The Relationship Between Proton Pump Inhibitor Use and Longitudinal Change in Bone Mineral Density: A Population-Based From the Canadian Multicentre Osteoporosis Study (CaMos).
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.
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ABSTRACT: Studies suggest that long-term use of proton pump inhibitors (PPIs) may be associated with an increased risk of fracture. However, the role of medication adherence in this association is not fully understood. A retrospective cohort study was conducted to examine the relationship between PPI use/adherence and fracture risk among elderly subjects by combining administrative pharmacy claims data, survey data, and Medicare data. The study cohort included 1,604 PPI users and 23,672 nonusers who were enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly program. PPI adherence was measured by the proportion of days covered (PDC). Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) of PPI use/adherence for fracture risk while controlling for demographics, comorbidity, body mass index, smoking, and non-PPI medication use. The overall incidence of any fracture per 100 person-years was 8.7 for PPI users and 5.0 for nonusers. A gradient in fracture risk according to PPI adherence was observed. Relative to nonusers, fracture HRs associated with the highest (PDC ≥ 0.80), intermediate (PDC 0.40-0.79), and lowest (PDC <0.40) adherence levels were 1.46 (p < 0.0001), 1.30 (p = 0.02), and 0.95 (p = 0.75), respectively. In addition, the fracture risk of PPI use was significant for hip (HR = 1.32, p = 0.04) and vertebral (HR = 1.69, p = 0.0005) fractures, and risk was similar between major osteoporotic and other fractures. These results provide further evidence that PPI use may increase fracture risk in the elderly and highlight the need for clinicians to periodically reassess elderly patients' individualized needs for ongoing PPI therapy, while weighing potential risks and benefits.Calcified Tissue International 04/2014; · 2.50 Impact Factor
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ABSTRACT: Proton pump inhibitors (PPIs) may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. PPIs are prescribed for virtually all patients with Barrett's esophagus, irrespective of the presence of reflux symptoms, and represent a de facto chemopreventive agent in this population. However, long-term PPI use has been associated with several adverse effects, and the cost-effectiveness of chemoprevention with PPIs has not been evaluated. The purpose of this study was to assess the cost-effectiveness of PPIs for the prevention of EAC in Barrett's esophagus without reflux. We designed a state-transition Markov microsimulation model of a hypothetical cohort of 50-year-old white men with Barrett's esophagus. We modeled chemoprevention with PPIs or no chemoprevention, with endoscopic surveillance for all treatment arms. Outcome measures were life-years, quality-adjusted life years (QALYs), incident EAC cases and deaths, costs, and incremental cost-effectiveness ratios. Assuming 50 % reduction in EAC, chemoprevention with PPIs was a cost-effective strategy compared to no chemoprevention. In our model, administration of PPIs cost $23,000 per patient and resulted in a gain of 0.32 QALYs for an incremental cost-effectiveness ratio of $12,000/QALY. In sensitivity analyses, PPIs would be cost-effective at $50,000/QALY if they reduce EAC risk by at least 19 %. Chemoprevention with PPIs in patients with Barrett's esophagus without reflux is cost-effective if PPIs reduce EAC by a minimum of 19 %. The identification of subgroups of Barrett's esophagus patients at increased risk for progression would lead to more cost-effective strategies for the prevention of esophageal adenocarcinoma.Digestive Diseases and Sciences 05/2014; · 2.26 Impact Factor
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ABSTRACT: Introduction. Charcot foot is a rare and devastating complication of diabetes. While some risk factors are known, debate continues regarding etiology. Elucidating other associated disorders and their temporal occurrence could lead to a better understanding of its pathogenesis. We applied a large data mining approach to Charcot foot for elucidating novel associations. Methods. We conducted an association analysis using ICD-9 diagnosis codes for every patient in our health system (n = 1.6 million with 41.2 million time-stamped ICD-9 codes). For the current analysis, we focused on the 388 patients with Charcot foot (ICD-9 713.5). Results. We found 710 associations, 676 (95.2%) of which had a P value for the association less than 1.0 × 10(-5) and 603 (84.9%) of which had an odds ratio > 5.0. There were 111 (15.6%) associations with a significant temporal relationship (P < 1.0 × 10(-3)). The three novel associations with the strongest temporal component were cardiac dysrhythmia, pulmonary eosinophilia, and volume depletion disorder. Conclusion. We identified novel associations with Charcot foot in the context of pathogenesis models that include neurotrophic, neurovascular, and microtraumatic factors mediated through inflammatory cytokines. Future work should focus on confirmatory analyses. These novel areas of investigation could lead to prevention or earlier diagnosis.Journal of diabetes research. 01/2014; 2014:214353.