Abstract: PO0520
Calcimimetics Alter Periosteal and Perilacunar Bone Matrix Properties in Early CKD
Session Information
- Bone and Mineral Metabolism: Causes and Consequences
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 401 Bone and Mineral Metabolism: Basic
Authors
- Damrath, John G., Purdue University Weldon School of Biomedical Engineering, West Lafayette, Indiana, United States
- Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Wallace, Joseph M., Indiana University Purdue University at Indianapolis School of Engineering and Technology, Indianapolis, Indiana, United States
Background
Chronic kidney disease (CKD) patients have an elevated fracture risk due to hyperparathyroidism, cortical porosity, and reduced bone material quality. Calcimimetic drugs are used to lower PTH in dialysis patients, but their impact on bone matrix quality in early CKD remains unknown. We hypothesized that tissue-level bone quality is altered in early CKD and that calcimimetic treatment improves bone quality.
Methods
Male Cy/+ rats fed a casein-based diet undergo progressive CKD with mineral and bone disorder. 18-week-old rats (stage 3 CKD, N=12) were treated with the calcimimetic KP-2326 (0.6 mg/kg i.p. 3x/wk). N=12 normal littermates (NL) and untreated CKD rats received the casein diet to control mineral intake. Calcein was administered 4 and 14 days prior to sacrifice at 28 weeks (stage 4 CKD). Blood was drawn and femora were harvested for MicroCT and 4-point bending. Femur sections were cut and polished for colocalized Raman spectroscopy and nanoindentation. Colocalization was run in fluid in periosteal bone using calcein as a guide and in concentric ellipses around osteocyte lacunae.
Results
PTH was 284% higher in CKD vs NL and KP reduced PTH by 92% vs CKD. Neither CKD nor KP altered cortical porosity and KP did not improve structural mechanical properties vs CKD. In new periosteal bone, CKD reduced carbonate substitution by 20% and elastic modulus by 15% vs NL while KP increased mineral crystallinity by 4% vs NL and restored elastic modulus to NL levels. In perilacunar bone, KP reduced carbonate substitution and increased elastic modulus and hardness vs CKD.
Conclusion
This study demonstrates that CKD and KP alter bone matrix composition and material properties on the tissue level prior to structural changes such as cortical porosity. The perilacunar data suggests that osteocytes may actively alter their surrounding matrix in CKD and that calcimimetics may help prevent these changes prior to a decline in bone structural integrity.
Funding
- NIDDK Support