ABSTRACT
PURPOSE: Fracture healing often requires extended convalescence as the bony fragments consolidate into restored viable tissue for load-bearing. Development of interventions to improve healing remains a priority for orthopaedic research. The goal of this study was to evaluate the ability of a naturally occurring matrix of amorphous calcium carbonate to affect fracture healing in an uninstrumented long bone model. METHODS: Complete transverse fracture was induced in the fibula of mature mice, followed by daily gavage of crushed gastrolith from crayfish at doses of 0 (control), 1 (1 MG), and 5 (5 MG) mg/kg. At Day 17, bones and sera were harvested. RESULTS: Morphologically, the 1 MG treated group had greater bone volume (BV), and both 1 MG and 5 MG had greater tissue volume (TV) than control (p < 0.05), as determined by µCT; BV/TV and mineral density did not yield a statistical difference. Histologically, regional variations in mineralized matrix were evident in all specimens, indicating a broad continuum of healing within the callus. Among serum proteins, bone-specific alkaline phosphatase, indicative of active mineralization, was greater in 5 MG than control (p < 0.05). Sclerostin, an inhibitor of osteogenesis, was lower in 5 MG than control (p < 0.05), also suggestive of enhanced healing. CONCLUSIONS: An increase in bone volume, tissue volume and cellular signaling for osteogenesis at 17 days following fibula fracture in this mouse model suggests that gastrolith treatment holds potential for improving fracture healing. Further study at subsequent time points is warranted to determine the extent to which the increase in callus size with gastrolith treatment may accelerate restoration of tissue integrity.
