The Clinical Characteristics of Fractures in Pediatric Patients Exposed to Proton Pump Inhibitors

Abstract

Objectives: There are increasing concerns regarding proton pump inhibitor (PPI) use and the risk of fractures in adults. Few studies have evaluated this risk among pediatric patients. This study examined fractures and fracture location among pediatric patients exposed to PPI compared with those without documented exposure. Study Design: Encounters for patients 6 months to 15.5 years were identified between July 1, 2011 to December 31, 2015 in the Pediatric Hospital Information System database. Exclusion criteria was applied for chronic illnesses, conditions or medications predisposing to fracture. Encounters were classified as PPI encounters if a charge for PPI was documented. PPI encounters were propensity matched to non-PPI encounters. Following initial encounter, patients were evaluated over a 2-year period for hospitalizations resulting from fracture. Results: There was a statistically significant higher rate of fractures among the PPI-exposed group (1.4% vs 1.2%, P = 0.019). Adjusting for remaining differences in sex, race, encounter type, payer, and resource intensity after matching, the difference remained statistically significant (P = 0.017) with an adjusted odds ratio (95% CI) of 1.2 (1.0--1.4). Upper extremity was the most common location for fracture; however, the PPI cohort was more likely to suffer from lower extremity, rib, and spinal fractures (P = 0.01). Conclusions: This study suggests an increased risk of fracture among pediatric patients taking PPI. Among patients hospitalized with a fracture, those with PPI exposure had a higher rate of lower extremity, rib, and spine fractures compared with controls. This appeared to be a class effect not related to individual PPI agent.

Gastroesophageal Reflux Treatment in Infancy Through Young Adulthood

“…Most recently, PPI studies have emerged showing a possible increased risk of the development of allergic diseases including eosinophilic esophagitis and food allergies (51,52). Finally, several studies have suggested an association between long bone fracture risk and PPIs in children (53,54). These combinations of studies support the use of short courses of medications at the lowest dose possible, but additional studies are needed to prove a causal relationship.…”

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.…”

“…The main characteristics of the included studies are summarized in Table 1. They were published between 2015 and 2020 including five cohort studies (Fedida et al, 2019;Malchodi et al, 2019;Wagner et al, 2019;Fleishman et al, 2020;Wang et al, 2020) and one case-control study (Freedberg et al, 2015a). Three studies were conducted in North America (Malchodi et al, 2019; Wagner et al, 2019;Fleishman et al, 2020), two in Europe (Freedberg et al, 2015a;Wang et al, 2020), and one in Israel (Fedida et al, 2019 selected observational studies showed a reasonably good quality.…”

Management of primary and secondary osteoporosis in children

“…34 However, another US study and a nationwide register-based cohort study from Sweden showed that PPI use was associated with a small but significant increased risk of any fracture in children; the effect was greater after 1 month and even greater after 1 year of use. 35 The most common sites for fractures were lower extremity, rib and spinal fractures. 35 Inflammatory bowel disease.…”

“…35 The most common sites for fractures were lower extremity, rib and spinal fractures. 35 Inflammatory bowel disease. Paediatric inflammatory bowel disease (IBD), especially Crohn's disease (CD), is commonly associated with poor skeletal health, due to the direct effects of chronic inflammation, prolonged use of glucocorticoid (GC), poor nutrition, delayed puberty and low muscle mass.…”