title: Fracture risk associated with use of nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and acetaminophen and the effects of rheumatoid arthritis and osteoarthritis.
abstract: We studied the effects of various nonmorphine pain medications as well as rheumatoid arthritis and osteoarthritis on fracture risk in a nationwide case-control study. Cases were all subjects with any fracture sustained during the year 2000 (n = 124,655) in Denmark. For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), or acetylsalicylic acid (ASA). Adjustments were made for several confounders. The effect of dose was examined by stratifying for cumulated dose (defined daily dose, DDD). For acetaminophen, a small increase in overall fracture risk was observed with use within the last year (odds ratio [OR] = 1.45, 95% confidence interval [CI] 1.41-1.49). For ASA, no increase in overall fracture risk was present with recent use. Significant heterogeneity was present for the NSAIDs; e.g., ibuprofen was associated with an increased overall fracture risk (OR = 2.09, 95% CI 2.00-2.18 for <20 DDD), while celecoxib was not (OR = 0.76, 95% CI 0.51-1.13 for <20 DDD, 2P < 0.01 for comparison). Osteoarthritis was associated with a decreased risk of any fracture if the diagnosis had been made more than 1 year ago (OR = 0.70, 95% CI 0.67-0.72). Rheumatoid arthritis was associated with an increase in overall fracture risk if the diagnosis had been made within the last year (OR = 1.86, 95% CI 1.68-2.07). Weak analgesics may be associated with fracture risk in a varying way. The effects in most cases were small. Falls may be one reason for the increase in fracture risk with some NSAIDs.
authors.affiliation: Department of Endocrinology and Metabolism, Aarhus Sygehus, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000, Aarhus C, Denmark. p-vest@post4.tele.dk
authors.forename: P
authors.initials: P
authors.lastname: Vestergaard
authors.forename: L
authors.initials: L
authors.lastname: Rejnmark
authors.forename: L
authors.initials: L
authors.lastname: Mosekilde
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D001241:Aspirin / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D050723:Fractures, Bone / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology*; D012042:Registries; D012306:Risk
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D001241:Aspirin