The Allergic Bone Marrow? The Immuno-Capacity of the Human Bone Marrow in Context of Metal-Associated Hypersensitivity Reactions

Abstract

Arthroplasty ranks among the greatest achievements of surgical medicine, with total hip replacement termed “the operation of the century.” Despite its wide success, arthroplasty bears risks, such as local reactions to implant derived wear and corrosion products. Prevalence of allergies across Western society increases and along the number of reported hypersensitivity reactions to orthopedic implant materials. In this context the main focus is on delayed hypersensitivity (DTH). This mechanism is mainly attributed to T cells and an overreaction of the adaptive immune system. Arthroplasty implant materials are in direct contact with bone marrow (BM), which is discussed as a secondary lymphoid organ. However, the mechanisms of sensitization toward implant wear remain elusive. Nickel and cobalt ions can form haptens with native peptides to activate immune cell receptors and are therefore common T helper allergens in cutaneous DTH. The rising prevalence of metal-related allergy in the general population and evidence for the immune-modulating function of BM allow for the assumption hypersensitivity reactions could occur in peri-implant BM. There is evidence that pro-inflammatory factors released during DTH reactions enhance osteoclast activity and inhibit osteoblast function, an imbalance characteristic for osteolysis. Even though some mechanisms are understood, hypersensitivity has remained a diagnosis of exclusion. This review aims to summarize current views on the pathomechanism of DTH in arthroplasty with emphasis on BM and discusses recent advances and future directions for basic research and clinical diagnostics.

Fatigue Crack Growth and Fracture of Internal Fixation Materials in In Vivo Environments—A Review

“…This phenomenon was particularly evident in those suffering metal hypersensitivity [ 90 ]. Through observation, the mature osteoclasts were able to erode the implant and release metal debris into the surrounding tissue [ 91 ]. The wear out on the surface facilitates fatigue crack growth and infiltration of inflammatory cells inhibits the formation of oxide layer.…”

Diagnosis of Metal Hypersensitivity in Total Knee Arthroplasty: A Case Report

“…In arthroplasty, the prognostic and diagnostic value of these methods is called into question on the basis of controversial results of clinical studies (28). One reason for inconclusive results could be that the systemic immune status does not sufficiently reflect the periprosthetic immune cell composition (16). It is also possible that the spectrum of locally released potential allergens in terms of physicochemical diversity is more distinct than displayable in the LTT by soluble salts.…”

“…Comparable mechanisms, characterized by perivascular lymphocytic infiltrate, have been identified in the peri-implant membrane (15). DTH reactions beyond the peri-implant membrane in the adjacent bone marrow are currently proposed and discussed (16).…”

Systemic Effects of Metals Released from Arthroplasty Implants – a Brief Summary

“…The relevance of the pa-tientʼs individual local immune status in bone marrow, of immune priming, and a possible immunosuppression of the individual patient is, however, the subject of ongoing research. Since joint prostheses are anchored in direct contact with cancellous bone, thus placing metallic components in direct contact with cancellous bone marrow, effects on the haematopoietic system and, apart from innate, also adaptive immune reactions within the bone marrow are conceivable after substantial exposure [10]. Thus, increased lymphocyte reactivity, myelotoxicity and reduced leukocyte counts, amongst other things, have been detected in the blood of patients with arthroplasty implants [63 -65].…”

“…The central and peripheral nervous systems, the cardiovascular system, and the thyroid gland in particular can be harmed by metals which enter the systemic circulation from joint prostheses. Furthermore, the potential immunotoxicity, cancerogenicity and teratogenicity of cobalt and chromium species, but also of all other types of metals released from joint prostheses, have become the focal point of interest of patients, doctors, scientists and legislation [1,10].…”