ArticlePDF Available

Titanium allergy or not?“Impurity” of titanium implant materials

Authors:
Article

Titanium allergy or not?“Impurity” of titanium implant materials

Abstract and Figures

For patients suffering from allergies to nickel, chrome and cobalt, titanium implants are the implants of choice. Nevertheless, titanium im-plant sensitivity has been reported in the form of "allergies" and an increasing number of pa-tients are confused. This paper aims to use spectral analysis as a diagnostic tool for ana-lyzing different titanium implant alloys in order to determine the percentage of the alloy com-ponents and additions that are known to cause allergies. Different materials, such as sponge titanium, TiAl6Nb7, Ti21SRx, TiAl6V4 [forged alloy], TiAl6V4 [cast alloy], TMZF, pure titanium [c. p. 1] and iodide titanium were analyzed for the presence of the elements that have been associated with allergic reactions using spectral analysis. All the implant material samples con-tained traceable amounts of Be, Cd, Co, up to a maximum of 0.001 percent by weight [wt.%], Cr up to 0.033 wt.%, Cu up to 0.007 wt.%, Hf up to 0.035 wt.%, Mn up to 0.007 wt.%, Ni up to 0.031 wt.%, and Pd up to 0.001 wt.%. This paper demonstrates that all the investigated implant material samples contained a low but consistent percentage of components that have been as-sociated with allergies. For example, low nickel contents are related to the manufacturing pro-cess and are completely dissolved in the tita-nium grid. Therefore, they can virtually be clas-sified as "impurities". Under certain circum-stances, these small amounts may be sufficient to trigger allergic reactions in patients suffering from the corresponding allergies, such as a nickel, palladium or chrome allergy.
Content may be subject to copyright.
Vol.2, No.4, 306-310 (2010) Health
doi:10.4236/health.2010.24045
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Titanium allergy or not? “Impurity” of titanium implant
materials
Thomas Harloff1, Wolfgang Hönle2, Ulrich Holzwarth3, Rainer Bader4, Peter Thomas5,
Alexander Schuh1
1Research Unit, Neumarkt Clinical Center, Neumarkt, Germany
2Orthopedic Clinic Neumarkt, Neumarkt, Germany
3MedTitan, Erlangen, Germany
4Orthopedic Clinic and Polyclinic, University of Rostock, Rostock, Germany
5Clinic and Polyclinic for Dermatology and Allergology of the Ludwig-Maximilians-University of Munich, Munich, Germany;
Alexander.Schuh@klinikum.neumarkt.de
Received 25 December 2009; revised 26 January 2010; accepted 30 January 2010.
ABSTRACT
For patients suffering from allergies to nickel,
chrome and cobalt, titanium implants are the
implants of choice. Nevertheless, titanium im-
plant sensitivity has been reported in the form
of “allergies” and an increasing number of pa-
tients are confused. This paper aims to use
spectral analysis as a diagnostic tool for ana-
lyzing different titanium implant alloys in order
to determine the percentage of the alloy com-
ponents and additions that are known to cause
allergies. Different materials, such as sponge
titanium, TiAl6Nb7, Ti21SRx, TiAl6V4 [forged
alloy], TiAl6V4 [cast alloy], TMZF, pure titanium
[c. p. 1] and iodide titanium were analyzed for
the presence of the elements that have been
associated with allergic reactions using spectral
analysis. All the implant material samples con-
tained traceable amounts of Be, Cd, Co, up to a
maximum of 0.001 percent by weight [wt.%], Cr
up to 0.033 wt.%, Cu up to 0.007 wt.%, Hf up to
0.035 wt.%, Mn up to 0.007 wt.%, Ni up to 0.031
wt.%, and Pd up to 0.001 wt.%. This paper
demonstrates that all the investigated implant
material samples contained a low but consistent
percentage of components that have been as-
sociated with allergies. For example, low nickel
contents are related to the manufacturing pro-
cess and are completely dissolved in the tita-
nium grid. Therefore, they can virtually be clas-
sified as “impurities”. Under certain circum-
stances, these small amounts may be sufficient
to trigger allergic reactions in patients suffering
from the corresponding allergies, such as a
nickel, palladium or chrome allergy.
Keywords: Allergy; Implant; Nickel; Spectral
Analysis; Titanium
1. INTRODUCTION
Numerous studies on allergic reactions to synthetic ma-
terials have been carried out, in particular on allergic
reactions to metallic components that are also used in
orthopedic surgery. In case histories, localized or gener-
alized eczemas, urticaria, persistent swelling, sterile os-
teomyelitis and cases of aseptic implant loosening are
described as examples of allergic reactions to metal im-
plants [1-28]. Nickel, cobalt and chrome are the classic
contact allergens [1,2,11,29-32]. However, in contrast to
the sensitization ratio of up to 12 percent of the general
population to nickel and of up to 5 percent to cobalt and
chrome [24,32], only a few cases of allergies to implant
materials have been documented. Precise details on the
frequency of such reactions are presently not available.
Furthermore, up to now, the frequency of allergic reac-
tions occurring in the peri-implant region, without any
prior patch test reactions, has not been established. For
example, inflammatory infiltrations of the peri-implant
region displaying characteristics of late-type allergic
reactions were found in a number of patients undergoing
revision operations related to complications [2]. Thomas
[24] and Willert [27] published cases of endoprosthesis
loosening with accompanying T-lymphocyte-dominated
immune reactions in the peri-implant region. In the
1970s, obvious allergic reactions to the cobalt-chrome
alloy components of the McKee-Farrar prosthesis un-
derwent scrutiny for the first time [3,11]. In case of a
nickel allergy, individual responsiveness can be very
diverse, with even minute quantities of nickel causing
contact eczemas in sensitive patients [3,11,32]. Their
high resistance to corrosion, the absence of any carcino-
genic risk, their excellent bio-compatibility and their
T. Harloff et al. / Health 2 (2010) 306-310
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
307
lack of sensitization make titanium implants or titanium
alloy implants the recommended alternative for patients
with nickel, cobalt or chrome allergies [33,34]. Admit-
tedly, there are also reports of incompatibility reactions
to titanium materials [10,25,35-42]. In his study, Walsh
[42] found several eyeglass frames made of a titanium
alloy to contain nickel traces. Likewise, Suhonen [41]
documented allergic contact dermatitis caused by tita-
nium eyeglass frames. However, in Suhonen’s case, pal-
ladium was established as the causative factor.
In his comparative histological and immuno-histo-
chemical analysis of tissues surrounding titanium im-
plants [n = 23] and implant steel [n = 8], Thewes [23]
documented the presence of peri-vascular infiltrations,
Langerhans cells, T helper cells, T suppressor cells,
monocytes, macrophages and memory cells, and did not
find any statistically significant difference between both
groups of implants. Thewes concluded that a metal sen-
sitization to both steel implants and titanium implants is
possible. Yamauchi [43] described an eczema reaction in
connection with a pacemaker made of titanium. Lalor et
al. [38] analyzed the granuloma tissue of five patients
that had undergone a revision operation following an
aseptic prosthesis loosening. The granuloma tissue was
found to contain primarily titanium. Each of the five
patients subjected to scratch testing using diluted solu-
tions of titanium salts yielded negative results. However,
two of the patients displayed a positive skin reaction to
titanium-containing ointments.
These above mentioned reports led to more and more
confused patients. This paper aims to examine different
titanium implant alloys in respect to impurity with com-
ponents that are known to potentially cause allergies.
2. MATERIAL AND METHOD
A Spectrolab spectral analysis unit from the Spectro
company [Kleve, Germany] was used to study the tita-
nium materials [listed in Table 1 with their respective
producers]. Prior to the test, the optical analysis unit was
calibrated using calibrated samples, the chemical com
Table 1. Materials analyzed.
Materials Producer/Supplier
Sponge titanium Source Japan
Sponge titanium Source Russia
TiAl6Nb7 TIMET USA
Ti21SRx TIMET Laboratories, Henderson,
USA
TiAl6V4 Allvac Teledyne, Monroe, USA
FG-TiAl6V4 ASTM F 1108
TMZF Stryker
Pure titanium rod, Ti-2 TIMET
Pure titanium plate, Ti-1 Deutsche Titan
Iodide titanium Metallgesellschaft Ff/M
position of which was determined via optical spectral
analysis by sparking sample slices [with a diameter of
6-60 mm and a thickness of 6 mm] under argon atmos-
phere using a 6 mm ceramic aperture. In this particular
case, the measuring depth obtained by sparking is 0.5
mm, making the thickness of the examined samples ir-
relevant. The described method pertains to a material
analysis and not to a layer analysis. A detailed analysis
was performed on pure titanium slices with a diameter of
6 and 12 mm.
TiAl6V4 slices with a diameter of 10, 16, 22, 35 and
60 mm, respectively, and TiAl6Nb7 slices with a diame-
ter of 14.5, 22 and 28 mm, respectively. Samples of rods
with different diameters were analyzed because the
various titanium alloys of the individual manufacturers
are available with different diameters. The analyses were
performed according to the established and [statistically]
recognized measuring methods used in material science
for determining alloy components. Since it has to be
assumed that the material is homogeneous over the en-
tire length of the respective [titanium or titanium alloy]
rod, only a 6 mm thick sample slice was analyzed in
each individual case. Three measurements and a final
verification measurement were conducted. Each of the
results indicated corresponds to the average value ob-
tained from the three measurements, with the standard
deviation being less than 0.01 percent by weight.
3. RESULTS
The results of the spectral analysis are shown in Table 2.
All the implant material samples contained traceable
amounts of Be, Cd, Co, up to a maximum of 0.001 per-
cent by weight, Cr, up to a maximum of 0.033 percent
by weight, Cu, up to a maximum of 0.007 percent by
weight, Hf, up to a maximum of 0.035 percent by weight,
Mn, up to a maximum of 0.007 percent by weight, Ni,
up to a maximum of 0.031 percent by weight, and Pd, up
to a maximum of 0.001 percent by weight [Table 2].
4. DISCUSSION
There is an increasing number of reports of incompati-
bility reactions to titanium materials [10,25,35-42]. All
the titanium materials examined in the present study
clearly showed consistently traceable amounts of addi-
tional components, such as nickel. Although contents
between 0.01 and 0.034 percent by weight are consid-
ered to be insignificant from a metallurgic perspective,
they are subject to discussion in the context of the high
nickel sensitization rate present in the general population.
The levels of additions found in iodide titanium corre-
spond to the expected levels and demonstrate that, in this
context, the absolutely lowest traces of nickel that are
technologically possible can be adhered to, namely close
T. Harloff et al. / Health 2 (2010) 306-310
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
308
Tab le 2. Analysis results (n.t.: not traceable).
Material Analysis values in % by weight
Al Be Cd Co Cr Cu Fe Hf Mn Mo Ni Pd V
Sponge titanium (Japan) 0,001 0,001 0,001 0,001 0,002 0,007 0,001 0,001 0,001 0,001 0,008 0,001 0,001
Sponge titanium (Russia) 0,001 0,001 0,001 0,001 0,001 0,001 0,002 0,001 0,007 0,001 0,001 0,001 0,001
TiAl6Nb7 5,980 0,001 0,001 0,001 0,011 0,001 0,150 0,001 0,002 0,001 0,014 0,001 0,001
Ti21SRx 0,005 0,001 0,001 0,001 0,005 n n. 0,037 0,001 0,002 15,00 0,017 0,001 0,001
TiAl6V4 5,930 0,001 0,001 0,001 0,033 0,001 0,160 0,001 0,004 0,002 0,031 0,001 3,880
FG-TiAl6V4 ASTM F 1108 6,20 0,0001 0,0001 0,001 0,012 0,001 0,170 0,001 0,001 0,001 0,011 0,001 4,15
TMZF 0,005 0,001 0,001 0,001 0,008 0,003 2,090 0,035 0,001 12,00 0,013 0,001 0,002
Pure titanium rod, Ti-2, Timet 0,021 0,001 0,001 0,001 0,014 0,001 0,041 0,001 0,002 0,001 0,013 0,001 0,012
Pure titanium Ti-1, Plate
(Deutsche Titan) 0,004 0,001 0,001 0,001 0,012 0,001 0,028 0,001 0,001 0,001 0,012 0,001 0,001
Iodide titanium 0,003 0,001 0,001 0,001 0,001 0,001 0,010 0,013 0,001 0,001 0,001 0,001 0,002
to the detection limit of less than 0.001 percent by
weight. All the other samples, independent of the pro-
ducer, were always found to contain a consistently low
percentage of additions, such as nickel, following their
further processing into rods of different sizes [diameters
between 6 and 60 mm were analyzed]. Numerous publi-
cations deal with hypersensitivity reactions to osteosyn-
thesis materials used in the treatment of fractures, the
majority of these materials being stainless steel implants
[7,19,32].
An immunological response to metals [partly as an
exaggerated allergic reaction] is discussed to be the
cause of impaired wound healing or the delayed healing
of fractures [19]. Allergic reactions to orthopedic im-
plants can thus also necessitate the removal of the im-
plant [24]. Lymphocyte infiltration was discovered in the
peri-prosthetic tissue, indicating T-lymphocyte-related
inflammation components [25-28]. This lymphocyte
infiltration can be considered a component of a delayed
hypersensitivity reaction [DTH, Delayed Type Hyper-
sensitivity] [2,26,27]. Vasculitis with lymphocyte infil-
tration of the vascular walls and substantial fibrin exuda-
tion have been described [11,27,32]. Nickel, cobalt and
chrome can cause allergic reactions in humans [2,19,31],
with nickel being one of the most common contact al-
lergens. The average sensitization ratio in the general
population lies between 2 percent and 12 percent, de-
pending on age, gender and living conditions. In addition
to the typical findings, such as hand eczeme, uncommon
manifestations, such as pseudo-lymphomas or implant-
associated intolerance reactions, are also known to occur
[24]. Many aspects of skin allergies have already been
analyzed, such as thresholds above which allergens, such
as nickel, chrome or cobalt trigger skin reactions, the use
of standardized provocation testing for the detection of
an allergy [patch test], [immuno-] histological character-
istics of such reactions, tracking elements, such as CLA
[cutaneous leukocyte antigen], which allow sensitized
T-cells to migrate into the skin, and the diminishing re-
activity following the avoidance of the allergens for
many years which leads to problems only after repeated
fresh contact with the respective allergen [booster], e.g.
in case of the repeated wear of fashion jewelry. Accord-
ingly, the “Nickel Directive” [31], which applies to items
that have a direct and prolonged contact with the skin,
determines that a maximum of 0.5 μg nickel/cm2/week
can be released and limits the nickel contents in piercing
metals to 0.05 percent. However, such guidelines do not
yet exist for implants or implant materials. In a study
carried out on 242 patients, Swiontkowski et al. [22]
reported a sensitization prevalence of 0.2 percent for
chromium, 1.3 percent for nickel and 1.8 percent for
cobalt. Subsequent to the implantation of orthopedic
implants, the sensitization rate increased to 2.7 percent
for chromium, 3.8 percent for nickel and 3.8 percent for
cobalt. In many cases, only minute amounts of nickel
suffice to trigger allergic reactions, such as contact ec-
zemas [32]. Therefore, titanium implants or titanium-
alloy implants are often used as an alternative for pa-
tients suffering from nickel, chrome or cobalt allergies
[30]. Duchna [10] conducted a study on 112 patients and
did not find any allergic reactions that were associated
with titanium implants. The biocompatibility of titanium
materials [32] is based on the passivation of its surface.
In its intact state, this surface consists of non-conductive
titanium oxide, a bio-inert material that chemically cor-
responds to ceramics. When corrosion occurs due to an
electron flow, an interaction between the body and the
implant takes place. In essence, these interactions are
dependent on the insulation provided by the oxide layers
and thus dependent on the dielectric constant and there-
fore on the insulating effect of the metal oxides. The
higher the dielectric constant is, the better the insulating
effect and the resulting stability in vivo. Depending on
the oxide type, titanium oxide has a value between ε =
48 and ε = 110, with water having a value of ε = 78 [32].
T. Harloff et al. / Health 2 (2010) 306-310
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
309
In contrast, the dielectric constant for cobalt oxide and
nickel oxide is not measurable [32]. Therefore, an inter-
action with body electrolytes is likely to occur on a
much larger scale than is the case for metals belonging
to the refractory group [oxide formation in milliseconds],
such as titanium, niobium, tantalum, vanadium and their
alloys. Alternatively, “ceramic” coatings, such as tita-
nium-niobium-oxynitride, can be used to artificially pro-
tect implant alloys against corrosion.
5. CONCLUSIONS
Our results demonstrate that titanium materials contain a
small yet consistent percentage of detectable impurities,
such as the elements Al, Be, Cd, Co, Cr, Cu, Fe, Hf, Mn,
Mo, Ni, Pd and V. All the implant material samples thus
contain a consistent yet low percentage of components to
which allergies have been attributed. Under specific cir-
cumstances, even small amounts of elements, such as
palladium, nickel or chromium, suffice to trigger an al-
lergic reaction in patients suffering from the corres-
ponding allergies. However, these allergic reactions
would not be directly attributable to titanium or its alloys,
but rather to the impurities contained therein. Additional
research on the release of the alloy components and the
reaction thresholds of the afflicted patients is urgently
required. Parallel to this research, alternative production
processes should be evaluated by the companies pro-
ducing these metals in order to produce pure titanium
and titanium alloys containing fewer impurities, for use
in the human body. Titanium continues to be the implant
material of choice for patients suffering from allergic
reactions to cement-free implants.
REFERENCES
[1] Banfield, C.C., Basketter, D.A. and Powell, S.M. (1998)
Cutaneous reactivity of the hands in nickel-sensitive pa-
tients with hand eczema. Contact Dermatitis, 38, 316-318.
[2] Baur, W., Hönle, W. and Schuh, A. (2005) Pathological
findings in tissue surrounding revised metal/metal arti-
culations. Der Orthopäde, 34, 225-233.
[3] Benson, M.K., Goodwin, P.G. and Brostoff, J. (1975)
Metal sensitivity in patients with joint replacement ar-
throplasties. British Medical Journal, 15, 374-375.
[4] Campbell, P., Mirra, J., Doorn, P., Mills, B., Alim, R. and
Catelas, I. (2001) Histopathology of metal-on-metal hip
joint tissues. In Rieker Ed., World Tribology Forum in
Arthroplasty, 167-180.
[5] Carlsson, A.S., Magnusson, B. and Moller, H. (1980)
Metal sensitivity in patients with metal-to-plastic total
hip arthroplasties. Acta Orthopaedica Scandinavica, 51,
57-62.
[6] Christiansen, K., Holmes, K. and Zilko, P.J. (1979) Metal
sensitivity causing loosened joint prosthesis. Annals of
Rheumatic Diseases, 38, 476-480.
[7] Cramers, M. and Lucht, U. (1977) Metal sensitivity in
patients treated for tibial fractures with plates of stainless
steel. Acta Orthopaedica Scandinavica, 48, 245-249.
[8] Davies, A.P., Willert, H.G., Campbell, P.A., Learmonth,
I.D. and Case, C.P. (2005) An unusual lymphocytic
perivascular infiltration in tissues around contemporary
metal-on-metal joint replacements. The Journal of Bone
and Joint Surgery-American Volome, 87, 18-27.
[9] Doorn, P.F., Mirra, J.M., Campbell, P.A. and Amstutz,
H.C. (1996) Tissue reaction to metal on metal total hip
prostheses. Clinical Orthopaedics, 329 (Suppl.), S187-
205.
[10] Duchna, H.W., Nowack, U., Merget, R., Muhr, G. and
Schultze-Werninghaus, G. (1998) Prospective study of
the significance of contact sensitization caused by metal
implants. Zentralbl Chir, 123, 1271-1276.
[11] Elves, M.W., Wilson, J.N., Scales, J.T. and Kemp, H.B.
(1975) Incidence of metal sensitivity in patients with
total joint replacements. British Medical Journal, 15,
376-378.
[12] Gawkrodger, D.J. (2003) Metal sensitivities and ortho-
paedic implants revisited: The potential for metal allergy
with the new metal-on-metal joint prostheses. British
Journal of Dermatology, 148, 1089-1093.
[13] Goodman, S.B. (1996) Does the immune system play a
role in loosening and osteolysis of total joint replace-
ments? Journal of Long-Term Effects of Medical Impl-
ants, 6, 91-101.
[14] Hallab, N., Merritt, K. and Jacobs, J.J. (2001) Metal sen-
sitivity in patients with orthopaedic implants. The Jour-
nal of Bone and Joint Surgery, 83-A(3), 428-436.
[15] Hallab, N.J., Anderson, S., Stafford, T., Glant, T. and
Jacobs, J.J. (2005) Lymphocyte responses in patients
with total hip arthroplasty. Journal of Orthopaedic Sur-
gery and Research, 23, 384-391.
[16] Kaplan, K., Della Valle, C.J., Haines, K., et al. (2002)
Preoperative identification of a bone-cement allergy in a
patient undergoing total knee arthroplasty. The Journal of
Arthroplasty, 17, 788-791.
[17] Kubba, R., Taylor, J.S. and Marks, K.E. (1981) Cuta-
neous complications of orthopedic implants. A two-year
prospective study. Archives of Dermatology, 117, 554-
560.
[18] McKenzie, A.W., Aitken, C.V. and Ridsdill-Smith, R.
(1967) Urticaria after insertion of Smith-Petersen Vital-
lium nail. British Medical Journal, 4, 36.
[19] Merritt, K. and Rodrigo, J.J. (1996) Immune response to
synthetic materials. Sensitization of patients receiving or-
thopaedic implants. Clinical Orthopaedics, 326, 71-79.
[20] Munro-Ashman, D. and Miller, A.J. (1976) Rejection of
metal to metal prosthesis and skin sensitivity to cobalt.
Contact Dermatitis, 2, 65-67.
[21] Schuh, A., Thomas, P., Holzwarth, U., Reinhold, R.,
Zeiler, G. and Mahler, V. (2006) Allergic reaction to com-
ponents of bone cement after total knee arthroplasty.
Zentralbl Chir, 131, 429-31.
[22] Swiontkowski, M.F., Agel, J., Schwappach, J., McNair, P.
and Welch, M. (2001) Cutaneous metal sensitivity in pa-
tients with orthopaedic injuries. Journal of Orthopaedic
Trauma, 15, 86-89.
[23] Thewes, M., Kretschmer, R., Gfesser, M., Rakoski, J.,
Nerlich, M., Borelli, S., et al. (2001) Immunohistochem-
cical characterization of the perivascular infiltrates cells
T. Harloff et al. / Health 2 (2010) 306-310
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
310
in tissues adjacent to stainless steel implants compared
with titanium implants. Archives of Orthopaedic and
Trauma Surgery, 121, 223-226.
[24] Thomas, P. (2003) Allergic reactions to implant materials.
Der Orthopäde, 32, 60-64.
[25] Thomas, P. (2006) Impaired fracture healing and eczema
from titanium based osteosynthesis with corresponding
T-cell hyperresponsiveness in vitro: A case of titanium
hypersensitivity? Contact Dermatitis, 55, 199-202.
[26] Thomas, P., Thomas, M., Summer, B., Naumann, T., San-
der, C.A. and Przybilla, B. (2000) Intolerance of osteo-
synthesis material: Evidence of dichromate contact al-
lergy with concomitant oligoklonal T-cell infiltrate and
TH1-type cytokine expression in the peri-implantar tis-
sue. Allergy, 55, 969-972.
[27] Willert, H.G., Buchhorn, G.H., Fayyazi, A., Flury, R.,
Windler, M., Koster, G., et al. (2005) Metal-on-metal
bearings and hypersensitivity in patients with artificial
hip joints. A clinical and histomorphological study. The
Journal of Bone and Joint Surgery-American Volome, 87,
28-36.
[28] Willert, H.G., Buchhorn, G.H., Gobel, D., Koster, G.,
Schaffner, S., Schenk, R., et al. (1996) Wear behavior
and histopathology of classic cemented metal on metal
hip endoprostheses. Clinical Orthopaedics and Related
Research, 329 (Suppl.), 160-186.
[29] Gawkrodger, D.J. (1996) Nickel dermatitis: How much
nickel is safe? Contact Dermatitis, 35, 267-271.
[30] Kreibich, D.N., Moran, C.G., Delves, H.T., Owen, T.D.
and Pinder, I.M. (2006) Systemic release of cobalt and
chromium after uncemented total hip replacement. The
Journal of Bone and Joint Surgery-British Volome, 78,
18-21.
[31] Liden, C. and Norberg, K. (2005) Nickel on the Swedish
market. Follow-up after implementation of the Nickel
Directive. Contact Dermatitis, 52, 29-35.
[32] Schuh, A., Thomas, P., Kachler, W., Göske, J., Wagner,
L., Holzwarth, U., et al. (2005) Allergic potential of tita-
nium implants. Der Orthopäde, 34, 327-333.
[33] Farronato, G., Tirafili, C., Alicino, C. and Santoro, F.
(2002) Titanium appliances for allergic patients. Journal
of Clinical Orthopaedics, 36, 676-679.
[34] Tan, M. and Suzuki, H. (1995) Usefulness of titanium
implants for systemic contact dermatitis due to ortho-
paedic prostheses. Contact Dermatitis, 33, 202.
[35] Basketter, D.A., Whittle, E. and Monk, B. (2000) Possi-
ble allergy to complex titanium salt. Contact Dermatitis,
42, 310-311.
[36] Bircher, A.J. and Stern, W.B. (2001) Allergic contact
dermatitis from “titanium” spectacle frames. Contact
Dermatitis, 45, 244-245.
[37] Breton, J.L., Louis, J.M. and Garnier, G. (1992) Asthma
caused by hard metals: Responsibility of titanium. Presse
Medicale Journal, 21, 997.
[38] Lalor, P.A., Revell, P.A., Gray, A.B., Wright, S., Railton,
G.T. and Freeman, M.A. (1991) Sensitivity to titanium. A
cause of implant failure? The Journal of Bone and Joint
Surgery-British Volome, 73, 25-28.
[39] Matthew, I. and Frame, J.W. (1998) Allergic responses to
titanium. Journal of Oral and Maxillofacial Surgery, 56,
1466-1467.
[40] Mitchell, D.L., Synnott, S.A. and VanDercreek, J.A.
(1990) Tissue reaction involving an intraoral skin graft
and CP titanium abutments: A clinical report. The Inter-
national Journal of Oral & Maxillofacial Implants, 5,
79-84.
[41] Suhonen, R. and Kanerva, L. (2001) Allergic contact
dermatitis caused by palladium on titanium spectacle
frames. Contact Dermatitis, 44, 257-258.
[42] Walsh, G. and Mitchell, J.W. (2002) Free surface nickel
in CE-marked and non-CE-marked spectacle frames.
Ophthalmic and Physiological Optics, 22, 166-171.
[43] Yamauchi, R., Morita, A. and Tsuji, T. (2000) Pacemaker
dermatitis from titanium. Contact Dermatitis, 42, 52-53.
... This phenomena was described by Harloff et al. who found that all implant materials (both Ti alloys and CpTi grade 1) contained traceable amounts of "impurities" i.e. Al, Be, Cd, Co, Cr, Cu, Hf, Mn, Ni, Pd and V (0.01-0.034% weight) irrespective of producer [43]. Maybe "impurities" can explain the presence of ions that were not expected to be found in the metal ion release test. ...
... Maybe "impurities" can explain the presence of ions that were not expected to be found in the metal ion release test. Harloff et al. suggest a better refinement of the production process of these materials to attain materials with fewer impurities [43]. In patients with nickel, palladium or chrome allergy these "impurities" may trigger allergic reactions [29,43]. ...
... Harloff et al. suggest a better refinement of the production process of these materials to attain materials with fewer impurities [43]. In patients with nickel, palladium or chrome allergy these "impurities" may trigger allergic reactions [29,43]. ...
Article
Full-text available
Objective: To investigate the metal ion release, surface roughness and cytoxicity for Co-Cr alloys produced by different manufacturing techniques before and after heat treatment. In addition, to evaluate if the combination of materials affects the ion release. Methods: Five Co-Cr alloys were included, based on four manufacturing techniques. Commercially pure titanium, CpTi grade 4 and a titanium alloy were included for comparison. The ion release tests involved both Inductive Coupled Plasma Optical Emission Spectrometry and Inductive Coupled Plasma Mass Spectrometry analyses. The surface analysis was conducted with optical interferometry. Cells were indirectly exposed to the materials and cell viability was evaluated with the MTT (3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide) method. Results: All alloys showed a decrease of the total ion release when CpTi grade 4 was present. The total ion release decreased over time for all specimens and the highest ion release was observed from the cast and milled Co-Cr alloy in acidic conditions. The cast and laser-melted Co-Cr alloy and the titanium alloy became rougher after heat treatment. All materials were within the limits of cell viability according to standards. Significance: The ion release from Co-Cr alloys is influenced by the combination of materials, pH and time. Surface roughness is influenced by heat treatment. Furthermore, both ion release and surface roughness are influenced by the manufacturing technique and the alloy type. The clinical implication needs to be further investigated.
... Less attention has been given to characterizing the elemental composition of the implant body. However, analyzes of biomedical Ti and Ti alloys have shown the presence of metal elements not described in the standards, such as chromium (Cr), molybdenum (Mo), and copper (Cu) [24]. ...
... Ni, Co, and Cr are potent contact allergens with estimated age-standardized sensitization rates of 14.5 %, 2.1 %, and 0.8 %, respectively, in European countries [36]. Due to a low dielectric constant, Ni oxides and Co oxides are likelier to interact with tissue electrolytes than Ti oxide or oxides of the refractory group (e.g., Nb, Ta, V) [24]. Previous studies have identified their presence in biomedical Ti substrates [24], and in this study, Ni and Cr were observed in all samples. ...
... Due to a low dielectric constant, Ni oxides and Co oxides are likelier to interact with tissue electrolytes than Ti oxide or oxides of the refractory group (e.g., Nb, Ta, V) [24]. Previous studies have identified their presence in biomedical Ti substrates [24], and in this study, Ni and Cr were observed in all samples. Co was found in a third of the samples measured. ...
Article
Full-text available
Objective Titanium (Ti) is considered bioinert and is still regarded as the “gold standard” material for dental implants. However, even ‘commercial pure’ Ti will contain minor fractions of elemental impurities. Evidence demonstrating the release of Ti ions and particles from ‘passive’ implant surfaces is increasing and has been attributed to biocorrosion processes which may provoke immunological reactions. However, Ti observed in peri-implant tissues has been shown to be co-located with elements considered impurities in biomedical alloys. Accordingly, this study aimed to quantify the composition of impurities in commercial Ti dental implants. Methods Fifteen commercial titanium dental implant systems were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). Results The elemental composition of implants manufactured from commercially pure grades of Ti, Ti-6Al-4V, and the TiZr alloy (Roxolid) conformed to the respective ISO/ASTM standards or manufacturers´ data (TiZr/Roxolid). However, all implants investigated included exogenous metal contaminants including Ni, Cr, Sb, and Nb to a variable extent. Other contaminants detected in a fraction of implants included As and the radionuclides U-238 and Th-232. Significance Although all Ti implant studies conformed with their standard compositions, potentially allergenic, noxious metals and even radionuclides were detected. Since there are differences in the degree of contamination between the implant systems, a certain impurity fraction seems technically avoidable. The clinical relevance of these findings must be further investigated, and an adaptation of industry standards should be discussed.
... In a critical review by Harlo et al, it was found that titanium dental implants contain small amounts of impurities, including nickel, beryllium, aluminum, palladium, and chromium, and if a patient is sensitive to these speci c biomaterials, a foreign body reaction might happen. 15 is reaction, though rare, has still been reported in the literature and may be de ned as aseptic bone loosening (ABL) or aseptic bone necrosis (ABN). is concept was initially reported in the orthopedic literature, and it is de ned as a non-infected (bacterial, viral or fungal) reaction leading to gradual bone loss surrounding implanted devices. [16][17][18] is is in accordance with the study of Albrektsson et al regarding the foreign body reaction in implanted devices. is is strictly correlated to an immunologic reaction leading to partial or complete loosening of the bony attachments and not solely related to microbiologic etiologies. ...
... As reported by Harlo et al, these added materials in sporadic cases might be considered as impurities as they may induce hypersensitivity reactions to the a ected patients. 15 Harlo et al used spectral analysis to investigate various titanium alloys, such as sponge titanium, TiAl6V4, ad iodide titanium. e results of their study showed that titanium alloys contained very small amounts of additional elements such as beryllium, cobalt, chromium, copper, iron, nickel, and palladium. ...
Article
Full-text available
Given the widespread use of titanium and its alloys in dental implantology, implant failures will most likely arise, and there will still remain many gray areas with regard to the biology and physiology of the interaction of dental implant alloys and the host. Medical literature is abundant with reports of aseptic prosthetic loosening following arthroplasty that may be attributed to many reasons, yet the most important factor appears to be the periprosthetic osteolysis due to unbalanced homeostasis of bone formation and re-sorption. Although it was previously believed to be a simple mechanical complication resulting from the instability of the implant, it is now widely accepted that particulate implant debris induces local in ammation and osteolysis. e purpose of the current study is to report the atypical and unexpected early implant loss of a titanium implant in an otherwise healthy 60-year-old patient with a previously undiagnosed nickel, palladium, and cobalt allergy. A er veri cation by MELISA Test© the patient was successfully treated with a ceramic implant. A literature review was performed , which demonstrated that there is abundant scientific evidence that suggests an established correlation between the di erent metals alloys and peri-implant aseptic bone loosening leading to a failure of implant osseointegration.
... It should be noted that even 'pure' titanium has impurities that can trigger allergic reactions. These include traces of aluminum, beryllium, cadmium, iron, manganese, molybdenum, nickel, palladium, or vanadium [1,3,[40][41][42][43]. ...
... In patients with a history of metal allergies, it is advisable to perform a titanium allergy test. The alloy and its purity must be identified together with any trace elements it may contain in order to optimize diagnosis [40,58,59]. ...
Article
Full-text available
The purpose of this scoping review was to describe the current state of knowledge and understanding of allergies to titanium dental implants. A scoping review was conducted following the Prisma Extension for Scoping Reviews checklist. An electronic search was performed in five databases complemented by manual and grey literature searches. Fifty-two relevant papers were included for final review. Titanium particles can be released from the surfaces of dental implants in a process called tribocorrosion, which may contribute to bone loss due to inflammatory reaction. Diverse mechanisms have been described that may trigger allergy to titanium, as well as the clinical signs that manifest as the allergy develops. Allergies to titanium are uncommon but represent a real possibility that should not be overlooked in patients requiring prosthodontic rehabilitation with dental implants. Allergy can trigger a range of symptoms. Patients who have already been diagnosed with allergies to other metals will be more predisposed to suffering an allergy to titanium. Further investigation is needed in order to measure the true scope of these allergies.
... Biocompatibility is an additional advantage of titanium regarding medical applications, especially due to postoperative complications in the case of using implants and surgical instruments made of materials sensitising patients, which the authors of article [12] pay attention to. According to [13,14], titanium does not cause an undesirable biological interaction in contact with living tissue. The beginnings of using titanium and its alloys for structural elements date back to the end of the 1940s. ...
Article
Full-text available
The paper analyses the forming of the surgical instrument handles made of Grade 2 titanium sheets. Sheet metal forming is a technology ensuring high strength and light weight of products. Replacing stainless steels with titanium further reduces instrument weight and additionally provides the required resistance to corrosive environments typical for surgeries. The low instrument weight is important to prevent fatigue of surgeons and allow them to maintain high operational accuracy during long term surgeries. The numerical analysis of the technological process was performed in order to adapt it to forming tool handles using titanium sheets instead of steel sheets. The numerical calculations were experimentally verified. It was found that, in the case of titanium handles, it is necessary to use a blank holder in the first forming operation to eliminate sheet wrinkling in the flange area. The shape and dimensional accuracy of the drawn part after trimming were high enough and the 4th forming operation became unnecessary. Moreover, the process modification included lubrication using rapeseed oil with the addition of boric acid, which effectively prevents the galling of titanium on the working surfaces of the steel tools and ensures a more uniform distribution of plastic strains in the drawn part.
... Pitting involves a loss of material due to corrosion by migration of the reaction product (titanium oxide) into the physiological medium. These particles released as a result of corrosion and/or mechanical treatment, such as implantoplasty, have been reported to cause adverse allergic reactions in humans [55,56]. There is no current consensus on the risk of particles released from titanium implants; however, it would be prudent for clinicians to carefully evaluate the materials used, and to consider the potential risks of the individual constituents of any alloy, as indicated in this study. ...
Article
Full-text available
In the field of implant dentistry there are several mechanisms by which metal particles can be released into the peri-implant tissues, such as implant insertion, corrosion, wear, or surface decontamination techniques. The aim of this study was to evaluate the corrosion behavior of Ti6Al4V particles released during implantoplasty of dental implants treated due to periimplantitis. A standardized protocol was used to obtain metal particles produced during polishing the surface of Ti6Al4V dental implants. Physicochemical and biological characterization of the particles were described in Part I, while the mechanical properties and corrosion behavior have been studied in this study. Mechanical properties were determined by means of nanoindentation and X-ray diffraction. Corrosion resistance was evaluated by electrochemical testing in an artificial saliva medium. Corrosion parameters such as critical current density (icr), corrosion potential (ECORR), and passive current density (iCORR) have been determined. The samples for electrochemical behavior were discs of Ti6Al4V as-received and discs with the same mechanical properties and internal stresses than the particles from implantoplasty. The discs were cold-worked at 12.5% in order to achieve the same properties (hardness, strength, plastic strain, and residual stresses). The implantoplasty particles showed a higher hardness, strength, elastic modulus, and lower strain to fracture and a compressive residual stress. Resistance to corrosion of the implantoplasty particles decreased, and surface pitting was observed. This fact is due to the increase of the residual stress on the surfaces which favor the electrochemical reactions. The values of corrosion potential can be achieved in normal conditions and produce corroded debris which could be cytotoxic and cause tattooing in the soft tissues.
... revealed that titanium can induce hypersensitivity in susceptible patients, and could play a major role in implant failure 7) . However, the dental materials containing titanium are associated with allergic symptoms is still controversial. ...
Article
Full-text available
The aim of this case study was to present the rare entity of hypersensitivity reaction in perioral skin which was associated with metal dental implants. A 69-year-old male patient was treated with complete upper and lower implant-supported overdentures. The patient was ended up with extra-oral blackish pigmentations on his skin of the entire neck region four months after placement of implants. This presentation seemed to be suspected association of allergic reactions to metal dental implants in an otherwise healthy individual. Even though titanium is considered a biocompatible metal for using human surgical procedures, there are some instances that can be allergic to titanium and other associated elements. Therefore, it would be better to perform the hypersensitivity reaction test prior to introduce the metal devices for the patients.
... Lastly, "impurities" have been reported in titanium based implant materials, for example, up to 0.5 wt% iron (Fe) in commercial pure titanium (grade 1, 2 and 4) and 0.013 wt% nickel (Ni) (grade 1 and 2) [36,47,48]. While these trace metals may not present health risk in a whole implant, ions and particles released as a result of corrosion and/or mechanical intervention such as implantoplasty have been reported to cause adverse allergic reactions in humans [49,50]. There is no current consensus agreement on the risk of particles released from Ti; however, it would be prudent for clinicians to carefully evaluate the materials used and to consider the potential risks of the individual constituents of any alloy, as indicated in this study. ...
Article
Full-text available
Background With increasing numbers of dental implants placed annually, complications such as peri-implantitis and the subsequent periprosthetic osteolysis are becoming a major concern. Implantoplasty, a commonly used treatment of peri-implantitis, aims to remove plaque from exposed implants and reduce future microbial adhesion and colonisation by mechanically modifying the implant surface topography, delaying re-infection/colonisation of the site. This in vitro study aims to investigate the release of particles from dental implants and their effects on human gingival fibroblasts (HGFs), following an in vitro mock implantoplasty procedure with a diamond burr. Materials and methods Commercially available implants made from grade 4 (commercially pure, CP) titanium (G4) and grade 5 Ti-6Al-4 V titanium (G5) alloy implants were investigated. Implant particle compositions were quantified by inductively coupled plasma optical emission spectrometer (ICP-OES) following acid digestion. HGFs were cultured in presence of implant particles, and viability was determined using a metabolic activity assay. Results Microparticles and nanoparticles were released from both G4 and G5 implants following the mock implantoplasty procedure. A small amount of vanadium ions were released from G5 particles following immersion in both simulated body fluid and cell culture medium, resulting in significantly reduced viability of HGFs after 10 days of culture. Conclusion There is a need for careful evaluation of the materials used in dental implants and the potential risks of the individual constituents of any alloy. The potential cytotoxicity of G5 titanium alloy particles should be considered when choosing a device for dental implants. Additionally, regardless of implant material, the implantoplasty procedure can release nanometre-sized particles, the full systemic effect of which is not fully understood. As such, authors do not recommend implantoplasty for the treatment of peri-implantitis.
Article
Irritant and allergic contact dermatitis from wound closure materials can occur in patients after surgical procedures. The resulting inflammation from contact dermatitis can compromise wound healing, mimic surgical site infections, and result in wound dehiscence. Components of wound closure material, such as antibiotic coatings, dyes, sterilizing compounds, or the material itself, have been implicated as contact allergens. This article provides the latest overview of the components of 3 major forms of wound closure materials-sutures, staples, and tissue adhesives-associated with contact dermatitis, discusses their cross-reactivity, and provides diagnostic and treatment guidelines.
Article
Full-text available
Aims and objectives The study aims were to: a) assess allergy screening practices, b) determine the awareness of metal hypersensitivity among frontline healthcare workers, and c) examine perceived barriers to implementing metal hypersensitivity screening into clinical practice. Background Adverse device‐related events, such as hypersensitivity to metals, are well documented in the literature. Hypersensitivity to metal is a type IV T‐cell mediated reaction that can occur after cardiac, orthopaedic, dental, gynaecological, and neurosurgical procedures where a device with metal components is implanted into the body. Patients with hypersensitivity to metal are likely to experience delayed healing, implant failure, and stent restenosis. Identifying patients with a history of metal hypersensitivity reaction could mitigate the risk of poor outcomes following device implant. Yet in clinical practice, healthcare workers do not routinely ask about the history of metal hypersensitivity when documenting allergies. The existing literature does not report why this is not included in allergy assessment. Design Following the STROBE checklist, a cross‐sectional, descriptive study was conducted. Methods Frontline healthcare workers were recruited using professional contacts and social online media to complete an online questionnaire. Quantitative data were summarized descriptively while thematic analysis was used to examine barriers to implementation. Results Three hundred forty‐five participants from 14 countries completed the questionnaire, with the majority (187/54%) practicing in Canada, in general medicine and intensive care units. Ninety percent of the participants did not routinely ask about metal hypersensitivity when evaluating allergy history. Of the respondents, 86% were unaware of the association between metal hypersensitivity and poor patient outcomes. After presented with the evidence, 81% indicated they were likely or very likely to incorporate the evidence into their clinical practice. Common themes about barriers to implementing were “Standards of Practice”, “Knowledge” and “Futility of Screening”. Conclusion The findings suggest lack of awareness as the main reason for not including metal in routine allergy assessment.
Article
Aim The aim of this investigation is to evaluate the allergic potential of titanium and titanium alloys for surgical implant applications. Materials and methods Discs cut from rods supplied by five different titanium suppliers in several diameters were investigated. The samples were cp-Titanium as well as Ti6Al4 V and Ti6Al7Nb, 6 mm thick with a diameter of between 6 and 60 mm. The material was checked by optical spectral analysis. Results In all samples except iodidtitanium, a Nickel content of 0.012—0,034 wt% could be detected. Conclusion The low nickel content in the implant material results from the production process. The nickel atoms are in solid solution in the titanium lattice. Nickel allergic patients may develop hypersensitivity reactions even due to this low nickel content. Hence, this reaction may be falsely attributed to the titanium material itself. Measurements of ion concentration in the body are helpful for quantifying the maximum content of nickel in titanium materials for surgical implant applications. In addition, technical questions related to the production of nickel free titanium materials for allergic patients have to be solved.
Article
Introduction The aim of the current study was to elucidate the incidence of allergic reactions to metal/metal articulations in revised total hip arthroplasties. Materials and methods Between 1 January 1997 and 31 January 2002 a consecutive series of tissue samples from 13 revised total hip arthroplasties with metal/metal articulations were histopathologically examined for signs of delayed type hypersensitivity (DTH). Mean age at the time of revision of the eight women and five men was 58.7 years. The prostheses were revised after a mean follow-up of 45 months. Indications for revision were progressive osteolysis of the proximal femur in 12 cases and instability in one case. All patients were clinically and radiologically evaluated after a mean follow-up of 52 months (min. 22, max. 74) after revision. Results No signs of infection were found in either histopathological or microbiological examinations. In ten cases, perivascular lymphocytic infiltrates could be found as a sign of DTH. After revision and changing of the articulation all osteolyses healed. Conclusion In 10/13 cases (76.9%) signs of DTH could be detected. The fact that all osteolyses healed after changing the articulation may give a strong hint that there is an immunological contribution to this radiological changes. Metal/metal articulations cannot be recommended as the optimum implant for young patients, as the number of patients with allergic reactions to nickel, chrome or cobalt is increasing continuously.
Article
In three patients a local dermatitis developed 3-3 1/2 months after tibial osteosynthesis with plates and screws of stainless steel 316 L (AO). Two of the patients had a positive patch test for chromium (and cobalt) and one for nickel. Infection was not indicated and it is suggested that the dermatitis was caused by a metallic sensitivity. The skin affection disappeared after removal of the metal.
Article
Metal to metal prostheses give satisfactory results in 90% of patients. About half of the failure rate may be due to allergic reaction to the metals involved, particularly cobalt. A total of 35 patients in this unsatisfactory group have been patch-tested; 16 were positive to metals, 13 to cobalt, 4 to nickel, and 2 to chromate. Only two patients showed any skin lesions - one a localized dermatitis round the knee joint from nickel sensitivity, and one to cobalt who had a widespread scattered circular erythematous lesion suggestive of a generalized allergic vasculitis. Patients requiring a metal/metal prosthesis should have a careful history taken for metal sensitivity and be patch-tested with the metals. All the patients in this investigation had metal/metal prostheses and no reaction was seen after metal/high density polyethylene implants. Titanium 318 may be a satisfactory substitute for cobalt chrome alloy if reactions are encountered.
Article
Sensitivity to chromium, cobalt, nickel, molybdenum, vanadium, and titanium was studied by patch tests in 50 patients who had received total joint replacements. Nineteen (38%) were sensitive to one or more of the metals. In 23 patients non-traumatic failure of the prosthesis had occurred, and 15 of these patients were sensitive to metal. Out of 27 patients with no evidence of prosthesis loosening, four were sensitive to nickel and cobalt or nickel only. Dermatological reactions occurred in 13 patients after surgery; in only eight, however, was there evidence of metal sensitivity. These findings indicate that metal-on-metal total joint replacements may sensitise the patient to metals contained in the prosthesis. Although there is a high incidence of prosthesis failure among metal-sensitive patients it remains uncertain whether the loosening causes the sensitisation or vice versa.
Article
A high incidence of unexpected metal sensitivity was found in patients with metal-to-metal (McKee) hip arthroplasties. Patients with metal-to-plastic (Charnley) prostheses had no greater incidence of metal sensitivity than a control group awaiting operation. If metal sensitivity does occur loosening of the prosthesis may be a complication.
Article
Tissues from five patients who underwent revision operations for failed total hip replacements were found to contain large quantities of particulate titanium. In four cases this metal must have come from titanium alloy screws used to fix the acetabular component; in the fifth case it may also have originated from a titanium alloy femoral head. Monoclonal antibody labelling showed abundant macrophages and T-lymphocytes, in the absence of B-lymphocytes, suggesting sensitisation to titanium. Skin patch testing with dilute solutions of titanium salts gave negative results in all five patients. However, two of them had a positive skin test to a titanium-containing ointment.