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Publication : Intermittent PTH treatment improves bone and muscle in glucocorticoid treated Mdx mice: A model of Duchenne Muscular Dystrophy.

First Author  Yoon SH Year  2019
Journal  Bone Volume  121
Pages  232-242 PubMed ID  30716510
Mgi Jnum  J:276686 Mgi Id  MGI:6287061
Doi  10.1016/j.bone.2019.01.028 Citation  Yoon SH, et al. (2019) Intermittent PTH treatment improves bone and muscle in glucocorticoid treated Mdx mice: A model of Duchenne Muscular Dystrophy. Bone 121:232-242
abstractText  Duchenne Muscular Dystrophy (DMD) is a progressive muscle disorder caused by genetic mutations of the dystrophin encoding gene. In the absence of functional dystrophin, DMD patients suffer from muscle inflammation and wasting, as well as compromised bone health with increased risk of fracture. The use of high dose glucocorticoids (GC) as the standard therapy also contributes to bone fragility. This study examined the effects of intermittent, daily administered parathyroid hormone (iPTH), an approved bone anabolic therapy, on growing bone and dystrophic muscle in the presence and absence of prednisone treatment using the Mdx mouse model of DMD. Five-weeks of prednisone treatment in Mdx mice decreased cortical bone thickness and area (p<0.001), with a large increase in endocortical osteoclasts that were significantly improved by PTH treatment (p<0.001). GC-induced decreases in cortical bone toughness and modulus were improved with iPTH therapy (p<0.05). Mdx mice showed significantly less bone mass in trabecular compartments of lumbar vertebrae and iPTH treatment, with or without glucocorticoids, significantly improved structural and material properties of this bone. Prednisone improved grip strength and endurance of treadmill running, which were maintained and further improved, respectively, in co-treated Mdx mice. Altogether, our study demonstrates that iPTH therapy significantly ameliorated GC-induced bone loss and maintained or further enhanced the positive effects of GCs on dystrophic muscle function. These findings give insight into the potential for use of teriparatide to treat growing bone in children with DMD.
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