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.

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B. Russo, E. Baroni, N. Saravia, V. Amelong, F. Lubiniecky, M. Asprea, G. Williams and S. Rodriguez, "Prevention of Femoral Head Deformity after Ischemic Necrosis Using Ibandronate Acid and Growth Factor in Immature Pigs," Surgical Science, Vol. 3 No. 4, 2012, pp. 194-199. doi: 10.4236/ss.2012.34037.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] H. K. W. Kim, P.-H. Su and Y.-S. Qiu, “Histopathologic Changes in Growth-Plate Cartilage Following Ischemic Necrosis of the Capital Femoral Epiphysis: An Experimental Investigation in Immature Pigs,” Journal of Bone & Joint Surgery, Vol. 83A, No. 5, 2001, pp. 688-697.
[2] H. K. W. Kim and P.-H. Su, “Development of Flattening and Apparent Fragmentation Following Ischemic Necrosis of the Capital Femoral Epiphysis in a Piglet Model,” Journal of Bone & Joint Surgery, Vol. 84, No. 8, 2002, pp. 1329-1334.
[3] H. K. W. Kim, T. S. Randall, H. Bian, J. Jenkins, A. Garces and F. Bauss, “Ibandronate for Prevention of Femoral Head Deformity After Ischemic Necrosis of the Capital Femoral Epiphysis in Immature Pigs,” Journal of Bone & Joint Surgery, Vol. 87, No. 3, 2005, pp. 550-557. doi:10.2106/JBJS.D.02192
[4] J. R. Lieberman, A. Daluiski and T. A. Einhorn, “The Role of Growth Factors in the Repair of Bone. Biology and Clinical Application,” Journal of Bone & Joint Surgery, Vol. 84, No. 6, 2002, pp. 1032-1034.
[5] J. E. Kenzora, R. E. Steele, Z. H. Yosipovitch and M. J. Glimcher, “Experimental Osteonecrosis of the Femoral Head in Adult Rabbits,” Clinical Orthopaedics, Vol. 130, 1978, pp. 8-46.
[6] A. Barquet, “Natural History of Avascular Necrosis Following Traumatic Hip Dislocation in Childhood: A Review of 145 Cases,” Acta Orthopaedica Scandinavica, Vol. 53, 1982, pp. 815-820. doi:10.3109/17453678208992299
[7] D. Pringle, T. Koob and H. Kim, “Indentation Properties of the Growing Femoral Head Deformity Following Ischemic Necrosis,” Journal of Orthopaedic Research, Vol. 22, No. 1, 2004, pp. 122-130. doi:10.1016/S0736-0266(03)00135-9
[8] A. Catterall, et al., “A Review of the Morphology of Perthes’ Disease,” Journal of Bone & Joint Surgery, British Volume, Vol. 64B, No. 3, 1982, pp. 269-275.
[9] S. L. Weinstein, “Legg-Calvé-Perthes Syndrome,” In: R. T. Morrisy and S. L. Weistein, Eds., Lovell and Winter’s Pediatrics Orthopaedics, 5th Edition, Lippincott Williams and Wilkins, Philadelphia, 2001, pp. 957-998.
[10] S. D. Stulberg, D. R. Cooperman and R. Wallensten, “The Natural History of Legg-Calvé-Perthes Disease,” Journal of Bone and Surgery, Vol. 63, 1981, pp. 1095-1098.
[11] F. Bauss, M. Wagner and L. H. Hothorn, “Total Administered Dose of Ibandronate Determines Its Effects on Bone Mass and Architecture in Ovatriectomized Aged Rats,” Journal of Rheumatology, Vol. 29, No. 5, 2002, pp. 990-998.
[12] D. Little, et al., “Zolendronic Acid Treatment Results in Retention of Femoral Head Structure after Traumatic Osteonecrosis in Young Winstar Rats,” Journal of Bone Mineral Research, Vol. 18, No. 11, 2003, pp. 2016-2022. doi:10.1359/jbmr.2003.18.11.2016
[13] D. Little, et al., “Zolendronic Acid Improves Femoral Head Sphericity in a Rat Model of Perthes Disease,” Journal of Orthopaedic Research, Vol. 23, No. 4, 2005, pp. 862-868. doi:10.1016/j.orthres.2004.11.015
[14] L. Y. Carreon, et al., “Platelet Gel (AGF) Fails to Increase Fusion Rates in Instrumented Posterolateral Fusions,” Spine, Vol. 30, No. 9, 2005, pp. E243-E246. doi:10.1097/01.brs.0000160846.85397.44

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