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BMP-2 Adverse Reactions Treated With Human Dose Equivalent Dexamethasone in a Rodent Model of Soft-Tissue Inflammation

Xiong, Chengjie, MD*; Daubs, Michael D., MD, FACS; Montgomery, Scott R., MD; Aghdasi, Bayan, BA; Inoue, Hirokazu, MD, PhD; Tian, Haijun, MD; Suzuki, Akinobu, MD, PhD; Tan, Yanlin, MD; Hayashi, Tetsuo, MD; Ruangchainikom, Monchai, MD; Chai, Timothy, BS; Corey, Megan, BS; Wang, Jeffrey C., MD

doi: 10.1097/BRS.0b013e31829cf348
Basic Science
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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 mm3 to 304.03 mm3 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 mm2 to 1.31 mm2 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.

Bone morphogenetic protein-2 (BMP-2) adverse effects can be effectively treated with 10 or 15 mg of human dose equivalent dexamethasone as demonstrated on histopathological, magnetic resonance image, and gross anatomical evaluation in this validated rodent model of soft-tissue inflammation. Edematous response follows a brisker time-course than cellular inflammatory processes in BMP-2-mediated inflammation.

*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.

Address correspondence and reprint requests to Michael D. Daubs, MD, FACS, Assistant Professor of Orthopaedic Surgery and Neurosurgery, UCLA Comprehensive Spine Center, UCLA Department of Orthopaedic Surgery, 1250 16th St, Ste 3145-E, Santa Monica, CA 90404; E-mail: michael.daubs@gmail.com

Acknowledgment date: March 26, 2013. Revision date: May 15, 2013. Acceptance date: May 20, 2013.

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work.

Relevant financial activities outside the submitted work: grants, board membership, royalties, stocks.

© 2013 by Lippincott Williams & Wilkins