The angiogenic response to skeletal injury is preserved in the elderly

Abstract

Angiogenesis is essential for normal bone formation and repair. Avascularity characterizes aberrant fracture union in the elderly, while angiogenic mechanisms during cutaneous wound repair are attenuated in aged humans. We hypothesized that skeletal injury results in local (circulating) and systemic (fracture site) 'angiogenic' responses and that these reparative mechanisms are attenuated with advanced patient age. This prospective study examined peripheral blood and fracture hematoma from 31 patients, 16 under 40 years and I6 over the age of 75, undergoing emergent surgery for isolated fracture. The angiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were assayed. Endothelial cell cultures were supplemented with patient plasma and fracture hematoma and angiogenesis determined in vitro by measuring cell proliferation and blood vessel tube formation. Angiogenesis was determined in vivo using a murine dorsal wound pocket model and quantification of new blood vessel formation after 7 days. We found that all injured patients, irrespective of age, have elevated plasma and fracture hematoma levels of VEGF and PDGF. These elevated cytokine concentrations translate into biologically significant angiogenic effects, in vitro and in vivo. These effects are primarily VEGF mediated and are not dependent on patient age. The biological activity of these growth factors does not diminish with advanced age. Thus skeletal injury does result in local and systemic angiogenic responses whereby angiogenic cytokine availability and activity is preserved in the aged suggesting alternative mechanisms for the development of avascularity in delayed and fracture non-union in the elderly. 0 100 1 Orthopaedic Research Society. Published by

Is the expression of Transforming Growth Factor-Beta1 after fracture of long bones solely influenced by the healing process?

“…Lu et al reported agerelated changes in fracture healing in rats [35]. Street et al found that angiogenesis at the fracture site and the response of growth factor to fracture in the elderly human was preserved [36]. Moreover, age was considered as factor for non-union after internal fixation of femoral neck fractures and clavicular non-union [37,38].…”

VEGF serum concentrations in patients with long bone fractures: A comparison between impaired and normal fracture healing

“…These results are in accordance with other reports showing a high concentration of VEGF during the inflammatory phase of fracture healing in humans. 26,27 Street et al 26 demonstrated highly elevated VEGF concentrations in fracture hematoma and peripheral blood of 32 patients immediately after trauma. Grad et al 27 also observed highly elevated VEGF concentrations in 55 polytraumatized patients within the first week after trauma, with the highest level in the second week.…”

Genes with greater up‐regulation in the fracture callus of older rats with delayed healing

“…3,4,9 The angiogenic response to fracture is also preserved in fracture repair in older individuals. 3,4,32 In contrast, in diabetic animals, there is impaired stimulation of PDGF associated with their delayed fracture repair. 33 These two processes, age and diabetes, then, appear to slow fracture repair through separate mechanisms.…”