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)

217861.pdf - Published Version
Available under License Creative Commons Attribution.



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
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 (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

University Staff: Request a correction | Enlighten Editors: Update this record