, Volume 79, Issue 2, pp 84-94
Date: 15 Aug 2006

Fracture Risk Associated with Use of Nonsteroidal Anti-Inflammatory Drugs, Acetylsalicylic Acid, and Acetaminophen and the Effects of Rheumatoid Arthritis and Osteoarthritis

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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.