Pantoprazole impairs fracture healing in aged mice
Open Access
- 23 December 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-14
- https://doi.org/10.1038/s41598-020-79605-3
Abstract
Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation.Keywords
Funding Information
- Projekt DEAL
This publication has 67 references indexed in Scilit:
- The biology of fracture healingInjury, 2011
- Regional and cellular localisation of BMPs and their inhibitors’ expression in human fracturesInternational Orthopaedics, 2008
- Acid-Suppressive Medications and Risk of Bone Loss and Fracture in Older AdultsCalcified Tissue International, 2008
- Use of proton pump inhibitors and risk of osteoporosis-related fracturesCMAJ : Canadian Medical Association Journal, 2008
- Effect of cell‐based VEGF gene therapy on healing of a segmental bone defectJournal of Orthopaedic Research, 2008
- Effect of age on vascularization during fracture repairJournal of Orthopaedic Research, 2008
- Cellular basis for age-related changes in fracture repairJournal of Orthopaedic Research, 2005
- Application of Histomorphometric Methods to the Study of Bone RepairJournal of Bone and Mineral Research, 2005
- Synergistic enhancement of bone formation and healing by stem cell–expressed VEGF and bone morphogenetic protein-4JCI Insight, 2002
- Effect of omeprazole, an inhibitor of H+, K+-ATPase, on bone resorption in humansCalcified Tissue International, 1993