Bone Abstracts

Osteogenesis imperfecta (OI) is not only characterized by fragile bones but also impaired muscle mass and function. Inhibition of signaling through the activin receptor IIB has the potential to improve both muscle and bone mass. Here we investigated the effect of a soluble activin receptor IIB ligand, ACE-2494 (10 mg/kg twice a week), in 4-week old Col1a1Jrt/+ male mice, a model of severe dominant OI caused by a Col1a1 splice site mutation. Four weeks of treatment with ACE-2494 alone resulted in a significant gain in muscle mass (quadriceps +42%, tibialis anterior +33%, extensor digitorum longus +46%, soleus +29%, gastrocnemius +15%) and femur length (+5%) compared to vehicle-treated OI mice (all P<0.001), but no significant treatment effect was found for bone mass or mechanical properties of the right femur using three-point bending test. We therefore combined ACE-2494 treatment with concomitant intraperitoneal zoledronate injections (0.05 mg/kg three times a week). Compared to ACE-2494 alone, this resulted in increased bone mass (+405% in trabecular BV/TV at the femoral distal metaphysis) and cortical thickness (+42% at the femoral midshaft) (all P<0.001). In conclusion, ACE-2494 stimulated growth in muscle mass and bone length. Combination treatment of ACE-2494 with zoledronate in addition increased trabecular and cortical bone mass.

Disclosure: Dr Frank Rauch: PreciThera Inc: Study grant to institution.