Addition of human recombinant bone morphogenetic protein-2 to inactive commercial human demineralized freeze-dried bone allograft makes an effective composite bone inductive implant material

Zvi Schwartz, Ann Somers, James T. Mellonig, David L. Carnes, John M. Wozney, David D. Dean, David L. Cochran, Barbara D. Boyan

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63 Scopus citations


COMMERCIAL PREPARATIONS OF HUMAN DEMINERALIZED freeze-dried bone allograft (DFDBA) vary in their ability to induce new bone formation. This study tested the hypothesis that inactive DFDBA can be used as an effective carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2). Two batches of active DFDBA were used as controls. Two batches of DFDBA, previously shown to be inactive, were treated with vehicle or with 5 or 20 μg rhBMP-2 and implanted into the calf muscle of male Nu/Nu (nude) mice. Each mouse received one implant in each hind limb, both of which were of the same formulation, resulting in 8 groups of 4 mice per group: active DFDBA batch A, active DFDBA batch B, inactive DFDBA batch A, inactive DFDBA batch B, inactive DFDBA batch A plus 5 μg rhBMP-2, inactive DFDBA batch A plus 20 μg rhBMP-2, inactive DFDBA batch B plus 5 μg rhBMP-2, and inactive DFDBA batch B plus 20 μg rhBMP-2. After 56 days, the implants were removed and histologically examined. A semiquantitative bone induction index was calculated based on the amount of new bone covering each histological section. Histomorphometry was also used to evaluate the area of new bone formed and the area of residual implant material. The results showed that active DFDBA induces new bone formation, whereas inactive DFDBA does not. Addition of rhBMP-2 to inactive DFDBA results in new bone formation with a bone induction index comparable to that of active DFDBA. Histomorphometric analysis, however, revealed that the rhBMP-2-containing implants caused a dose-dependent increase in new bone area that exceeded that induced by active DFDBA. At the highest concentration of rhBMP-2, bone formation was exuberant. rhBMP-2 also caused the resorption of residual implant material to levels comparable to that seen in sites treated with active DFDBA, suggesting that this growth factor may regulate resorptive cells either directly or indirectly. This study shows that addition of rhBMP-2 to inactive DFDBA provides reproducible, consistent bone induction, and suggests that inactive commercial preparations may contain inadequate amounts of BMP to cause bone induction compared to active preparations.

Original languageEnglish (US)
Pages (from-to)1337-1345
Number of pages9
JournalJournal of periodontology
Issue number12
Publication statusPublished - Dec 1998



  • Bone morphogenetic protein
  • Bone regeneration
  • Bone, demineralized
  • Bone, freeze-dried
  • Grafts, bone
  • Ostegenesis

ASJC Scopus subject areas

  • Periodontics

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