and Hardy et al. [3, 22] found that calcium uptake was decreased in hypochlorhydric subjects, whereas other studies did not observe any effect [23–25]. Only during fasting conditions calcium uptake was decreased among patients using PPIs [2, 22] and among achlorhydric patients [23, 26]. Furthermore, some in vitro [6, 7] and in vivo [5] studies suggested that PPIs could inhibit the osteoclastic proton pump and thereby reduce bone resorption. Conversely, short-term omeprazole treatment did not alter osteoclast or osteoblast function in paediatric users [27]. Moreover, no selleck chemicals significant differences were

observed in BMD among postmenopausal women using acid suppressants (PPIs and H2RA), while in men, even lower cross-sectional bone masses were observed [28]. In addition, the most recent study performed by Targownik et al. [29] showed that both chronic PPI use and high daily doses of PPIs were not www.selleckchem.com/products/th-302.html associated with osteoporosis or accelerated

BMD loss. Several observational studies that investigated the association between duration of acid suppressant use and fracture risk found discrepant results as well [8, 10–12]. Both Yang et al. and Targownik et al. [8, 10] found that fracture risk increased with longer durations of PPI use. In contrast, members of our group found results which are similar to the present study (i.e. PPI use for a duration ≤1 year is associated with the highest fracture risk) Selleckchem Buparlisib using the same database as Yang et al. [11]. Moreover, our sensitivity analysis, in which we resembled the definitions of Yang et al., did not support a duration-of-use effect. Additionally, Kaye et al. [12] who also used the GPRD database did not find any association between the number of PPI prescriptions and hip fracture. The reasons for these discrepancies remain unclear. There are alternative explanations for the small, overall 1.2-fold increased risk among current users of acid suppressants. These include the inability of the current and previous studies, to measure (or only partially measure) alcohol consumption, smoking history and low body mass index. All these factors are associated

with an increased risk of fracture [30–32]. Besides, PPIs are often used for the eradication of Helicobacter pylori [33], which may be associated with an increased risk clonidine of osteoporosis [34]. In addition, PPIs are associated with the onset of Clostridium difficile [35], which may be an alternative explanation for the increased risk of fracture. Finally, celiac disease, which is associated with the onset of reflux oesophagitis [36], has recently been associated with an increased risk of both osteoporosis and fracture [37]. Nevertheless, we were unable to fully adjust for these three potential confounders, because PHARMO RLS has missing data of diagnoses determined outside the hospital. Our study has several strengths. As we used a population-based design, our study represents the entire population of the Netherlands.