The effect of naturally occurring chronic kidney disease on the micro-structural and mechanical properties of bone.

Anna Shipov,Ron Shahar,Gilad Segev,Ayelet Atkins,Hagar Meltzer,Moran Milrad,Ori Brenner,Luc Malaval

doi:10.1371/journal.pone.0110057

Anna Shipov, Ron Shahar + Show 6 more

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https://doi.org/10.1371/journal.pone.0110057

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Abstract

Chronic kidney disease (CKD) is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies) or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD). Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD.

Highlights

Chronic kidney disease (CKD) is a growing public health concern worldwide, with increasing incidence in all age groups
CKD-associated bone diseases include several different types of bone pathologies, such as adynamic bone disease and osteomalacia which are characterized by low bone turnover, osteitis fibrosa cystica which is characterized by high bone turnover and mixed uremic osteodystrophy which is characterized by either high or low turnover and abnormal mineralization [3]
This study demonstrates that advanced CKD in cats results in deterioration of bone quality, in particular a dramatic increase of resorption cavities and decreased bone mineral density

Summary

Introduction

Chronic kidney disease (CKD) is a growing public health concern worldwide, with increasing incidence in all age groups. The disease is irreversible and progressive in nature, and as it progresses, metabolic derangements worsen. This is true in the ageing population, where CKD has become a major cause of morbidity and mortality. One of the inevitable metabolic consequences of CKD is secondary renal hyperparathyroidism (SRH) [4]. Serum levels of FGF23 increase already in the early stages of CKD, when patients are still normo-phosphatemic and have normal PTH levels [7,8,9]. When PTH levels increase, they promote bone resorption, and persistently high PTH concentrations, as documented in CKD patients, eventually lead to, osteopenia, and increased risk of pathological fractures [10]

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