Osseous implications of proton pump inhibitor therapy: An umbrella review
Abdullah S. Alanazi,
Hadiah Almutairi,
Jeetendra Kumar Gupta,
Dibyalochan Mohanty,
Deepankar Rath,
Ali A. AlOdan,
Ahmed Mahal,
Mahalaqua Nazli Khatib,
Shilpa Gaidhane,
Quazi Syed Zahiruddin,
Sarvesh Rustagi,
Prakasini Satapathy,
Hashem Abu Serhan
Affiliations
Abdullah S. Alanazi
Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Al-Jouf, Saudi Arabia
Hadiah Almutairi
Department of Pharmacy Practice, College of Pharmacy, University of Hafr Albatin, Saudi Arabia
Jeetendra Kumar Gupta
Institute of Pharmaceutical Research, GLA University Mathura, Uttar Pradesh, India
Dibyalochan Mohanty
Centre for Nano Medicine, Department of Pharmaceutics, School of Pharmacy, Anurag University, Hyderabad, India
Deepankar Rath
Department of Pharmacology, School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Odisha, India
Ali A. AlOdan
Department of Family Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
Ahmed Mahal
Department of Medical Biochemical Analysis, College of Health Technology, Cihan University-Erbil, Erbil, Kurdistan Region, Iraq
Mahalaqua Nazli Khatib
Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India
Shilpa Gaidhane
One Health Centre (COHERD), Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, Wardha, India
Quazi Syed Zahiruddin
South Asia Infant Feeding Research Network (SAIFRN), Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India
Sarvesh Rustagi
School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
Prakasini Satapathy
Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; School of Pharmacy, Graphic Era Hill University, Dehradun, India; Medical Laboratories Techniques Department, AL-Mustaqbal University, 51001 Hillah, Babil, Iraq; Correspondence to: P. Satapathy, Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Hashem Abu Serhan
Department of Ophthalmology, Hamad Medical Corporation, Doha, Qatar; Correspondence to: H. A. Serhan, School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India.
Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications worldwide for acid-related disorders. While their short-term efficacy and safety are well-established, concerns regarding their long-term effects on bone health have emerged. This umbrella review aimed to synthesize the available findings on the associations between PPI use and bone metabolism outcomes. Methods: An electronic search was conducted using PubMed, Web of Science, Embase, and the Cochrane Database up to September 16, 2023. Systematic reviews and meta-analyses of randomized controlled trials (RCTs) and observational studies that evaluated the relationship between PPIs and bone metabolism outcomes were included. Data extraction, quality appraisal, and synthesis were performed in line with the Joanna Briggs Institute and PRISMA guidelines. The strength of the evidence was graded using the GRADE criteria. Statistical analysis was performed in R version 4.3. Results: Out of 299 records, 27 studies met the inclusion criteria. The evidence indicated a statistically significant increased risk of fractures, notably hip, spine, and wrist fractures, in PPI users. PPI use was associated with changes in Bone Mineral Density (BMD) across various bones, though the clinical relevance of these changes remains uncertain. Furthermore, PPI-induced hypomagnesemia, which can influence bone health, was identified. A notable finding was the increased risk of dental implant failures in PPI users. However, the certainty of most of the evidence ranged from very low to low based on GRADE criteria. Conclusion: The long-term use of PPIs may be associated with adverse bone health outcomes, including increased fracture risk, alterations in BMD, hypomagnesemia, and dental implant failure. While these findings highlight potential concerns for long-term PPI users, the current evidence's low certainty underscores the need for robust, high-quality research to clarify these associations.
