Midpalatal expansion has been used in orthodontics to address maxillary deficiency in the transverse dimension. The separation of the palate causes micro tears along the suture and repair ensues in the resulting space. However, even after a period of stabilization, relapse can occur to adversely affect the orthodontic treatment outcomes. Currently, there is no consensus as to the cause of relapse; whether, it is mediated by the bony palatine shelves or the dense connective tissue covering them. Therefore, elucidating the molecular and cellular mechanism involved in the midpalatal suture expansion can be used as a foundation to explore ways to reduce relapse in orthodontic patients who undergo maxillary expansion. This is especially critical in many craniofacial patients, such as those with cleft lip and/or palate (CLP) malformations, in which maxillary expansion provides a sound foundation for dental development. The current therapeutic modalities do not provide a stable maintenance of the expansion, as relapse can occur in up to 45% of patients. In addition, prior research has shown that the anti-resorptive drug class of bisphosphonates (BP) can reduce the relapse ratio following expansion. However, the process by which BP affect relapse is still unclear. The long-term goal of this study is to understand the etiology of relapse and to diminish relapse after maxillary expansion. This study hypothesized that oral myofibroblasts in soft tissue played a role in relapse following palatal expansion and that BP decreased relapse by inhibiting myofibroblast differentiation of normal human oral fibroblasts (NHOFs). The specific aims of this study were (1) to examine the changes that BP have on myofibroblasts and their differentiation of NHOFs; and (2) to establish a mouse model for studying palatal expansion using a modified expander. BP inhibited gene expression and protein expression of ?-SMA in NHOF cells in a time-dependent and dose-dependent manner. A functional collagen matrix assay demonstrated the anti-contractile effect of BP on myofibroblasts. The establishment of the mouse model involved mice that underwent 7 days of palatal expansion using an expander with a helical spring and arms that loop around the central incisors. Midpalatal skeletal expansion was successfully achieved in mice. After expansion, the control group (n=15) were injected with physiologic saline solution (5mg/kg, 0.9% sodium chloride) and the experimental group (n=15) were subcutaneously injected with 0.1mg/kg of Zoledronate dissolved in physiologic saline solution. The expanders were then be converted to retention appliances and allowed 7 days of retention. At the end of retention, half from each group was immediately sacrificed. The other half was sacrificed after undergoing 7 days of relapse in which the retention device were removed. Data analysis conducted through micro-CT analysis and histology demonstrated that BP administration reduced relapse following expansion and that higher bone volume and density after BP injection enhanced post-expansion stability.