Sclerostin antibody (SclAb) has been shown to increase bone mass in clinical trials of adult diseases of low bone mass, such as osteoporosis, and osteogenesis imperfecta (OI). Lifelong sclerostin deficiency or loss of function, such as that observed in patients with Sclerosteosis or Van Buchem disease, is associated with patterns of excessive bone growth, resulting in cranial compression and facial palsy associated with nerve impingement. The cranial effects of pharmacologic sclerostin inhibition during periods of rapid growth and development have not yet been described. However, the effect of morphological changes due to SclAb has significant implications in determining the efficacy of utilizing SclAb for a treatment.

To determine whether SclAb induces morphologic changes in the cranium that could reflect patterns associated with lifelong sclerostin deficiency, dimensional and volumetric measurements in the skulls of growing OI mice treated with SclAb were obtained through micro-computed tomography. Results indicate that SclAb demonstrates site-specific action in the crania. Anticipated gains in calvarial thickness were observed, while treatment-induced narrowing of cranial foramen was found at some sites, but not others. Despite this, no overt phenotypic changes in animal behavior, or symptoms associated with nerve compression were noted in this high-dose, long-duration experiment. These findings suggest that differences in foramen function of the sites measured here may dictate local susceptibility to SclAb-induced narrowing.