The Relationship Between Proton Pump Inhibitor Use and Longitudinal Change in Bone Mineral Density: A Population-Based From the Canadian Multicentre Osteoporosis Study (CaMos).

University of Manitoba, Winnipeg, Manitoba, Canada.
The American Journal of Gastroenterology (Impact Factor: 9.21). 07/2012; 107(9):1361-1369. DOI: 10.1038/ajg.2012.200
Source: PubMed

ABSTRACT OBJECTIVES:Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk.METHODS:We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years.RESULTS:In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up.CONCLUSIONS:PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Postmenopausal women in the Western world are highly burdened by osteoporotic fractures. The aim of this study is to investigate risk factors at baseline for fracture in 6416 postmenopausal women during long-term follow-up. At baseline, all women completed a questionnaire regarding background factors, diseases, current use of medications and reproductive and contraceptive history, a physical examination and laboratory analyses. Fracture occurrence after inclusion in the study was recorded with the help of official registries. All significant variables in univariate logistic regression with a decreased or increased risk for fracture were analysed in a multivariate logistic regression. Increased fracture risk was observed in women currently using proton pump inhibitors (PPI), odds ratio (OR) 2.53 (95% confidence interval (CI)) 1.28-4.99, and women having had a fracture after the age of 40, but before inclusion in the study, OR 1.70 (95% CI 1.24-2.32). A protective effect against fractures was observed in women with a positive family history of diabetes OR 0.66 (95% CI 0.44-0.98). A significant interaction was observed between fracture risk, use of PPI and HT status (p=0.014) and women with HT had an increased fracture risk with use of PPI (OR 3.37 (95% CI 1.96-5.80)) compared to women without HT (OR 1.13 (95% CI 0.57-2.24)). In conclusion, usage of PPIs was associated with a doubled risk for fracture in postmenopausal women. Women with previous fractures using PPI should be considered for prophylactic treatment reducing fracture risk.
    Maturitas 06/2014; · 2.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases such as gastroesophageal reflux disease (GERD). They are recommended by the American College of Gastroenterology for healing erosive esophagitis (EO) and as long-term treatment in patients with healed EO. The available PPIs differ somewhat in their pharmacokinetics and clinical properties, but whether these differences are of clinical relevance is a matter of debate. Some safety concerns have been raised with the use of PPIs, mostly an increased incidence of infectious diseases such as community-acquired pneumonia or Clostridium difficile diarrhea. Areas covered: This article explores the results of clinical studies on the pharmacokinetics and pharmacodynamics of esomeprazole , as well as on its clinical efficacy to manage patients with GERD. Expert opinion: GERD is a public health concern as its worldwide incidence and associated complications are increasing alongside the exponentially increasing problem of obesity. PPIs are the first pharmacological option because of their efficacy and overall positive risk-to-benefit ratio. Improved efficacy with the use of stereospecific isomers of PPIs, such as esomeprazole, has not yet been convincingly demonstrated. Nevertheless, because of individual experience with former treatment, some patients may report better symptom control when treated with a specific PPI rather than with others.
    Expert Opinion on Drug Metabolism &amp Toxicology 07/2014; · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Proton pump inhibitors (PPIs) have been associated with diminished bone mineral density (BMD) and an increased risk of fracture, however prior studies have not yielded consistent results and many have sub-optimal ascertainment of both PPI use and BMD. We used data from the Study of Women's Health Across the Nation (SWAN), a multi-center, multi-ethnic community-based longitudinal cohort study of women across the menopause transition to examine the association between annualized BMD changes and new use of PPIs. We compared changes in BMD in new PPI users with changes in BMD in new users of Histamine 2 receptor antagonists (H2RAs) and with changes in BMD in subjects who did not use either class of medications. Mixed linear regression models included recognized risk factors for osteoporosis, including demographics, menopausal transition stage, BMI, lifestyle factors, as well as comorbidities and concomitant medications. To provide further evidence for the validity of our analytic approach, we also examined the effects of hormone therapy (HT), a class of medications that should reduce bone loss, on changes in BMD as an internal positive control group. We identified 207 new users of PPIs, 185 new users of H2RAs and 1,676 non-users. Study subjects had a mean age of 50 years and were followed for a median of 9.9 years. Adjusted models found no difference in the annualized BMD change at the lumbar spine, femoral neck or total hip in PPI users compared with H2RA users or non-users. These results were robust to sensitivity analyses. BMD increased as expected in HT users, supporting the validity of our study design. These longitudinal analyses plus similar prior studies argue against an association between PPI use and BMD loss. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2014; · 6.04 Impact Factor