Combination therapy with BMP-2 and psoralen enhances fracture healing in ovariectomized mice

The advantages of combining local delivery of bone morphogenetic protein (BMP)-2 with systemic or local anti-osteoporosis treatments have also been studied for enhancing osteoporotic fracture healing. The aim of the present study was to evaluate the effect of combination therapy with BMP-2 and psoralen on fracture repair in ovariectomized mice. At 6 weeks after bilateral ovariectomy, mice (n=30) underwent unilateral transverse osteotomy on the femur and were divided into 3 groups. In the model group (n=10), animals were implanted with an absorbable collagen sponge (ACS) alone and administered physiological saline intragastrically (i.g.). In the recombinant human (rh)BMP-2 group (n=10), animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered physiological saline i.g. In the psoralen + rhBMP-2 group (n=10) animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered psoralen i.g. The mice were euthanized after 21 days and their fractured femurs were assessed by micro computed tomography, histological analysis and biomechanical testing. Furthermore, the serum of the animals was analyzed. Psoralen + rhBMP-2 exerted more beneficial effects on callus consolidation and biomechanical strength. In addition, increased bone-specific alkaline phosphatase levels and decreased C-terminal telopeptide of type-1 collagen were observed in the Psoralen + rhBMP-2 group. However, no difference in estrogen levels was detected between the groups. In conclusion, the present study demonstrated that in ovariectomized mice, combination of locally delivered BMP-2 and systemically administered psoralen improved bone healing compared with BMP-2 alone.