title: Posterolateral intertransverse spinal fusion possible in osteoporotic rats with BMP-7 in a higher dose delivered on a composite carrier.
abstract: METHODS
  Posterolateral intertransverse process spinal fusion (PLF) was performed in ovariectomized female rats using recombinant human BMP-7 (OP-1) delivered on a composite carrier.
  
  
  OBJECTIVE
  To investigate whether BMP-7 collagen on a composite carrier in a higher dose will enhance posterolateral spinal fusion in an estrogen deficiency rat model.
  
  
  BACKGROUND
  Osteoporosis is a systemic disease characterized by bone remodeling skewed in favor of excess bone resorption. This makes new bone formation and fixation of metallic implants difficult. Thus, treating osteoporotic patients who require posterior spinal fusion is challenging. Ovariectomized rats have been used as an osteoporotic model for posterolateral intertransverse process fusion. We have demonstrated in the past that endochondral bone formation in osteoporotic rats is delayed when compared with rats without osteoporosis. We have also shown that OP-1 Putty (BMP-7, collagen, and carboxy-methyl-cellulose) can overcome the effects of osteoporosis in a rat fracture model. However, it has not yet been demonstrated whether BMP-7 collagen composite carrier (Calstrux) can achieve a fusion in a process spinal fusion model in osteoporotic bone.
  
  
  METHODS
  A total of 42 ovariectomized Sprague-Dawley female rats were randomly assigned to 4 control and 2 experimental groups: (1) no Calstrux, no BMP; (2) 400 mg Calstrux alone; (3) 30 microg lactose + 400 mg Calstrux; (4) 90 microg lactose + 400 mg Calstrux; (5) 30 microg rhBMP-7 + 400 mg Calstrux; and (6) 90 microg rhBMP-7 + 400 mg Calstrux. Spinal fusion was evaluated by manual motion testing, microradiographs, computed tomographic scans, DEXA scans, and histology.
  
  
  RESULTS
  Ovariectomized rats receiving Calstrux alone or either dose of lactose and Calstrux did not show spinal fusion. Ovariectomized rats receiving 90 microg BMP-7 + 400 mg Calstrux showed significantly higher fusion rates than these control animals. (P < 0.0001). The rats receiving 30 microg BMP-7 + 400 mg Calstrux exhibited only partial fusion.
  
  
  CONCLUSIONS
  BMP-7, delivered on a composite carrier, is able to overcome the detrimental effects of estrogen deficiency on posterolateral spinal fusion and generate a relatively robust fusion. The effect seems to be dose dependent.
authors.affiliation: Spine Service, Department of Orthopaedic Surgery, St George Hospital Campus, University of New South Wales, Sydney, Australia.
authors.forename: Jike
authors.initials: J
authors.lastname: Lu
authors.forename: Divya
authors.initials: D
authors.lastname: Bhargav
authors.forename: Ai-Qun
authors.initials: AQ
authors.lastname: Wei
authors.forename: Ashish
authors.initials: A
authors.lastname: Diwan
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D009068:Movement; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000601:surgery* / Q000628:therapy*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion / Q000379:methods*; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen