An unexpected outcome during testing of commercially available demineralized bone graft materials - How safe are the nonallograft components?

Design. Radiographic and histologic analyses of commercially available bone graft materials were performed. Objective. To compare the osteoinductive efficacy of commercially available demineralized bone matrix material. Summary of Background Data. The relative in vivo bone formation and toxicology of the nonallograft components: the make up various commercially available demineralized mineralized bone matrix products are not known. Methods. An in vivo bone formation model was used in 30 athymic rats. Six different bone grafting materials were tested in subcutaneous and intermuscular locations. After 4 weeks, radiographic and histologic testing of bone formation was performed. Results. Eight of nine rats implanted with Grafton demineralized bone matrix products died 1 to 4 days after implantation of the bone graft material. None of the remaining 10 animals implanted with the four other grafting materials died. The experiment was modified and completed with a lower dose of bone graft material. Pathologic analysis indicated that the cause of death was hemorrhagic necrosis of the kidneys, most likely caused by a toxic effect on the glomeruli and tubules. A possible causative factor may have been the glycerol in the graft material. Conclusions. Although the volume of Grafton product per kilogram of body weight used in this study was approximately eight times the maximum volume used in humans, the authors believe that this data must be reported because this product is used substantially in clinical settings. In addition, the osteoinductive performance and relative safety of the nonallograft components in all commercially available demineralized bone grafts are not known.