The Effects of Bisphosphonates on the Development of Glucocorticoid-induced Osteoporosis in a Mouse Model of Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a disease of progressive muscle inflammation and weakness. Glucocorticoids delay muscle damage but lead to loss of bone mineral and increased bone fragility. In this study, C57BL10ScSn-Mdx mice (Mdx), a commonly used animal model for DMD, received continuous glucocorticoid or placebo treatment from 5 to 13 weeks of age. Pamidronate, a bisphosphonate, was given for the first two weeks of glucocorticoid therapy in some mice to ameliorate glucocorticoid-induced bone loss. Mice treated with glucocorticoids lost cortical bone while those treated with both glucocorticoids and bisphosphonates showed improved cortical bone. Trabecular bone mass was not lost with glucocorticoid treatment, and was remarkably increased in the glucocorticoids and bisphosphonate treated Mdx mice. Muscle function was improved by glucocorticoid treatment with or without pamidronate. Thus, early bisphosphonate treatment was demonstrated to ameliorate glucocorticoid-induced cortical bone loss without any negative effects on dystrophic muscles in growing Mdx mice.M.Sc