Pos0285 Detrimental Effects of Proton Pump Inhibitors on Bone Mineral Density Are Not Mediated by Changes in Serum Calcium or Parathyroid Hormone in Patients With Inflammatory Rheumatic Diseases: A Cross-Sectional Study

Background: In a previous study, we found daily proton pump inhibitor (PPI) intake to be associated with decreased bone mineral density of the femoral neck and the lumbar spine in patients with inflammatory rheumatic diseases (IRMDs) even after comprehensive adjustment for confounders [1]. The underlying pathomechanism is unclear. Similar findings in other populations in the past were repeatedly explained by decreased intestinal calcium absorption and increased levels of intact serum parathyroid hormone (PTH) [2, 3]. Objectives: To assess whether daily PPI use is associated with changes in serum calcium or PTH in patients with IRMDs. Methods: We used cross-sectional baseline data from the single-center Rh-GIOP cohort [4]. Patients with IRMDs have been prospectively enrolled since 2015. Included patients receive DXA scans, laboratory testing and complete bone-health-related questionnaires. This study excluded patients with hyperthyroidism and multiple myeloma as treatable causes of secondary osteoporosis. The exposure - daily PPI use - was ascertained by a combination of self-reporting by patients and chart review. Co-primary outcomes were serum levels of calcium and PTH. Analyses were based on general linear models, considering complete cases only. As part of a gatekeeping procedure, adjusted analyses were performed for the respective outcomes only if unadjusted analyses identified statistically significant differences between PPI users and non-users. For adjustment, we used 1) a conventional multiple regression approach and 2) inverse probability of treatment weighting. Potential confounders were based on findings from literature review and expert opinion and included age, body mass index (BMI), self-reported degree of physical activity, smoking status, presence of diabetes mellitus type I or II, chronic kidney disease stage (based on the estimated glomerular filtration rate), cumulative and current glucocorticoid (GC) dose and serum C-reactive protein. For weighting, included covariates were allowed to affect the outcome only [5], so 25-OH-vitamin D deficiency was additionally included. A sensitivity analysis excluded patients with a prior diagnosis of hyperparathyroidism. Results: 1,504 patients (75.3% women; mean age 62.6 ± 13.1 years; 49% daily PPI use) were included (Table 1). Most patients (79.6%) received vitamin D3 supplements and were within normal ranges as measured by 25-OH-vitamin D3. Missingness regarding exposure and outcome variables was as follows: PPI use: 0%; calcium: 7%; PTH: 17%. In unadjusted analyses, serum PTH was higher in PPI users (difference = 2.49pg/mL; 95% CI 0.23 to 4.74; p = 0.031). Serum calcium was similar in PPI users and non-users and omitted from further adjusted analyses. After adjustment for confounders, statistically significant differences in serum PTH between PPI users and non-users vanished with both adjustment procedures (Figure 1). In the conventional multiple regression model, age, BMI, chronic kidney disease stage and current GC intake were statistically significantly associated with serum PTH. These results were similar after excluding patients with a prior diagnosis of hyperparathyroidism. Conclusion: In our cohort of patients with IRMDs, the previously observed reduction in bone density with PPI does not seem to be mediated by changes in serum calcium or PTH. Prior studies with such findings might have been subject to confounding. REFERENCES: [1] Palmowski A "Proton pump inhibitor use and bone health in patients with rheumatic diseases: A cross-sectional study" Accepted in Mayo Clinic Proceedings. [2] Fitzpatrick D Osteoporos Int. 2023. [3] Hinson AM J Am Geriatr Soc. 2015. [4] Wiebe E Ann Rheum Dis. 2022. [5] Brookhart MA Am J Epidemiol. 2006. Acknowledgements: Rh-GIOP is or was supported by a joint funding of Abbvie, Amgen, Almirall, Biogen, BMS, Chugai, Galapagos, Generic Assays, GSK, Hexal, Horizon Therapeutics, Lilly, Medac, Mundipharma, Novartis, Pfizer, Roche, Sanofi-Genzyme, and UCB. The Parker Institute is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL). DS is supported by a 2022 GRAPPA Pilot Research Grant and the "Forschungsinitiative 2025" of the Deutsche Gesellschaft für Rheumatologie (DGRh). Disclosure of Interests: Andriko Palmowski Novartis, Zhivana Boyadzhieva: None declared, Paula Hoff UCB Pharma Germany, Sandra Hermann: None declared, Burkhard Muche UCB Pharma Germany, Amgen Germany, Stadapharm, UCB Pharma Germany, Amgen Germany, Stadapharm, David Simon: None declared, Gerhard Krönke: None declared, Edgar Wiebe Novartis, Novartis, Frank Buttgereit: None declared.