Specific demands of osteoporotic fractures call for improved bone substitute materials. Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) are well known from the central nervous system where they stimulate neuronal outgrowth and survival of neurons. Recently, BDNF and TrkB were found in hard tissue cells like osteoblasts and its expression was up-regulated during human fracture healing. In the present study we asked if BDNF and TrkB were regulated at the interface of bone substitute materials in a rat osteoporotic fracture model.
Osteoporosis was induced in Sparque-Dawley rats by ovariectomy and additional deficiency diet with reduced calcium and Vitamin D3 concentrations. A wedge-shaped osteotomy was created in the metaphyseal area of the distal femur and filled with one of eight different implants that were based on calcium phosphate cement (CPC), iron foam (Fe), a composite of silica and collagen (B30) and modifications of these materials with strontium.
The expression of TrkB was significantly down regulated at the interface of CPC (p = 0.009), CPC with strontium (p = 0.001), B30 (p < 0.001), Fe (p < 0.001), and Fe with strontium (p < 0.001) compared to the empty fracture gaps that served as controls. BDNF mRNA expression was unchanged at the interface of the most substitute materials and only in samples with strontium modified Fe a down-regulation was measured.
In conclusion, our results showed that no up-regulation of BDNF and its receptor TrkB could be measured at the interface of several bone substitute materials in a rat osteoporotic model. In contrast, a decrease in TrkB expression was found at the interface of the most bone substitute materials. Thus, we suppose that a substitute material that would be able to increase BDNF and TrkB expression - like in human fracture healing - might be able to stimulate fracture healing. In addition, it might be helpful to integrate BDNF into bone substitute materials to increase the survival and proliferation of osteoblasts.