Proton-pump inhibitors and risk of fractures: an update meta-analysis

Abstract

In this update meta-analysis of observational studies, PPI use modestly increased the risk of hip, spine, and any-site fracture, but no evidence of duration effect in subgroup analysis.

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

“…Additionally, PPI use has been linked to osteoporosis and fractures. A recent meta-analysis of 18 observational studies found 58%, 26%, and 33% greater risk of spine fracture, hip fracture, and fracture at any site, respectively, among PPI users compared to nonusers [86]. …”

Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use

“…PPI users (even after short-term, i.e.<1 year) showed modestly higher risks of bone fractures, of hip (26%), of spine (58%), and of any site (33%), according to a meta-analysis of 18 studies (Zhou et al, 2016). FDA published a safety alert in May 2010 about possible increased risk of the hip, wrist, and spine, which was updated in March 2011 (FDA, 2012).…”

“First Do No Harm”: Adverse Events from Pharmaceutical Treatment of Gastroparesis and Dyspepsia

“…Dementia [14] Osteoporosis and fracture [19] Kidney disease [16] Gastrointestinal [18] and prulmonary [15] RR relative risk, CI confidence interval, OR odds ratio, CAP community-acquired pneumonia, CKD chronic kidney disease, AIN acute interstitial nephritis, GRADE grading of recommendations assessment, development, and evaluation…”

“…Although a critical review of the relevant literature does demonstrate associations between PPIs and serious skeletal, renal, gastrointestinal, and neurological events, these findings are based on epidemiological evidence. In Table 1, a summary of the criteria proposed by Bradford Hill for assessing causality and the association between PPIs and adverse events are presented; much of the data are weak and potentially subject to major bias including confounding [14][15][16][17][18][19]. Notably, no reports of hypomagnesemia due to acid-suppressing medications were described by Bielefeldt, despite this being a recognized adverse effect of PPI, probably due to its extreme rarity [20].…”

“…Histamine antagonism may thus be an alternative therapy in functional dyspepsia with equal efficacy and lower risk of adverse events than with other drugs. Table 1 Reported complications of proton pump inhibitor (PPI) use and assessment of the strength of evidence using the Bradford Hill criteria and summary of Oxford Centre for Evidence-Based Medicine (OCEBM) level of evidence [25] Determinant of causality criteria Postulated adverse effect Dementia [14] Osteoporosis and fracture [19] Kidney disease [16] Gastrointestinal [18] and prulmonary [15] In the study by Bielefeldt, there were no FAERS reports of an adverse event associated with tricyclic antidepressants or with mirtazapine as treatments for dyspepsia. There are data to support the efficacy of low doses of tricyclic antidepressants and possibly mirtazapine in functional dyspepsia but not gastroparesis, especially in the epigastric pain syndrome subtype [10,23].…”