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Effect of 25-HydroxyVitamin D Deficiency and Its Interaction with Prednisone Treatment on Musculoskeletal Health in Growing Mdx Mice

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Abstract

Duchenne muscular dystrophy (DMD) results from genetic mutations of the gene encoding dystrophin, leading to muscle inflammation and degeneration that is typically treated with glucocorticoids. DMD and its treatment with glucocorticoids result in poor bone health and high risk of fractures. Insufficient levels of 25-hydroxyvitamin D (25-hydroxy D) that may contribute to weakened bone are routinely found in DMD patients. To determine the effect of 25-hydroxy D deficiency, this study examined the effects of low vitamin D dietary intake with and without glucocorticoids on the musculoskeletal system of the Mdx mouse model of DMD. At 10 weeks of age, Mdx mice on control diet had low trabecular bone mineral density of distal femurs and lumbar vertebrae with increased osteoclast numbers compared to wild-type mice. Low vitamin D intake resulted in 25-hydroxy D deficiency but had no effect on trabecular or cortical bone. Cortical bone loss and bone weakness were induced by glucocorticoids while they improved muscle grip strength in Mdx mice. 25-hydroxy D deficiency did not result in any significant effects on growing bone or muscle in the Mdx mice. In combination with glucocorticoid treatment, low 25-hydroxy D resulted in no change in cortical bone mineral density but bone ductility was significantly increased suggesting lower bone mineralization.

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Acknowledgements

This work was supported by a Grant to MDG and JM from the Canadian Institutes of Health Research (CIHR MOP-123265), S-HY received support from the Ontario Student Opportunity Trust Funds Award and an Ontario Graduate Studies Award.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Sung-Hee Yoon, Kim S. Sugamori & Jane Mitchell

  2. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Health System, Toronto, ON, Canada

    Sung-Hee Yoon & Marc D. Grynpas

  3. Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle, Room 4342, Toronto, ON, M5S 1A8, Canada

    Jane Mitchell

Authors
  1. Sung-Hee Yoon
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  2. Kim S. Sugamori
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  3. Marc D. Grynpas
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  4. Jane Mitchell
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Correspondence to Jane Mitchell.

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Conflict of interest

Sung-Hee Yoon, Kim S. Sugamori, Marc D. Grynpas, and Jane Mitchell declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

All animal care procedures were reviewed and approved by University of Toronto Animal Care Committee. For this type of study formal consent is not required.

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Yoon, SH., Sugamori, K.S., Grynpas, M.D. et al. Effect of 25-HydroxyVitamin D Deficiency and Its Interaction with Prednisone Treatment on Musculoskeletal Health in Growing Mdx Mice. Calcif Tissue Int 103, 311–323 (2018). https://doi.org/10.1007/s00223-018-0423-3

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