Finally, adherence to treatment may be overestimated since drug prescribing does not necessarily equate with drug use, though sensitivity analyses using various definitions of drug exposure gave similar results. Further caveats to our study include the absence of a control group without osteoporosis and the use of propensity matching for our cases and controls. This leaves open the potential for confounding by indication, with regard to treatment

using alendronate or strontium ranelate, following diagnosis of osteoporosis. The reduced risk of MI among predominantly alendronate users might represent just such a selection artefact. Finally, the pattern of osteoporosis prescribing in the UK [14] left the selected cohort of women treated for osteoporosis, as predominantly receiving alendronate (84 %). Only 6 % of the treated women received #selleck chemical randurls[1|1|,|CHEM1|]# strontium ranelate; and only 14 % had never used either Gilteritinib strontium ranelate or alendronate. Thus, the ability to contrast strontium ranelate treatment with the cardiovascular experience of women in the UK population as a whole or with women using osteoporosis treatment other than alendronate was limited. The study sample utilised was necessary to maximise the prevalence of the exposure of interest (strontium ranelate), but future research could

include a more traditional retrospective cohort study in patients treated with strontium ranelate, alendronate, osteoporosis with other treatments, and women selected from the CPRD as a whole. Nonetheless, much effort was made to reduce bias in this retrospective observational study. The sensitivity of the algorithm for first definite MI has been tested and confirmed [13], and the reliability of the identification Calpain of cardiac outcomes is further reinforced by the use of hard endpoints and linkage to ONS/HES data. The case–control analysis was nested in a cohort of women who were all treated for osteoporosis to reduce selection bias due to potential heterogeneity between patients. The design also accounts for the two main confounders related to clinical

use of strontium ranelate in the UK [14]: calendar date, because strontium ranelate has been available for a short time relative to other osteoporosis treatments, and disease duration, because strontium ranelate is recommended second or third line, while alendronate, for example, is usually prescribed first line. This is clear from the patient characteristics, which show that patients treated with strontium ranelate were older than the patients with osteoporosis treated with other agents and had a longer time since diagnosis. Our study highlights a substantial relative risk for cardiac events associated with previous hospitalisation with MI in patients with treated postmenopausal osteoporosis.