Chronic Kidney Disease Impairs Bone Defect Healing in Rats

Weiqing Liu,Xing Liang,Yunfeng Lin,Liyan Zhou,Dutmanee Seriwatanachai,Ling Ye,Yuliang Dong,Quan Yuan,Ning Kang

doi:10.1038/srep23041

Weiqing Liu, Xing Liang + Show 7 more

Open Access

https://doi.org/10.1038/srep23041

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Journal: Scientific Reports	Publication Date: Mar 9, 2016
Citations: 17	License type: CC BY 4.0

Affiliation: Sichuan University, Mahidol University

Abstract

Chronic kidney disease (CKD) has been regarded as a risk for bone health. The aim of this study was to evaluate the effect of CKD on bone defect repair in rats. Uremia was induced by subtotal renal ablation, and serum levels of BUN and PTH were significantly elevated four weeks after the second renal surgery. Calvarial defects of 5-mm diameter were created and implanted with or without deproteinized bovine bone mineral (DBBM). Micro-CT and histological analyses consistently revealed a decreased newly regenerated bone volume for CKD rats after 4 and 8 weeks. In addition, 1.4-mm-diameter cortical bone defects were established in the distal end of femora and filled with gelatin sponge. CKD rats exhibited significantly lower values of regenerated bone and bone mineral density (BMD) within the cortical gap after 2 and 4 weeks. Moreover, histomorphometric analysis showed an increase in both osteoblast number (N.Ob/B.Pm) and osteoclast number (N.Oc/B.Pm) in CKD groups due to hyperparathyroidism. Notably, collagen maturation was delayed in CKD rats as verified by Masson’s Trichrome staining. These data indicate that declined renal function negatively affects bone regeneration in both calvarial and femoral defects.

Highlights

Chronic kidney disease (CKD) has clearly been considered a major public health concern according to the National Kidney Foundation[1,2]
Patients on dialysis exhibited significant mineralized bone loss characterized by generalized thinning of cortical bone[11], and patients with predialysis CKD and fractures have lower areal bone mineral density according to dual-energy x-ray absorptiometry and lower volumetric BMD, thinner cortices, and trabecular loss according to HR-pQCT12
Serum blood urea nitrogen (BUN) (Fig. 1C) increased by approximately 4-fold in the CKD group compared with the sham-operated group, indicating a successful establishment of the uremic rat model

Summary

Introduction

Chronic kidney disease (CKD) has clearly been considered a major public health concern according to the National Kidney Foundation[1,2]. In the United States, its prevalence is 13.1%, affecting 26.3 million people[3] Dwarfing this figure, an estimated 119.5 million Chinese people (10.8%) have some stage of CKD4. Declined renal function is often complicated with phosphocalcic metabolic disorders, which subsequently impact bone structural integrity[5] and eventually lead to mineral and bone disorders (CKD-MBD)[6]. Patients with end-stage renal disease (ESRD) are at considerably higher risk for vertebral fracture[8] and hip fracture[9], which increase while kidney function declines[10]. With the prevalence of CKD dramatically increasing worldwide[1,3,4,15,16,17], the number of the individuals with missing teeth who will require dental implants is expected to grow. Our previous study revealed that the bone/implant contact ratio and strength of bone-implant integration were significantly lower in the CKD group at 2-week healing, which indicated that CKD negatively affects an early www.nature.com/scientificreports/

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