{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:46:17Z","timestamp":1790484377554,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>BMD was examined in users of NSAIDs (by COX selectivity) and aspirin in the Health ABC cohort (n = 2853). Significantly higher BMD was found in users of relative COX-2 selective NSAIDs with aspirin (COX-2\/ASA) compared with nonusers. This suggests a role for COX-2\/ASA in osteoporosis.<\/jats:p>\n               <jats:p>Introduction: The purpose of this study was to determine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use, by cyclo-oxygenase selectivity (COX), and aspirin use on bone mineral density (BMD) in participants from the Health, Aging, and Body Composition (Health ABC) population-based cohort. It is known that NSAIDs inhibit the COX enzyme and decrease production of prostaglandins, which are involved in regulation of bone turnover. COX has two isoforms, COX-1 and COX-2. Production of prostaglandins associated with bone loss is primarily mediated through the COX-2 pathway. In addition, aspirin may have effects on bone independent of the prostaglandin pathway.<\/jats:p>\n               <jats:p>Materials and Methods: NSAID (by COX selectivity) and aspirin use and BMD were assessed in 2853 adults (49.5% women, 50.5% men; 43.1% black, 56.9% white; mean age: 73.6 years) from the Health ABC cohort. For the purposes of this analysis, relative COX-1 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of &amp;gt;1 in whole blood, and relative COX-2 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of &amp;lt;1 in whole blood. Analysis of covariance was used to compare BMD across each NSAID use and aspirin use category adjusting for age, race, gender, weight, height, study site, calcium and vitamin D supplementation, Womac score, history of rheumatoid arthritis, history of arthritis other than rheumatoid, and smoking status.<\/jats:p>\n               <jats:p>Results: After adjustment for possible confounders, current use of relative COX-2 selective NSAIDs with aspirin was associated with higher BMD at the whole body (4.2%, 1.2\u20137.3 CI) and total hip (4.6%, 0.5\u20138.8 CI) by DXA and at both trabecular (34.1%, 15.4\u201352.7 CI) and cortical spine (12.8%, 2.3\u201323.3 CI) by quantitative computed tomography.<\/jats:p>\n               <jats:p>Conclusions: Our data suggest that the combination of relative COX-2 selective NSAIDs and aspirin is associated with higher BMD at multiple skeletal sites in men and women.<\/jats:p>","DOI":"10.1359\/jbmr.2003.18.10.1795","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T21:41:02Z","timestamp":1146087662000},"page":"1795-1802","source":"Crossref","is-referenced-by-count":112,"title":["Association Between Bone Mineral Density and the Use of Nonsteroidal Anti-Inflammatory Drugs and Aspirin: Impact of Cyclooxygenase Selectivity"],"prefix":"10.1093","volume":"18","author":[{"given":"Laura D","family":"Carbone","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances A","family":"Tylavsky","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A","family":"Cauley","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara B","family":"Harris","sequence":"additional","affiliation":[{"name":"Epidemiology, Demography and Biometry Program, National Institute of Aging, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas C","family":"Bauer","sequence":"additional","affiliation":[{"name":"Prevention Sciences Group, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen D","family":"Barrow","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B","family":"Kritchevsky","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019115631600_bib1","doi-asserted-by":"crossref","first-page":"2024S","DOI":"10.1093\/jn\/125.suppl_7.2024S","article-title":"Physiologic and pathologic roles of prostaglandins and other eicosanoids in bone metabolism","volume":"125","author":"Raisz","year":"1995","journal-title":"J Nutr"},{"key":"2024013019115631600_bib2","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1002\/jbmr.5650110909","article-title":"Anabolic effects of prostaglandins in cultured fetal rat calvariae: Structure-activity relations and signal transduction pathway","volume":"11","author":"Woodiel","year":"1996","journal-title":"J Bone Miner Res"},{"key":"2024013019115631600_bib3","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S8756-3282(97)00147-6","article-title":"The in vivo anabolic actions of prostaglandins in bone","volume":"21","author":"Jee","year":"1997","journal-title":"Bone"},{"key":"2024013019115631600_bib4","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1080\/15513819609168686","article-title":"Prostaglandin E1-induced hyperostosis: Clinicopathologic correlations and possible pathogenetic mechanisms","volume":"16","author":"Faye-Petersen","year":"1996","journal-title":"Pediatr Pathol Lab Med"},{"key":"2024013019115631600_bib5","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/BF01621888","article-title":"Prostaglandins: Mechanisms of action and regulation of production in bone","volume":"3","author":"Raisz","year":"1993","journal-title":"Osteoporos Int"},{"key":"2024013019115631600_bib6","doi-asserted-by":"crossref","first-page":"43S","DOI":"10.1016\/S0002-9343(00)00684-7","article-title":"Potential impact of selective cyclooxygenase-2 inhibitors on bone metabolism in health and disease","volume":"110","author":"Raisz","year":"2001","journal-title":"Am J Med"},{"key":"2024013019115631600_bib7","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1210\/endo.138.6.5192","article-title":"Transcriptional induction of cyclooxygenase-2 in osteoblasts is involved in interleukin-6-induced osteoclast formation","volume":"138","author":"Tai","year":"1997","journal-title":"Endocrinology"},{"key":"2024013019115631600_bib8","doi-asserted-by":"crossref","first-page":"11202","DOI":"10.1073\/pnas.91.23.11202","article-title":"Mechanism of selective inhibition of the inducible isoform of prostaglandin G\/H synthase","volume":"91","author":"Copeland","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019115631600_bib9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0005-2760(93)90003-R","article-title":"Mammalian non-pancreatic phospholipases A2","volume":"1170","author":"Kudo","year":"1993","journal-title":"Biochim Biophys Acta"},{"key":"2024013019115631600_bib10","doi-asserted-by":"crossref","first-page":"9049","DOI":"10.1016\/S0021-9258(18)52976-8","article-title":"Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines","volume":"268","author":"Jones","year":"1993","journal-title":"J Biol Chem"},{"key":"2024013019115631600_bib11","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1073\/pnas.91.8.3228","article-title":"Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic","volume":"91","author":"Masferrer","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019115631600_bib12","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s000180050432","article-title":"The pleiotropic functions of aspirin: Mechanisms of action","volume":"15","author":"Amin","year":"1999","journal-title":"Cell Mol Life Sci"},{"key":"2024013019115631600_bib13","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1210\/endo.142.3.8003","article-title":"4-hydroxytamoxifen trans-represses nuclear factor-kappa B activity in human osteoblastic U2-OS cells through estrogen receptor (ER)alpha, and not through ER beta","volume":"142","author":"Quaedackers","year":"2001","journal-title":"Endocrinology"},{"key":"2024013019115631600_bib14","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1359\/jbmr.1999.14.12.2137","article-title":"Evidence for a pathogenic role of nitric oxide in inflammation-induced osteoporosis","volume":"14","author":"Armour","year":"1999","journal-title":"J Bone Miner Res"},{"key":"2024013019115631600_bib15","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/jbmr.5650110106","article-title":"Aspirin and NSAID use in older women: Effect on bone mineral density and fracture risk. Study of Osteoporotic Fractures Research Group","volume":"11","author":"Bauer","year":"1996","journal-title":"J Bone Miner Res"},{"key":"2024013019115631600_bib16","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1359\/jbmr.1998.13.12.1924","article-title":"Nonsteroidal anti-inflammatory drugs and bone mineral density in older women: The Rancho Bernardo Study","volume":"13","author":"Morton","year":"1998","journal-title":"J Bone Miner Res"},{"key":"2024013019115631600_bib17","first-page":"1132","article-title":"Aspirin and nonsteroidal anti-inflammatory drug use in elderly women: Effects on a marker of bone resorption. The Study of Osteoporotic Fractures Research Group","volume":"24","author":"Lane","year":"1997","journal-title":"J Rheumatol"},{"key":"2024013019115631600_bib18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/BF01719664","article-title":"Drug data coding and analysis in epidemiologic studies","volume":"10","author":"Pahor","year":"1994","journal-title":"Eur J Epidemiol"},{"key":"2024013019115631600_bib19","first-page":"1705","article-title":"Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases","volume":"271","author":"Patrignani","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"2024013019115631600_bib20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/BF02265118","article-title":"A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors","volume":"45","author":"Brideau","year":"1996","journal-title":"Inflamm Res"},{"key":"2024013019115631600_bib21","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0002-9343(98)00091-6","article-title":"Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs","volume":"104","author":"Cryer","year":"1998","journal-title":"Am J Med"},{"key":"2024013019115631600_bib22","doi-asserted-by":"crossref","first-page":"134","DOI":"10.7326\/0003-4819-132-2-200001180-00008","article-title":"Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional nonsteroidal anti-inflammatory drugs, with less gastrointestinal toxicity?","volume":"132","author":"Feldman","year":"2000","journal-title":"Ann Intern Med"},{"key":"2024013019115631600_bib23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/newbio231232a0","article-title":"Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs","volume":"231","author":"Vane","year":"1971","journal-title":"Nat New Biol"},{"key":"2024013019115631600_bib24","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/S0891-5849(00)00425-1","article-title":"Synergistic inhibition of cyclooxygenase-2 expression by vitamin E and aspirin","volume":"29","author":"Abate","year":"2000","journal-title":"Free Radic Biol Med"},{"key":"2024013019115631600_bib25","volume-title":"WOMAC Osteoarthritis Index. A User's Guide","author":"Bellamy","year":"1995"},{"key":"2024013019115631600_bib26","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1172\/JCI8195","article-title":"Prostaglandin G\/H synthase-2 is required for maximal formation of osteoclast-like cells in culture","volume":"105","author":"Okada","year":"2000","journal-title":"J Clin Invest"},{"key":"2024013019115631600_bib27","first-page":"779","article-title":"Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: Development of a specific 15-epi-LXA4 ELISA","volume":"287","author":"Chiang","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"2024013019115631600_bib28","doi-asserted-by":"crossref","first-page":"9475","DOI":"10.1073\/pnas.92.21.9475","article-title":"Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions","volume":"92","author":"Claria","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019115631600_bib29","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa003199","article-title":"Cyclooxygenase inhibitors and the antiplatelet effects of aspirin","volume":"345","author":"Catella-Lawson","year":"2001","journal-title":"N Engl J Med"},{"key":"2024013019115631600_bib30","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1001\/jama.286.8.954","article-title":"Risk of cardiovascular events associated with selective COX-2 inhibitors","volume":"286","author":"Mukherjee","year":"2001","journal-title":"JAMA"},{"key":"2024013019115631600_bib31","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/00004728-199901000-00027","article-title":"Assessment of vertebral bone mineral density using volumetric quantitative CT","volume":"23","author":"Lang","year":"1999","journal-title":"J Comput Assist Tomogr"},{"key":"2024013019115631600_bib32","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1359\/jbmr.2001.16.7.1291","article-title":"Does body size account for gender differences in femur bone density and geometry?","volume":"16","author":"Looker","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2024013019115631600_bib33","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/BF00310253","article-title":"Influence of degenerative joint disease on spinal bone mineral measurements in postmenopausal women","volume":"57","author":"Yu","year":"1995","journal-title":"Calcif Tissue Int"},{"key":"2024013019115631600_bib34","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1056\/NEJM199511303332201","article-title":"Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group","volume":"333","author":"Liberman","year":"1995","journal-title":"N Engl J Med"},{"key":"2024013019115631600_bib35","doi-asserted-by":"crossref","first-page":"7563","DOI":"10.1073\/pnas.96.13.7563","article-title":"Nonsteroidal drug selectivities for cyclooxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: A full in vitro analysis","volume":"96","author":"Warner","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019115631600_bib36","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/00002281-200009000-00021","article-title":"Bone mineral density in osteoarthritis","volume":"12","author":"Stewart","year":"2000","journal-title":"Curr Opin Rheumatol"},{"key":"2024013019115631600_bib37","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1359\/jbmr.2001.16.11.2142","article-title":"Determinants of bone mineral density in older men and women: Body composition as mediator","volume":"16","author":"Pluijm","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2024013019115631600_bib38","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/00004728-198803000-00013","article-title":"Vertebral mineral determination by quantitative computed tomography (QCT): Accuracy of single and dual energy measurements","volume":"12","author":"Gluer","year":"1988","journal-title":"J Comput Assist Tomogr"},{"key":"2024013019115631600_bib39","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1002\/jbmr.5650111019","article-title":"Evaluation of cortical bone by computed tomography","volume":"11","author":"Hangartner","year":"1996","journal-title":"J Bone Miner Res"},{"key":"2024013019115631600_bib40","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/0140-6736(93)92555-8","article-title":"Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group","volume":"341","author":"Cummings","year":"1993","journal-title":"Lancet"},{"key":"2024013019115631600_bib41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s001980050010","article-title":"Randomized trial of effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group","volume":"11","author":"Reginster","year":"2000","journal-title":"Osteoporos Int"},{"key":"2024013019115631600_bib42","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0002-9343(00)00490-3","article-title":"A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: The prevent recurrence of osteoporotic fractures study. PROOF Study Group","volume":"109","author":"Chesnut","year":"2000","journal-title":"Am J Med"},{"key":"2024013019115631600_bib43","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1001\/jama.282.7.637","article-title":"Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators","volume":"282","author":"Ettinger","year":"1999","journal-title":"JAMA"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2Fjbmr.2003.18.10.1795","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/18\/10\/1795\/56469338\/5650181011.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/18\/10\/1795\/56469338\/5650181011.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:05:52Z","timestamp":1710342352000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/18\/10\/1795-1802\/7592281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,1]]},"references-count":43,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[2003,10,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.2003.18.10.1795","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,10,1]]},"published":{"date-parts":[[2003,10,1]]}}}