Response to Letter to the Editor for “What Is the Evidence Supporting Osteobiologic Use in Revision Anterior Cervical Discectomy and Fusion?”

Dear Editor

We appreciate the thoughtful and insightful commentary provided in response to our recent publication, “What Is the Evidence Supporting Osteobiologic Use in Revision Anterior Cervical Discectomy and Fusion?”. ¹ We are grateful for the opportunity to engage in this communication that advances our collective understanding of the complexities surrounding revision ACDF procedures.

The letter rightly highlights an emerging and clinically significant concern around the role of occult low-grade infections, particularly those caused by Cutibacterium acnes, in influencing outcomes following revision cervical spine surgery. We concur that this is a critical factor that warrants further attention, both in clinical practice and in future research evaluating osteobiologic efficacy.

Our systematic review was designed to assess the current literature on the use of osteobiologics in revision ACDF, with a focus on identifying comparative clinical outcomes across different biologic agents. As noted in our article, we found a striking paucity of studies specifically addressing this topic. The available literature remains heavily skewed toward primary ACDF procedures, leaving a significant gap in evidence for revision contexts.

While our review did not explicitly evaluate infection-related variables, we acknowledge that occult infections, particularly those that evade standard diagnostic criteria, can profoundly impact fusion outcomes and may confound interpretations of osteobiologic performance. This is especially relevant in cases of pseudarthrosis, where the etiology may be multifactorial and not solely attributable to graft material or surgical technique.

The letter references compelling data suggesting that up to 40% of revision ACDF cases may harbor occult infections, often without overt clinical signs. Studies such as those by Calek et al ² and Burkhard et al ³ have demonstrated the prevalence of C. acnes in presumed aseptic pseudarthrosis revisions, underscoring the limitations of conventional culture techniques. These findings are further supported by advanced imaging modalities like 18F-FDG PET/CT and enhanced microbiologic methods such as sonication and extended anaerobic cultures.

We agree that the presence of biofilm-forming organisms can alter the local biologic environment, potentially impairing osteogenesis and masking the true efficacy of graft materials. This introduces a confounding variable that must be accounted for in future studies aiming to compare osteobiologic agents. Without stratifying outcomes based on infection status, we risk attributing suboptimal fusion rates to the graft material itself rather than to an underlying infectious process.

From a clinical standpoint, the integration of routine microbiologic sampling using optimized techniques during revision ACDF procedures is both feasible and advisable. This includes obtaining multiple deep tissue samples from the fusion site, employing extended anaerobic cultures for up to 14 days, sonication of retrieved hardware to disrupt biofilm and enhance pathogen recovery. ⁴ These practices not only improve diagnostic accuracy but also inform postoperative management, including the need for targeted antimicrobial therapy. Moreover, identifying occult infection at the time of revision may guide the selection of osteobiologic agents, as certain materials may perform differently in infected vs sterile environments.

We strongly support the letter’s call for future osteobiologic studies to incorporate infection screening protocols. Specifically, we recommend that future investigations to stratify patients based on microbiologic findings, distinguishing between truly aseptic and occultly infected cases; report fusion outcomes separately for each subgroup to assess the impact of infection on graft performance; evaluate the interaction between infection status and graft type, including autograft, allograft, DBM, CBM, and BMPs; include long-term follow-up to determine whether initial infection status correlates with delayed complications or fusion failure. ⁵ Such stratification will enable a more accurate assessment of osteobiologic efficacy and may reveal differential performance profiles that are currently obscured by unrecognized infection.

We acknowledge that our review did not include grey literature or non-English publications, which may have limited the scope of included studies. Additionally, the absence of infection-related variables in our analysis reflects the limitations of the existing literature rather than an oversight in our methodology. Nonetheless, we recognize the importance of incorporating infection screening into future systematic reviews and clinical trials.

We thank the author of the letter for raising this important issue and for contributing to the ongoing discussion surrounding revision ACDF surgery. The role of occult infection, particularly C. acnes, is a critical consideration that must be integrated into both clinical practice and research design. As we strive to improve outcomes for patients undergoing revision cervical fusion, a multidisciplinary approach that includes microbiologic vigilance, biologic optimization, and rigorous study design will be essential.

We remain committed to advancing the field through collaborative research communications and welcome further discussion on this topic.

ORCID iDs

Sathish Muthu https://orcid.org/0000-0002-7143-4354

Vibhu Krishnan Viswanathan https://orcid.org/0000-0002-3804-1698