Abstract: PO0352
Effect of PTH Dosing Frequency and Amplitude on Bone Health: From Anabolism to Catabolism
Session Information
- Biochemical Aspects of Mineral and Bone Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Cherif, Alhaji, Renal Research Institute, New York, New York, United States
- Kotanko, Peter, Renal Research Institute, New York, New York, United States
Background
In patients with chronic kidney disease or primary hyperparathyroidism, chronically elevated parathyroid hormones (PTH) levels exert catabolic effects on the bone. In contrast, PTH cycling or daily application of teriparatide (TP) promotes bone formation. These responses have important clinical and therapeutic implications. Although the anabolic effects of PTH cycling are widely accepted, the underlying dynamics are not well understood.
Methods
We developed a physiology-based model quantitating the interrelations of osteoclasts, osteoblasts and osteocytes on bone remodeling (Cherif et. al., NDT 33(1), 2018, i165-6). Using the validated model, we explore the effect of altered PTH (TP) dosing (e.g., dosing frequency and amplitude) on bone catabolism and anabolism, respectively.
Results
The model accurately predicts differential responses of anabolic and catabolic effects of continuously and intermittently elevated PTH (TP) levels, respectively. We observe that intermittent dosing of PTH with a high frequency and amplitude induces bone catabolism similar to that seen with chronically elevated PTH. We see a more than 3-fold change from baseline in osteoclastic over osteoblastic activities, resulting in catabolism. Low PTH frequency with high dosing amplitude induces both osteoclastic and osteoblastic activities, but the net result is bone anabolism. Figure 1 shows a region where high osteoblastic activities exceed osteoclastic resorption. These findings suggest the existence of optimal PTH (TP) frequency-amplitude values that enhance anabolic gains, beyond which there can be a detrimental effect on bone.
Conclusion
Our results suggest that both frequency and amplitude of PTH (TP) cycling affect the balance of catabolic and anabolic effects. Understanding the underlying mechanism of differential responses induced by intermittent and continuous levels of PTH, respectively, may provide new therapeutic options for patients and minimize unintended consequences of intervention.
Illustrates regions with high osteoblastic and osteoclastic activities corresponding to anabolic gains and/or catabolic loss in bone health as a function of dosing frequency and amplitude.