In both GPRD studies, the risk of hip fracture decreased with prolonged PPI use [11, 12]. The discrepancies between the different “duration of use” analyses in the studies mentioned above are important, because “duration of use” analyses provide indirect evidence that may support a causal effect. Therefore, the objective of this study was to evaluate the association between the (duration of) use of PPIs and the risk of hip/femur fracture

in a different study population. Methods Study design The Dutch PHARMO Record Linkage System (RLS) was used to conduct a case-control study. PHARMO RLS (http://​www.​pharmo.​nl) SB202190 price includes the virtually complete pharmacy dispensing histories of community-dwelling residents in the Netherlands, which are linked to hospital admission records. Pharmacy data include information about the drug dispensed, the date of dispensing, the prescriber, the amount dispensed, the prescribed dosage regimen and the estimated duration of use. Hospital discharge records include detailed information on date of admission, discharge diagnoses and procedures. The version of the database used for this study, represents about 7% of the general Dutch population. Patients are included irrespective of their health insurance or socio-economic status. Moreover, validation studies have shown that the PHARMO RLS has a high level of data

completeness and validity [13], especially with regards to recording of hip fractures [14, 15]. A case-control analysis was conducted within PHARMO RLS between January 1, 1991 and December 31, 2002. MEK activation Cases were 18 years or older and sustained a hip or femur fracture

during the study period. The first hospital admission date for a hip/femur fracture defined the index date. The ICD codes 820–821 were used to identify hip/femur fractures. Up to four control patients were matched Ribonucleotide reductase to each case by year of birth, gender and geographical region. The selected control patients were PHARMO RLS participants without any fracture during enrolment. Controls were assigned the same index date as their matched case. Exposure assessment Current users of PPIs or histamine H2-receptor antagonists (H2RAs) were defined as patients who had received at least one PPI or H2RA dispensing within the 30 days before the index date. Recent, past and distant past users received their last dispensing in respectively the 31–91 days, 92–365 days or >1 year before the index date. For each current user, we calculated the average daily dose by division of the cumulative dose by the treatment time, using defined daily dosages (DDD) [16]. One DDD is equivalent to 20 mg orally administered omeprazole, 40 mg pantoprazole, 30 mg lansoprazole, 20 mg rabeprazole, 30 mg esomeprazole, 800 mg cimetidine, 300 mg ranitidine, 300 mg nizatidine, 150 mg roxatidine and 40 mg famotidine.