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

Christopher L. Newman, Amy Creecy, Mathilde Granke, Jeffry S. Nyman, Nannan Tian, Max A. Hammond, Joseph M. Wallace, Drew M. Brown, Neal Chen, Sharon M. Moe, Matthew R. Allen

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalKidney international
Volume89
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • bone quality
  • chronic kidney disease
  • raloxifene

ASJC Scopus subject areas

  • Nephrology

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    Newman, C. L., Creecy, A., Granke, M., Nyman, J. S., Tian, N., Hammond, M. A., Wallace, J. M., Brown, D. M., Chen, N., Moe, S. M., & Allen, M. R. (2016). Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease. Kidney international, 89(1), 95-104. https://doi.org/10.1038/ki.2015.315