Research Article Open Access

Action of Calciotropic Hormones on Bone Metabolism-Role of Vitamin D3 in Bone Remodeling Events

Catharine Andresen1, Ellen Olson1, Chudy I. Nduaka1, Rich Pero1 and Cedo M. Bagi1
  • 1 Safety Sciences, Pfizer Inc, United States

Abstract

Vitamin D3 is known to have immunosuppressive effects that can be beneficial for treatment of immune disorders and transplant rejection, however therapeutic application is limited due to hypercalcemia and hypercalcuria. The goal of our studies was to explore both the acute and steady state effects of vitamin D3 on bone remodeling as potential limiting factors to broader use of vitamin D3 in the clinic. Vitamin D3 was evaluated for its skeletal effects in both thyroparathyroidectomized (TPTx) and intact rat models. In TPTx rats, deprivation of thyroid and parathyroid hormones and calcitonin creates a low state of bone modeling and remodeling ideal for evaluation of changes imposed by drug intervention. The use of both models allowed for discrimination of individual (TPTx) versus combined (intact) effects of calciotropic hormones on bone and calcium metabolism. Our studies have confirmed the limitations of using vitamin D3 for treatment/co- treatment of immune disease in humans due to the intrinsic hypercalcemic properties of the hormone, and also highlighted the potential of vitamin D3 to negatively impact skeletal integrity due to excessive bone remodeling driven by bone resorption. Taken together our data emphasize the importance of including biomarkers of bone remodeling as an integral part of clinical and preclinical studies using vitamin D3 to treat immune disorders and suggest the need for co-treatment with an antiresorptive agent to counteract hypercalcemia and deterioration of bone.

American Journal of Immunology
Volume 2 No. 2, 2006, 40-51

DOI: https://doi.org/10.3844/ajisp.2006.40.51

Submitted On: 4 April 2006 Published On: 30 June 2006

How to Cite: Andresen, C., Olson, E., Nduaka, C. I., Pero, R. & Bagi, C. M. (2006). Action of Calciotropic Hormones on Bone Metabolism-Role of Vitamin D3 in Bone Remodeling Events. American Journal of Immunology, 2(2), 40-51. https://doi.org/10.3844/ajisp.2006.40.51

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Keywords

  • Calcitriol
  • Parathyroid hormone
  • Calcitonin
  • Rats
  • Thyroparathyroidectomy
  • Biomarkers