Bone Abstracts

Objective: Osteogenesis imperfecta (OI) is primarily characterized by bone fragility but is also associated with lower muscle mass and function. As muscle mass and bone mass are closely linked, an intervention that increases muscle mass should also increase bone mass. Here we investigated the effect of a novel activin receptor IIB ligand trap, ACE-2494 (Acceleron Pharma), on skeletal muscle mass and bone properties in a mouse model of severe dominant OI, the Col1a1^Jrt/+ mouse.

Methods: ACE-2494 (3 mg or 10 mg per kg body mass) or vehicle was injected subcutaneously twice per week for 4 weeks into male OI and wild-type (WT) mice, starting at 8 weeks of age.

Results: At baseline, OI mice had 20% lower body mass than control littermates. This difference persisted during the intervention as OI and WT exhibited a similar dose-dependent increase in body mass during ACE-2494 treatment. ACE-2494 injections led to a dose-dependent gain in muscle mass in OI and WT cohorts (Figure 1). In WT, ACE-2494 treatment also increased soleus weights (by 16 and 34%) and EDL weights (by 20 and 65%) in a dose-dependent manner. In OI mice, ACE-2494 increased soleus and EDL mass to a similar extent in both dose groups (by 65 and 75%, respectively). ACE-2494 had no effect on heart muscle mass or liver mass. There was also no effect on either femoral length or trabecular bone volume in the distal femoral metaphysis. However, ACE-2494 treatment resulted in an increased mid-diaphyseal periosteal diameter in OI mice only, leading to an improved polar moment of inertia.

Conclusion: ACE-2494 increases muscle mass and seem to improve diaphyseal bone geometry in a model of severe OI.

Disclosure: The authors declared no competing interests.