64 54 7,274 0.74 1.15 (0.71–1.88) Vertebral 87 3,572 2.43 122 7,274 1.68 0.69 (0.52–0.91) We examined whether different levels of fracture risk at the start of therapy modified the longitudinal change in fracture incidence—by using stratification to limit the analyses to subgroups of check details similar baseline characteristics of fracture risk. The strata were based upon prior clinical fracture (yes

or no), prior bisphosphonate use (yes or no), age (one quantile above or below population median of 75 years), and date of study entry (period before or after all three therapies were on the market). For every subgroup, its 95% confidence interval included the point estimate of overall analyses (Fig. 2). Fig. 2 Ratio and 95% confidence interval of hip fracture incidence for subsequent click here 1 year on therapy (follow-up) versus 3-month period after starting therapy (baseline)—subgroup analyses Discussion In this observational study of cohorts containing patients starting alendronate, risedronate, or ibandronate, there were

apparent selleck compound differences among the cohorts in age and prior fracture history, in prior use of bisphosphonates, and in the fracture incidence during the short period after starting therapy and before any expected clinical benefit. These differences in the risk profile of patients prescribed each bisphosphonate are significant for the consideration of bias in interpretation of results of any observational study of bisphosphonates. In this study and prior studies [7, 20, 22, 23], the inclusion criterion for new use of bisphosphonate was defined by a subject having at least 6 months of no other bisphosphonate use. In order to further evaluate this criterion, we were able to examine up to four prior

years for a subset of the population. As evident by the large number of ibandronate patients in this study with prior bisphosphonate use, the six month criterion was not always adequate to truly define new users of bisphosphonates. Indeed, the median gap between stopping and restarting bisphosphonate therapy has been reported to be 16 months [33]. Since bisphosphonates have residual treatment effects, for example, alendronate has effects for up to 5 years after stopping treatment [34], it may not be readily possible to disentangle the fracture outcome with the current bisphosphonate exposure from past bisphosphonate exposure [35]. Avelestat (AZD9668) The study approach to account for differences in patient profiles is often techniques of regression modeling, propensity score modeling, or instrument variable analysis [36]. However, statistical techniques cannot exclude the possibility of bias arising from the nonrandom allocation of subjects [37]. In the current study, given the differences between cohorts in patient profiles including prior use of bisphosphonates, we proposed a study design that estimated bisphosphonate effectives by measuring the change in fracture incidence over time within a cohort.