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

Heveran, Chelsea M.; Schurman, Charles A.; Acevedo, Claire; Livingston, Eric W.; Howe, Danielle; Schaible, Eric G.; Hunt, Heather B.; Rauff, Adam; Donnelly, Eve; Carpenter, R. Dana; Levi, Moshe; Lau, Anthony G.; Bateman, Ted A.; Alliston, Tamara; King, Karen B.; Ferguson, Virginia L.

doi:10.1016/j.bone.2019.04.019

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

Journal Article · Thu May 02 00:00:00 EDT 2019 · Bone

DOI:https://doi.org/10.1016/j.bone.2019.04.019· OSTI ID:1760182

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]; ^[7]; Carpenter, R. Dana ^[1]; Levi, Moshe ^[8]; ^[9]; Bateman, Ted A. ^[4]; Alliston, Tamara ^[2]; King, Karen B. ^[10]; Ferguson, Virginia L. ^[1]

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

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 not 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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

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

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1760182

Journal Information:: Bone, Journal Name: Bone Vol. 127; ISSN 8756-3282

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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