Do Proton Pump Inhibitors (PPIs) contribute to osteoporosis?

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Last updated: May 13, 2025View editorial policy

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From the Guidelines

Long-term use of proton pump inhibitors (PPIs) may contribute to osteoporosis, although the relationship is not definitively established, and patients taking PPIs long-term should consider calcium citrate supplements and adequate vitamin D intake to mitigate this risk. PPIs like omeprazole, esomeprazole, pantoprazole, and lansoprazole can potentially reduce calcium absorption by decreasing stomach acid, which is needed to convert calcium into an absorbable form 1. According to the American College of Physicians, risk factors for osteoporotic fracture include increasing age, female sex, and low body weight, among others 1. The most recent guideline from the American College of Rheumatology recommends optimizing dietary and supplemental calcium and vitamin D in addition to lifestyle modifications for adults beginning long-term glucocorticoid therapy 1.

Key Considerations

  • Long-term use of PPIs (typically considered as daily use for more than 1 year) has been associated with a modest increase in fracture risk, particularly hip fractures 1.
  • The risk appears to be dose-dependent, with higher doses and longer durations of use carrying greater risk.
  • Patients taking PPIs long-term should consider:
    • Calcium citrate supplements (which don't require stomach acid for absorption) rather than calcium carbonate.
    • Ensuring adequate vitamin D intake (800-1000 IU daily).
    • Discussing bone density monitoring with their healthcare provider.
  • Other risk-reduction strategies include:
    • Regular weight-bearing exercise.
    • Limiting alcohol consumption.
    • Avoiding smoking.
    • Considering the shortest effective duration of PPI therapy.
  • For those with multiple osteoporosis risk factors, healthcare providers might consider alternative acid-reducing medications like H2 blockers, which have not shown the same association with bone loss 1.

From the FDA Drug Label

5.4 Bone Fracture Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer) Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines

PPIs may contribute to osteoporosis, as several published observational studies suggest an increased risk for osteoporosis-related fractures of the hip, wrist, or spine, particularly with high-dose and long-term PPI therapy 2, 2, and 2.

  • Key points:
    • Increased risk of osteoporosis-related fractures
    • High-dose and long-term PPI therapy
    • Patients at risk should be managed according to established treatment guidelines It is essential to use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated to minimize the risk of osteoporosis-related fractures.

From the Research

PPIs and Osteoporosis

  • The relationship between Proton Pump Inhibitors (PPIs) and osteoporosis has been investigated in several studies 3, 4, 5.
  • According to a 2019 study, PPIs have been associated with bone fractures, which is a potential indicator of osteoporosis 3.
  • A 2022 narrative review found that recent studies have potentially associated PPIs with osteoporosis-related fractures, suggesting a possible link between long-term PPI use and increased risk of osteoporosis 4.
  • Another study from 2021 discussed the side effects of long-term PPI use, including increased risk of fractures and impaired magnesium absorption, which can contribute to osteoporosis 5.
  • However, it is essential to note that the evidence for this association is still limited and requires further validation 4, 5.

Key Findings

  • PPIs are widely used and have been linked to various adverse events, including bone fractures and osteoporosis-related fractures 3, 4.
  • Long-term use of PPIs may increase the risk of osteoporosis, particularly in elderly patients or those with pre-existing kidney disease 4, 5.
  • The benefits of PPI treatment seem to outweigh the potential adverse effects, but clinicians should review PPI prescriptions regularly and deprescribe when necessary 6, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

SAFETY OF LONG-TERM PROTON PUMP INHIBITORS: FACTS AND MYTHS.

Arquivos de gastroenterologia, 2022

Research

Proton pump inhibitor use: systematic review of global trends and practices.

European journal of clinical pharmacology, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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