Original ResearchFull Report: Clinical—Alimentary TractDexlansoprazole and Esomeprazole Do Not Affect Bone Homeostasis in Healthy Postmenopausal Women
Section snippets
Study Design
We conducted a phase 4, randomized, double-blind, placebo-controlled study in healthy postmenopausal women from November 4, 2010 (first participant in) to August 7, 2014 (last participant out), at 12 US centers. Institutional review board approval and participant consent were obtained before the study. This study was funded by Takeda Pharmaceuticals International, Inc. Takeda Pharmaceuticals International, Inc., was responsible for and sponsored the study design, data collection, data
Subjects
Of the 556 women screened at 11 centers, 115 were enrolled, and 93 participants completed the study (Supplementary Figure 1). No substantial differences in baseline demographics were observed between treatment groups (Table 1). Most participants (>90%) were white, with mean age of 62 ± 6 years, and mean body mass index of 25.2 ± 2.8 kg/m2. Subjects’ serum 25(OH)D levels were 39 ± 10 ng/mL at randomization. The calcium absorption substudy enrolled 34 participants (30 completing) with
Discussion
Recent population-based epidemiological studies have generated conflicting results about a relationship between chronic PPI therapy and fracture risk.4, 5, 11, 12, 13, 36 Low odds ratios (<2), lack of dose response, biological implausibility, and uncontrolled potential confounders limit any firm conclusions about the causal nature between PPI therapy and osteoporosis.37, 38 Although some studies have detected an association between PPI use and fractures in postmenopausal women, prospective
Conclusions
Overall, this prospective, randomized, double-blind clinical trial detected minimal changes in bone homeostasis related to 26 weeks of PPI therapy. Increases in bone turnover were detected, but formation and resorption both increased and remained coupled. There were no PPI-associated declines in BMD, serum or urine mineral levels, PTH, or TFCA. Our study provides strong evidence against PPI-mediated alterations in calcium absorption or mineral homeostasis. If there is a causal relationship
Acknowledgments
This study was supported by Takeda Development Center Americas, Inc, Deerfield, Illinois. Medical writing assistance was provided by Nikhilesh Sanyal, PhD, and Jacob Edelstein, PhD, of inVentiv Medical Communications, LLC, a Syneos Health group company, and supported by Takeda Development Center Americas, Inc.
Sai Nudurupati’s current affiliation: AbbVie Inc, North Chicago, Illinois.
Author contributions: Drs Hansen, Nudurupati, Metz, and Perez contributed to the study design. Drs Hansen and
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Conflicts of interest Dr Hansen was paid for her work as a consultant in the design and conduct of the study and received a grant to conduct the study. Dr Nieves received a research grant from Takeda to conduct this research. Dr Nudurupati was an employee of Takeda Pharmaceuticals at the time this study was conducted. Dr Metz received administrative and editorial support for study design and analysis of the data. Dr Perez is employed by Takeda Pharmaceuticals.
Funding This study was funded by Takeda Pharmaceuticals International, Inc. Takeda Pharmaceuticals International, Inc., was responsible for and sponsored the study design, data collection, data interpretation, and writing of this manuscript.
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Authors share co-first authorship