title: rhBMP-2 enhancement of posterolateral spinal fusion in a rabbit model in the presence of concurrently administered doxorubicin.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612, USA.
authors.forename: Kern
authors.initials: K
authors.lastname: Singh
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Smucker
authors.forename: John L
authors.initials: JL
authors.lastname: Ugbo
authors.forename: P Justin
authors.initials: PJ
authors.lastname: Tortolani
authors.forename: Luke
authors.initials: L
authors.lastname: Tsai
authors.forename: Qinming
authors.initials: Q
authors.lastname: Fei
authors.forename: Sunguk
authors.initials: S
authors.lastname: Kuh
authors.forename: Mustasim
authors.initials: M
authors.lastname: Rumi
authors.forename: John G
authors.initials: JG
authors.lastname: Heller
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boden
authors.forename: S Tim
authors.initials: ST
authors.lastname: Yoon
mesh_terms: 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*
chemical_list: 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