Gastrin for prevention of steroid-associated osteonecrosis in rats

Summary Background/Objective Steroid-associated osteonecrosis (SAON) mostly occurs in large joints such as hip that finally results in joint collapse and replacement. An effective strategy for preventing SAON is inhibition of bone resorption and lipid formation, whereas promoting bone formation at osteonecrotic-sensitive skeletal sites. The objective of this study was to investigate whether gastrin administration could effectively prevent SAON in vivo and had a significant effect on osteogenesis, osteoclast differentiation and/or adipogenesis in vitro. Methods SAON was induced in rats by injection of both lipopolysaccharide and methylprednisolone. SAON rats were divided into three groups (untreated, low- ​and high-dose gastrin) and treated for two weeks. Lesions in SAON were identified, and efficacy of gastrin was evaluated in osteoclast activity, osteogenesis ​and adipogenesis. In vitro experiments evaluated the osteogenic and adipogenic potential of induced bone marrow stem cells, as well as osteoclast differentiation of stimulated bone marrow cells. Results Gastrin administration effectively prevented the development of SAON in vivo and significantly downregulated osteoclastogenesis, and upregulated osteogenesis in vitro. The underlying mechanism was potentially involved in the inhibited nuclear factor kappa-B (NF-κB) pathway leading to not only suppressed osteoclastogenesis but also facilitated osteoblastogenesis. Conclusion The present study demonstrated for the first time that gastrin could effectively prevent SAON in vivo and had a significant effect on osteogenesis, osteoclast differentiation and/or adipogenesis in vitro that should be an important link between gastrointestinal hormone and metabolic bone diseases. Translational potential of this article Gastrin prevents steroid-associated osteonecrosis with decreasing bone resorption and apoptosis, also enhancing bone formation. These findings provide in vivo evidence to support the use of gastrin to treat osteonecrosis.