Background: Femoral head deformity is the most serious sequela of
ischemic necrosis of the immature femoral head. The purpose of this study was
to determine if a highly potent antiresorptive agent, ibandronate, can inhibit
bone resorption during the repair of the infarcted femoral head and thus alter
the repair process. We hypothesized that preservation of the trabecular
framework by inhibiting osteoclastic bone resorption would minimize the
development of deformity in a piglet model of ischemic necrosis. The effect of
ibandronate on long-bone growth was also assessed.
Methods: Ischemic necrosis of the right femoral head was produced in
twenty-four piglets by placing a ligature tightly around the femoral neck. The
animals were divided into three groups according to whether they received
saline solution, prophylactic treatment, or post-ischemia treatment. The
contralateral, untreated femoral heads from the animals that had received
saline solution served as the normal control group. At eight weeks, the
femoral heads were assessed for deformity with radiography and for trabecular
bone indices with histomorphometry. Also, the length of femur from the
untreated side was measured on the radiographs and compared among the
groups.
Results: Radiographic assessment showed that the epiphyseal
quotient, determined by dividing the maximum height of the osseous epiphysis
by the maximum diameter, was better preserved in the prophylactic (p <
0.001) and post-ischemia (p = 0.02) treatment groups than in the group treated
with saline solution. Histomorphometric assessment also showed that the
trabecular bone indices were better preserved in the prophylactic and the
post-ischemia treatment groups than in the group treated with saline solution
(p < 0.01). The mean femoral length on the untreated side of the animals
treated with ibandronate was reduced compared with the length on the untreated
side of the animals that had received saline solution (p = 0.01).
Conclusions: Ibandronate preserves the trabecular structure of the
osseous epiphysis and prevents femoral head deformity during the early phase
of repair of ischemic necrosis in the piglet model.
Clinical Relevance: Administration of an anti-osteolytic agent,
ibandronate, during the fragmentation stage of Legg-Calvé-Perthes
disease may prevent early flattening of the osseous epiphysis. Additional
preclinical studies are needed to determine the optimum dose and delivery of
the drug to prevent the deformity while minimizing its effect on long-bone
growth. Studies are also needed to determine the long-term effects of
ibandronate in terms of preventing deformity.