ORIGINAL ARTICLE Proton pump inhibitors use and change in bone mineral density Abbas ARJ, 1 Mohsen RAZAVI ZADE, 1 Maryam YAVARI, 1 Hossein AKBARI, 2 Batol ZAMANI 3,4 and Zatollah ASEMI 5* 1 Departments of Gastroenterology, 2 Biostatistics, 3 Autoimmune Diseases Research Center, 4 Department of Internal Medicine, and 5 Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran Abstract Objective: Limited data are available reporting the effect of proton pump inhibitor (PPI) use on changes in bone mineral density (BMD). The aim of this study was to investigate the relationship between PPI use and BMD. Methods: The current cross-sectional study included 80 patients (31 male and 49 female) aged 20–45 years old without history of hip fracture with a follow-up of at least 2 years. The study was carried out in 40 daily PPI users and 40 PPI non-users. Femur and posterior-anterior spine BMD were quantified by dual-energy X-ray absorptiometry in all participants. The relationship between use of PPI and BMD was tested by multivariate lin- ear regression analysis adjusted for age, sex, BMI and serum vitamin D levels. Results: Our study demonstrated that mean femoral T-scores were significant between PPI and non-user groups ( 0.44 1.11 vs. +0.19 0.95, P = 0.007). In addition, the frequency of femoral osteoporosis and osteopenia in the exposed group was significantly more in the control group (P = 0.04). Mean femoral Z-scores, lumbar spine T-score and lumbar spine Z-score were not statistically different between PPI and non-user groups. The linear regression analysis revealed that there was no association between PPI and non-users, and lumbar spine T-score. Conclusion: Overall, the results of this study showed that PPI use in subjects without risk factors of osteoporosis determined by the femoral T-score compared with the control group was associated with increased risk of devel- oping osteoporosis and osteopenia in the femur bones. Key words: bone mineral density, osteopenia, osteoporosis, proton pump inhibitors. INTRODUCTION Proton pump inhibitors (PPIs) are the common medi- cations suppressing gastric acid which are prescribed in management of acid-related disorders such as gastroe- sophageal reflux disease (GERD) and peptic ulcer dis- ease, with long-term therapy needed to manage the chronic symptoms of these diseases. 1 Previous studies have shown evidence for associations between PPI use and fracture risk. 2–4 It is unclear if this is a causal rela- tionship and what mechanism explains this association – one theory is that PPI affects uptake of calcium. 5 Limi- tations of previous studies were that most of these stud- ies were conducted in older subjects or in patients who had other risk factors, including the use of corticos- teroid medications. Several large epidemiological studies have indicated that PPI use is associated with increased osteoporotic fracture risk due to decreasing bone mineral density (BMD). 5–8 However, such a relationship was not Correspondence: Dr Mohsen Razavi Zade, Department of Gastroenterology, Kashan University of Medical Sciences, PO Box 8715988-141, Kashan, Iran. Tel/Fax: +98-31-55540021. Email: mohsen_razavizade@yahoo.com *Co-correspondence: Dr Zatollah Asemi, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, PO Box 8715988-141, Kashan, Iran. Tel/Fax: +98-31-55540021. Email: asemi_r@yahoo.com © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd International Journal of Rheumatic Diseases 2016