Abstract
G A A b st ra ct s at least one year of follow-up within THIN who also lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined by the first Read code for incident fracture at any site and the control pool consisted of individuals without a diagnosis of fracture at the time when the corresponding case had his or her first fracture. Using incidence density sampling, cases were matched with up to 5 control subjects by age (within 1 year), sex, THIN practice, and start of follow-up in THIN (within 1 year). PPI exposure was defined as 180 or more cumulative doses of PPIs. We additionally examined the PPI-fracture relationship at varying levels of PPI exposure. As potential confounders, we extracted information related to age, sex, body mass index, and use of other medications. The primary outcome was calculated using conditional logistic regression as the odds of PPI exposure in cases compared to controls. Because the epidemiology of fracture varies by age, we stratified analyses using a cut-off of 18 years old or more. RESULTS: 508,740 children age 4 to 17 years old and 207,181 young adults age 18 to 29 years old within the THIN database were included in the study. We identified 124,799 cases of incident fracture and 605,643 matched controls. In young adults but not children, PPIs were a risk factor for fracture in both unadjusted and adjusted models. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children and 1.39 (95% CI 1.26 to 1.53) among young adults. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend <.001). CONCLUSIONS: PPI use was associated with non-osteoporotic fracture in young adults but not children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.
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