Host response - Orthopaedic Biomaterials in Research and Practice - page 353

role of metals in
biologic activity

It is reasonable that there be an emphasis on the examination of metal
release and distribution in the consideration of systemic and remote site
effects. Metals play a central role in metabolic and catabolic activity,
with metals involved to some degree in all enzymatic processes. For
this reason, when metals are metabolically active, they are seen to have
an effect far out of proportion to their prevalence. Two examples of this
“multiplier” effect have been given by Mertz (1981) and are shown in
Figure 14.3.

Immune response “Metal allergy” is a well-recognized, everyday phenomenon frequently

associated in women with the use of cheap, high-nickel alloy costume
jewelry or earrings. Metal ions, by themselves, lack the structure and
complexity required to challenge the immune system. However, when
combined with proteins, such as those available in the skin, connective
tissues, and blood, a wide variety of metals produce immune responses
and thus must be considered haptens. Cobalt, chromium, and nickel are
included in this category, with nickel perhaps the most potent. Aluminum,
titanium, molybdenum, and manganese are not believed to be haptens,
whereas the immune role played by vanadium remains unclear.
As a rule of thumb, it may be considered that at least 10% of a normal
population will be sensitive by epicutaneous (skin) test to one or more of
these metals, at some threshold level. Nickel sensitivity is probably the

Cobalt Chromium

Turnover Turnover

10 -10 g/day 10 -9 g/day

Vitamin B 12 Glucose tolerance factor

Methyl transferase Potentiation

of insulin
Turnover

�ymidine synthesis

2 × 10 -3 g/day

DNA synthesis

RNA, MRNA

Protein
synthesis
Turnover

Regulation
of energy metabolism
Turnover

1-50 g/day 1.5-4.0 kcal/day

FIGUre 14.3 magnification of effect of trace metals. (adapted from
mertz, W., Science 213:1332-1338, 1981.)