COX-2 selective NSAID decreases bone ingrowth in vivo.
Whether non-steroidal anti-inflammatory drug (NSAID)-induced suppression of bone ingrowth is due to cyclooxygenase-1 (COX-1) inhibition, cyclooxygenase-2 (COX-2) inhibition, or through a yet unidentified pathway is unknown. In this study, the effects of a non-specific COX-1 and COX-2 inhibitor, versus a specific COX-2 inhibitor on bone ingrowth and tissue differentiation are examined in vivo. Harvest chambers were implanted unilaterally in the tibiae of eight mature, New Zealand white rabbits. After a 6-week period for osseointegration of the chamber, the following oral treatments were given for 4 weeks each, followed by a harvest in each case: drinking water with no NSAID (control 1), Naproxen sodium--a COX-1 and COX-2 non-specific inhibitor at a dose of 110 mg/kg/day in the drinking water, drinking water with no NSAID (control 2), and Rofecoxib-a COX-2 inhibitor at a dose of 12.5 mg/day inserted directly into the rabbit's mouth. Harvested specimens were snap frozen, cut into serial 6 microm sections and stained with hematoxylin and eosin for general morphological characterization, and alkaline phosphatase (osteoblast marker). Sections were also processed for immunoperoxidase staining using monoclonal antibodies to identify cells expressing the vitronectin receptor (osteoclast-like cells). With drinking water alone, the percentage of bone ingrowth averaged 24.8 +/- 2.9% and 29.9 +/- 4.5% respectively. Naproxen sodium in the drinking water and oral Rofecoxib decreased bone ingrowth significantly (15.9 +/- 3.3%. p = 0.031 and 18.5 +/- 2+/-4%, p = 0.035 compared to drinking water respectively). Both Naproxen sodium (p = 0.026) and Rofecoxib (p = 0.02) decreased the number of CD51 positive osteoclast-like cells per section compared with drinking water alone. Rofecoxib decreased the area of osteoblasts per section area (p = 0.014) compared to controls, although the value for Naproxen sodium did not reach statistical significance. The results of the present study suggest that bone formation is suppressed by oral administration of an NSAID which contains a COX-2 inhibitor. COX-2 inhibitors currently taken for arthritis and other conditions may potentially delay fracture healing and bone ingrowth.
Goodman
Stuart
S
Division of Orthopaedic Surgery, Orthopaedic Research Laboratory, Stanford University Medical Center, 300 Pasteur Drive, R144, Stanford, CA 94305, USA. goodbone@stanford.edu
Ma
Ting
T
Trindade
Michael
M
Ikenoue
Takashi
T
Matsuura
Ippe
I
Wong
Neal
N
Fox
Nora
N
Genovese
Mark
M
Regula
Don
D
Smith
R Lane
RL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009288:Naproxen / Q000494:pharmacology*; D016348:Osseointegration / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D019736:Prostheses and Implants; D011817:Rabbits; D013977:Tibia; D014025:Titanium
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009288:Naproxen; D014025:Titanium; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases