Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease.
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.
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Christopher L
CL
Newman
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Amy
A
Creecy
Department of Orthopaedic Surgery and Rehabilitation and Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Mathilde
M
Granke
Department of Orthopaedic Surgery and Rehabilitation and Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Jeffry S
JS
Nyman
Materials Engineering, Purdue University, West Lafayette, Indiana, USA.
Nannan
N
Tian
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
Max A
MA
Hammond
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA; Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, Indiana, USA.
Joseph M
JM
Wallace
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Drew M
DM
Brown
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Neal
N
Chen
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; Roudebush VA Medical Center, Indianapolis, Indiana, USA.
Sharon M
SM
Moe
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, Indiana, USA; Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. Electronic address: matallen@iupui.edu.
Matthew R
MR
Allen
D000818:Animals; D001806:Blood Urea Nitrogen; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D005269:Femur / Q000737:chemistry / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D055595:Mechanical Phenomena / Q000187:drug effects; D010281:Parathyroid Hormone / Q000097:blood; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000188:drug therapy*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy*; D013131:Spine / Q000737:chemistry / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology
D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D020849:Raloxifene Hydrochloride; D003094:Collagen
bone quality; chronic kidney disease; raloxifene