Current therapies for pediatric osteoporosis, regardless of cause, are limited. There are no therapies to prevent fractures; nor do we have any way to identify which patients at risk for osteoporosis will fracture. The long-term goal of my research is to better identify and treat pediatric patients at risk for osteoporosis, even before they present with fractures.

To better understand the causes of pediatric osteoporosis, it is important to first understand bone growth and development. My laboratory uses rare genetic bone disorders as a model through which to gain knowledge of the mechanisms underlying bone growth and to develop new therapeutic targets. The current genetic model we use is Osteogenesis Imperfecta (OI). In the US, about 90-95% of patients with OI have dominant mutations one of the two type I collagen genes, COL1A1 or COL1A2. Patients with OI typically present with multiple fractures and can go on to develop bone deformities and significant disability over the course of their lives. My lab has previously shown that dominant mutations in the cell surface receptor low-density liproprotein receptor-related protein 5 (LRP5) increase bone mass and reduce fracture risk in mouse models of OI. Interestingly, this mutation also improves mutation collagen trafficking in osteoblasts with OI. We are now focused on understanding the mechanisms behind this improvement in osteoblast function.

A second aim of my laboratory is focused on identifying modifying mutations in OI. It is well known that patients with OI have varying phenotypes, even when they have the exact same mutation and are members of the same family. We also see variations in phenotypes among mice with OI when they are outbred. We are now utilizing these findings to identify modifying genes in OI using outbred mouse strains and zebrafish models of OI. At the same time, we have an ongoing clinical study to enroll patients who have differing OI phenotypes so that we can confirm any genetic findings from our animal studies. We hypothesize that many of the genes that we find that modify the OI phenotype will also be genes that increase the risk of pediatric osteoporosis in other patients.