Effect of age on vascularization during fracture repair

Abstract

Age affects fracture repair; however, the underlying mechanisms are not well understood. The goal of this study was to assess the effects that age has on vascularization during fracture healing. Tibial fractures were created in juvenile (4-week-old), middle-aged (6-month-old), and elderly (18-month-old) mice. The length density and surface density of blood vessels within fracture calluses were analyzed using stereology at 7 days after fracture. The expression of molecules that regulate vascular invasion of the fracture callus was also compared among the three age groups by immunohistochemistry and in situ hybridization. At 7 days after fracture, juvenile mice had a higher surface density of blood vessels compared to the middle-aged and elderly. Hypoxia-inducible factor-1a protein and transcripts of vascular endothelial growth factor were detected at 3 days postinjury in juvenile but not middle-aged and elderly mice. Stronger Mmp-9 and -13 expression was detected in fracture calluses at day 7 in the juvenile compared to the middle-aged and elderly mice. At 21 days postfracture, expression of both Mmps was more robust in the elderly than juvenile and middle-aged animals. These data indicate that age affects vascularization during fracture repair, and the changes we observed are directly correlated with altered expression of biochemical factors that regulate the process of angiogenesis. However, whether the increased vascularization is the cause or result of accelerated bone repair in juvenile animals remains unknown. Nonetheless, our results indicate that enhancing vascularization during fracture repair in the elderly may provide unique therapeutic opportunities. ß

Pulp Revascularization on Permanent Teeth with Open Apices in a Middle-aged Patient

“…Depletion and/or senescence of these cells may result in age-related tissue degeneration as well as decreased regenerative potential (20,21). Animal studies have shown significantly reduced bone regeneration capacity with aging (22,23). When compared with 4-week-old mice, middle-aged (6 months) and old mice (18 months) present less vascularized fracture callus and less bone regeneration (22).…”

“…Animal studies have shown significantly reduced bone regeneration capacity with aging (22,23). When compared with 4-week-old mice, middle-aged (6 months) and old mice (18 months) present less vascularized fracture callus and less bone regeneration (22). Up-regulation of the inflammatory response results in a lowlevel, long-lasting, systemic proinflammatory state, which underlies most age-associated diseases (24).…”

Multiple roles for CCR2 during fracture healing

“…The length density (the length of blood vessels per unit volume of the reference space) and the surface density (the area of the outer surface of blood vessels per unit volume of the reference space) of the blood vessels within the fracture callus were analyzed using an Olympus CAST system, as described previously (Lu et al, 2008).…”

Radius Fracture Repair Using Volumetrically Expanding Polyurethane Bone Cement

“…Displacement is more common, and efficacies of some fracture repair techniques decrease relative to younger healthy patients. [3][4][5] Displaced distal radius fractures typically are repaired by closed reduction and casting or open reduction with internal plate fixation, although this treatment dichotomy can be inadequate for certain elderly patients. Re-displacement rates after closed reduction with splinting 6 approach 50%.…”