Fracture risk of young adults receiving proton‐pump inhibitors and H2‐receptor antagonists

Abstract

Summary Introduction Proton‐pump inhibitors (PPI) and histamine (type 2) receptor antagonists (H2RA) have the potential to interfere with calcium metabolism. Several authors have evaluated the effect of these medications on fracture incidence in older adults. A recent large epidemiologic study demonstrated a higher risk of fractures in young adults receiving PPI. Aim To evaluate the effect of PPI and H2RA use on fracture incidence in a large retrospective cohort of military recruits representative of general population of young adults. Methods A retrospective cohort of 254 265 male and 234 670 female non‐combat military conscripts ages 18‐25. Subjects were divided into three groups by PPI use (no PPI use, 1‐100 tablets and more than 100 tablets) and two groups by H2RA use (no H2RA use, any H2RA use). Multivariate logistic regression was used to adjust fracture risk for age, BMI, education level, socio‐economic level, ethnic origin, occupation and duration of follow‐up in months. Main outcome measures At least one fracture during the study period. Results Use of PPI and H2RA was not associated with an increased risk of fractures. In men, the predictors of an increased fracture risk were higher BMI (OR = 1.007, P < 0.001), origin from a developing country (OR = 1.15, P < 0.001) and service as a driver (OR = 1.11, P < 0.001). Higher education, higher socioeconomic status and service as an officer or as an administrative worker had a protective effect on fracture incidence. In women, fractures were associated with higher BMI (OR = 1.035, P < 0.001). Origin from a developed country, as well as service as an officer or an administrative worker was associated with lower fracture risk. Conclusions There was no association between the use of PPI or H2‐antagonists and fracture incidence in this retrospective cohort of healthy young military recruits.

Proton pump inhibitors use and fracture risk in young adults

“…Recently one cohort study conducted by Fedida et al published in International Journal of Clinical Practice revealed that no significant association could be detected between proton pump inhibitors use and fracture risk in young adults. 1 The similar finding was also observed in older adults. 2,3 Some points need to be discussed.…”

“…First, the relative risk of fracture was lower in young male adults with proton pump inhibitors use than those without use in Fedida et al’s study (relative risk 0.73) . In a crude estimation, the incidence of fracture risk was lower in young male adults with proton pump inhibitors use than those without use (180.6 vs 377.7 per 10 000 patient‐years) . The absolute risk reduction was approximately 197.1 per 10 000 patient‐years of follow‐up.…”

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…Moreover, use of PPIs may also increase risk of falls [ 291 , 292 , 293 ]. These associations, however, have not been confirmed in a number of longitudinal studies and reviews [ 259 , 280 , 294 , 295 , 296 , 297 , 298 , 299 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 , 308 , 309 ]; even a modest reduction in fracture risk with PPI use has been reported [ 307 , 310 ]. Some researchers who are not supporting the association of PPI therapy with BMD recognize, nevertheless, that in PPI users the risk of fractures and falls could be higher [ 311 , 312 ] as the unadjusted HR was significantly elevated (1.36, 95% CI 1.19–1.55).…”

Acid-Suppressive Drugs and Risk of Fracture in Children and Young Adults: A Meta-Analysis of Observational Studies

“…Six studies (Freedberg et al, 2015a;Fedida et al, 2019;Malchodi et al, 2019;Wagner et al, 2019;Fleishman et al, 2020;Wang et al, 2020) were included in our meta-analysis following the abovementioned exclusion and selection procedure. The main characteristics of the included studies are summarized in Table 1.…”