Oral bisphosphonates do not increase the risk of severe upper gastrointestinal complications: a nested case-control study

Abstract

Background: Data on the effect of oral bisphosphonates (BPs) on risk of upper gastrointestinal complications (UGIC) are conflicting. We conducted a large population-based study from a network of Italian healthcare utilization databases aimed to assess the UGIC risk associated with use of BPs in the setting of secondary prevention of osteoporotic fractures.

Methods: A nested case-control study was carried out within a cohort of 68,970 patients aged 45 years or older, who have been hospitalized for osteoporotic fracture from 2003 until 2005. Cases were the 804 patients who experienced hospitalization for UGIC until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current and past use of BPs (i.e. for drug dispensation within 30 days and over 31 days prior the outcome onset, respectively) after adjusting for several covariates.

Results: Compared with patients who did not use BPs, current and past users had OR (and 95% confidence interval) of 0.86 (0.60 to 1.22) and 1.07 (0.80 to 1.44) respectively. There was no difference in the ORs estimated according with BPs type (alendronate or risedronate) and regimen (daily or weekly), nor with co-therapies and comorbidities.

Conclusions: Further evidence that BPs dispensed for secondary prevention of osteoporotic fractures are not associated with increased risk of severe gastrointestinal complications is supplied from this study. Further research is required to clarify the role BPs and other drugs of co-medication in inducing UGIC.

Figure 1

Study flow diagram. AIFA-BEST Project, Italy, 2003–2007. Flow chart of inclusion and exclusion criteria. BPs: Bisphosphonates.

Figure 2

Adjusted odds ratios (and 95% confidence intervals) of upper gastrointestinal complications associated with anytime, current and past exposure to bisphosphonates as a whole (all) as well as to type (alendronate and risedronate) and regimen (daily and weekly) of the latest dispensed bisphosphonates. AIFA-BEST Project, Italy, 2003–2007. Odds ratios estimated with conditional logistic regression model. Estimates concerning main analysis (all) were adjusted for use of other medicaments in the 60-day period and for the Charlson index measured before the index date. Estimates concerning subgroup analysis were obtained by including the interaction terms combining the effect of anytime, current or past exposure to BPs together with type and regimen of the dispensed BPs. P-values concern comparison of BPs effect across patient subgroups. BPs: Bisphosphonates.

Figure 3

Combined action of current exposure to bisphosphonates, concurrent exposure to other medicaments and categories of Charlson comorbidity index on the risk of upper gastrointestinal complications. AIFA-BEST Project, Italy, 2003–2007. Odds ratios estimated with conditional logistic regression model. Estimates were obtained by including the interaction terms combining the effect of current exposure to BPs together with concurrent use of other medicaments and the categories of the Charlson index. P-values concern comparison of BPs effect across patient subgroups. BPs: Bisphosphonates.

Figure 4

Influences of diagnostic criteria for defining upper gastrointestinal complications (panel A), and of the time-window length for defining current use of BPs (panel B) on the observed odds ratio of upper gastrointestinal complications associated with current exposure to bisphosphonates. AIFA-BEST Project, Italy, 2003–2007. Odds ratios estimated with conditional logistic regression model. Estimates were adjusted for use of medicaments in the 60-day period and for the Charlson index measured before the index date. Details for diagnostic criteria are reported in Additional file 1. BPs: Bisphosphonate.