Background: Particle-induced osteolysis is currently
a major problem affecting the long-term survivorship of total joint
replacements. Alendronate is a third-generation bisphosphonate that blocks
osteoclastic bone resorption. The objective of this study was to
determine whether alendronate could prevent particle-induced osteolysis
or restore (reverse) bone loss in established osteolysis.
Methods: A rat model of particle-induced osteolysis
was used. A specially designed polyethylene implant was placed in
the proximal part of the right tibia of seventy-two animals. Following four
weeks of healing, the animals were randomized into control groups,
a prevention group, or a treatment group. In the prevention group,
animals received intra-articular injections of high-density polyethylene
particles (mean size, 2 m; all <10 m) at four, six, and
eight weeks postoperatively. Alendronate (0.01 mg/kg/day)
was administered concomitantly through an implantable pump from
the fourth week through the tenth week. In the treatment group,
animals were also exposed to polyethylene particles at four, six,
and eight weeks, to establish bone loss, but they received alendronate subsequently,
from the tenth week through the sixteenth week, to treat the bone
loss. Positive (particle-only) and negative (saline-solution-only)
control groups were assessed as well. Tissues were harvested at
ten weeks in the prevention group and at sixteen weeks in the treatment
group. Histological analyses and histomorphometric determinations
of the periprosthetic bone volume were carried out.
Results: Histological examination showed a rim of
new bone (neocortex) around the implant in the untreated and saline-solution-treated
control animals (no polyethylene particles). Treatment with saline
solution (no polyethylene particles) did not affect periprosthetic
bone. Animals exposed to polyethylene particles had bone loss. In
those that received alendronate, the bone loss was either prevented
or reversed, and the quantity of neocortical and trabecular bone
was increased compared with that of the controls. Alendronate effectively
preserved periprosthetic bone in both the prevention and treatment groups.
In the prevention arm, the mean periprosthetic bone volume of
the neocortex and the surrounding trabecular bone, as determined
with histomorphometry, was 21.5% %plusmn; 6.5% in
the saline-solution-treated controls (no particles), 13.1% %plusmn;
5.9% in the particle-treated animals, and 32.6% %plusmn;
6.4% in the alendronate-treated animals (p < 0.001).
In the treatment arm, the mean periprosthetic bone volume was 27.2% %plusmn;
5.6% in the saline-solution-treated controls, 17.7% %plusmn;
6.2% in the particle-treated animals, and 30.2% %plusmn;
5.9% in the alendronate-treated animals (p = 0.002).
Conclusions: In our model, the intra-articular injection
of polyethylene particles caused substantial bone loss around a
loaded implant. Alendronate effectively prevented and treated the particle-induced
periprosthetic bone loss.
Clinical Relevance: Alendronate may be useful in
preventing particle-induced osteolysis around total joint implants.
It may also elicit bone formation in established osteolytic lesions.