Beyond NSAIDs: Could Proton-Pump Inhibitors (PPIs) Also Increase Nonunion Risk?

by Vince Vacketta, DPM

Orthopedic surgeons have long debated the effect of NSAIDs on bone healing. The spine literature, in particular, shows an increased risk of pseudarthrosis following prolonged or high-dose postoperative use. But NSAIDs may not be the only commonly prescribed medications that deserve our attention. 

Retrospective review of hindfoot and ankle arthrodesis

A new study suggests chronic PPI therapy may also negatively impact fusion healing following hindfoot and ankle arthrodesis.

Researchers performed their retrospective review of patients who underwent triple arthrodesis, ankle fusion, or isolated subtalar fusion. They compared patients taking PPIs at the time of surgery with matched controls to determine whether chronic PPI use affected fusion outcomes. 

PPI use linked to nearly double the risk of nonunion

• PPI use was associated with a significantly higher risk of nonunion –nearly twice that of nonusers – following hindfoot and ankle arthrodesis.

• The increased risk persisted after adjusting for demographic and medical comorbidities.

• These findings add to a growing body of evidence that medications affecting bone metabolism may influence arthrodesis success.

A different mechanism, a similar concern

Unlike NSAIDs, which impair prostaglandin-mediated bone healing, PPIs are thought to affect fusion through different mechanisms:

• Reduced calcium absorption

• Altered osteoclast function

• Impaired bone remodeling

• Potential suppression of osteogenesis

Although the mechanism differs, the clinical consequence may be similar: a less favorable biologic environment for fusion.

Adding PPIs to the preoperative risk assessment

NSAIDs have traditionally received the most attention regarding impaired bone healing, but this study suggests that PPIs may also warrant consideration in preoperative risk assessment. While additional prospective studies are needed to establish causation, chronic PPI use appears to be another potentially modifiable factor that surgeons should consider when optimizing patients for ankle and hindfoot fusion.