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Sclerostin antibody: a promising treatment of osteogenesis imperfecta?


Sinder et al. used an established mouse model of osteogenesis imperfecta (OI; commonly called brittle bone disease) to investigate whether an antibody specific for sclerostin may work via the canonical Wnt pathway to stimulate osteoblasts to increase bone mass and reduce fracture risk.

Brtl/+ mice, which have a G349C point mutation on col1al that induces very similar effects to OI in patients, were treated with an antibody specific to sclerostin (Scl-Ab), which is currently being tested in clinical trials as an osteoporosis therapy. After two weeks, Brtl/+ mice and wildtype mice showed elevated serum osteocalcin, which indicated an increase in osteoblast activity and bone formation.

Both groups of mice subsequently showed improvements in bone mass and increased ultimate load and stiffness of the long bones. The authors conclude the use of Scl-Ab warrants further investigation as an anabolic therapy for pediatric OI.

Editor's comment: This study of the effects of sclerostin antibody in a mouse model of OI demonstrates that pushing osteoblasts to synthesize greater amounts of abnormal collagen actually improves bone mass, quality, and ultimately strength, which is surprising. The results provide the basis of a new treatment paradigm in OI.

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