Associations between Proton Pump Inhibitor and Histamine-2 Receptor Antagonist and Bone Mineral Density among Kidney Transplant Recipients

Abstract

Background: In the general population, use of proton pump inhibitor (PPI) has been linked to higher risk of osteoporotic fractures. PPI is commonly prescribed in kidney transplant recipients (KTRs). However, the effect of PPI on osteoporosis in KTRs is largely unstudied. Methods: A total of 1,774 adult KTRs in the Wisconsin Allograft Recipient Database with at least one eligible bone mineral density (BMD) measurement at least 3 months after transplantation were included in the analyses. Associations between use of PPI and histamine-2 receptor antagonist (H2RA) at 3 months after transplantation and subsequent slope of T-score were assessed. Results: A total of 1,478 (83.3%) participants were using a PPI at 3 months after transplantation. Compared to the use of H2RA, use of PPI was not significantly associated with annualized slope of hip T-score (β = -0.0039, 95% CI -0.00497 to 0.0021) or annualized slope of spine T-score (β = -0.017, 95% CI -0.049 to 0.083) after adjustment for potential confounders. Similarly, no significant association between use of PPI and slope of T-score was observed when defining PPI/H2RA exposure as use within 6 months of the initial BMD measurement, or only including participants with at least 2 BMD measurements, or stratified by different age and sex. Conclusions: Use of PPI was not associated with an increased rate of BMD loss in KTRs. Our results support previous findings that PPI use does not have a significant effect on bone mineral loss.

Proton pump inhibitors inhibit PHOSPHO1 activity and matrix mineralisation in vitro

“…The copyright holder for this preprint (which this version posted April 29, 2021. ; https://doi.org/10.1101/2021.04.29.441931 doi: bioRxiv preprint that the association between fractures and PPI used is mediated by reduced calcium absorption due to achlorhydria [3,[11][12][13][14][15]33]. The = data presented here is consistent with this and suggests that inhibition of PHOSPO1 may be an alternative mechanism by which PPIs, affect bone health.…”

“…Other potential mechanisms include (i) impaired bone resorption resulting in altered bone remodelling and (ii) hypergastrinemia resulting in parathyroid hyperplasia and decreased bone mineral density [30,31]. The H2RAs are also widely used to suppress gastric acid production in the treatment of GORD, dyspepsia and peptic ulcers these have not been associated with fractures in epidemiological studies which calls into question the hypothesis that the association between fractures and PPI used is mediated by reduced calcium absorption due to achlorhydria [3,[11][12][13][14][15]33]. The = data presented here is consistent with this and suggests that inhibition of PHOSPO1 may be an alternative mechanism by which PPIs, affect bone health.…”

“…However, in healthy subjects, short term treatment with the PPI omeprazole was not found to have inhibitory effects on calcium absorption [9,10]. Furthermore, epidemiological studies with histamine 2 receptor antagonists (H2RAs), which also supress gastric acid secretion, have not shown an association with fractures [3,[11][12][13][14][15]. Likewise, a recent meta-analysis reported that the use of PPIs, but not H2RAs, is associated with an increased risk of hip fracture [16].…”

Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro

“…Other potential mechanisms include (i) impaired bone resorption resulting in altered bone remodelling and (ii) hypergastrinemia resulting in parathyroid hyperplasia and decreased bone mineral density [30,31]. The H2RAs are also widely used to suppress gastric acid production in the treatment of GORD, dyspepsia and peptic ulcers these have not been associated with fractures in epidemiological studies which calls into question the hypothesis that the association between fractures and PPI used is mediated by reduced calcium absorption due to achlorhydria [3,[11][12][13][14][15]. The data presented here is consistent with this and suggests that inhibition of PHOSPO1 may be an alternative mechanism by which PPIs, affect bone health.…”

“…However, in healthy subjects, short-term treatment with the PPI omeprazole was not found to have inhibitory effects on calcium absorption [9,10]. Furthermore, epidemiological studies with histamine 2 receptor antagonists (H2RAs), which also supress gastric acid secretion, have not shown an association with fractures [3,[11][12][13][14][15]. Likewise, a recent meta-analysis reported that the use of PPIs, but not H2RAs, is associated with an increased risk of hip fracture [16].…”