The effect of cyclooxygenase-2 inhibitors on bone mineral density: results from the Canadian Multicentre Osteoporosis Study
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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.
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/cm2).
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.
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.
KeywordsBone mineral density Cyclooxygenase-2 inhibitors Inflammation Osteoporosis
The authors wish to acknowledge the assistance of Claudie Berger and Cristine Leroux with data management and the assistance of Dr. Suzanne Morin with data analysis.
Investigators for the CaMos Study Group:
CaMos Coordinating Centre, McGill University, Montreal, Quebec: David Goltzman (co-principal investigator), Nancy Kreiger (co-principal investigator), Alan Tenenhouse (senior researcher), Suzette Poliquin (national coordinator), Suzanne Godmaire (research assistant), Claudie Berger (study statistician), Lawrence Joseph (former study statistician).
Memorial University, St. John’s Newfoundland: Carol Joyce (director), Emma Sheppard (coordinator).
Dalhousie University, Halifax, Nova Scotia: Susan Kirkland, Stephanie Kaiser (codirectors), Barbara Stanfield (coordinator).
Laval University, Quebec City, Quebec: Jacques P. Brown (director), Louis Bessette (co-director), Evelyne Lejeune (coordinator), Marc Gendreau (Imaging Coordinator).
Queen’s University, Kingston, Ontario: Tassos Anastassiades (director), Tanveer Towheed (co-director), Barbara Matthews (coordinator).
University of Toronto, Toronto, Ontario: Bob Josse (director), Tim Murray (co-director), Barbara Gardner-Bray (coordinator).
McMaster University, Hamilton, Ontario: Jonathan D. Adachi (director), Alexandra Papaioannou (co-director), Laura Pickard (coordinator).
University of Saskatchewan, Saskatoon, Saskatchewan: Wojciech P. Olszynski (director), Jola Thingvold (coordinator).
University of Calgary, Calgary, Alberta: David A. Hanley (director), Jane Allan (coordinator).
University of British Columbia, Vancouver, British Columbia: Jerilynn C. Prior (director), Yvette Vigna (coordinator).
- 3.Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA, the Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352(11):1092–1102PubMedCrossRefGoogle Scholar
- 4.Solomon SD, McMurray JJV, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M, the Adenoma Prevention with Celecoxib (APC) Study Investigators (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352(11):1071–1080PubMedCrossRefGoogle Scholar
- 18.Carbone LD, Tylavsky FA, Cauley JA, Harris TB, Lang TF, Bauer DC, Barrow KD, Kritchevsky SB (2003) Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J Bone Miner Res 18(10):1795–1802PubMedCrossRefGoogle Scholar
- 21.Kreiger N, Tenenhouse A, Joseph L, Mackenzie T, Poliquin S, Brown JP, Prior JC, Rittmaster RS (1999) Research notes: the Canadian Multicentre Ssteoporosis Study (CaMos): background, rationale, methods. Can J Aging 18(3):376–387Google Scholar
- 24.Pearson J, Dequeker J, Henley M, Bright J, Reeve J, Kalender W, Lavaljeantet AM, Ruegsegger P, Felsenberg D, Adams J, Birkenhager JC, Braillon P, Curiel MD, Fischer M, Galan F, Geusens P, Hyldstrup L, Jaeger P, Jonson R, Kalefezras J, Kotzki P, Kroger H, Vanlingen A, Nilsson S, Osteaux M, Cano RP, Reid DM, Reiners C, Ribot C, Schneider P, Slosman DO, Wittenberg G (1995) European semi-anthropomorphic spine phantom for the calibration of bone densitometers: assessment of precision, stability and accuracy. The European Quantitation of Osteoporosis Study Group. Osteoporos Int 5(3):174–184PubMedCrossRefGoogle Scholar
- 27.Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, Masaki K, Coker LH, for the Women’s Health Initiative Memory Study (2004) Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: women’s health initiative memory study. JAMA 291(24):2947–2958PubMedCrossRefGoogle Scholar
- 29.Brunner RL, Gass M, Aragaki A, Hays J, Granek I, Woods N, Mason E, Brzyski R, Ockene J, Assaf A, LaCroix A, Matthews K, Wallace R, for the Women’s Health Initiative Investigators (2005) Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the women’s health initiative randomized clinical trial. Arch Intern Med 165(17):1976–1986PubMedCrossRefGoogle Scholar
- 35.Meunier PJ, Slosman DO, Delmas PD, Sebert JL, Brandi ML, Albanese C, Lorenc R, Pors-Nielsen S, De Vernejoul MC, Roces A, Reginster JY (2002) Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis—a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 87(5):2060–2066PubMedCrossRefGoogle Scholar
- 36.Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW, Dequeker J, Favus M, Seeman E, Recker RR, Capizzi T, Santora AC, Lombardi A, Shah RV, Hirsch LJ, Karpf DB, The Alendronate Phase III Osteoporosis Treatment Study Group (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 333(22):1437–1444PubMedCrossRefGoogle Scholar
- 37.Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH III, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD, for the Vertebral Efficacy with Risedronate Therapy Study Group (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 282(14):1344–1352PubMedCrossRefGoogle Scholar
- 38.Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR, for the Multiple Outcomes of Raloxifene Evaluation Investigators (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 282(7):637–645PubMedCrossRefGoogle Scholar