G-protein coupled receptors are involved in many signal transduction pathways. The Gαs protein becomes activated following ligand binding, to stimulate downstream adenylyl cyclase. Previously, Zhang et al. generated a transgenic murine model with osteoblastic Gαs overexpression, which led to increased bone mass. µCT showed a marked increase in closed cortical porosity, which histologically showed intracortical pores lined with osteoclasts.

Pamidronate is clinically used for excessive bone loss. It inhibits farnesyl pyrophosphate, an enzyme involved in synthesis of regulatory proteins, leading to osteoclastic apoptosis. Our objective was to use pamidronate to ameliorate intracortical porosity. Low dose pamidronate led to increased trabecular bone mass in wild-type mice only. High dose pamidronate led to increased trabecular bone mass in both wild-type and Gs-Tg mice. Cortical porosity was not affected at both dosages. There is evidence to suggest that pamidronate unsuccessful in affecting intracortical porosity due to lack of penetration into the intracortical space.