Local administration with tauroursodeoxycholic acid could improve osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats

Despite advances in the pathogenesis of Tauroursodeoxycholic acid (TUDCA) on bone, the understanding of the effects and mechanisms of bone osseointegration in TUDCA-associated Hydroxyapatite (HA)-coated titanium implants remains poor. Therefore, the present work was aimed to evaluate the effect of local administration with TUDCA on HA-coated titanium implants osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: sham operation(Sham) group, OVX group and TUDCA group, and all the rats from Sham group and OVX group received HA implants and animals belonging to group TUDCA received TUDCA-HA implants until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. TUDCA increased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed systemic TUDCA showed positive effects than OVX group on bone formation in osteopenic rats, with beneficial effect on via activation OPG/RANKL pathway and BMP-2/Smad1 pathway and microarchitecture as well as by reducing protein expression of TNF-α and IFN-γ. The present study suggests that local use of TUDCA may bring benefits to the osseointegration of HA-coated titanium implants in patients with osteoporosis, and this effect may be related to the inhibition of inflammatory reaction and promotion of osteogenesis.