Role of Bone Turnover Biomarkers in Early Prediction of Delayed Union in Long Bone Fractures Following Internal Fixation

Abstract

Background: Delayed union after internal fixation of long-bone fractures remains a major clinical problem, while conventional radiographs may identify impaired healing relatively late. Bone turnover biomarkers may provide earlier evidence of altered fracture biology and improve risk stratification.

Material and Methods: This prospective observational cohort study included 100 adults with femoral, tibial, or humeral fractures treated by internal fixation between June 2022 and June 2023 at Mekran Medical College Teaching Hospital, Turbat, and Benazir Bhutto Hospital, Rawalpindi. Serum procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), osteocalcin, and C-terminal telopeptide of type I collagen (CTX) were measured postoperatively and at six weeks. Patients were followed for 24 weeks. Receiver operating characteristic analysis and multivariable logistic regression were performed.

Results: Normal union occurred in 82 patients, while 18 developed delayed union. At six weeks, delayed-union patients had significantly lower P1NP (52.6 ± 18.4 vs. 83.1 ± 25.8 µg/L), BSAP (15.6 ± 5.6 vs. 22.4 ± 7.2 µg/L), and osteocalcin (18.9 ± 6.7 vs. 27.1 ± 8.2 ng/mL) levels (all p<0.001). P1NP showed the highest predictive accuracy (AUC=0.85). A P1NP level <61 µg/L independently predicted delayed union (aOR=4.48, 95% CI: 1.55–12.94). Adding P1NP to clinical risk factors improved the model AUC from 0.79 to 0.89.

Conclusion: Reduced six-week bone-formation marker responses, particularly P1NP, may facilitate earlier identification of patients at increased risk of delayed union and complement clinical and radiographic assessment after internal fixation.

Keywords: Bone turnover biomarkers; delayed union; long-bone fractures; internal fixation; P1NP; osteocalcin; fracture healing