Murakami T, Murakami H, Ramp W K, Hudson M C, Nousiainen M T
Baxter Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, NC 28232-2861, USA.
Bone. 1997 Nov;21(5):411-8. doi: 10.1016/s8756-3282(97)00169-5.
Results from this laboratory have shown that bone metabolism is directly related to extracellular pH and that high concentrations of tobramycin released from impregnated polymethylmethacryrate (PMMA) beads has pH-dependent toxic effects on bone. In the present study, beneficial effects of calcium hydroxide-impregnated PMMA were investigated regarding tobramycin toxicity and bone metabolism in chick embryo tibiae in vitro. Also using Ca(OH)2 as a pH regulator, the antibiotic efficacy of tobramycin-impregnated PMMA was evaluated with respect to inhibition of Staphylococcus aureus growth. When Ca(OH)2 was added to PMMA beads containing tobramycin, the beads released hydroxyl and calcium ions into the culture medium and released more antibiotic than beads containing only tobramycin. Bone metabolism (glycolysis, total protein synthesis, and collagen synthesis) was enhanced by Ca(OH)2-impregnated beads with or without tobramycin. Additionally, bacterial growth was inhibited more strongly when S. aureus was incubated with tobramycin- and Ca(OH)2-impregnated PMMA disks than with disks containing only tobramycin. This study demonstrates the feasibility of adding Ca(OH)2 to tobramycin-impregnated PMMA beads as a regulator of local pH and a promoter of bone metabolism for protection of bone when high concentrations of tobramycin are used to treat osteomyelitis. It also suggests that lower concentrations of antibiotic may be effective if Ca(OH)2 and tobramycin are administered simultaneously.
该实验室的研究结果表明，骨代谢与细胞外pH值直接相关，并且从浸渍聚甲基丙烯酸甲酯（PMMA）珠中释放的高浓度妥布霉素对骨具有pH依赖性毒性作用。在本研究中，研究了氢氧化钙浸渍的PMMA在体外对鸡胚胫骨妥布霉素毒性和骨代谢的有益作用。还使用Ca(OH)2作为pH调节剂，评估了妥布霉素浸渍的PMMA对金黄色葡萄球菌生长抑制的抗菌效果。当将Ca(OH)2添加到含有妥布霉素的PMMA珠中时，珠子向培养基中释放羟基和钙离子，并且比仅含有妥布霉素的珠子释放更多的抗生素。无论有无妥布霉素，氢氧化钙浸渍的珠子均可增强骨代谢（糖酵解、总蛋白合成和胶原蛋白合成）。此外，当金黄色葡萄球菌与妥布霉素和氢氧化钙浸渍的PMMA盘一起孵育时，细菌生长的抑制作用比仅含有妥布霉素的盘更强。本研究证明了在妥布霉素浸渍的PMMA珠中添加Ca(OH)2作为局部pH调节剂和骨代谢促进剂以在使用高浓度妥布霉素治疗骨髓炎时保护骨的可行性。这也表明，如果同时给予Ca(OH)2和妥布霉素，较低浓度的抗生素可能有效。
