Positive effects of bisphosphonates on bone and muscle in a mouse model of Duchenne muscular dystrophy

• We treated growing Mdx mice with pamidronate for 2 weeks.
• Pamidronate treatment increased cortical bone mineral density and bone strength.
• Pamidronate treatment suppressed trabecular bone remodeling.
• Pamidronate treatment improved muscle strength and suppressed serum and muscle creatine kinase levels.

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.