Proton Pump Inhibitors and the Risk for Fracture at Specific Sites: Data Mining of the FDA Adverse Event Reporting System

Abstract

Proton pump inhibitors (PPIs) are widely used to treat gastric acid-related disorders. Concerns have been raised about potential fracture risk, especially at the hip, spine and wrist. However, fracture risk at other bone sites has not been as well studied. We investigated the association between PPIs and specific fracture sites using an aggregated knowledge-enhanced database, the Food and Drug Administration Adverse Event Reporting System Data Mining Set (AERS-DM). Proportional reporting ratio (PRR) was used to detect statistically significant associations (signals) between PPIs and fractures. We analyzed both high level terms (HLT) and preferred terms (PT) for fracture sites, defined by MedDRA (Medical Dictionary for Regulatory Activities). Of PPI users reporting fractures, the mean age was 65.3 years and the female to male ratio was 3.4:1. Results revealed signals at multiple HLT and PT fracture sites, consistent for both sexes. These included fracture sites with predominant trabecular bone, not previously reported as being associated with PPIs, such as ‘rib fractures’, where signals were detected for overall PPIs as well as for each of 5 generic ingredients (insufficient data for dexlansoprazole). Based on data mining from AERS-DM, PPI use appears to be associated with an increased risk for fractures at multiple sites.

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…A positive, albeit modest, association between PPIs and OP was reported in animal [ 262 , 263 , 264 ] and numerous of human studies. Many studies and meta-analyses suggested that acid inhibitors, especially the PPIs, moderately increase risk of fractures, particularly in older adults (who are already at higher fracture risk); the risk increases with longer durations of PPI use, often only in the presence of at least one other RF for OP such as older age, female gender and a higher comorbidity score [ 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 , 289 , 290 ]. Moreover, use of PPIs may also increase risk of falls [ 291 , 292 , 293 ].…”

Proton Pump Inhibitor Use Affects Pseudarthrosis Rates and Influences Patient-Reported Outcomes

“…22 This has been acknowledged by Federal Drug Administration, which has labeled PPIs as being known to increase the likelihood of a fracture. 10 There is also growing evidence of an association between prolonged PPI use and increased risk of spine fractures. 16,17 This growing body of evidence relating PPIs and fractures suggest that these medications have an adverse effect on bone quality and may affect stability with instrumentation in elective spine fusion.…”

The role of proton pump inhibitors in renal disease - the risk of using OTC drugs

“…Wyniki badań z ostatnich lat prezentują jednak wyraźną zależność między stosowaniem IPP a występowaniem rzadkich, lecz ważnych klinicznie, skutków ubocznych długotrwałej terapii. W licznych publikacjach pojawiły się doniesienia o wpływie IPP między innymi na rozwój zakażenia Clostridium difficile, otępienia u osób starszych czy na istotne zwiększenie podatności kości na złamania [11][12][13]. Istnieją również podejrzenia dotyczące wpływu IPP na powstawanie niedoboru witaminy B 12 [14], co wynikać może z obniżenia kwaśności soku żołądkowego.…”