Open Access

Effects of etidronate on the Enpp1-/- mouse model of generalized arterial calcification of infancy

  • Authors:
    • Carmen Huesa
    • Katherine A. Staines
    • Jose Luis Millán
    • Vicky E. MacRae
  • View Affiliations

  • Published online on: May 15, 2015     https://doi.org/10.3892/ijmm.2015.2212
  • Pages: 159-165
  • Copyright: © Huesa et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder of spontaneous infantile arterial and periarticular calcification which is attributed to mutations in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) gene. Whilst the bisphosphonate, etidronate, is currently used off-label for the treatment for GACI, recent studies have highlighted its detrimental effects on bone mineralisation. In the present study, we used the Enpp1-/- mouse model of GACI to examine the effects of etidronate treatment (100 µg/kg), on vascular and skeletal calcification. Micro-computed tomography (µCT) analysis revealed a significant decrease in trabecular bone mass, as reflected by the decrease in trabecular bone volume/tissue volume (BV/TV; %), trabecular thickness, trabecular separation, trabecular number and pattern factor (P<0.05) in the Enpp1-/- mice in comparison to the wild-type (WT) mice. Mechanical testing revealed that in the WT mice, treatment with etidronate significantly improved work to fracture and increased work post-failure (P<0.05, in comparison to the vehicle-treated WT mice). This significant increase, however, was not observed in the Enpp1-/- mice. Treatment with etidronate had no effect on bone parameters in the WT mice; however, the Enpp1-/- mice displayed an increased structural model index (SMI; P<0.05). We used a recently developed 3D µCT protocol to reconstruct and quantify the extensive aortic calcification in Enpp1-/- mice in comparison to the WT mice. However, treatment with etidronate did not prevent de novo calcification, and did not arrest the progression of established calcification of the aorta.
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July-2015
Volume 36 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Huesa C, Staines KA, Millán JL and MacRae VE: Effects of etidronate on the Enpp1-/- mouse model of generalized arterial calcification of infancy. Int J Mol Med 36: 159-165, 2015
APA
Huesa, C., Staines, K.A., Millán, J.L., & MacRae, V.E. (2015). Effects of etidronate on the Enpp1-/- mouse model of generalized arterial calcification of infancy. International Journal of Molecular Medicine, 36, 159-165. https://doi.org/10.3892/ijmm.2015.2212
MLA
Huesa, C., Staines, K. A., Millán, J. L., MacRae, V. E."Effects of etidronate on the Enpp1-/- mouse model of generalized arterial calcification of infancy". International Journal of Molecular Medicine 36.1 (2015): 159-165.
Chicago
Huesa, C., Staines, K. A., Millán, J. L., MacRae, V. E."Effects of etidronate on the Enpp1-/- mouse model of generalized arterial calcification of infancy". International Journal of Molecular Medicine 36, no. 1 (2015): 159-165. https://doi.org/10.3892/ijmm.2015.2212