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.

Efficacy and Safety of Denosumab for the Treatment of Osteoporosis in Patients with Chronic Kidney Disease

“…Several factors could explain the association between CKD and osteoporosis and osteopenia. Patients with CKD are likely to be older and have lower levels of vitamin D. In addition, there is increasing evidence that CKD itself is a risk factor for low BMD [4][5][6][7]. Patients with impaired renal function have been found to have greater rates of bone loss [7,20].…”

“…More than half of individuals older than 70 years have a decreased estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m 2 ) [3]. CKD is an independent risk factor for osteoporosis [4][5][6][7]. Individuals with CKD may have an increased risk for osteoporosis for several reasons, including shared risk factors for both conditions such as advanced age and female gender.…”

Sclerostin

“…Patients with CKD may develop various types of bone disease, spanning the spectrum of extreme situations such as severe osteitis fibrosa, osteomalacia, mixed osteopathy, and adynamic bone disease. In addition, patients may have osteoporosis, which increases the risk for fractures, both in advanced and in less severe CKD stages (2)(3)(4), which, in turn, result in excess mortality (5,6). In many instances, the pathogenesis of the precise type of ROD in a given patient seems to be obvious, for instance secondary hyperparathyroidism for osteitis fibrosa, vitamin D deficiency or aluminum overload for osteomalacia, hypoparathyroidism for adynamic bone disease, and advanced age and female gender for osteoporosis.…”

Comparison of laboratory and imaging methods associated with bone metabolism in patients with or without renal failure under the age of 45 years with elevated parathyroid hormone levels

“…DXA measures areal BMD, rather than volumetric BMD. In addition, it cannot distinguish between cortical and trabecular bone, and it cannot assess bone microarchitecture or bone turnover [16,17].…”