Persistent expression of mitogenic/transforming factors at the site of failed orthopaedic implants: the impact on immune reactivity

The response to wear particles from orthopaedic implants can lead to inflam mation, osteolytic lesions, and aseptic loosening. To gain an insight into the development of this pathogenetic process, immunohistochemical technique s were used to identify the expression and tissue distribution of the poten t cell mitogen epidermal growth factor (EGF), and the epidermal growth fact or receptor (EGF-R) at the site of bone erosion in 30 patients with clinica lly failed orthopaedic implants. The results showed a large proportion of t he macrophage subsets (M phi) which expressed EGF and EGF-R, also contained wear particles, indicating their expression is a consequence of M phi phag ocytosis of implant material. The surface membrane expression of EGF-R on f using M phi suggests its presence is fundamental to the formation of bone-r esorbing multi-nucleated giant cells, and the development of osteolysis. Ad ditionally, there is increasing evidence of the long-term systemic spread o f wear particles and their accumulation at distal sites including lymph nod es, liver, and spleen. Elevated expression of mitogenic factors in response to wear particles may result in deviation from normal cell growth and regu lation, resulting in changes to immune cell function. Such potential transf ormations at distal sites are clinically significant, as alterations to the patient's immune system may result in acute divergence from normal immune cell responses. (C) 1998 Kluwer Academic Publishers.