Immunologic studies of nonunited fractures

Abstract

We studied tissue samples of noninfected delayed union or nonunion of diaphyseal bones in 10 patients immunopathologically and neuroimmunologically 4 to 25 months after the primary injury. Samples mostly consisted of vascularized connective tissue of varying density with the proline-4-hydroxylase-containing fibroblast as the major cell type. Most inflammatory cells were CD4 T-lymphocytes and their number was always twice that of the CD8 positive cells. Staining for CD11b positive monocyte/macrophages showed in all samples positive cells scattered in the connective tissue stroma with perivascular enrichments. Mast cells were absent or very rare. Our findings suggest that delayed union and nonunion tissue consists of vascularized connective tissue, which mostly contains 5B5 fibroblasts, CD11b macrophages and vascular endothelial cells with only few immigrant recently recruited monocytes or lymphoid cells. Almost all resident cells seem to be involved in tissue remodeling as suggested by their content of fibroblast-type MMP-1 and its proteolytic activator MMP-3 or stromelysin. The most striking finding was the paucity or total lack of peripheral innervation, which may have to do with the nonunion of the fracture.

Macrophages Inhibit Migration, Metabolic Activity and Osteogenic Differentiation of Human Mesenchymal Stem Cells in vitro

“…Depletion of macrophages in mice resulted in impaired vascularization and severe hemorrhage [Lucas et al, 2010]. However, in delayed union and nonunion fractures, CD11b-positive monocytes/macrophages were consistently distributed in the connective tissue stroma with perivascular enrichment as long as 4-25 months after the fracture [Santavirta et al, 1992]. Unlike normal healing involving short-term macrophage activation, the long-term activation of macrophages could be detrimental for de novo bone formation.…”

Bone morphogenetic proteins in human bone regeneration

“…It is not clear whether the inflammatory reaction is a wanted or an unwanted side effect. Inflammatory cells release cytokines, which may mediate the bone formation process (139)(140)(141)(142). Indeed, enhanced BMPdependent bone formation, probably mediated by interleukin-1, was seen in mice with a systemically induced inflammation (143).…”

Seudoartrosis atrófica. Efecto de la aplicación de ondas de choque extracorpóreas en un modelo experimental en tibia de conejos. [Atrophic pseudoarthrosis. Effect of extracorporeal shock waves aplication in an experimental model in tibia of rabbits].

“…13,14 Estudios histológicos y de inmunofluorescencia sobre la seudoartrosis atrófica señalan un aumento de la vascularización, de los terminales nerviosos a nivel focal y de la presencia de factores de crecimiento. 3,4,19 Justamente la hipótesis sobre la cual se fundamenta el presente estudio consistió en dichas observaciones histológicas a la vez que en el demostrado efecto de las oCEC sobre el tejido óseo.…”