Proton Pump Inhibitor Use, Hip Fracture, and Change in Bone Mineral Density in Postmenopausal Women

Abstract

Background Proton pump inhibitor (PPI) medications have been inconsistently shown to be associated with osteoporotic fractures. The objective was to examine the association of PPI use with bone outcomes (fracture, bone mineral density [BMD]) Methods This prospective analysis included 161,806 postmenopausal women ages 50 to 79 years without history of hip fracture enrolled in the Women’s Health Initiative (WHI) Observational Study and Clinical Trials with a mean (SD) follow-up of 7.8 (1.6) years. Analyses were conducted on 130,487 women with complete information. Medication information was taken directly from drug containers during in-person interviews (baseline, year 3). Main outcome measures were self-reported fractures (hip [adjudicated], clinical spine, lower arm or wrist, and total fractures) and for a subsample (3 densitometry sites), 3-year change in BMD. Results During 1,005,126 person-years of follow-up, 1500 hip fractures, 4881 lower arm or wrist fractures, 2315 clinical spine fractures and 21247 total fractures occurred. The multivariate-adjusted hazard ratios for current PPI use were 1.00 (95% CI, 0.71 to 1.40) for hip fracture, 1.47 (CI 1.18–1.82) for clinical spine fracture, 1.26 (CI, 1.05 to 1.51) for lower arm or wrist fracture, and 1.25 (CI, 1.15 to 1.36) for total fractures. BMD measurements did not vary between PPI users and nonusers at baseline. PPI use was associated with only a marginal effect on 3-year BMD change at the hip (p=0.05) but not at other sites. Conclusion PPI use was not associated with hip fractures, but was modestly associated with clinical spine, lower arm or wrist and total fractures.

The effect of dose and type of proton pump inhibitor use on risk of fractures and osteoporosis treatment in older Australian women: A prospective cohort study

“…[7] confirmed an increased fracture risk after the use of PPIs . In contrast, only one [13] of five prospective studies [11][12][13][14][15] found a significant negative association between PPI use and BMD at the hip, but not at other sites.…”

“…Except for the prospective cross-sectional study by Targownik et al [11], the studies investigating PPI use and BMD were prospective cohort studies (Canadian Multicentre Osteoporosis Study (CaMos) [12], Women's Health Initiative (WHI) Observational Study and Clinical Trials [13], Osteoporotic Fractures in Men Study (MrOS) and Study of Osteoporotic Fractures (SOF) [14], and Study of Women's Health Across the Nation (SWAN) [15]). …”

“…If a causal relationship exists between PPIs and fractures, the predisposing factors for fractures are expected to be affected. However, studies examining associations between PPI use and bone mineral density (BMD) found none or little evidence for an association between PPI use and the development of osteoporosis [11][12][13][14][15]. In contrast, a study by Maggio et al [16] found that PPI use was significantly associated with decreased trabecular BMD, possibly an early marker of osteoporosis.…”

Effets indésirables des inhibiteurs de la pompe à proton : faut-il craindre de les prescrire au long cours ?

“…[6]. Une méta-analyse récente a étudié plus spécifiquement le risque de fracture du col du fémur ; elle a mis en évidence une augmentation de ce risque chez les patients traités par IPP (OR poolé 1,24 ; IC95 % 1,15-1,34), mais les auteurs eux-mêmes restent prudents dans leurs conclusions compte tenu des résultats contradictoires obtenus dans l'analyse en sous-groupes en fonction de la durée d'exposition [7].…”

“…À l'inverse, d'autres auteurs ont mis en évidence un effet positif des IPP sur la résorption osseuse via une inhibition d'une pompe à proton au niveau des ostéoclastes [11]. Ces données semblent concorder avec les résultats de Gray et al qui n'ont pas observé de variation significative de la densité minérale osseuse dans leur étude et font l'hypothèse que l'effet direct des IPP sur la résorption osseuse pourrait compenser leur impact négatif sur l'absorption intestinale du calcium [6].…”