Objectives：To explore the effect of depression on fracture healing and its underlying mechanism. Methods：Sprague Dawley rats were randomly divided into Control（group A），Sham Control（group B） and Depression（group C） groups. Upper 1/3 transverse tibia fracture model and intramedullary fix were applied to Group A and C and sham operations（similar surgeries with no fracture and fix） were applied to Group B. The serum calcium（Ca），phosphorus（P） and alkaline phosphatase（ALP） were measured on day 7，14，and 21 after operations； the tibia image（DR） and pathology（HE stain） were examined on day14，28，and 56 after operations； the biomechanics（three-point bending test） were implemented on day 35 and 56 after operation； and the micro-CT were performed on day 28 and 56 after operation. Results：The serum P and ALP concentrations of group C were significantly lower than those of group A and B on day 7，14，and 21（P<0.05，P<0.01，n=10，respectively） after operations，while the serum Ca concentrations did not show any significant changes（P>0.05，n=10）. The tibia image（DR） showed no significant difference in callus volume between groups A and C on day 14 after operation（P>0.05，n=10），but had significant difference on day 28 and 56 after operation（P<0.05，n=10）.HE staining showed significantly worse recovery of the fracture zone in group C than in group A on day 14，28，and 56 after operations. The results from three point bending experiment revealed a significantly worse recovery of all bending indices（stiffness，strength，deflection，load，and movement） of group C than the control group A on day 35 and 56 after operations（P<0.05，n=10）. Micro-CT also showed that the osteogenesis indicators，including bone volume fraction，thickness of trabecular bone，and number of trabecular bone，were significantly lower in group C than that in the group A on day 28 and 56 after operation（P<0.05，n=10）. The volume of interstitial bone trabecular space and area of trabecular bone of group C was significantly greater than that of control group A（P<0.05，n=10）. Conclusions：Depression may delay the primary callus and tibia fracture healing through an effect on the metabolism of phosphorus which caused a down-regulation of serum P and ALP concentrations in rats. These results provide a novel underlying mechanism and also a potential therapeutic strategy for depression caused delay of bone fracture healing.
