Bone Abstracts (2013) 1 OC2.1 | DOI: 10.1530/boneabs.01.OC2.1

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of duchenne muscular dystrophy

Tero Puolakkainen1, Hongqiang Ma3, Arja Pasternack4, Heikki Kainulainen3, Olli Ritvos4, Kristiina Heikinheimo5, Juha Hulmi3 & Riku Kiviranta1,2


1University of Turku, Turku, Finland; 2Turku University Hospital, Turku, Finland; 3University of Jyväskylä, Jyväskylä, Finland; 4University of Helsinki, Helsinki, Finland; 5Department of Oral and Maxillofacial Surgery, University of Turku.


Patients with Duchenne muscular dystrophy (DMD) carry a mutation in the dystrophin gene that leads to progressive muscle degeneration. In addition, DMD patients develop low bone mass especially in long bones and have high incidence of fractures. The underlying mechanisms for decreased bone mass remain unclear but muscle weakness and increased IL6 levels may play a role. Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and strength in DMD. The aim of our study was to test whether inhibition of this pathway in MDX mice, a model for DMD, would improve bone properties in addition to muscle strength.

Sixteen MDX mice were randomised 1:1 to receive either PBS or an in-house soluble activin type IIB-receptor (sAct-RIIB-Fc) 5 mg/kg i.p. once weekly for 7 weeks. Hind limbs and vertebrae were harvested and subjected to μCT and biomechanical testing.

As expected, treatment of MDX mice with sAct-RIIB-Fc resulted in significantly increased body and muscle weights compared to PBS group. μCT analysis of the femurs showed increased bone volume and trabecular number (BV/TV +70%, Tr.N+60%, P<0.05 in both) in sAct-RIIB-Fc treated group. sAct-RIIB-Fc increased bone mass also in vertebrae (BV/TV +20%, Tr.N+30%, P<0.05 in both) but the effects were more modest in axial skeleton than in long bones. Increased bone mass in femurs translated into enhanced bone strength as the maximum force (+19%, P<0.01) and stiffness (+19%, P<0.01) were significantly elevated in sAct-RIIB-Fc-treated mice.

Our results indicate that treatment of MDX mice with the soluble activin type IIB-receptor results in a robust increase in both bone mass and strength in long bones but positively affects also axial skeleton. Thus sAct-RIIB-Fc could be an attractive option in the treatment of DMD, addressing both muscular and skeletal sequelae of the disease.

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