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Abstract: PO0519

PTH Suppression Improves Cortical Bone Parameters in Aging Mice with CKD

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Tippen, Samantha P., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Metzger, Corinne E., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Swallow, Elizabeth A., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Sacks, Spencer, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Allen, Matthew R., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Chronic kidney disease (CKD) and aging are each independently associated with higher risk of fracture due to significant loss of bone mass and quality. In CKD, cortical thinning and cortical porosity are driven by elevated parathyroid hormone (PTH) and directly linked to increased fracture risk in CKD patients. Overlaying CKD and aging produces cortical porosity that is higher than either condition alone. Previously, we discovered potent suppression of PTH in rodents with CKD infilled existing pores; however, it is unknown if aged bone may react similarly given attenuated osteoblast function. The goal of this study was to assess the impacts of PTH suppression on cortical porosity in young and aging CKD mice.

Methods

Male C57Bl/6J mice were used at 16 and 66 weeks of age. CKD was induced via dietary adenine (AD, 0.2% for 6 weeks + 2 weeks of maintenance on control diet). Control mice were fed normal control diet for the duration of the study. After 8 weeks of CKD induction, calcium water was provided for 4 weeks to suppress PTH (n=8/group). Outcome measures included biochemical assays and bone architecture via µCT.

Results

Aging AD mice had more than six-fold higher PTH levels than age-matched controls and more than two-fold higher PTH levels than young AD mice. Administration of calcium water led to lower PTH in both young AD and aging AD mice, 85% and 82%, respectively. Regardless of age, AD mice showed lower cortical bone area (~32%) and cortical thickness (32-40%) versus age-matched controls; mice given calcium water had higher cortical bone area (11%, 8%) and cortical thickness (20%, 10%) compared to untreated age-matched AD. Due to large variability, there were no statistical differences in cortical porosity between groups, although porosity did trend lower in both calcium water-treated young AD (-74%) and aging AD (-29%) groups compared to age-matched controls.

Conclusion

These data demonstrate the beneficial impact of PTH suppression on cortical bone in young and aging animals; however, PTH suppression alone may not be enough to sufficiently reduce cortical porosity, particularly in aging bone. This lays the groundwork for future studies to assess clinically available therapies of PTH suppression and their efficacy in reducing cortical porosity in a broad spectrum of CKD patients.

Funding

  • Other NIH Support