We used a fibula osteotomy model with associated damage to lateral compartment muscles (fibularis longus and brevis) in mice to test the hypothesis that blocking active myostatin with systemic injections of a recombinant myostatin propeptide would improve muscle and bone repair. Mice were assigned to two treatment groups after undergoing a fibula osteotomy: those receiving either vehicle (saline) or recombinant myostatin propeptide (20 mg/kg). Mice received one treatment on the day of surgery, another injection five days following surgery, and a third injection 10 days following surgery. Mice were euthanized 15 days following the osteotomy procedure. Bone repair was assessed using microCT and histological evaluation of the fracture callus. Muscle healing was assessed using Masson trichrome staining of the injury site, and image analysis used to quantify the degree of fibrosis and muscle regeneration.

Three propeptide injections over a period of 15 days increased body mass by 7% and increased muscle mass by almost 20% (P<.001). MicroCT analysis of the osteotomy site shows that by 15 days post-osteotomy, bony callus tissue was observed bridging the osteotomy gap in 80% of the propeptide- treated mice, but only 40% of the control (vehicle)-treated mice (P<.01). MicroCT quantification shows that bone volume of the fracture callus was increased by approximately 30% (P<.05) with propeptide treatment, and the increase in bone volume was accompanied by a significant increase in cartilage area (P=.01). Propeptide treatment significantly decreased the fraction of fibrous tissue in the wound site, and increased the fraction of muscle relative to fibrous tissue by 20% (P<.01).