| Summary: | Indiana University-Purdue University Indianapolis (IUPUI) === Patients with chronic kidney disease (CKD) are at an alarming risk of
fracture and cardiovascular disease-associated mortality. There is a critical need
to better understand the underlying mechanism driving altered cardiovascular
and skeletal homeostasis, as well as any connection between the two. CKD has
been shown to have negative effects on many vascular properties including endorgan
perfusion. Surprisingly, exploration of skeletal perfusion and vasculature
has not been undertaken in CKD. Alterations in bone perfusion are linked to
dysregulation of bone remodeling and mass in multiple conditions. An
understanding of the detrimental impact of CKD on bone perfusion is a crucial
step in understanding bone disease in these patients. The goal of this series of
studies was to test the global hypothesis that skeletal perfusion is altered in CKD
and that alterations can be modulated through treatments that affect metabolic
dysfunction. These studies utilized a rat model of CKD to conduct metabolic
assessments, bone perfusion measurements, bone imaging studies, and isolated
vessel reactivity experiments. Our results showed that animals with CKD had
higher levels of parathyroid hormone (PTH), leading to substantial bone
resorption. Bone perfusion measurements showed CKD-induced elevations in
cortical bone perfusion with levels progressing alongside CKD severity.
Conversely we show that marrow perfusion was lower in advanced CKD. PTH
suppression therapy in animals with CKD resulted in the normalization of cortical
bone perfusion and cortical bone mass, but did not normalize marrow bone perfusion. These results show a clear association between bone deterioration
and altered bone perfusion in CKD. While the relationship of altered bone
perfusion and bone deterioration in CKD necessitates further work, these results
indicate that determining the mechanisms of bone perfusion alterations and
whether they are drivers, propagators, or consequences of skeletal deterioration
in CKD could help untangle a key player in CKD-induced bone alterations.
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