PTH treatment is effective in the Aga2/+ mouse model of moderate to severe osteogenesis imperfecta.

Abstract

Osteogenesis imperfecta (OI) is a genetically heterogenous disorder characterized by brittle bone and recurrent fractures. The majority of OI is clinically categorized into mild, moderate, severe, and perinatal lethal forms. A clinical study on the use of intermittent parathyroid hormone (PTH) as an anabolic therapy for OI found PTH was effective in mild, but not in individuals with moderate/severe OI. However, this sub-group analysis was relatively small and considered preliminary by the authors. Since then, research on PTH therapy in OI has focused on mild OI and no studies of PTH use in moderate/severe OI patients or animal models have been reported. In this work, we used the Aga2/+ mouse, an established autosomal dominant model of moderate/severe OI, to investigate whether PTH treatment has an effect on bone. In vitro, Aga2/+ osteoblasts were sensitive to PTH and exhibited similar transcriptional changes compared to WT. In vivo, PTH treatment improved lumbar trabecular bone, increased cortical bone area fraction in the mid-femur, and, in females, led to improved biomechanical properties. These results demonstrate the Aga2/+ model responded to PTH and support further investigation into whether PTH is effective in adult individuals with moderate/severe OI who have limited treatment options.