Copyright © 2009 by The Journal of Bone and Joint Surgery, Inc.
Commentary & Perspective
Commentary & Perspective by
Thomas W. Bauer, MD, PhD*,
Cleveland Clinic Foundation, Cleveland, Ohio
Posted February 2009
Prospective, randomized clinical trials can be among the
most powerful tools available to influence medical practice. With this fact in
mind, the manuscript entitled "The Effect of a Single Infusion of Zoledronic
Acid on Early Implant Migration in Total Hip Arthroplasty: A Randomized,
Double-Blind, Controlled Trial" by Friedl et al. is potentially important. In
this study, fifty patients undergoing total hip arthroplasty without cement for
the treatment of osteonecrosis of the femoral head were randomized to receive
either a single postoperative infusion of 4 mg zoledronic acid, or saline
solution. Selected indices of bone turnover were monitored, and radiographs
were made periodically to assess implant migration with a minimum end point of two
years postoperatively. The investigators were blinded with respect to drug
treatment. The difference in acetabular migration between groups was only a
fraction of a millimeter, but that difference is reported to be statistically
significant (p < 0.05). No significant difference was identified in the
magnitude of femoral stem subsidence between the two groups.
Early implant migration has been correlated with long-term failure
of the prosthesis1, so a safe medical treatment that might reduce
implant migration could have important implications for patients at high risk
for aseptic implant loosening, especially patients with osteonecrosis. The
results described in this study are encouraging but raise several questions:
First, even if significant, are the differences in implant
migration described in this study large enough to be clinically important?
Based on the data illustrated in Figures 1-C and 1-D, the authors seem to have
divided cup migration into medial and cranial components. Curiously, the cups
in the control patients seem to have moved approximately 0.6 mm in one
direction, presumably medially, while the cups in the treated patients moved,
on the average, approximately 0.15 mm laterally. Apparent migration in different
directions would be difficult to explain, and while the magnitude of apparent
lateral migration in the zoledronic acid group is probably within the range of
error of measurement, one wonders if the outcome measure described as
"significant" was calculated on the basis of the difference in average final
location (about 0.75 mm), or between the absolute value of migration (about
0.45 mm) for the two groups, a selection that might influence statistical significance.
Setting aside the rather confusing data for migration in the transverse plane,
the difference in average vertical cup migration between the two groups as
shown in Figure 1-D seems more straightforward, amounting to approximately 0.6
mm. Although the magnitude of this difference is small, the results of previous
studies that used Roentgen stereophotogrammetric analysis to measure implant
migration suggested that as little as 0.2-mm migration over a two-year period may
be predictive of ultimate failure1. It should also be noted, however,
that zoledronic acid did not prevent femoral stem subsidence in this study; the
magnitude of femoral stem subsidence in both groups was in the same range as
that previously reported for patients with osteonecrosis2, so there
is still concern regarding eventual aseptic loosening.
Second, might zoledronic acid be more effective in patients
who have poor rather than good bone quality at the time of arthroplasty? No
tests of bone density were performed in this study, and, although one would
expect randomization to minimize differences in bone quality between groups, as
it turns out, there were three patients in the zoledronic acid treatment group
who were undergoing hemodialysis for the treatment of chronic renal failure but
there were no patients with chronic renal failure in the control group.
Furthermore, five of the six patients whose osteonecrosis was attributed to
corticosteroids were in the zoledronic acid group, and for some reason the preoperative
Harris Hip scores of the zoledronic acid group were significantly lower (p =
0.017) than those of the control group. The authors state that the results are
"essentially the same" after excluding patients with probable poor bone
quality, but a closer look at that data as well as other indices of initial bone
quality would be of interest and might help identify subsets of patients most
likely to benefit from postoperative bisphosphonate treatment.
The mechanism whereby zoledronic acid might decrease early
implant migration is uncertain. Surgeons often attribute early implant
migration to operative technique, implant surface properties, initial bone
quality (density), or expected "settling" of an uncemented implant into the
bone, and some surgeons would anticipate bisphosphonates to be most effective
at preventing late aseptic loosening, a process often attributed to
osteoclastic bone resorption induced by particles of wear debris. On the other
hand, on the basis of the results of roentgen stereophotogrammetric analysis
studies, Ryd et al.1 suggested that loosening represents "a
prolonged adverse biological process established very early" that eventually
becomes symptomatic. As such, there is some rationale to early medical
inhibition of osteoclastic bone resorption. Furthermore, the Friedl study is
not the first to present data supporting the use of postoperative
bisphosphonates. In 2006, Hilding and Aspenberg3 reported reduced
migration of total knee prostheses in patients who received treatment with an
oral bisphosphonate as compared with the migration seen in untreated control
patients at a follow-up time of four years. They also emphasized the importance
of evaluating "outliers," or the small number of patients in whom excessive
motion is shown, to help demonstrate efficacy of bisphosphonates. The
confidence intervals seen in Figure 1 of the Friedl study seem to be somewhat
larger for the control patients than for those who received zoledronic acid,
providing another hint that a subset of patients with the most implant motion
may be largely responsible for the mean differences between groups and hence
the most likely to benefit from bisphosphonate treatment. Further follow-up is
necessary to determine if implant motion reaches a plateau, but interpreted
together, the recent study by Friedl et al. and the previously published study
by Hilding and Aspenberg3 suggest that adverse bone remodeling may
be a more important mechanism of early implant migration than previously
thought and that bisphosphonate treatment may be something to consider for
patients at increased risk of early aseptic loosening.
*The author did not receive any outside funding or grants in support of his research for or preparation of this work. Neither he nor a member of his immediate family received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.
References
1. Ryd L, Albrektsson BE, Carlsson L, Dansgård F, Herberts P, Lindstrand A, Regnér L, Toksvig-Larsen S. Roentgen stereophotogrammetric analysis as a predictor of mechanical loosening of knee prostheses. J Bone Joint Surg Br. 1995;77:377-83.
2. Radl R, Hungerford M, Materna W, Rehak P, Windhager R. Higher failure rate and stem migration of an uncemented femoral component in patients with femoral head osteonecrosis than in patients with osteoarthrosis. Acta Orthop. 2005;76:49-55.
3. Hilding M, Aspenberg P, Postoperative clodronate decreases prosthetic migration: 4-year follow-up of a randomized radiostereometric study of 50 total knee patients. Acta Orthop. 2006;77:912-6.
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