COX-2 (Which NSAIDS Inhibit) Plays An Essential Role In Bone Repair

I read that NSAIDS damage joints, and that those which inhibit more COX-2 than COX-1 enzymes, as Vioxx and Celebrex do, were less damaging. They carried a higher risk for stroke and heart attack, however. (Vioxx is off the market for that reason.)

So, is a COX-2 inhibitor like Celebrex safe for joints?

This study says that "COX-2 plays an essential role in bone formation during skeletal repair." It raises the question of whether inhibiting it could affect bone repair:

Reduced COX-2 Expression In Aged Mice Is Associated With Impaired Fracture Healing, Journal of Bone and Mineral Research, 2009

From their press release:

"Researchers found further proof that COX-2 is responsible for loss of bone healing ability with age when they were able to reverse the process with a drug known to encourage the COX-2 signaling effect."

"Prior work in other labs had established that the ability of PGE2 to create new bone growth occurs in particular through its interaction with the EP4 receptor. In the current study, the team showed that delayed fracture healing observed in aged mice could be rescued with local delivery of an experimental drug, CP-734432, which directly activates the EP4 receptor in place of the missing COX-2 (an EP4 agonist). The drug, provided to the team by Pfizer Inc., was also recently used to prevent osteoporosis in early animal studies. Local injection of an EP4 agonist to the fracture site of aged mice compensated for the reduced fracture repair observed with aging, with a significant reduction in immature cartilage seen and more efficient formation of mature bone."

So, a drug that compensates for missing COX-2 results in more efficient formation of bone. And is being used to prevent osteoporosis. This just doesn't look good for the safety of NSAIDS relative to bone health, especially for older people.
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