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Abstract: FR-PO515

PTH Suppression Normalizes CKD-Induced Elevations in Cortical Bone Perfusion in an Animal Model of Progressive CKD

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Aref, Mohammad Walid, IU School of Medicine, Indianapolis, Indiana, United States
  • Swallow, Elizabeth A., Indiana University, Indianapolis, Indiana, United States
  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Allen, Matthew R., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Patients with chronic kidney disease (CKD) have accelerated bone loss, vascular calcification and abnormal biochemistries, together contributing to an increased risk of cardiovascular disease and fracture-associated mortality. Despite evidence of vascular pathologies and dysfunction in CKD, our group has shown that cortical bone tissue perfusion is higher in a rat model of high-turnover CKD. The goal of this experiment was to test the hypothesis that suppression of high turnover through calcium-induced suppression of PTH would normalize cortical bone vascular perfusion in the setting of CKD.

Methods

35-week-old animals in one of three groups: normal (NL), Cy/+ (CKD), and Cy/+ treated with 3% calcium water (CKD+Ca) for 10 weeks (n=6/group) underwent intra-cardiac fluorescent microsphere injection to assess bone tissue perfusion.

Results

CKD animals had serum blood urea nitrogen (BUN) and PTH levels significantly higher than NL (+182% and +958%; p<0.05). CKD+Ca animals had BUN levels that were similar to CKD, while PTH levels were significantly lower and comparable to NL. Dynamic bone histomorphometry of the proximal tibia demonstrated that active remodeling surfaces were significantly increased in the CKD animals compared to normal (+88%); levels were normalized to NL levels by calcium supplementation. MicroCT analysis of the proximal tibia cortical porosity showed a trend toward higher values in CKD (+401%; p=0.0962) but not CKD+Ca (+111%; p = 0.3787) compared to NL. Both femoral cortex (+220%, p=0.0083) and tibial cortex (+336, p=0.0009) tissue perfusion were significantly higher in CKD animals when compared to NL; perfusion was normalized to those of NL in CKD+Ca animals.

Conclusion

These data demonstrate that the combination of bone remodeling suppression and serum PTH reduction normalizes cortical bone perfusion in the setting of CKD. Further work will focus on uncoupling the effects of PTH reduction and turnover suppression on cortical bone perfusion in the setting of CKD.

Funding

  • NIDDK Support