Prevention of Femoral Head Deformity after Ischemic Necrosis Using Ibandronate Acid and Growth Factor in Immature Pigs

Abstract

Background: Femoral head deformity is the most severe sequela of ischemic necrosis in skeletally immature patients. Development of severe deformity shortens useful survival time of the joint due to the appearance of early degenerative changes. Preservation of the trabecular architecture through inhibition of osteoclastic bone resorption may minimize the development of the deformity in an animal model of ischemic necrosis of the femoral head. Aims: To determine if a highly potent antiabsorptive agent, ibandronate, would inhibit bone resorption during necrotic femoral head repair to avoid subsequent flattening and deformity, to determine if the use of platelet-rich plasma stimulates bone repair and neovascularization of the damaged femoral head, and to evaluate if the combination of both therapies can preserve the femoral head while stimulating new bone formation in an animal model of ischemic necrosis. Methods: Ischemic necrosis of the femoral head was induced by surgical ligature of the circumflex vessels in 10 Landrace pigs. The animals were divided into four different groups and were administered ibandronate acid, platelet-rich plasma, or both. The contralateral, untreated femoral heads with surgical ligature of the circumflex vessels served as the control group. All animals were killed three months after surgery and the femoral head was evaluated both radiographically and histologically. The femur length was measured on radiographs and compared among the groups.Results: Final femoral length was significantly longer in the group treated with a combination of both therapies (platelet-rich plasma-ibandronate acid) compared to the others groups, with a significant difference between groups. The histological findings showed increased osteoblastic activity and thickened trabiculae, a higher rate of neovascularization, and focal hyperplasia greater bone resorption and neovascularization. Only slight changes (femoral length) were observed in the animals that received platelet-rich plasma in situ favoring revascularization that was, however, only seen in the first months of administration. Conclusions: Radiographic and histological studies showed that a combination of both therapies (platelet-rich plasma and ibandronate acid) preserved the trabecular architecture and prevented femoral head deformity in the early phase of ischemic necrosis repair in immature pigs, coinciding with reports by other authors. Clinical Relevance: These findings support the concept that a combination of antiresorptive and anabolic agents can significantly improve bone healing and decrease femoral head deformity following ischemic necrosis in the fragmentation stage. Further studies would be necessary to determine the optimal dose and longterm effectiveness for the use in pediatric patients

Padronização de modelo animal para o estudo da necrose isquêmica da cabeça femoral na doença de Legg-Calvé-Perthes

“…The scarcity of human material for the study of LCPD makes it necessary to use experimental animal models. [3][4][5][6][7][8][9][10] Among emerging countries, only Argentina has a study published in this area. 10 Our objective is to standardize an experimental model of femoral head ischemic necrosis (FHIN) for the study of feasible LCPD in Brazil.…”

“…A escassez de material humano para o estudo da DLCP torna necessário o uso de modelos experimentais com animais. [3][4][5][6][7][8][9][10] Entre os países emergentes, apenas a Argentina possui um estudo publicado nessa área. 10 Nosso objetivo é padronizar um modelo experimental de necrose isquêmica da cabeça femoral (NICF) para o estudo da DLCP factível no Brasil.…”

“…[3][4][5][6][7][8][9][10] Entre os países emergentes, apenas a Argentina possui um estudo publicado nessa área. 10 Nosso objetivo é padronizar um modelo experimental de necrose isquêmica da cabeça femoral (NICF) para o estudo da DLCP factível no Brasil. Também, propõem-se introduzir os testes de avaliação da marcha para análise funcional.…”

“…[3][4][5][6][7][8][9][10] Among emerging countries, only Argentina has a study published in this area. 10 Our objective is to standardize an experimental model of femoral head ischemic necrosis (FHIN) for the study of feasible LCPD in Brazil. Also, we proposed to introduce gait evaluation tests for functional analysis.…”

“…The scarcity of human material for the study of LCPD makes it necessary to use experimental animal models. 3 4 5 6 7 8 9 10 …”