Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.

OBJECTIVES: Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone. MATERIAL AND METHODS: An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels. RESULTS: Labelling indices were significantly lower for Msx-1 (P < 0.03) and RANKL (P < 0.003) and significantly higher (P < 0.02) for BMP-2 in ONJ compared with healthy bone. Expression was sevenfold lower (P < 0.03) for Msx-1, 22-fold lower (P < 0.001) for RANKL and eightfold higher (P < 0.02) for BMP-2 in ONJ bone. CONCLUSIONS: Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future.

Radiation-induced impairment of osseous healing with vascularized bone transfer: experimental model using a pedicled tibia flap in rat.

Aim of this study was to establish an appropriate animal model for investigating the healing of vascularized osseous transplants to irradiated recipient sites applying metabolic, vascular and immunologic experimental studies. In 20 Wistar rats (male, weight 300-500 g), a pedicled osseous tibia flap was raised and transferred to a subcutaneous pocket in the ipsilateral groin. The remaining tibia was stabilized with a monocortical titanium miniplate. To create a pre-irradiated transplant bed, the donor-area including the adjacent bone of the tibia was irradiated with a total dose of 50Gy (5 x 10 Gy) in 10 animals. The interval between irradiation and retransfer of the non-irradiated pedicled tibia flap was 4 weeks. Ten animals received no radiation. Evaluation of osseous healing and the success of the transferred flap were based on a clinical and quantitative histomorphometric assessment. Testing for significant differences was performed using the non-parametric Mann-Whitney U-test. The rate of complete osseous healing in the non-irradiated animals was 90%. In contrast there was no significant bone union observed in the group of the pedicled flaps grafted to the pre-irradiated (50Gy) recipient site (P = 0.001). Similarly bone formation in the transitional zone between bone graft and recipient bone was significantly lower in the preirradiated group (P < 0.001) (16.9 +/- 3%) in contrast to the non-irradiated transplant bed (47.9 +/- 6%).