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Association Between the Use of Proton Pump Inhibitors and Osteoporosis/Fracture: Nested Case-Control Studies Using a
Hyun Youk1,2, Jeong Mi Park3, Yoon Ji Kim2
1Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea.
Journal of Clinical Medicine
|May 27, 2026
Summary
Current use of proton pump inhibitors (PPIs) significantly increases osteoporosis and fracture risk in Asian populations, with risk escalating with duration. Past PPI exposure did not show significant fracture risk.
Area of Science:
- Pharmacology
- Bone Health
- Epidemiology
Background:
- Proton pump inhibitors (PPIs) are frequently prescribed for acid-related gastrointestinal disorders.
- Concerns exist regarding a potential link between PPI usage and increased risks of osteoporosis and fractures.
- This study investigated the association between PPI use and these bone health outcomes.
Purpose of the Study:
- To examine the association between proton pump inhibitor (PPI) use and the risk of developing osteoporosis.
- To evaluate the association between PPI use and the risk of fractures at various sites (distal radius, hip, spine).
- To assess the impact of PPI use duration on osteoporosis and fracture risks.
Main Methods:
- Two nested case-control studies were conducted using the Korean National Health Insurance Service-Health Screening Cohort (2002-2019).
- Participants included over 500,000 individuals, with specific cohorts for osteoporosis and fractures, matched by demographics and socioeconomic factors.
- Propensity score overlap-weighted logistic regression analyzed associations between current PPI use (≤30 days) and recent exposure (31-365 days) and outcomes.
Main Results:
- Current PPI use demonstrated a strong association with osteoporosis (OR = 37.4) and fractures at all sites (distal radius OR = 37.4, hip OR = 20.3, spine OR = 29.8).
- A significant duration-response relationship was observed for current PPI use and osteoporosis risk.
- No significant association was found between past PPI exposure (31-365 days) and fracture risk.
Conclusions:
- Current PPI use is strongly linked to increased odds of osteoporosis and fractures in the Asian population.
- The risk of osteoporosis associated with PPIs shows a clear dose-response relationship with duration of use.
- Healthcare providers should monitor bone health in patients on long-term PPI therapy and consider the lowest effective doses.
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