proton pump inhibitors (PPIs) and fracture risk

Last edited 08/2020 and last reviewed 01/2023

There is epidemiological evidence of an increased risk of fracture with long-term use of PPIs (1,2,3,4)

• observational studies on a risk of fracture associated with PPIs suggest there may be a modest increase in the risk of hip, wrist, or spine fracture, especially if PPIs are used in high doses and over long durations (>1 year)
  • increased risk was observed mainly in elderly patients, and it is possible that other risk factors contribute to the increase in risk (2)
• meta-analyses of published pharmacoepidemiology studies suggest the risk of fracture is increased by 10-40% above baseline (3)
• a systematic review suggests a modest increase in the risk of hip fracture and vertebral fracture associated with PPIs, although some studies showed conflicting result (4)
  • three studies evaluated the risk of BMD reduction associated with PPIs but did not find consistent changes in baseline or subsequent BMD

The MHR advise that healthcare professionals should:

• treat patients at risk of osteoporosis according to current clinical guidelines and ensure they have an adequate intake of vitamin D and calcium
• take into account any use of PPIs obtained over-the-counter

People over the age of 50 taking PPIs may be considered for fracture-risk assessment, particularly in the presence of other risk factors (5)

Reference:

• MHRA (April2012). Drug and Safety Update; 5 (9).
• Eom CS, et al. Ann Fam Med 2011; 9: 257-67.
• Kwok CS, et al. Bone 2011; 48: 768-76.
• Lau YT, Ahmed NN. Fracture risk and bone mineral density reduction associated with proton pump inhibitors.Pharmacotherapy. 2012 Jan;32(1):67-79.
• SIGN (June 2020). Management of osteoporosis and the prevention of fragility fractures