title: A comparison of calcium to zoledronic acid for improvement of cortical bone in an animal model of CKD.
abstract: Patients with chronic kidney disease (CKD) have increased risk of fractures, yet the optimal treatment is unknown. In secondary analyses of large randomized trials, bisphosphonates have been shown to improve bone mineral density and reduce fractures. However, bisphosphonates are currently not recommended in patients with advanced kidney disease due to concern about oversuppressing bone remodeling, which may increase the risk of developing arterial calcification. In the present study we used a naturally occurring rat model of CKD with secondary hyperparathyroidism, the Cy/+ rat, and compared the efficacy of treatment with zoledronic acid, calcium given in water to simulate a phosphate binder, and the combination of calcium and zoledronic acid. Animals were treated beginning at 25 weeks of age (approximately 30% of normal renal function) and followed for 10 weeks. The results demonstrate that both zoledronic acid and calcium improved bone volume by micro-computed tomography (µCT) and both equally suppressed the mineral apposition rate, bone formation rate, and mineralizing surface of trabecular bone. In contrast, only calcium treatment with or without zoledronic acid improved cortical porosity and cortical biomechanical properties (ultimate load and stiffness) and lowered parathyroid hormone (PTH). However, only calcium treatment led to the adverse effects of increased arterial calcification and fibroblast growth factor 23 (FGF23). These results suggest zoledronic acid may improve trabecular bone volume in CKD in the presence of secondary hyperparathyroidism, but does not benefit extraskeletal calcification or cortical biomechanical properties. Calcium effectively reduces PTH and benefits both cortical and trabecular bone yet increases the degree of extra skeletal calcification. © 2014 American Society for Bone and Mineral Research.
authors.affiliation: Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, USA; Richard L. Roduebush Veterans Affairs Medical Center, Indianapolis, IN, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Newman
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Gattone
authors.forename: Jason M
authors.initials: JM
authors.lastname: Organ
authors.forename: Xianming
authors.initials: X
authors.lastname: Chen
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Allen
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology*; D002319:Cardiovascular System / Q000503:physiopathology; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D051381:Rats; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D002118:Calcium
keywords: BIOMECHANICS; BONE; CALCIUM; CKD; FGF23; PARATHYROID HORMONE; VASCULAR CALCIFICATION; ZOLEDRONIC ACID
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