Titanium-Alloy Particle Lymphocyte Reactivity is Associated with a Higher Degree of Lymphocyte Stimulation to
Aluminum and Vanadium Ions.
1,2
Caicedo, MS; 2Samelko, L; 2Ott, S; +1,2Hallab, NJ
Orthopedic Analysis LLC, Chicago, IL. +2Rush University Medical Center, Chicago, IL
[email protected]
DISCUSSION: The higher average of Aluminum and Vanadium
specific lymphocyte reactivity observed in individuals classified as Tialloy particle reactive vs. non-reactive supports our hypothesis that the
degree (i.e. SI to nickel) and incidence (i.e. percent of reactive subjects)
of Aluminum and Vanadium lymphocyte reactivity correlates with Tialloy particle “allergic” subjects. These results represent the first
reported correlation between Ti-alloy particle reactivity with reactivity
to the other components of the metal alloy (i.e. Aluminum and
Vanadium). Elevated lymphocyte reactivity to Aluminum and Vanadium
at both concentration tested (0.01 mM and 0.1 mM) in the particle
reactive group suggests that the observed specific lymphocyte reaction
could be partially or fully due to a response to the other ionic
components in the alloy and not to Titanium itself. It is important to note
that while Ti-alloy reactive vs. non-reactive groups were statistically
significant there was great overlap in Aluminum and Vanadium SI in
individual subjects.. Further investigation is being performed to more
accurately determine a correlation between Aluminum, Vanadium and
Ti-alloy particle lymphocyte reactivity.
SIGNIFICANCE: These findings counter claims that Titanium-alloys
are inert biomaterials that can be used in people without regard to known
metal allergies. Reactivity to Ti-alloy particles was clearly
demonstrated. Additionally, our data suggests that reactivity to
Aluminum and/or Vanadium are likely major contributing factors to Tialloy particle/material reactivity.
REFERENCES: 1. Hallab N, et al. J Bone Joint Surg Am 2001 Mar;83A(3):428-36
Fig.1 Aluminum SI of subjects reactive and non-reactive to Ti-alloy particles. * = p<0.05
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Fig.2 Vanadium SI of subjects reactive and non-reactive to Ti-alloy particles. * = p<0.05
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Poster No. 1955 • ORS 2012 Annual Meeting
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INTRODUCTION: Over one million total joint arthroplasties are
performed in the United States alone per year. While the vast majority of
TJAs are successful and can last for long periods of time (>8 years),
biocompatibility of implants remains a limiting factor for the short and
long term performance of the implant. An ever-increasing number of
implant designs and biomaterials have become available in the past few
years to fit the specific needs of implant recipients. Co-alloys and Tialloys are two of the most common materials used. Specifically,
Titanium-alloys (6% Aluminum and 3%Vanadium) are commonly used
for their high biocompatibility or “bio-inert” qualities. However, several
reports of possible Titanium implant allergies, both in orthopedics and
dentistry, have come to surface raising the question if Titanium is truly
an inert material that does not trigger immune responses compared to
others, such as the popular nickel-containing Cobalt alloys. Are specific
lymphocyte responses to Ti-alloy implant particles a true reaction to
Titanium itself or a hypersensitivity to its other alloy components (i.e.
Aluminum and Vanadium)? We hypothesized that Titanium-alloy
particle hypersensitivity responses as determined by a metal-lymphocyte
transformation test (metal-LTT) will correlate with higher Aluminum
and Vanadium hypersensitivity responses in the same subjects. We
tested this hypothesis by comparing metal specific reactivity (e.g. metalLTT proliferation responses) of primary lymphocytes to soluble metal
challenge of Aluminum and Vanadium at 0.1mM and 0.01mM using
two groups of subjects with different Titanium-alloy particle stimulation
indexes (SI). Group 1- Ti-alloy particle non-reactive (SI < 2) Group 2Ti-alloy particle reactive (SI > 2). We tested our hypothesis by plotting
lymphocyte SI to Aluminum and Vanadium against Ti-alloy reactive and
non-reactive groups and analyzed for non-parametric statistical
significance.
MATERIALS AND METHODS: Subject Groups: Blinded deidentified data from 700 subjects tested for metal hypersensitivity using a
metal-LTT was collected. Subjects tested for Titanium-alloy particle
lymphocyte proliferation were split into two groups. Group 1 – Subjects
with no reactivity to Ti-alloy particles (n= 330 SI < 2) and group 2 Subjects reactive to Ti-alloy particles (n= 192 SI > 2). Metal-LTT (as
performed by Orthopedic Analysis, LLC): Peripheral blood mononuclear
cells were collected from 30mL of peripheral blood by Ficoll gradient
separation. Collected PBMCs were cultured with various implant metals
(Al, Co, Cr, Mo, Ni, V, Zr, Fe, TiALV) at two different concentrations
(0.01 mM and 0.1 mM). 3H Thymidine was added at day 5 of culture and
3
H thymidine incorporation was read using a beta scintillation counter at
day 6. A stimulation Index (SI) of reactivity was calculated by dividing
scintillation counts per minute of metal-treated cells over untreated
controls. Statistical Analysis: Ti-alloy particle reactive vs. non-reactive
groups were analyzed for statistical differences in SI to Aluminum and
Vanadium at 0.01 and 0.1. Non-parametric Mann Whitney test was used
to determine statistical significance between groups at p<0.05.
RESULTS: Incidence of Aluminum reactivity in Ti-alloy particle
reactive vs. non reactive subjects: To calculate incidence of metal
hypersensitivity between Ti-alloy particle-reactive vs. non reactive
subjects, SIs in response to Aluminum at 0.01 mM (Fig. 1A) and 0.1
mM (Fig.1B) were plotted against these two groups. Each dot represents
each subject tested. Ti-alloy particle reactive subjects exhibited
statistically significant higher average SI (2.16) to Aluminum at 0.01mM
compared to the Ti-alloy particle non-reactive group (1.24). The average
SI Index in response to Aluminum at 0.1 mM was also significant when
comparing Ti-alloy particle reactive group (2.21) to the non-reactive
group (1.29) (Fig 1). Incidence of Vanadium reactivity in Ti-alloy
particle reactive vs. non-reactive subjects: Similar Vanadium metal
hypersensitivity trends were observed between Ti-alloy particle- reactive
vs. non-reactive groups. Ti-alloy particle reactive subjects exhibited
significantly higher average SI (2.5) to Vanadium at 0.01mM compared
to the Ti-alloy particle non-reactive group (1.3) (Fig.2A). The average SI
Index in response to Vanadium at 0.1 mM was also significant when
comparing Ti-alloy particle reactive group (1.0) to the non-reactive
group (0.4) (Fig 2B).
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