Title: Chronic kidney disease and aging differentially diminish bone material and microarchitecture in C57Bl/6 mice

Abstract

Chronic kidney disease (CKD) is a common disease of aging and increases fracture risk over advanced age alone. Aging and CKD differently impair bone turnover and mineralization. We thus hypothesize that the loss of bone quality would be greatest with the combination of advanced age and CKD. We evaluated bone from young adult (6 mo.), middle-age (18 mo.), and old (24 mo.) male C57Bl/6 mice three months following either 5/6th nephrectomy, to induce CKD, or Sham procedures. CKD exacerbated losses of cortical and trabecular microarchitecture associated with aging. Aging and CKD each resulted in thinner, more porous cortices and fewer and thinner trabeculae. Bone material quality was also reduced with CKD, and these changes to bone material were distinct from those due to age. Aging reduced whole-bone flexural strength and modulus, micrometer-scale nanoindentation modulus, and nanometer-scale tissue and collagen strain (small-angle x-ray scattering [SAXS]. By contrast, CKD reduced work to fracture and variation in bone tissue modulus and composition (Raman spectroscopy), and increased percent collagen strain. The increased collagen strain burden was associated with loss of toughness in CKD. In addition, osteocyte lacunae became smaller, sparser, and more disordered with age for Sham mice, yet these age-related changes were notmore » clearly observed in CKD. However, for CKD, larger lacunae positively correlated with increased serum phosphate levels, suggesting that osteocytes play a role in systemic mineral homeostasis. This work demonstrates that CKD reduces bone quality, including microarchitecture and bone material properties, and that loss of bone quality with age is compounded by CKD. Finally, these findings may help reconcile why bone mass does not consistently predict fracture in the CKD population, as well as why older individuals with CKD are at high risk of fragility.« less

Authors:

Heveran, Chelsea M. ^[1]; Schurman, Charles A. ^[2]; Acevedo, Claire ^[3]; Livingston, Eric W. ^[4]; Howe, Danielle ^[5]; Schaible, Eric G. ^[6]; Hunt, Heather B. ^[7]; Rauff, Adam ^[1]; Donnelly, Eve  ^[7];

• Search DOE PAGES for author "Donnelly, Eve"
• Search DOE PAGES for ORCID "0000-0001-8165-9568"

Carpenter, R. Dana ^[1]; Levi, Moshe ^[8]; Lau, Anthony G.  ^[9];

• Search DOE PAGES for author "Lau, Anthony G."
• Search DOE PAGES for ORCID "0000-0002-1094-4289"

Bateman, Ted A. ^[4]; Alliston, Tamara ^[2]; King, Karen B. ^[10]; Ferguson, Virginia L. ^[1]

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+ Show Author Affiliations

1. Univ. of Colorado, Boulder, CO (United States)
2. Univ. of California, San Francisco, CA (United States)
3. Univ. of Utah, Salt Lake City, UT (United States)
4. Univ. of North Carolina, Chapel Hill, NC (United States)
5. College of New Jersey, Ewing, NJ (United Sates)
6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
7. Cornell Univ., Ithaca, NY (United States)
8. Georgetown Univ., Washington, DC (United States)
9. College of New Jersey, Ewing, NJ (United States)
10. Univ. of Colorado, Aurora, CO (United States)

Publication Date:

Thu May 02 00:00:00 EDT 2019

Research Org.:

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Institutes of Health (NIH)

OSTI Identifier:

1760182

Grant/Contract Number:  

AC02-05CH11231; T32 AG000279; UL1 TR001082

Resource Type:

Accepted Manuscript

Journal Name:

Bone

Additional Journal Information:

Journal Volume: 127; Journal ID: ISSN 8756-3282

Publisher:

Elsevier

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; CKD; aging; bone quality; bone fragility; collagen