rhBMP-2 enhancement of posterolateral spinal fusion in a rabbit model in the presence of concurrently administered doxorubicin.
BACKGROUND
Spinal fusions can be necessary in patients undergoing chemotherapy with doxorubicin. In a previous study, doxorubicin was shown to decrease spinal fusion rates in a rabbit model of lumbar intertransverse process spinal fusion with autograft iliac crest bone. In the current study, we determine whether spinal fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2) can overcome the inhibitory effect of doxorubicin in spinal fusion.


OBJECTIVE
To determine if rhBMP-2 can overcome the inhibitory effects of doxorubicin (adriamycin) in an animal model of posterolateral spinal fusion.


METHODS
Prospective, controlled, rabbit model of posterolateral lumbar fusion.


METHODS
Spine fusion was assessed by manual palpation (by observers blinded to the treatment group) at the level of arthrodesis. Fusion was graded according to a five-tiered classification (0-4). Posteroanterior radiographs of the excised spines were also graded in a blinded fashion using a six-point scoring system (0-5) devised to describe the amount of bone observed between the L5-L6 transverse processes.


METHODS
Thirty-two New Zealand White rabbits underwent posterolateral fusion at L5-L6 with either autograft (iliac crest autograft bone) or rhBMP-2 (rhBMP-2/absorbable collagen sponge (0.86 mg/level). All animals received a dose of doxorubicin (2.5 mg/kg) known to inhibit spine fusion via the central vein of the ear immediately postoperatively. Five weeks postoperatively the rabbits were euthanized. Spine fusion was assessed by manual palpation, and graft quality was assessed with posteroanterior radiographs.


RESULTS
Four of the 16 spines (25%) in the autograft group and 16 of the 16 spines (100%) in the rhBMP-2 group fused in the presence of doxorubicin administration (p<.05). There was significantly increased bone formation in the rhBMP-2 group (p<.05). One unilateral, subclinical wound infection was observed in each group at the time of euthanization (autograft [n=1, 6%] and rhBMP-2 [n=1, 6%]).


CONCLUSIONS
We confirm that when autograft is used, doxorubicin decreases spinal fusion rate (25%) compared with historical controls (60-75%). More importantly, using rhBMP-2 overcomes the inhibitory effect of doxorubicin, resulting in 100% fusion in our animal model. This study suggests that rhBMP-2 has the potential to improve fusion rates in human patients undergoing chemotherapy with doxorubicin.
Singh
Kern
K
Department of Orthopedic Surgery, Rush University Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612, USA.
Smucker
Joseph D
JD
Ugbo
John L
JL
Tortolani
P Justin
PJ
Tsai
Luke
L
Fei
Qinming
Q
Kuh
Sunguk
S
Rumi
Mustasim
M
Heller
John G
JG
Boden
Scott D
SD
Yoon
S Tim
ST
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D016025:Bone Transplantation / Q000379:methods; D004317:Doxorubicin / Q000009:adverse effects*; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D013123:Spinal Fusion / Q000379:methods*; D013131:Spine / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D004317:Doxorubicin