Raloxifene increases the risk of gastroesophageal reflux disease, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis

Abstract

Background and AimsEstrogen‐based therapies may increase the risk of gastroesophageal reflux (GERD) and its complications. We aimed to determine the effect of raloxifene on the development of GERD, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis.MethodsThis was a population‐based, propensity‐matched cohort study using the TriNetX platform. Patients 50 years and older with a diagnosis of “menopause” and “osteoporosis” were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for new GERD, esophageal stricture and Barrett's esophagus after raloxifene exposure. The control cohort consisted of patients who did not start any hormonal replacement therapy. We conducted a multivariable logistic regression analysis to evaluate the effect of confounding variables and also addressed common confounding medications with 1:1 propensity score‐matching. Internal validity was confirmed by comparing to negative controls (lisinopril, atorvastatin) and positive controls (metformin, ibuprofen, aspirin).ResultsFive thousand four hundred and seventy two postmenopausal women with osteoporosis were on raloxifene of which 1908 (34.86%) developed GERD, compared to 296,067 postmenopausal who were not on raloxifene of which 90,643 (30.62%) developed GERD (OR 1.2; 95% CI 1.10–1.31, p < 0.0001). This persisted after adjusting for common medications known to affect GERD. Raloxifene was identified as a risk factor for GERD in a multivariate analysis, controlling for factors including age, obesity, smoking, and alcohol use (OR 1.51, 95% Wald CI 1.47–1.53). Raloxifene was associated with esophageal stricture (OR 1.60; 95% Wald CI 1.51–1.69) and Barrett's esophagus (OR 1.50; 95% Wald CI 1.37–1.63) in multivariate analysis. These associations persisted using sensitivity analyses.ConclusionRaloxifene increases the risk of GERD, esophageal stricture and Barrett's esophagus in postmenopausal women with osteoporosis. Further studies are needed to confirm our findings.

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“…Another treatment for osteoporosis is estrogen replacement therapy. Liu's research found that using Raloxifene may increase the risk of several gastroesophageal diseases, such as gastroesophageal reflux disease and Barrett's esophagus in postmenopausal women with osteoporosis [34]. In recent years, finding new drugs for osteoporosis has become a key research area.…”