The effects of local and systemic alendronate delivery on wear debris-induced osteolysis in vivo.
We investigated the effects of locally and systemically administered alendronate on wear debris-induced osteolysis in vivo. Endotoxin-free titanium particles were injected into rabbit femurs, prior to insertion of a nonweight-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 at three different concentrations (0.1, 0.5, and 1.0 wt %) into bone cement for local delivery. For systemic delivery, alendronate was subcutaneously injected (1.0 mg/kg/week) 1 week after the implantation and then once a week until sacrifice. Eight weeks postoperatively, there was significant evidence of osteolysis surrounding the plug in the control group compared with markedly blocked osteolysis in the 0.5 wt % and the 1.0 wt % groups, and the systemic group. There was a concentration-dependent effect of alendronate-loaded bone cement on the improvement of peri-prosthetic bone stock. Notably, no significant differences were found between the 0.5 wt % and the systemic group in peri-prosthetic bone stock and implant fixation. Collectively, although the biological efficacy after the systemic delivery of alendronate was slightly higher than that in the local treatment groups, alendronate-loaded bone cement may be therapeutically effective in inhibiting titanium particle-induced osteolysis in vivo.
Zhu
Fang-Bing
FB
Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, People's Republic of China.
Cai
Xun-Zi
XZ
Yan
Shi-Gui
SG
Zhu
Han-Xiao
HX
Li
Rui
R
D015502:Absorptiometry, Photon; D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D001706:Biopsy; D001843:Bone Cements / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D010014:Osteolysis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019904:Polymethyl Methacrylate; D011817:Rabbits; D014025:Titanium / Q000009:adverse effects
D001843:Bone Cements; D050071:Bone Density Conservation Agents; D019904:Polymethyl Methacrylate; D014025:Titanium; D019386:Alendronate