WASHINGTON (AP) -- Broke your leg? Some doctors are warning to carefully consider which painkiller you use.

New research suggests some of the most widely used painkillers may delay healing of a broken bone -- and one study, albeit in animals, that's getting lots of doctors' attention suggests the blockbuster sellers Vioxx and Celebrex are among the culprits.

There's no proof yet that anti-inflammatory painkillers cause major bone problems, and the makers of Vioxx and Celebrex deny any link.

But some bone experts call the research compelling enough that doctors should explain the risk before patients choose a painkiller for a broken bone, spinal surgery or other bone injury.

"It's time to tell the public," concludes Dr. Thomas Einhorn, Boston University's orthopedic surgery chairman -- who says he'd choose a mild narcotic over more common painkillers if he broke a leg.

It's an important question, as more Americans regularly use Vioxx, Celebrex and other anti-inflammatory painkillers called NSAIDS that also are implicated. Doctors increasingly offer bone surgery or fracture patients higher and higher doses of such painkillers in place of narcotics.

At issue is the discovery that an enzyme called cox-2, which causes pain and inflammation, also appears to play a crucial role in bone healing.

Vioxx and Celebrex fight pain by blocking cox-2. They're wildly popular because they're easier on the stomach than the older NSAIDs that block, to varying degrees, both cox-2 and the related cox-1 enzyme. NSAIDS range from ibuprofen to hospital-used indomethacin and Toradol.

Researchers at the University of Medicine and Dentistry of New Jersey gave 253 young rats with a splinted broken leg either Vioxx, Celebrex, indomethacin or no drug.

Indomethacin-treated rats took a week longer to heal than untreated rats; the resulting bone was as strong.

But rats given Vioxx or Celebrex hadn't fully healed after two months -- and what new bone formed sometimes was only a weakened shell, researcher J. Patrick O'Connor reports in this month's Journal of Bone and Mineral Research.

O'Connor then tested mice engineered to not produce any cox-2. Their fractures also didn't heal normally.

A flurry of additional studies suggests any NSAID, not just cox-2 inhibitors, hinders bone healing, Einhorn cautions. How much? That's far from clear -- a week or several. So delay might bother some people, not others.

"If it were my fracture ... to me every day counts," he says.

O'Connor says his findings prompted some colleagues to withhold cox-2 inhibitors from broken-bone patients. The American Academy of Orthopedic Surgeons just alerted all its members to the study. And the Arthritis Foundation's medical director urges more research to see if people really are at risk -- but meanwhile says patients should discuss with their doctors if they should temporarily quit any anti-inflammatory painkiller until a broken bone heals.

There are few human studies. But surgeons made the surprise discovery a few years ago that high doses of the intravenous NSAID Toradol delays spinal surgery healing, and a recent British study concluded using NSAIDS was the biggest factor in delayed healing of a broken leg.

No one has examined Vioxx and Celebrex effects on people's broken bones. But a recent review of some spinal surgery patients' medical records found no healing delay among users of those drugs.

"It is confusing. ... You see this muddy picture," says Dr. Scott Reuben of Baystate Medical Center in Springfield, Mass., who conducted that study -- and calls for targeted research on broken-bone sufferers to settle the issue.

Why would blocking cox-2 hurt bone?

Cox-2 apparently is important in helping bone-forming stem cells and growth factors do their work, says Dr. Regis O'Keefe of the University of Rochester. He just compared regular mice with those whose bodies don't make any cox-1 or any cox-2, and only found a problem with lack of cox-2, he reports in the Journal of Clinical Investigation.

Giving broken-bone sufferers different painkillers to test for delayed healing would be unethical, says Einhorn, a paid consultant for Vioxx maker Merck & Co. and Celebrex maker Pharmacia Corp. Despite the companies' displeasure, he concludes "a prudent approach" is to temporarily quit using either NSAIDS, Vioxx or Celebrex if you break a bone.

"If you don't know, you should err on the side of caution."

Copyright 2002 The Associated Press. All rights reserved.