Osteogenesis imperfecta (OI) is a potentially crippling congenital condition affecting approximately 6 out of every 100,000 children worldwide. Infants born with this condition develop malformed and very brittle bones. Researchers from NIH, Amgen, and the University of Michigan found success treating OI with a sclerostin antibody in a Brtl/+ mouse model.
OI is known as “brittle bone disease” because of a collagen deficiency causing defective bone connective tissue. This brings about bulges in the bone and very low bone density because of steric inefficiencies in bone formation as if the bones put together by a bad Tetris® player. The current treatment for OI makes use of anti-resorptive bisphosphonate (BP), which works to increase bone mineral density short term. However, the effect on long bones and longer term bone growth has been equivocal. Introducing a sclerostin anti-body (Scl-Ab) was the answer to this caveat.
Sclerostin is a naturally occurring protein in the body that hinders bone synthesis. It was hypothesized that by blocking sclerostin, one would have increased bone growth causing greater bone density. Brtl/+ (OI induced) mice and wild type (WT) mice were randomly injected with either Scl-Ab or placebo, and subsequent bone strength tests were done to test.
After two weeks of treatment, mice showed increased cortical bone formation rate (76% in Brtl/+, 108% in WT), spongy bone thickness, and cortical bone shape and size. These results were seen due to increased osteoblast activity as they were not hindered by sclerostin. This leads to consistent bone anabolism.
The effects of the Scl-Ab were successful in promoting bone synthesis, opposing the hollow bone forming nature of the dysfunctional collagen seen in OI patients. This therapy proved more potent in increasing bone mass and reducing fragility than the classic BP treatment. If adopted, this treatment may prove beneficial for OI patients and their families by not only preventing broken bones, but healing broken hearts.
Benjamin P. Sinder, Mary M. Eddy, Michael S Ominsky, Michelle S. Caird, Joan C. Marini, Kenneth M. Kozloff. 2013. Sclerostin Antibody Improves Skeletal Parameters in a Brtl/+ Mouse Model of Osteogenesis Imperfecta. Journal of Bone and Mineral Research.