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 5/6 th 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. 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.