In our study, according to the outcome explored, the CPRD data were linked to the Hospital Episode Statistics (HES) and the Office of National Statistics AZD2014 solubility dmso (ONS) databases to obtain additional information on hospitalisations and fatalities, respectively. The study protocol was approved by the Independent Scientific Advisory Committee of the Medicines and Healthcare Products Regulatory

Agency (MHRA). We identified all male and female patients who had received a prescription for osteoporosis treatment or a medical record of primary osteoporosis between 1 January 2002 and 30 April 2012. The cohort entry date was fixed as the date of the first prescription of osteoporosis treatment during the study period. Patients were excluded if they had had a prescription for an osteoporosis treatment

in the previous year or had received a prescription for bisphosphonate for indications other than osteoporosis (e.g., Paget’s disease, hypercalcaemia, breast cancer, or myeloma). Patients could also be excluded if they came from a practice with less than 1 year of UTS CPRD data at their cohort entry date. From this population, we then excluded successively patients who had never received a treatment for their osteoporosis, and then all male patients, to reach a population of women with treated osteoporosis. The follow-up period extended from the cohort entry date to the date of the last data collection from ARRY-438162 the practice, the date of transfer if the patient left the practice, or the date of death. Outcomes and selection of controls O-methylated flavonoid The primary

outcomes of our nested case–control study were first CP673451 concentration definite MI (fatal or nonfatal), hospitalisation with MI (fatal or nonfatal, first or subsequent), and cardiovascular death occurring after the cohort entry date. The index date for cases was defined as the date of event. Cases of MI were qualified as definite [13] if there was a CPRD record of MI, and the patient either (1) died within 30 days, or (2) was initiated on relevant treatment (e.g., statins, nitrates, and/or beta-blockers), and had other supporting evidence (e.g., location of infarct, coronary artery revascularisation, and/or elevated cardiac enzymes) within 2 months of the MI. Analyses on first definite MI excluded patients with previous MI. Cases of hospitalisation with MI were identified in the HES dataset in patients eligible for linkage, which ensured detection of cases not otherwise apparent in the GP record. Analyses of cases of hospitalisation with MI did not exclude patients with previous MI. Cases of cardiovascular death were identified in the ONS death dataset in patients eligible for linkage. This dataset provides information on cause and date of death, which may be missing in the general practice-based CPRD. Three case–control analyses were performed successively.