Copyright © 2007 by The Journal of Bone and Joint Surgery, Inc.
Commentary & Perspective
Commentary & Perspective by
Michael A. Mont, MD*,
The Sinai Hospital of Baltimore, Baltimore, Maryland
Posted August 2007
The authors of this paper evaluated bisphosphonate therapy
for the treatment of seventeen adolescent patients who had osteonecrosis of the
femoral head following trauma.
Bisphosphonate therapy is possibly an exciting new
therapeutic option. With treatment, the patients had minimal to no clinical
symptoms attributable to osteonecrosis of the femoral head at a mean follow-up
of slightly over three years. The rationale behind this treatment is that in osteonecrosis
of the femoral head, bone resorption precedes femoral head collapse. In various
animal studies1-3, it has been shown that bisphosphonate treatment
led to retention of trabecular bone structure and was associated with new bone
formation with repair.
A few clinical trials have used one of the bisphosphonates—alendronate—for
the treatment of osteonecrosis of the hip in adults4-6. Although
these were relatively short-term studies, the results have been encouraging. In
one study, collapse was reported to occur in only two of twenty-nine femoral
heads in the alendronate study group as compared with nineteen of twenty-five femoral
heads in a control group4.
Thus, there is animal and clinical evidence supporting the use of bisphosphonates
for the treatment of osteonecrosis of the femoral head.
The reader must regard the present study on adolescent
patients as preliminary, however, and should exercise guarded optimism
regarding the results. This is still a small study from one center and is primarily
an observational study. It should by no means be regarded as supplying the
definitive answer for treatment of this disease. Of note, the osteonecrosis in seventeen
of the twenty-eight patients in this study occurred after trauma.
It should be noted that the authors used technetium-99m bone
scans for the diagnosis and follow-up of these patients. In my opinion, bone
scans are nonspecific and may either miss lesions or overdiagnose them. It
would have been preferable to use magnetic resonance imaging scans, which have
been shown to be more sensitive and specific. The authors note in their
Discussion that technetium-99m bone scanning is a "reliable predictor, with
excellent sensitivity and predictive value," yet they describe one study7 in which five of six hips that
had "cold" pretreatment bone scans progressed to osteonecrosis of the femoral
head. I would hope that future authors use magnetic resonance imaging scans
rather than bone scans to monitor patients with osteonecrosis.
The authors used two different types of bisphosphonates—pamidronate
in ten patients and zoledronic acid in seven patients—and both types were begun
three months after the traumatic event. It would have been interesting to see
if the results in these small groups could be further improved if
administration of these medications began immediately after the traumatic
episode in suspected patients. If the number of side effects is proved to be truly
small, then early treatment might be feasible for every patient who had a
similar traumatic episode and was at risk for osteonecrosis.
In reviewing the traumatic events, twelve of twenty-two
patients had unstable hips after slipped capital femoral epiphysis, four of
four patients with transcervical hip fractures sustained osteonecrosis of the
femoral head, and one of two patients with a hip dislocation sustained osteonecrosis
of the femoral head. Of note, the authors did not have any matching group but administered
bisphosphonates to all of the patients who were seen to have a "hot" femoral
head on bone scanning. At the time of treatment, all patients had Class-I
staging according to the radiographic classification system of Stulberg et al.8.
Patients were treated for a mean of twenty months (range, seven to thirty-nine
months). Thus, the treatment time was not standardized, nor was the dosage or type
of bisphosphonate medication.
At the time of final follow-up, fourteen of the seventeen
patients were completely pain-free and thirteen had a normal gait. However,
eight of the seventeen hips had advanced to radiographic Stulberg Class III and
IV with nine hips still at Class I or II. Without a control group, a major
question remains: Would radiographic progression have been different without
the use of bisphosphonates? In addition, without a sufficient control group, it
cannot be ascertained how many of these patients would have had a different
clinical result if they had not been treated with bisphosphonates.
The reader should also be aware that the follow-up is still
short and that 23% of the patients with slipped capital femoral prostheses (five
of twenty-two) eventually had a collapsed femoral head. This may be lower than
the 47% to 58% range that has been reported in the literature9,10,
but the period of follow-up in those studies was much longer. Another note of
caution is that various animal studies have shown diminution of growth with the
use of bisphosphonates11.
Although this finding may not be significant, it does emphasize the importance
of following skeletally immature patients for growth disorders.
In summary, I believe that this is a possible promising treatment
method for the prevention as well as treatment of early onset osteonecrosis in
adolescent patients. Caution should be utilized with this treatment in terms of
monitoring future growth and any other possible side effects. Further work is
necessary to define the exact medications that should be used as well as
appropriate dosages and time of treatment. A more definitive answer might be
obtained with a randomized controlled multicenter study, which would better
define the effect of this potentially useful treatment method.
*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. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the author, or a member of his immediate family, is affiliated or associated.
References
1. Little DG, Cornell MS, Briody J, Cowell CT, Arbuckle S, Cooke-Yarborough CM. Intravenous pamidronate reduces osteoporosis and improves formation of the regenerate during distraction osteogenesis. A study in immature rabbits. J Bone Joint Surg Br. 2001;83:1069-74.
2. Little DG, Smith NC, Williams PR, Briody JN, Bilston LE, Smith EJ, Gardiner EM, Cowell CT. Zoledronic acid prevents osteopenia and increases bone strength in a rabbit model of distraction osteogenesis. J Bone Miner Res. 2003;18:1300-7.
3. Amanat N, Brown R, Bilston LE, Little DG. A single systemic dose of pamidronate improves bone mineral content and accelerates restoration of strength in a rat model of fracture repair. J Orthop Res. 2005;23:1029-34.
4. Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM. The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am. 2005;87:2155-9.
5. Agarwala S, Jain D, Joshi VR, Sule A. Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A prospective open-label study. Rheumatology (Oxford). 2005;44:352-9. Erratum in: Rheumatology (Oxford). 2005;44:569.
6. Nishii T, Sugano N, Miki H, Hashimoto J, Yoshikawa H. Does alendronate prevent collapse in osteonecrosis of the femoral head? Clin Orthop Relat Res. 2006;443:273-9.
7. Rhoad RC, Davidson RS, Heyman S, Dormans JP, Drummond DS. Pretreatment bone scan in SCFE: a predictor of ischemia and avascular necrosis. J Pediatr Orthop. 1999;19:164-8.
8. Stulberg SD, Cooperman DR, Wallensten R. The natural history of Legg-Calvé-Perthes disease. J Bone Joint Surg Am. 1981;63:1095-108.
9. Loder RT, Richards BS, Shapiro PS, Reznick LR, Aronson DD. Acute slipped capital femoral epiphysis: the importance of physeal stability. J Bone Joint Surg Am. 1993;75:1134-40.
10. Peterson MD, Weiner DS, Green NE, Terry CL. Acute slipped capital femoral epiphysis: the value and safety of urgent manipulative reduction. J Pediatr Orthop. 1997;17:648-54.
11. Evans KD, Lau ST, Oberbauer AM, Martin RB. Alendronate affects long bone length and growth plate morphology in the oim mouse model for Osteogenesis Imperfecta. Bone. 2003;32:268-74.
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