Abstract: PO0550
Etelcalcetide Suppresses Trabecular and Cortical Bone Remodeling Without Altering Bone Quality in Patients with ESKD
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
- Metzger, Corinne E., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Allen, Matthew R., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Damrath, John G., Indiana University Purdue University at Indianapolis, Indianapolis, Indiana, United States
- Surowiec, Rachel K., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Wallace, Joseph M., Indiana University Purdue University at Indianapolis, 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
- Nickolas, Thomas, Columbia University Irving Medical Center, New York, New York, United States
Background
A key treatment goal in chronic kidney disease–mineral and bone disease (CKD-MBD) is suppression of chronically elevated parathyroid hormone (PTH). High PTH in CKD is associated with high bone turnover and fracture risk. Calcimimetics, such as etelcalcetide, are pharmacologic agents used clinically to reduce PTH to target levels. The goal of this study was to test whether 9-months of etelcalcetide treatment suppresses bone remodeling in patients with end stage kidney disease (ESKD) on hemodialysis with renal hyperparathyroidism (rHPT).
Methods
Five patients were enrolled. Mean age was 52±16 yrs and 80% were female. A quadruple label method was used to quantify pre- and post-treatment effects of etelcalcetide on bone turnover and quality. Prior to treatment, patients underwent tetracycline double labeling (3 days, 15 day interval, 3 days). Over 3 months, etelcalcetide was dose-titrated to maintain serum PTH at the lower half of the KDIGO recommended target (2-9x the upper limit of normal of the PTH assay). Patients were maintained on etelcalcetide at the specified PTH level for 6 months. At end of treatment, demeclocycline was administered (3 days, 15 day interval, 3 days) followed by transiliac crest bone biopsy.
Results
Mean PTH (pg/mL) levels at baseline and 9-months were 616±135 and 282±340, respectively. Following 9-months of treatment, trabecular bone formation rate was 80% lower (range of -54 to -96%) while intracortical rate was 83% lower (range of -61 to -94%). Suppressed remodeling of both trabecular and intracortical bone occurred through a reduction in both the amount of bone undergoing remodeling (~65%) and the mineral apposition rate (-35%). Static histomorphometry showed osteoclast surfaces (~1%) and eroded surfaces (5.3%) were within normal ranges. Raman and nano-indentation measures showed no differences in trabecular bone mineral/matrix properties between the two timepoints.
Conclusion
This work shows that etelcalcetide corrects high bone turnover in patients with rHPT on dialysis without affecting bone quality. More research is needed to determine whether the potent remodeling suppression by etelcalcetide can be used as a primary strategy to reduce risk of fracture in patients with ESKD.
Funding
- NIDDK Support –