OTA 2005 Posters

Scientific Poster #51 Basic Science

Oral COX-2 Inhibition Does Not Decrease Bone Formation in a Murine Distraction Osteogenesis Model

Ankur Chawla, BS (a- Howard Hughes Fellowship);

John T. Gorczyca, MD; Regis O'Keefe, MD, PhD

(all authors-a-OTA/Zimmer Grant);

University of Rochester Medical Center, Rochester, New York, USA

Purpose/Hypothesis: Distraction osteogenesis (DO) is an important technique for limb lengthening and treatment of bone loss. However, DO is associated with numerous complications, including delayed bone healing. COX-2 inhibition is commonly used for pain control in DO. Although recent studies suggest that COX-2 inhibition delays fracture healing, its effects on bone formation during DO are unknown. The purpose of the study was to examine COX-2 inhibition in a murine DO model. Our hypothesis was that bone formation would be decreased in mice receiving pharmacologic COX-2 inhibition (celecoxib).

Methods: 37 wild type (C57B6) male mice (aged 10 weeks) were randomized to receive either placebo (water) or PO celecoxib (25 mg/kg/day). A customized external frame was fixed to the tibia via four 0.25-mm transfixion wires, with further stabilization via an intramedullary pin. A midshaft osteotomy was made with a #11 scalpel. After an 8-day latency period, distraction was initiated at 0.17 mm/day. Distraction was continued for 10 days (1.7 mm total, 9% of total tibia length) followed by a 20-day period of consolidation. The mice were sacrificed at days 8, 13, 18, 28, and 38. Specimens were prepared for histomorphometric and micro CT analysis.

Results: Histomorphometry did not reveal a significant difference in quantity of bone formed (mm²) within the distraction gap: 0.12 ± 0.03 (control) versus 0.073 ± 0.02 (celecoxib) day 8 (P = 0.29); 0.77 ± 0.12 (control) versus 0.72 ± 0.12 (celecoxib) day 13 (P = 0.36); 0.95 ± 0.03 (control) versus 0.86 ± 0.10 (celecoxib) day 18 (P = 0.15); 1.3 ± 0.1 (control) versus 1.7 ± 0.3 (celecoxib) day 28 (P = 0.48); and 3.0 ± 0.1 (control) versus 2.32 ± 0.3 (celecoxib) day 38 (P = 0.28). Micro CT analysis of bone formation volume (mm³) did not reveal a significant difference between the groups: 1.99 ± 0.35 (control) versus 1.39 ± 0.1 (celecoxib) day 28 (P = 0.24); and 2.96 ± 1.24 (control) versus 2.56 ± 0.76 mm³ (celecoxib) day 38 (P = 0.86).

Conclusion/Significance: We were unable to demonstrate significant effect of celecoxib on bone healing and formation in a murine DO model. The role of COX-2 in bone formation remains controversial, and may be dependent upon the healing process and target cells. Our study suggests that COX-2 inhibition does not alter healing in DO; however, further confirmation is warranted.