title: BMP-2 adverse reactions treated with human dose equivalent dexamethasone in a rodent model of soft-tissue inflammation.
abstract: METHODS
  Basic science rodent model of bone morphogenetic protein-2 (BMP-2) soft-tissue inflammation.
  
  
  OBJECTIVE
  This study investigated the anti-inflammatory effect of human dose equivalent (HDE) dexamethasone (DM) for treatment of BMP-2-related soft-tissue inflammation in a rodent model and suggests an appropriate dose for utilization in the clinical practice of spine surgeons.
  
  
  BACKGROUND
  BMP-2 is frequently used in spinal surgery to augment fusion. Yet, side effects of soft-tissue inflammation have been observed. DM decreases proinflammatory cytokine production and cellular immune response. However, the anti-inflammatory effects of HDE DM in a rodent model of BMP-2-associated soft-tissue inflammation have not been reported.
  
  
  METHODS
  Five, 10, and 15 mg of HDE DM were administered 3 times perioperatively to rodent cohorts receiving BMP-2 paraspinal implants and compared against BMP-2 only positive controls and phosphate buffer negative controls (n = 6 subjects per group). Histopathology, magnetic resonance imaging, and gross dissection were used as measures of cellular, edematous, and exudative inflammatory response. Serial killings were made on day 2 and day 7 postoperatively.
  
  
  RESULTS
  Magnetic resonance imaging volume rendering demonstrated inflammatory edema decreased by 49% from 605.4 mm to 304.03 mm in subjects treated with 5, 10, or 15 mg of HDE DM (P < 0.05). Histopathological analysis demonstrated inflammatory cross-sectional area decreased 28.8% from 1.84 mm to 1.31 mm in subjects treated with 5, 10 or 15 mg of HDE DM (P < 0.05). Immune cellular infiltration depth decreased 38.5% from 0.26 mm to 0.16 in subjects treated with 15 mg of HDE DM (P < 0.05). Gross anatomical inflammatory exudates were prevented in 100% of subjects treated with 10 or 15 mg of HDE DM (P < 0.05).
  
  
  CONCLUSIONS
  Low-dose DM administration is effective in controlling the cellular inflammation and edema resulting from BMP-2. Ten or 15 mg of DM might be considered by spine surgeons for controlling the inflammation and edema seen in spine surgery with BMP-2.
authors.affiliation: *Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China †Department of Orthopaedic Surgery, University of California at Los Angeles (UCLA), Los Angeles, CA; and ‡Orthopaedic Spine Department, Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.forename: Michael D
authors.initials: MD
authors.lastname: Daubs
authors.forename: Scott R
authors.initials: SR
authors.lastname: Montgomery
authors.forename: Bayan
authors.initials: B
authors.lastname: Aghdasi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.forename: Akinobu
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Tan
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hayashi
authors.forename: Monchai
authors.initials: M
authors.lastname: Ruangchainikom
authors.forename: Timothy
authors.initials: T
authors.lastname: Chai
authors.forename: Megan
authors.initials: M
authors.lastname: Corey
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D017695:Soft Tissue Injuries / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D003907:Dexamethasone