Prophylactic Bisphosphonate Therapy to Reduce Glucocorticoid-Induced Osteoporosis in a Mouse Model of Duchenne Muscular Dystrophy
Year: 2018
Type: dissertation
Abstract: Glucocorticoids (GCs) is a standard therapy to prolong muscle function in Duchenne Muscular Dystrophy (DMD) but induce osteoporosis. Bisphosphonates are used prophylactically in adults starting chronic GC treatment but are not in DMD patients until after they sustain fractures. C57BL/10ScSn-mdx mice, a common DMD animal model, was treated with prednisone (0.083 mg/day) from 5-10 weeks of age. Prophylactic pamidronate (8 mg/kg) was administered over 2 or 6 weeks starting at 4 weeks of age to assess the two dosing regimens in ameliorating GCinduced osteoporosis. Pamidronate did not attenuate GC’s improvement on muscle function. GC caused cortical bone loss and decreased cortical bone strength. Two- and 6-week pamidronate treatment improved bone architecture but only 2-week pamidronate improved cortical bone strength. The improvement of bone strength seen only with 2-week pamidronate highlights the importance of when and how much bisphosphonate is administered prior to glucocorticoid exposure, rather than the total cumulative dose.
Source: TSpace (University of Toronto)
Author: Jinghan Jenny Chen
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2942174725