Positive effects of bisphosphonates on bone and muscle in a mouse model of Duchenne muscular dystrophy.
Patients with Duchenne muscular dystrophy are at increased risk of decreased bone mineral density and bone fracture as a result of inactivity. To determine if antiresorptive bisphosphonates could improve bone quality and their effects on muscle we studied the Mdx mouse, treated with pamidronate during peak bone growth at 5 and 6 weeks of age, and examined the outcome at 13 weeks of age. Pamidronate increased cortical bone architecture and strength in femurs with increased resistance to fracture. While overall long bone growth was not affected by pamidronate, there was significant inhibition of remodeling in metaphyseal trabecular bone with evidence of residual calcified cartilage. Pamidronate treatment had positive effects on skeletal muscle in the Mdx mice with decreased serum and muscle creatine kinase and evidence of improved muscle histology and grip strength.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Canada and Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada.
Sung-Hee
SH
Yoon
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Kim S
KS
Sugamori
Canada and Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada.
Marc D
MD
Grynpas
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Electronic address: jane.mitchell@utoronto.ca.
Jane
J
Mitchell
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D003402:Creatine Kinase / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005452:Fluoresceins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D053580:Muscle Strength / Q000187:drug effects / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects*; D009137:Muscular Dystrophy, Animal / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D000077268:Pamidronate; D012333:RNA, Messenger / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005452:Fluoresceins; D012333:RNA, Messenger; C083098:calcein green; D003402:Creatine Kinase; D000077268:Pamidronate
Bisphosphonates; Bone mineral density; Bone strength; Creatine kinase; Duchenne muscular dystrophy