Serology of abnormal fracture healing: The role of PIIINP, PICP, and BsALP

Objective: To determine whether poorly healing tibial shaft fractures exhibit a serological response of bone-specific alkaline phosphatase (BsALP), collagen I carboxy-terminal propeptide (PICP), collagen III amino-terminal propeptide (PIIINP), and collagen I carboxy-terminal telopeptide (ICTP) different from that of normally healing fractures. Design: Prospective. Participants: Twenty consecutive patients with isolated tibial shaft fractures with or without fracture of the fibula. Main Outcome Measurements: Assays of BsALP, PICP, PIIINP, and ICTP were performed with serum samples taken at standard intervals from twenty-four hours to twenty weeks after fracture. Fracture healing was assessed at five, ten, fourteen, and twenty weeks for clinical and radiological evidence of union. Results: Seventeen fractures united within the twenty-week study period. The three fractures exhibiting delayed union demonstrated significantly lower PICP levels and marginally lower BsALP levels at twenty weeks. PIIINP levels were significantly higher in these three fractures at ten weeks. There was no difference in ICTP between the seventeen united and the three ununited fractures. Conclusions: This study identified three serological features of a poor healing response in tibial shaft fractures. First, matrix collagen I and III production in the first ten weeks of healing was adequate, with evidence of significantly increased production of type III collagen. Second, there was no serological evidence of a deficient osteoblast response, as indicated by normal levels of BsALP and PICP, during this early period. Third, evidence of a deficient osteoblast response appeared only at twenty weeks after injury.