Objective To investigate the effects of locally and systemically administered alendronate on wear-debris induced osteolysis in vivo. Methods Endotnxin-free titanium particles were injected into rabbit femurs prior to insertion of a non-weight-bearing polymethylmethacrylate plug into the distal femur canal. Then the particles were repeatedly injected into the knee 2, 4 and 6 weeks after the implantation. Alendronate was incorporated into bone cement for local delivery at three different concentrations [0.1, 0.5, and 1.0 weight%(wt%)]. For systemic delivery, alendronate was subcutaneously injected ( 1.0 mg· kg-1·week-1).Results Eight weeks after operation, there was significant evidence of osteolysis surrounding the plug in the control group, while markedly-blocked osteolysis was noted in the local delivery group (0.5 wt% and 1.0 wt%), and the systemic delivery group. It was found that alendronate had improved peri-prosthetic bone mineral density in a dose-effect model. Notably, no significant difference was found between local delivery of 0.5 wt% alendronate and systemic delivery in bone mineral density and implant fixation. Conclusion Alendronate-loaded bone cement (0.5 wt% ) may be as effective as the systemic delivery in inhibiting titanium particle-induced osteolysis.

Dura mater, rich in vasculature and immune cells, is the outermost layer of the central nervous system, and thus acts as the first barrier to protect brain. Meningeal lymphatic vessels and immune cells are main components of dural immunity, which respond to a variety of central nervous system diseases. Meanwhile, compared with brain parenchyma, dura mater communicates more with peripheral tissues and is more susceptible to medical interventions. Therefore, dura mater is a promising target to prevent, diagnose and treat intracranial diseases. Here dural immunity is clarified based on meningeal lymphatic vessels and dural immune cells, and current researches inquiring the role of dural immunity in infectious and immune diseases of central nervous system are summarized.