Abstract: PO0548
Effects of Etelcalcetide on the Evolution of Cortical Porosity in Patients and Rats with CKD
Session Information
- Bone and Mineral Metabolism: Clinical
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Swallow, Elizabeth A., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Surowiec, Rachel K., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Metzger, Corinne E., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Sung, Joshua C., Columbia University Irving Medical Center, New York, New York, United States
- Agarwal, Sanchita, Columbia University Irving Medical Center, New York, New York, United States
- Khairallah, Pascale, Baylor College of Medicine, Houston, Texas, United States
- Hammond, Max A., Indiana University Purdue University at Indianapolis, Indianapolis, Indiana, United States
- Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Nickolas, Thomas, Columbia University Irving Medical Center, New York, New York, United States
- Allen, Matthew R., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
Suppression of chronically elevated parathyroid hormone (PTH) is a key treatment goal in patients with chronic kidney disease–mineral and bone disease (CKD-MBD). High PTH leads to increased cortical porosity which is associated to increased fracture risk. We tested the hypothesis that etelcalcetide, a calcimimetic agent, suppresses cortical pore development in CKD.
Methods
For our clinical cohort, etelcalcetide was dose-titrated to maintain serum PTH at 2-5 times the upper limit of normal of the local PTH assay, corresponding to the lower half of the KDIGO recommended target level. Patients were scanned at the distal tibia by high resolution peripheral QCT before and after 9-months of treatment. For our preclinical cohort, etelcalcetide was administered to an established model of progressive CKD (Male Cy/+ rat) for 3-5 weeks with in vivo microCT scans at the distal tibia taken at baseline and endpoint. Clinical and preclinical scans were registered across the two timepoints and individual cortical pores tracked for their dynamic action (filled, contracting, expanding, developed).
Results
Etelcalcetide significantly suppressed PTH in both the clinical (-64%) and pre-clinical (-77%) cohorts. Total cortical porosity did not increase over the course of treatment in either humans (baseline 5.8%; endpoint 5.8%) or rats (baseline 3.3%; endpoint 3.7%). However, changes were detected at the individual pore level by individual cortical pore analysis. In humans, of the baseline pores, 3% were unchanged, 25% had completely infilled, 40% had become smaller and 27% had increased in size. Twenty-one percent of the total pores at the end of treatment were formed de novo during treatment. The preclinical data followed similar trends, 43% of baseline pores had completely infilled, 20% had decreased in size, 22% had increased in size and 63% of the total pores end of treatment had formed de novo.
Conclusion
PTH suppression by etelcalcetide stabilizes overall cortical porosity yet permits dynamic activity of individual cortical pores during treatment. Further studies are needed to determine if de novo cortical porosity can be prevented by more aggressive PTH reduction.
Funding
- Veterans Affairs Support –