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.
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