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Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease.
- Source :
-
Kidney international [Kidney Int] 2016 Jan; Vol. 89 (1), pp. 95-104. Date of Electronic Publication: 2016 Jan 04. - Publication Year :
- 2016
-
Abstract
- Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties.<br /> (Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Blood Urea Nitrogen
Bone Density Conservation Agents therapeutic use
Bone Remodeling drug effects
Collagen analysis
Disease Models, Animal
Femur chemistry
Femur diagnostic imaging
Femur physiopathology
Male
Mechanical Phenomena drug effects
Parathyroid Hormone blood
Polycystic Kidney, Autosomal Dominant complications
Raloxifene Hydrochloride therapeutic use
Rats
Renal Insufficiency, Chronic complications
Spine chemistry
Spine diagnostic imaging
Spine physiology
Bone Density Conservation Agents pharmacology
Femur drug effects
Polycystic Kidney, Autosomal Dominant drug therapy
Raloxifene Hydrochloride pharmacology
Renal Insufficiency, Chronic drug therapy
Spine drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1755
- Volume :
- 89
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 26489025
- Full Text :
- https://doi.org/10.1038/ki.2015.315