Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

Affiliations

¹ Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
³ 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.
⁴ Materials Engineering, Purdue University, West Lafayette, Indiana, USA.
⁵ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
⁶ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA; Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, Indiana, USA.
⁷ Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁸ Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; Roudebush VA Medical Center, Indianapolis, Indiana, USA.
⁹ 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.

PMID: 26489025
PMCID: PMC4840093
DOI: 10.1038/ki.2015.315

Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

Christopher L Newman et al. Kidney Int. 2016 Jan.

. 2016 Jan;89(1):95-104.

doi: 10.1038/ki.2015.315. Epub 2016 Jan 4.

Authors

Affiliations

¹ Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
³ 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.
⁴ Materials Engineering, Purdue University, West Lafayette, Indiana, USA.
⁵ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
⁶ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA; Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, Indiana, USA.
⁷ Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁸ Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; Roudebush VA Medical Center, Indianapolis, Indiana, USA.
⁹ 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.

PMID: 26489025
PMCID: PMC4840093
DOI: 10.1038/ki.2015.315

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.

Keywords: bone quality; chronic kidney disease; raloxifene.

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Conflict of interest statement

DISCLOSURES

The authors have no conflicts of interest related to the described work.

Figures

**Figure 1**
Cancellous bone structure in the proximal tibia and lumbar vertebra as determined by microCT. *, p<0.05 compared to NL; #, p<0.05 compared to CKD-VEH

**Figure 2**
Bone formation rates in the proximal tibia and caudal lumbar vertebra as determined by dynamic histomorphometry. *, p<0.05 compared to NL; #, p<0.05 compared to CKD-VEH

**Figure 3**
Structural and apparent material properties of the femur as determined by four-point bending: (a) ultimate load, (b) energy to fracture, (c) ultimate stress, and (d) modulus of toughness. *, p<0.05 compared to NL; #, p<0.05 compared to CKD-VEH

**Figure 4**
Collagen fibril D-periodic spacing as determined by AFM imaging. #, p<0.05 compared to CKD-VEH

See this image and copyright information in PMC

Comment in

Bone strength: more than just bone density.
Ott SM. Ott SM. Kidney Int. 2016 Jan;89(1):16-9. doi: 10.1016/j.kint.2015.11.004. Kidney Int. 2016. PMID: 26759040

References

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Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

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Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

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Conflict of interest statement

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