COX-2 Inhibitors Slow Bone Growth and Impede Healing

Researchers working with a rabbit model have found that selective COX-2 inhibitors such as rofecoxib (Vioxx) and celecoxib (Celebrex) interfere with the healing process after a bone fracture or cementless joint implant surgery. These findings were published in the November 2002 issue of the Journal of Orthopedic Research.

"It is very common. You break a bone and go to the ER. The doctor sets it in a splint and prescribes one of these anti-inflammatory drugs (including COX-2 inhibitors) for pain,” said first author Dr. Stuart Goodman, MD, professor of orthopedic surgery at the Stanford School of Medicine (Stanford, CA, USA). "We now know that could actually delay healing.”

The investigators implanted a titanium device called a harvest chamber into the tibia bone of eight New Zealand white rabbits. The device has a removable, hollow inner core that allows periodic removal of the tissue growing inside. The growth of new bone into the chamber simulates healing of a fracture or joint implant. The rabbits were given oral treatments of naproxen (a nonspecific COX inhibitor) or rofecoxib separated by four weeks without treatment. After each treatment, the harvest chamber's core was removed and the tissue growing inside extracted and examined under the microscope using special stains, including monoclonal antibodies.

Since the harvest chamber allows new tissue to be extracted multiple times as it grows back, the rabbits served as their own control groups (after consuming plain water). The researchers found that while the tissue in the control group contained 24.8% and 29.9% new bone growth, the tissue harvested after the rabbits consumed naproxen and rofecoxib contained significantly less: 15.9% and 18.5%, respectively. As the difference in new bone growth associated with the two drugs was statistically insignificant, the COX-2 inhibitor impeded new bone growth as much as the nonspecific NSAID.

Dr. Goodman said this study "has great applicability to humans, because the healing process is virtually the same” for rabbit and human bones.



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