Addition of human recombinant bone morphogenetic protein-2 to inactive commercial human demineralized freeze-dried bone allograft makes an effective composite bone productive implant material
Z. Schwartz et al., Addition of human recombinant bone morphogenetic protein-2 to inactive commercial human demineralized freeze-dried bone allograft makes an effective composite bone productive implant material, J PERIODONT, 69(12), 1998, pp. 1337-1345
COMMERCIAL PREPARATIONS OF HUMAN DEMINERALIZED freeze-dried bone allograft
(DFDBA) vary in their ability to induce new bone formation. This study test
ed the hypothesis that inactive DFDBA can be used as an effective carrier o
f 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 mu g rhBMP-2 and
implanted into the calf muscle of male Nu/Nu (nude) mice. Each mouse receiv
ed one implant in each hind limb, both of which were of the same formulatio
n, 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 DFD
BA batch A plus 5 mu g rhBMP-2 inactive DFDBA batch A plus 20 mu g rhBMP-2,
inactive DFDBA batch B plus 5 mu g rhBMP-2, and inactive DFDBA batch B plu
s 20 pg rhBMP-2. After 56 days, the implants were removed and histologicall
y examined. A semiquantitative bone induction index was calculated based on
the amount of new bone covering each histological section. Histomorphometr
y was also used to evaluate the area of new bone formed and the area of res
idual implant material. The results showed that active DFDBA induces new bo
ne formation, whereas inactive DFDBA does not. Addition of rhBMP-2 to inact
ive DFDBA results in new bone formation with a bone induction index compara
ble to that of active DFDBA. Histomorphometric analysis, however, revealed
that the rhBMP-2-containing implants caused a dose-dependent increase in ne
w bone area that exceeded that induced by active DFDBA. At the highest conc
entration 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 t
hat addition of rhBMP-2 to inactive DFDBA provides reproducible, consistent
bone induction, and suggests that inactive commercial preparations may con
tain inadequate amounts of BMP to cause bone induction compared to active p
reparations.