Evaluation of serum biochemical markers of bone metabolism for early diagnosis of nonunion and infected nonunion fractures in rabbits

OBJECTIVE: To evaluate the use of serum concentrations of biochemical markers of bone metabolism (osteocalcin OC], bone-specific alkaline phosphatase BS-ALP], and deoxypyridinoline DPYR]) to compare healing in infected versus noninfected fractures and in fractures with normal repair versus delayed (nonunion) repair in rabbits. ANIMALS: 32 female 9- to 10-month-old New Zealand White rabbits. PROCEDURE: A femoral fracture defect was made in each rabbit. Rabbits were assigned to the following groups: the bone morphogenetic-2 gene treatment group with either noninfected nonunion or infected (ie, inoculation of defects with Staphylococcus aureus) nonunion fractures or the luciferase (control) gene treatment group with either noninfected nonunion or infected nonunion fractures. Serum samples were obtained before surgery (time 0) and 4, 8, 12, and 16 weeks after surgery. Callus formation and lysis grades were evaluated radiographically at 16 weeks. RESULTS: Serum OC and BS-ALP concentrations decreased from time 0 at 4 weeks, peaked at 8 weeks, and then decreased. Serum DPYR concentration peaked at 4 weeks and then decreased, independent of gene treatment group or fracture infection status. Compared with rabbits with noninfected fractures, those with infected fractures had lower serum OC and BS-ALP concentrations at 4 weeks, higher serum OC concentrations at 16 weeks, and higher serum DPYR concentrations at 4, 8, and 16 weeks. Combined serum OC, BS-ALP, and DPYR concentrations provided an accuracy of 96% for prediction of fracture infection status at 4 weeks. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of multiple serum biochemical markers of bone metabolism could be useful for clinical evaluation of fracture healing and early diagnosis of osteomyelitis.