT of the radius of the patient with ESKD demonstrates cortical thinning and extreme trabecular dropout. In comparison with DXA imaging of the same bone, HR-pQCT provides superior resolution with visualization of both trabecular and cortical bone compartments.