title: Effects of recombinant human bone morphogenetic protein-2 on midsagittal sutural bone formation during expansion.
abstract: BACKGROUND
  The goal of this study was to evaluate whether human recombinant bone morphogenetic protein-2 (rhBMP-2) enhances sutural bone formation or causes premature sutural fusion.
  
  
  METHODS
  Thirty 6-week-old rabbits underwent midsagittal sutural expansion. The animals were randomly assigned to receive 0 (control), 0.1 mg per milliliter, or 0.4 mg per milliliter of rhBMP-2, delivered by an absorbable collagen sponge placed over the suture. A 100-g constant force was delivered for 33 days by using a nickel-titanium spring to expand the suture between 2 miniscrew implants anchored in the frontal bone. At days 10, 20, and 30, sutural separation was evaluated and modeled over time as polynomials by using multilevel statistical procedures. Bone formation and sutural gaps were analyzed histomorphometrically between days 10 and 20 and days 20 and 30.
  
  
  RESULTS
  The control group showed significantly greater overall sutural bone formation than did the 2 rhBMP-2 groups. Over time, bone formation decreased significantly in all groups. Between days 10 and 20, the 0.4 mg per milliliter group produced significantly more (58%) bone than did the 0.1 mg per milliliter group; there were no significant differences in bone formation between the 2 experimental groups between days 20 and 30. Both 0.1 and 0.4 mg per milliliter of rhBMP-2 in the absorbable collagen sponge caused premature fusion by forming a bony bridge connecting the ectocranial aspect of the sutural margins. Premature fusion significantly reduced sutural separation between 10 and 30 days (to 56% and 62% of control values for the 0.1 and 0.4 mg per milliliter groups, respectively). There were no significant differences in sutural separation between the 0.1 and 0.4 mg per milliliter groups.
  
  
  CONCLUSIONS
  Compared with the 0.1 mg per milliliter group, 0.4 mg per milliliter of rhBMP-2 accelerated sutural bone formation between days 10 and 20. After 10 to 20 days, rhBMP-2 in the absorbable collagen sponge caused premature sutural fusion, despite the constant expansion forces.
authors: Department of Orthodontics and Oral Facial Genetics, School of Dentistry, Indiana University, Indianapolis, IN 46202, USA. SSLiu@iupui.edu
authors: Sean Shih-Yao
authors: SS
authors: Liu
authors: Lynne A
authors: LA
authors: Opperman
authors: Peter H
authors: PH
authors: Buschang
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000502:physiology*; D003094:Collagen / Q000008:administration & dosage; D003393:Cranial Sutures / Q000502:physiology*; D003398:Craniosynostoses / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006801:Humans; D008297:Male; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D019857:Osteogenesis, Distraction / Q000379:methods; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins; D016037:Single-Blind Method; D018709:Statistics, Nonparametric
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011994:Recombinant Proteins; D003094:Collagen