ALENDRONATE DOES NOT INHIBIT EARLY BONE APPOSITION OR REMODELING AROUND HA-COATED IMPLANTS.
*Mochida, Y (A-Stryker/Howmedica/Osteonics); +*Bauer, T (A-Stryker/Howmedica/Osteonics); *Akisue, T (A-Stryker/Howmedica/Osteonics); **Brown, P (AStryker/Howmedica/Osteonics)
+*The Cleveland Clinic Foundation, Cleveland, Ohio. Dept. of Anatomic Pathology, L-25, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland,
OH44195, 216-444-6830, Fax: 216-445-6967, [email protected].
INTRODUCTION: Hydroxyapatite (HA) coatings are biocompatible,
osteoconductive, and have been shown to enhance bone apposition to metal
substrates. Bone apposition, coating durability and long-term implant stability
are likely to be influenced by local bone remodeling, a process thought to be
initiated by osteoclasts. Alendronate (ALN) is a bisphosphonate that inhibits
osteoclasts and is likely to find clinical application in the treatment of Paget’s
disease, hypercalcemia of malignancy, and especially osteoporosis. It is
anticipated that many patients who are receiving ALN may also qualify for
total joint replacement, so it is important to understand the influence of ALN
on bone apposition and remodeling around HA-coated implants. The purposes
of this study were to use a canine total hip arthroplasty model to determine the
influence of ALN on early bone apposition to HA-coated femoral components
and on the overall volume of regional trabecular and cortical bone.
MATERIALS AND METHODS:
Study design: Sixteen skeletally mature adult canines (approximately 20 kg)
underwent staged bilateral uncemented hip arthroplasty with operations 20
weeks apart. Four animals experienced either a femoral fracture (n=2), sciatic
nerve palsy (n=1), or hip dislocation (n=1) and were excluded from the study.
The remaining 12 animals (24 hips) were sacrificed 4 weeks after the second
operation, resulting in implants with 4 and 24 weeks in vivo. Six of the dogs
received oral ALN therapy, 0.2 mg/kg/day, prior to surgery and continued
until sacrifice. The other 6 dogs were untreated controls.
Implant: The hip prostheses were composed of a Ti alloy stem with a proximal
1/3 surface texture prepared by arc-deposited CP titanium with a plasmasprayed coating of highly crystalline HA (nominal thickness 50 um)
(Howmedica/Osteonics, Rutherford, NJ). The final implant roughness was
approximately 31 Ra. Modular CoCr alloy femoral heads were used with
cemented, all-polyethylene acetabular cups.
Surgery: All dogs were allowed immediate weight bearing and ambulation.
Antero-posterior and lateral radiographs were taken before, immediately after
surgery, and at the time of sacrifice.
Sacrifice: Dogs were sacrificed using an overdose of intravenous
pentobarbital. The hip joint was opened immediately after sacrifice and the
femur was harvested en block. The surface of the esophageal and the gastroduodenal wall were carefully observed for evidence of inflammation or ulcers,
recognized complications of oral ALN therapy.
Specimens: Femora were fixed in 70% ethanol, embedded in Spurr's plastic;
sections were cut and ground to 50 um thickness. Matched sites at three levels
(proximal, middle and distal of HA-coating) were used for histomorphometry.
Analyses: The fractional linear extents of bone apposition and the extent of
HA coating were measured by interactive image analysis (Bioquant, Nashville
TN) and expressed as a percent of the circumference of the implant. The HA
coating thickness was measured and expressed in microns. The areas of
cortical and cancellous bone were also quantified and expressed as percent of
total area with reference to the implant (anterior, posterior, medial and lateral).
Statistics: Measured parameters were compared between treated and untreated
groups using student’s t-test or Mann-Whitney U-test with 95% confidence
interval. Analysis of variance (ANOVA) with Fisher's PLSD test was used to
assess the influence of location the section (proximal to distal).
RESULTS: Dogs tolerated the surgical procedures well. Localized areas of
erythema suggestive of mild esophagitis, a recognized complication of ALN,
were identified in several of the ALN-treated dogs.
Radiographic findings: No cases showed specific changes around the stems
at 4 weeks. At 24 weeks some femora showed cancellous condensation around
the stem with a slight increase in femoral diameter. No differences between
the two groups were identified.
Histologic findings: Small cracks in the superior medial cortex were present
in 10 femora from the ALN-treated group, and 3 femora from the untreated
group (chi square p=0.01). Most of the cracks occurred early in the course of
the study. With additional surgical experience the rate of femoral cracks was
reduced. Areas involved by these proximal cortical cracks showed endosteal
and periosteal new bone formation, minimal adjacent bone apposition to the
implant, and a localized increase in peri-implant fibrous tissue. Areas away
from the cortical cracks showed features typical of mechanically stable
implants, including extensive bone apposition and the absence of fibrous
membranes. Occasional osteoclasts associated with bone remodeling were
identified in femora from both treatment groups.
Histomorphometry:
Bone Apposition: There was no significant difference in the extent of bone
apposition between the treated and untreated group at either 4 or 24 weeks
(p=0.61 and 0.19 respectively). There was no significant difference in bone
apposition with respect to section level (proximal to distal).
Residual HA: We found no significant difference in the thickness of residual
HA coating between the two treatment groups. There was no significant
difference in the linear extent of coating between the two groups, but the
extent of implant surface covered by HA decreased significantly with time in
both groups (p=0.002 for ALN+ group, and 0.002 for control).
Bone area: There were no significant differences in the overall trabecular or
cortical bone areas between the two groups.
Table
Alendronate Treatment
Bone apposition (%)
Extent of HA coating (%)
HA thickness (um)
Cortical bone area (%)
Trabecular bone area (%)
4 weeks
Yes
No
69.1 ± 8.6
67.3 ± 10.6
62.3 ± 13.6
61.3 ± 12.0
43.0 ± 6.7
42.0 ± 5.6
97.0 ± 2.8
94.9 ± 6.5
39.3 ± 9.0
39.2 ± 7.2
24 weeks
Yes
No
63.5 ± 11.3
69.0 ± 13.3
46.4 ± 13.1
49.1 ± 8.6
40.9 ± 3.8
39.6 ± 4.2
95.1 ± 5.2
98.6 ± 0.7
37.4 ± 6.5
35.9 ± 9.0
(mean ± SD)
DISCUSSION: The bone remodeling process is generally thought to be
initiated by osteoclastic bone resorption. Because both short-term and longterm stability of HA-coated total joint implants are dependent upon bone
formation and remodeling, it is appropriate to test the influence of osteoclast
inhibiting medications on bone apposition. Our results show no significant
influence of alendronate on the extent of bone apposition to HA-coated
femoral stems. The overall amount of bone apposition in this study (63 –
69%) is similar to that seen in previous experimental studies and human
retrievals. We also found no significant difference in regional trabecular or
cortical bone area based on alendronate treatment. Of interest is the higher
rate of small proximal cortical cracks seen in canines treated with alendronate.
We suspect this more closely reflects surgical technique (a greater proportion
of ALN-treated animals underwent surgery early in the study), rather than
altered mechanical properties of ALN-treated femora, but this complication
deserves further study. Additional studies also are needed to determine the
influence of osteoclast inhibitors on long term bone remodeling, but our
results suggest that ALN treatment does not interfere with short term bone
apposition or remodeling around HA-coated total hip prostheses
**Johns Hopkins University, Baltimore, Maryland.
Poster Session - Implant Fixation - VALENCIA FOYER
46th Annual Meeting, Orthopaedic Research Society, March 12-15, 2000, Orlando, Florida
0527