Bimagrumab (BYM338) is a novel fully human monoclonal antibody that exerts 
strong promyogenic effects on skeletal muscle by blocking activin type II 
receptors (ActRII). We investigated whether such blockade of ActRII by 
bimagrumab manifests any detrimental effect on outcomes of bone healing in a rat 
fibula osteotomy model. Animals (n = 150) were divided into 11 groups and 
received weekly treatment with either bimagrumab (10 or 100 mg/kg) or vehicle. 
Progression and outcomes of bone healing were assessed by lateral radiographs in 
vivo as well as by peripheral quantitative computed tomography (pQCT), 4-point 
bending test, and microscopic examination of the excised fibula at Day 29 or 
later. The radiographic progression of bone healing showed no significant 
differences between treatment groups in any comparative setting. In 3-month-old 
animals, pQCT revealed slightly reduced immature callus size and bone mineral 
content in bimagrumab-treated animals compared with vehicle-treated animals at 
Day 29 (p < 0.05). There were, however, no differences in mature callus size, 
bone mineral density, or biomechanical competency. The aforementioned effects on 
immature callus size were not present when the treatment was initiated 4 weeks 
post osteotomy or when treating 6-month-old animals. In summary, these findings 
suggest that there is no major impact of ActRII blockade on overall fracture 
healing, and delayed treatment initiation can bypass the small and transient 
effect of the therapy on immature callus formation observed in younger animals. 
Verification of these findings in humans is the subject of an ongoing clinical 
trial on elderly hip fracture patients.