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

Huesa, C., Staines, K. A., Millan, J. L. and MacRae, V. E. (2015) Effects of etidronate on the Enpp1−/− mouse model of generalized arterial calcification of infancy. International Journal of Molecular Medicine, 36(1), pp. 159-165. (doi: 10.3892/ijmm.2015.2212) (PMID:25975272) (PMCID:PMC4494596)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Huesa, Dr Carmen
• Authors: Huesa, C., Staines, K. A., Millan, J. L., and MacRae, V. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: International Journal of Molecular Medicine
• Publisher: Spandidos Publications
• ISSN: 1107-3756
• ISSN (Online): 1791-244X
• Published Online: 15 May 2015
• Copyright Holders: Copyright © Huesa et al.
• First Published: First published in International Journal of Molecular Medicine 36:159-165
• Publisher Policy: Reproduced under a Creative Commons Licence