SERUM 1-ALPHA,25-DIHYDROXYVITAMIN D-3 ACCUMULATES INTO THE FRACTURE CALLUS DURING RAT FEMORAL FRACTURE-HEALING

1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) is thought to be an importa nt systemic factor in the fracture repair process, but the mechanism o f action of 1,25(OH)(2)D-3 has not been clearly defined. In this study , I;he role of 1,25(OH)(2)D-3 in the fracture repair process was analy zed in a rat closed femoral fracture model. The plasma concentration o f 1,25(OH)(2)D-3 rapidly decreased on day 3 and continued to decrease to 10 days after fracture. We assessed whether this decrease was based on the accelerated degradation or retardation of the synthesis rate o f 1,25(OH)(2)D-3 from 25(OH)D-3. After radiolabeled H-3-1,25(OH)(2)D-3 or H-3-25(OH)D-3 was injected iv into fractured or control (unfractur ed) rats, the concentrations of 25(OH)D-3 and 1,25(OH)(2)D-3 metabolit es were measured by HPLC. The plasma concentrations of these radiolabe led metabolites in fractured group were similar to those in control ra ts early after operation. However, radioactivity in the femurs of frac tured rats was higher than that of the control group. Furthermore, the radioactivity was concentrated in the callus of the fractured group a nalyzed by autoradiography. 1,25(OH)(2)D-3 receptor gene expression wa s detected early after fracture and, additionally, both in the soft an d hard callus on days 7 and 13 after fracture. These results showed th at the rapid disappearance of 1,25(OH)(2)D-3 in the early stages after fracture was not due to either increased degradation or decreased syn thesis of 1,25(OH)(2)D-3, but rather to increased consumption. Further , these results suggest the possibility that plasma 1,25(OH)(2)D-3 bec omes localized in the callus and may regulate cellular events in the p rocess of fracture healing.