Spine - 2026-08-25 - Journal Article
Early Postoperative Increase in Procollagen Type 1 N-Propeptide (P1NP) Predicts One-Year Pseudarthrosis Following Anterior Cervical Discectomy and Fusion: A Prospective Cohort Study.
Lovecchio FC, Bay A, Zhang J, Colón LF, Owusu-Sarpong S, Araghi K, Singleton Q, Musharbash F, Durbas A, Samuel J, Knopp R, Dowdell JE, Farmer JC, Albert TJ, Huang RC, Iyer S, Qureshi S, Stein EM, Kim HJ
Topics
Key Takeaway
A postoperative rise in P1NP (ΔP1NP +38.5 vs -16.9 ng/mL, p=0.013) independently predicts one-year pseudarthrosis after ACDF, occurring in 30% of this cohort.
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Summary
This prospective cohort evaluated whether serum bone turnover markers drawn preoperatively and at six weeks predict radiographic pseudarthrosis at one year in 1–3 level ACDF patients. Pseudarthrosis occurred in 30% of patients; ΔP1NP was significantly greater in the pseudarthrosis group (+38.5 vs -16.9 ng/mL, p=0.013) and remained an independent predictor on logistic regression (p=0.039), while CTX, baseline demographics, and surgical variables did not differ between groups. The authors propose that paradoxical early anabolic upregulation may reflect failed fusion biology and identify a window for postoperative anabolic agent intervention.
Key Limitation
The 43% dropout rate at the six-week lab draw leaves only 33 analyzable patients, making the logistic regression model underpowered and the 30% pseudarthrosis rate potentially unrepresentative of the enrolled population.
Original Abstract
STUDY DESIGN
Prospective cohort study.
OBJECTIVE
To evaluate whether bone turnover markers (BTMs) predict pseudarthrosis after cervical spine surgery.
SUMMARY OF BACKGROUND DATA
Pseudarthrosis is a major reason for reoperation after ACDF. However, prediction of pseudarthrosis remains elusive. Patient-level factors have proven unreliable, and optimization of modifiable risk factors may be precluded by urgent neurological indications for surgery. Bone turnover markers are directly modifiable and may help predict fusion before and after surgery.
MATERIALS AND METHODS
Patients undergoing 1-3 level ACDF for degenerative pathology were enrolled. Exclusion criteria included metabolic bone disease, current osteoporosis treatment, inflammatory arthritis, chronic steroid use, and chronic kidney disease. Serum collagen type 1 C-telopeptide (CTX) and procollagen type 1 N-propeptide (P1NP) were used as markers of bone resorption and formation, respectively. Labs were collected preoperatively and at six weeks postoperatively for CTX and P1NP with changes in values (Δ) calculated. The primary outcome was radiographic pseudarthrosis at one year, defined as interspinous distance change >1 mm on dynamic lateral radiographs. Associations between pseudarthrosis and BTMs, demographics, comorbidities, surgical variables, and osteometabolic labs were assessed. A stepwise (Wald) logistic regression model evaluated independent predictors of pseudarthrosis.
RESULTS
Fifty-eight consecutive patients were enrolled, 25 missed six‑week labs, leaving 33 patients (60 levels) for analysis. Pseudarthrosis occurred in 30% of patients. Baseline demographics, surgical factors, and laboratory values were similar between fused and pseudarthrosis cohorts. Six‑week P1NP tended to be higher in the pseudarthrosis group (95.0±84.8 vs. 55.1±23.4, P=0.074), and ΔP1NP was significantly greater (38.5±70.6 vs. -16.9±97.1, P=0.013). Logistic regression identified ΔP1NP as a significant predictor of one‑year fusion status (P=0.039), whereas BMI, 25‑hydroxyvitamin D, and number of fused levels showed borderline associations.
CONCLUSION
Patients at risk for pseudarthrosis after ACDF show a larger early increase in P1NP compared to their fused counterparts while CTX levels remained comparable between the groups. Considering that these changes occur early after surgery, there may be a role for trials testing the efficacy of postoperative anabolic agents in preventing pseudoarthrosis in high-risk patients.
EVIDENCE LEVEL
Level II (Prospective Cohort Study).