Do both Proton Pump Inhibitors (PPI) and H2 receptor antagonists (H2 agonists) increase the risk of osteoporosis?

From the Guidelines

Proton pump inhibitors (PPIs) have been associated with an increased risk of osteoporosis and fractures, particularly with long-term use, while H2 receptor antagonists (H2 blockers) have a much weaker association with bone health issues. PPIs like omeprazole, esomeprazole, and pantoprazole may increase osteoporosis risk through several mechanisms, including reduced calcium absorption due to decreased stomach acid, potential interference with bone remodeling, and possible vitamin B12 deficiency that can affect bone health 1. This risk appears to be dose-dependent and increases with duration of use, becoming more significant after 1-2 years of regular use. Some key points to consider include:

• A meta-analysis of 24 observational studies involving PPI use and hip fractures found that individuals who used PPIs had a 20% greater risk of hip fracture compared with controls 1.
• H2 blockers such as famotidine and ranitidine have a much less pronounced effect on bone health, with studies showing minimal to no significant increase in fracture risk with their use.
• For patients requiring long-term acid suppression therapy, especially those with existing osteoporosis risk factors, it may be prudent to use the lowest effective dose of PPIs, consider H2 blockers as alternatives when appropriate, ensure adequate calcium and vitamin D intake, and undergo periodic bone density monitoring if on extended PPI therapy.
• The American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis provides recommendations for the management of osteoporosis in patients taking glucocorticoids, which may be relevant to patients taking PPIs or H2 blockers 1.

From the FDA Drug Label

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)

PPIs and Osteoporosis Risk: The FDA drug labels for omeprazole and lansoprazole indicate that long-term use of PPIs may be associated with an increased risk of osteoporosis-related fractures.

• Key Points:
  • PPI therapy may increase the risk of osteoporosis-related fractures
  • The risk is higher with long-term use (a year or longer) and high-dose therapy
  • Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines
• H2 Agonists: There is no information in the provided drug labels that directly supports the association of H2 agonists with an increased risk of osteoporosis. 2 3 2

From the Research

Risk of Osteoporosis with PPI and H2 Agonists

• The use of Proton Pump Inhibitors (PPIs) has been associated with an increased risk of osteoporosis-related fractures 4, 5.
• A study found that long-term use of PPIs was associated with a higher risk of bone fractures, including osteoporotic fractures 4.
• However, the evidence for H2 agonists is less clear, with one study finding that chronic use of H2-receptor antagonists had little influence on bone mineral density (BMD) 6.
• Another study found that histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke or myocardial infarction, suggesting that H2 agonists may not have the same level of risk as PPIs 7.
• It is worth noting that the relationship between PPI use and osteoporosis is still being researched, and the causal association is subject to validation 5.

Comparison of PPI and H2 Agonists

• PPIs have been shown to have a higher risk of adverse events, including osteoporosis-related fractures, compared to H2 agonists 7, 5.
• H2 agonists, on the other hand, have been found to have a lower risk of adverse events, although the evidence is not as extensive as for PPIs 6, 7.
• The choice between PPIs and H2 agonists should be based on the individual patient's needs and medical history, with consideration given to the potential risks and benefits of each medication 5, 8.

Recommendations for Use

• PPIs should be used at the lowest effective dose and for the shortest possible duration to minimize the risk of adverse events, including osteoporosis-related fractures 5, 8.
• Patients should be monitored regularly for signs of osteoporosis and other adverse events, and alternative treatments should be considered if necessary 5, 8.
• H2 agonists may be a suitable alternative for patients who are at risk of osteoporosis or other adverse events associated with PPI use 6, 7.