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

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

<b>Table 3.</b> Mechanical properties of the cortical bone of CKD and control groups.

<p><b>Table 3.</b> Mechanical properties of the cortical bone of CKD and control groups.</p

Dot plots depicting the data of CKD and control cats; the horizontal line represents the median.

<p>(a) resorption cavity density (b) porosity, (c) BMD and (d) Young's modulus.</p

Morphometry of cortical bone of the mid-diaphyseal femur in CKD and healthy controls.

<p>Morphometry of cortical bone of the mid-diaphyseal femur in CKD and healthy controls.</p

Morphometric characteristics of cortical bone of the distal femur in CKD and healthy controls by light microscopy.

<p>Morphometric characteristics of cortical bone of the distal femur in CKD and healthy controls by light microscopy.</p

Light microscopy images of three transverse cross-sections of the femoral mid-diaphysis of (a, c, e) cats with CKD and (b, d, f) healthy cats.

<p>Note dramatic increase in unfilled resorption cavities in CKD cats compared to the healthy cats.</p

Trabecular bone analysis: Trabecular thickness (a) and bone volume/total volume (BV/TV, b) in the cancellous bone of CKD and control cats for both the femora (F) and the vertebrae (V).

<p>Data are presented as dot plots. The horizontal line represents the median. Data from the femur and vertebra are similar within the study groups; however, there is a significant difference for both parameters between the study and the control groups. Micro-CT scans of cancellous bone of a control (c) and CKD (d) cat.</p

Bone cavity analysis.

<p>(a) Light microscopy image of a typical transverse cross section of the bone created by stitching together of many individual images. Classification of voids was performed on based on their size. (b) An individual image from the cross sectional image (marked by a white rectangle in image a). (c) Each image was first binarized, separating it into ‘bone’ (white) and ‘void’ (black) (right image). Cavities within the range of 9–50 µm² were considered to be lacunae (long arrows), cavities within the range of 151–2000 µm² were considered to be Haversian canal (short arrows) and cavities larger than 2000 µm² were considered resorptive lesions (arrowheads).</p