An unexpected outcome during testing of commercially available demineralized bone graft materials: how safe are the nonallograft components?
METHODS
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.


BACKGROUND
The relative in vivo bone formation and toxicology of the nonallograft components the make up various commercially available demineralized 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.
Bostrom
M P
MP
Hospital for Special Surgery, New York, New York 10021, USA. Bostromm@hss.edu
Yang
X
X
Kennan
M
M
Sandhu
H
H
Dicarlo
E
E
Lane
J M
JM
D000818:Animals; D018488:Bone Demineralization, Pathologic / Q000139:chemically induced*; D001857:Bone Matrix / Q000637:transplantation*; D018786:Bone Substitutes / Q000009:adverse effects*; D016025:Bone Transplantation / Q000009:adverse effects*; D003451:Cryoprotective Agents / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005990:Glycerol / Q000009:adverse effects; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D009336:Necrosis; D051381:Rats; D011923:Rats, Nude
D018786:Bone Substitutes; D003451:Cryoprotective Agents; D005990:Glycerol