Romoff et al performed a study entitled “Proton pump inhibitors are associated with increased risk of pseudoarthrosis after lumbar fusion” that was published in the North American Spine Society Journal. This study utilized a national database to assess the correlation of postoperative proton pump inhibitor (PPI) use with pseudarthrosis after varying types of lumbar fusion.

The authors note that prior literature has established an association of impaired bone healing and pseudarthrosis with PPI use following cervical fusion, and lumbar fusion in smaller sample populations. This was hypothesized to be related to alteration in calcium absorption, impaired magnesium and vitamin B12 homeostasis, suppressed osteoclast activity, and reduced bone turnover.

However, as prior studies have been limited based on study size, the current study leveraged the large TriNetX database, which is increasingly being used in related literature.

The reviewed study identified adult patients (aged 18 years or older) who underwent lumbar fusion of varying approach with or without decompression between 2015 and 2023. Patients in the PPI group were prescribed any PPI within 30 days after the date of lumbar fusion. Pseudarthrosis was identified using ICD codes and included a diagnosis of failed spinal fusion in addition to pseudarthrosis.

An age-stratified analysis of this primary outcome was conducted for patients in 4 age groups: <55 years old, 56-65 years old, 66-75 years old, and ≥76 years old. Patients with less than 1 year follow-up were excluded. PPI and non-PPI users were 1:1 propensity score matched on demographic factors as well as clinical factors expected to affect bone health.

With 122,584 patients in each matched cohort (PPI and non-PPI), the study detected a significant difference in pseudarthrosis rates at 1 year (7.38% in the PPI group versus 3.93% in the non-PPI group, p < 0.0001). This translated to a Cox proportional hazards model ratio of 1.88, indicating an approximately 88% greater risk of pseudarthrosis for those in the PPI group. The observation that the Kaplan-Meier survival curves separate early was suggested to mean that postoperative PPI use could affect early phases of bone healing.

Age-stratified analysis revealed significantly and consistently higher pseudarthrosis risk among PPI users across all age groups with decreasing relative impact in increasing age groups. In fact, the highest relative impact of PPI use was in those <55 years old. The authors suggested that this finding may be due to greater reliance on tightly coupled osteoblast-osteoclast activity in this population. This age-stratified analysis challenged a cognitive bias that medication-related fusion risk matters primarily in older, sicker, or frailer patients.

Overall, this is an interesting study that calls into question the routine use of PPI prophylaxis for lumbar fusion patients given the correlation with pseudarthrosis. Of course, each intervention must be a balance of risks and benefits. It would have been interesting to know what percent of lumbar fusions in the database had PPI prophylaxis, but only matched numbers were presented.  Notably, the specific PPI agent, dosing, and continuation of PPI use beyond 30 days were not assessed for the PPI group. While a limitation, the general applicability of the data is clear.

The study also combined different lumbar fusion approaches. This increased the power of the study, but limited ability to discern the correlation of PPIs on outcomes following specific lumbar fusion types. Other limitations included potential difficulty identifying and coding pseudarthrosis, as well as the lack of longer-term fusion outcomes. Nonetheless, they were able to control for factors thought to affect bone healing and discern an important correlation.

In summary, the currently reviewed study provided insightful results related to perioperative PPI use for patients undergoing lumbar fusion. This study reframes perioperative PPI as a potentially consequential factor in fusion biology and not simply a benign prophylactic therapy. This study may lead surgeons to reassess PPI use for patients without a compelling indication.