The effect of cyclooxygenase-2 inhibitors on bone mineral density: results from the Canadian Multicentre Osteoporosis Study

Osteoporos Int. 2006;17(9):1410-9. doi: 10.1007/s00198-006-0142-x. Epub 2006 Jun 22.


Introduction: The use of cyclooxygenase-2 (COX-2) inhibitors has been demonstrated to not only impair load-induced bone formation but also prevent menopause-associated bone loss. We hypothesized that COX-2 inhibitor use would be associated with increased bone mineral density (BMD) in postmenopausal women not using estrogen therapy and, conversely, with decreased BMD in men.

Methods: The Canadian Multicentre Osteoporosis Study is a longitudinal, randomly selected, population-based community cohort. We present data from men (n=2,004) and postmenopausal women age 65 and older (n=2,776) who underwent a BMD measurement and structured interview in the 5th year of the study. The outcome measure was percent difference in BMD (g/cm(2)).

Results: Daily COX-2 inhibitor use was reported by 394 subjects. In men, daily use of COX-2 inhibitors was associated with a lower BMD at all hip sites, with a percent difference of -3.1% [95% confidence interval (CI), -6.0, -0.3] between users and nonusers at total hip. In postmenopausal women not using estrogen replacement therapy, daily COX-2 inhibitor use was associated with higher BMD at most sites [percent difference at total hip: +3.0% (95% CI, 0.3, 5.8)]. These effects appeared to be dose-dependent.

Conclusion: COX-2 inhibitor use was associated with a lower BMD in men and, on the other hand, with a higher BMD in postmenopausal women not using estrogen replacement therapy. Men who have used COX-2 inhibitors may wish to seek BMD measurement to assess their fracture risk. However, COX-2 inhibitors may have utility in postmenopausal women if bone-selective analogs can be developed.

Publication types

  • Multicenter Study

MeSH terms

  • Acetaminophen / pharmacology
  • Adult
  • Aged
  • Body Mass Index
  • Bone Density / drug effects*
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Dose-Response Relationship, Drug
  • Estrogen Replacement Therapy
  • Female
  • Femur / physiology
  • Hip Joint / physiology
  • Humans
  • Lumbar Vertebrae / physiology
  • Male
  • Middle Aged
  • Osteoarthritis / drug therapy
  • Osteoporosis / chemically induced*
  • Osteoporosis / physiopathology
  • Prospective Studies
  • Sex Factors


  • Cyclooxygenase 2 Inhibitors
  • Acetaminophen