BMP-2 adverse reactions treated with human dose equivalent dexamethasone in a rodent model of soft-tissue inflammation

Spine (Phila Pa 1976). 2013 Sep 1;38(19):1640-7. doi: 10.1097/BRS.0b013e31829cf348.

Abstract

Study design: 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.

Summary of background data: 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).

Conclusion: 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.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / adverse effects*
  • Dexamethasone / administration & dosage*
  • Disease Models, Animal*
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / pathology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Male
  • Random Allocation
  • Rats
  • Rats, Inbred Lew
  • Soft Tissue Injuries / chemically induced*
  • Soft Tissue Injuries / drug therapy*
  • Soft Tissue Injuries / pathology
  • Treatment Outcome

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Dexamethasone