STUDY DESIGN: A relative risk assessment was performed to determine the safety of three commercially available Grafton demineralized bone matrix quantities used in athymic rats. OBJECTIVE: To evaluate the possible dose-dependent adverse effects of a commercially available demineralized bone matrix containing glycerol. SUMMARY OF BACKGROUND DATA: Commercially available Grafton demineralized bone matrix contains glycerol. The toxic effects of glycerol leading to acute renal failure have been documented. The toxicity of this glycerol-containing substance in higher doses has not been reported. METHODS: Three doses of Grafton putty were implanted in the upper hind limb muscles of athymic nude rats. The rats were observed for adverse effects and early death. Histologic studies were performed. RESULTS: All eight of the rats implanted with the highest dose of Grafton putty (0.008 mL/g) died, five of them within 12 hours of implantation and three in 48 to 72 hours. One rat with the intermediate dose (0.004 mL/g) died within 12 hours of implantation. By 72 hours after implantation, three of the six rats (50%) with the intermediate dose had died. All six of the rats receiving the lowest dose (0.002cc/g) survived. The median lethal dose of Grafton putty in athymic rats was estimated to be 0.00469 mL/g body weight. Histologic analysis of the animals that received the high dose showed acute tubular necrosis, probably secondary to rhabdomyolysis. CONCLUSIONS: In athymic rats, large amounts of Grafton putty lead to death in a dose-dependent manner. Because the median lethal doses of Grafton putty (0.00469 mL/g) and glycerol (0.00442 mL/g) are comparable, a potential source of toxicity is the glycerol contained in the material. The results of this study suggest that high doses have the potential to cause acute renal failure. The authors suggest that clinical usage of Grafton putty in humans should be limited to no more than 2 mL/kg body weight of this material.
STUDY DESIGN: A relative risk assessment was performed to determine the safety of three commercially available Grafton demineralized bone matrix quantities used in athymic rats. OBJECTIVE: To evaluate the possible dose-dependent adverse effects of a commercially available demineralized bone matrix containing glycerol. SUMMARY OF BACKGROUND DATA: Commercially available Grafton demineralized bone matrix contains glycerol. The toxic effects of glycerol leading to acute renal failure have been documented. The toxicity of this glycerol-containing substance in higher doses has not been reported. METHODS: Three doses of Grafton putty were implanted in the upper hind limb muscles of athymic nude rats. The rats were observed for adverse effects and early death. Histologic studies were performed. RESULTS: All eight of the rats implanted with the highest dose of Grafton putty (0.008 mL/g) died, five of them within 12 hours of implantation and three in 48 to 72 hours. One rat with the intermediate dose (0.004 mL/g) died within 12 hours of implantation. By 72 hours after implantation, three of the six rats (50%) with the intermediate dose had died. All six of the rats receiving the lowest dose (0.002cc/g) survived. The median lethal dose of Grafton putty in athymic rats was estimated to be 0.00469 mL/g body weight. Histologic analysis of the animals that received the high dose showed acute tubular necrosis, probably secondary to rhabdomyolysis. CONCLUSIONS: In athymic rats, large amounts of Grafton putty lead to death in a dose-dependent manner. Because the median lethal doses of Grafton putty (0.00469 mL/g) and glycerol (0.00442 mL/g) are comparable, a potential source of toxicity is the glycerol contained in the material. The results of this study suggest that high doses have the potential to cause acute renal failure. The authors suggest that clinical usage of Grafton putty in humans should be limited to no more than 2 mL/kg body weight of this material.
Authors: Wei Shui; Wenwen Zhang; Liangjun Yin; Guoxin Nan; Zhan Liao; Hongmei Zhang; Ning Wang; Ningning Wu; Xian Chen; Sheng Wen; Yunfeng He; Fang Deng; Junhui Zhang; Hue H Luu; Lewis L Shi; Zhenming Hu; Rex C Haydon; James M Mok; Tong-Chuan He Journal: J Biomed Mater Res A Date: 2013-10-29 Impact factor: 4.396