title: Effects of unfractionated heparin on renal osteodystrophy and vascular calcification in chronic kidney disease rats.
abstract: Unfractionated heparin (UFH) is the most widely used anticoagulant in hemodialysis for chronic kidney disease (CKD) patients. Many studies have verified that UFH can induce bone loss in subjects with normal bone, but few have focused on its effect on renal osteodystrophy. We therefore investigated this issue in adenine-induced CKD rats. As CKD also impairs mineral metabolism systemically, we also studied the impacts of UFH on serum markers of CKD-mineral and bone disorder (CKD-MBD) and vascular calcification. We administered low and high doses of UFH (1U/g and 2U/g body weight, respectively) to CKD rats and compared them with CKD controls. At sacrifice, the serum markers of CKD-MBD did not significantly differ among the two UFH CKD groups and the CKD control group. The mean bone mineral densities (BMDs) of the total femur and a region of interest (ROI) constituted of trabecular and cortical bone were lower in the high-dose UFH (H-UFH) CKD group than in the CKD control group (P<0.05 and P<0.01, respectively). The BMD of the femoral ROI constituted of cortical bone did not differ between the H-UFH CKD group and the CKD control group. Histomorphometrical changes in the CKD rats indicated secondary hyperparathyroidism, and the femoral trabecular bone volume, but not cortical bone volume, significantly decreased with increasing UFH dose. The same decreasing trend was found in osteoblast parameters, and an increasing trend was found in osteoclast parameters; however, most differences were not significant. Moreover, no distinct statistical differences were found in the comparison of vascular calcium or phosphorus content among the CKD control group and the two UFH CKD groups. Therefore, we concluded that UFH could induce bone loss in CKD rats with secondary hyperparathyroidism, mainly by reducing the trabecular volume and had little effect on cortical bone volume. The underlying mechanism might involve inhibition of osteoblast activity and promotion of osteoclast activity by UFH. We did not find any effect of UFH on vascular calcification in CKD rats with secondary hyperparathyroidism.
authors.affiliation: Renal Division, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Li
authors.forename: Qingnan
authors.initials: Q
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D003720:Densitometry; D004195:Disease Models, Animal; D005269:Femur / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D061205:Vascular Calcification / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D010758:Phosphorus; D006493:Heparin
keywords: BFR/BS; BFR/BV; BMD; BUN; CKD; CKD–MBD; Chronic kidney disease; Ct.B.Ar; DXA; ELISA; FGF-23; GPWi; H-UFH; ICP-OES; KDIGO; Kidney Disease: Improving Global Outcomes; L-UFH; LGR; MAR; MLT; N.Ob/BS; N.Oc/BS; OS/BS; OV/BV; Ob.S/BS; Oc.S/BS; PTH; Po.Ar; Po.Ar%; QCT; ROI; Renal osteodystrophy; SPA; Secondary hyperparathyroidism; Tb.N; Tb.Sp; Tb.Th; UFH; Unfractionated heparin; Vascular calcification; blood urea nitrogen; bone formation rate (bone area referent); bone formation rate (bone surface referent); bone mineral density; chronic kidney disease; chronic kidney disease–mineral and bone disorder; cortical bone area (porosity area reduced); dual-energy X-ray absorptiometry; enzyme-linked immunosorbent assay; fibroblast growth factor-23; growth plate width; high-dose unfractionated heparin; inductively coupled plasma optical emission spectrometer; longitudinal growth rate; low-dose unfractionated heparin; mineral apposition rate; mineralization lag time; osteoblast number per millimeter bone perimeter; osteoblast surface; osteoclast number per millimeter bone perimeter; osteoclast surface; osteoid surface; osteoid volume; parathyroid hormone; porosity area; porosity area percent; primary BV/TV; primary spongiosa bone volume; quantitative computed tomography; region of interest; secondary BV/TV; secondary spongiosa bone volume; single photon absorptiometry; trabecular number; trabecular separation; trabecular thickness; unfractionated heparin