Does Chemotherapy Impair the Bone Healing and Biomechanical Stability of Vascularized Rib and Fibula Grafts?

Andreas Eisenschenk; Christiane Witzel; Martin Lautenbach; Axel Ekkernkamp; Ulrich Weber; Markus V. Küntscher

doi:10.1055/s-2006-958700

Journal of Reconstructive Microsurgery, Table of Contents

J Reconstr Microsurg 2007; 23(1): 035-040
DOI: 10.1055/s-2006-958700

Does Chemotherapy Impair the Bone Healing and Biomechanical Stability of Vascularized Rib and Fibula Grafts?

Andreas Eisenschenk¹ , Christiane Witzel² , Martin Lautenbach³ , Axel Ekkernkamp⁴ , Ulrich Weber⁵ , Markus V. Küntscher⁶

¹Department for Hand-, Replantation- and Microsurgery, Unfallkrankenhaus Berlin
²Hand-, Plastic and Reconstructive Surgery, Charité-University Medicine Berlin, Campus Benjamin Franklin
³Division of Hand surgery, Immanual-Krankenhaus Berlin, Department of Orthopedic Surgery
⁴Department of Orthopedic and Reconstructive Surgery, Unfallkrankenhaus Berlin
⁵Department for Orthopedic Surgery, Charité-University of medicin Berlin, Campus Benjamin Franklin
⁶Burn Center/Department of Plastic Surgery, Unfallkrankenhaus Berlin

Abstract

ABSTRACT

The purpose of this study was to observe the impact of chemotherapy on the healing and biomechanical properties of vascularized bone grafts.

Ten male beagle dogs were divided into two experimental groups: a chemotherapy group (CH) and control group (C). Group CH received adjuvant and neo-adjuvant chemotherapy. Each animal of both groups underwent the following operative procedures. The 5th and 7th rib were removed and replaced by vascularized pedicle transfers of the adjacent 4th and 8th rib. Additionally, a free fibular flap was elevated and retransferred to the same anatomic position.

The rate of bony union on plain x-ray was 100 percent in group C, 30 percent in the vascularized rib, and 80 percent in the fibula grafts of group CH. Microangiography demonstrated no avascular bone segments in group C and in the fibula flaps of group CH. The vascularized ribs of group CH presented with 20 percent avascular bone segments.

Biomechanical tests focusing on the durability of the vascularized grafts against bending and torsion forces demonstrated a reduction of the average maximum bending times by 17 percent and 23.9 percent compared to the controls (p < 0.05). The twisting times were reduced by 13.8 percent (n.s.) and 32.5 percent (p < 0.05).

The data demonstrated a clear worsening in bone healing and stability after simulated adjuvant and neo-adjuvant chemotherapy. Thus, a large animal model was established for the further determination of the effects of chemotherapy on different vascularized bone transfers.

KEYWORDS

Vascularized bone grafts - chemotherapy

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References

REFERENCES

1 Weiland A J, Daniel R K, Riley Jr L H. Application of the free vascularized bone graft in the treatment of malignant or aggressive bone tumors. Johns Hopkins Med J. 1977; 140 85-96
2 Weiland A J, Kleinert H E, Kutz J E, Daniel R K. Free vascularized bone grafts in surgery of the upper extremity. J Hand Surg Am. 1979; 4 129-144
3 Wood M B, Cooney 3rd W P, Irons Jr G B. Skeletal reconstruction by vascularized bone transfer: indications and results. Mayo Clin Proc. 1985; 60 729-734
4 Gidumal R, Wood M B, Sim F H, Shives T C. Vascularized bone transfer for limb salvage and reconstruction after resection of aggressive bone lesions. J Reconstr Microsurg. 1987; 3 183-188
5 Eisenschenk A, Lautenbach M, Schwetlick G, Weber U. Treatment of femoral head necrosis with vascularized iliac crest transplants. Clin Orthop Rel Res. 2001; 386 100-105
6 Lee K S, Han S B, Baek J R. Free vascularized osteocutaneous fibular graft to the tibia in 51 consecutive cases. J Reconstr Microsurg. 2004; 20 277-284
7 Kasashima T, Minami A, Kutsumi K. Late fracture of vascularized fibular grafts. Microsurgery. 1998; 18 337-343
8 Wei F C, El-Gammal T A, Lin C H, Ueng W N. Free fibula osteoseptocutaneous graft for reconstruction of segmental femoral shaft defects. J Trauma. 1997; 43 784-792
9 Chew W Y, Low C K, Tan S K. Long-term results of free vascularized fibular graft. A clinical and radiographic evaluation. Clin Orthop Relat Res. 1995; (311) 258-261
10 Minami A, Kutsumi K, Takeda N, Kaneda K. Vascularized fibular graft for bone reconstruction of the extremities after tumor resection in limb-saving procedures. Microsurgery. 1995; 16 56-64
11 Hazan E J, Hornicek F J, Tomford W, Gebhardt M C, Mankin H J. The effect of adjuvant chemotherapy on osteoarticular allografts. Clin Orthop Relat Res. 2001; 385 176-181
12 Bieling P, Bielack S, Delling G, Jurgens H, Kotz R, Dose C, Astheimer H, Exner G, Gadner H, Graf N et al.. Neoadjuvant chemotherapy of osteosarcoma. Preliminary results of the cooperative COSS-86 osteosarcoma study. Klin Padiatr. 1991; 203 220-230
13 Rosenstock J G, Morris Jones P, Pearson D, Palmer M K. Ewing's sarcoma, adjuvant chemotherapy and pathologic fracture. Europ J Cancer. 1978; 14 799-803
14 Bielack S, Kempf-Bielack B, Schwenzer D et al.. [Neoadjuvant therapy for localized osteosarcoma of extremities. Results from the Cooperative osteosarcoma study group COSS of 925 patients.] Klin Padiatr. 1999; 211 260-270
15 Claude L, Rousmans S, Carrie C et al.. Federation nationale des centres de lutte contre le cancer (FNCLCC); Federation hospitaliere de France (FHF); Federation nationale de cancerologie des CHRU (FNCCHRU); Federation francaise de cancerologie des CHG (FFCCHG); centres regionaux de lutte contre le cancer (CRLCC); Societe francaise de lutte contre les cancers de l'enfant et de l'adolescent (SFCE). [Standards and Options for the use of radiation therapy in the management of patients with osteosarcoma.] Cancer Radiother. 2005; 9 104-121
16 Sauer H D, Sommer-Tsilenis E, Borchers D, Schmidt H. The modification of fracture healing by the cytostatic agent cyclophosphamide-an experimental interdisciplinary study. Z Orthop Ihre Grenzgeb. 1982; 120 783-789
17 Friedlaender G E, Tross R B, Doganis A C, Kirkwood J M, Baron R. Effects of chemotherapeutic agents on bone. I. Short-term methotrexate and doxorubicin (adriamycin) treatment in a rat model. J Bone Joint Surg Am. 1984; 66 602-607
18 Nilsson O S, Bauer H C, Brostrom L A. Comparison of the effects of adriamycin and methotrexate on orthotopic and induced heterotopic bone in rats. J Orthop Res. 1990; 8 199-204
19 Nilsson O S, Bauer F C, Brostrom L A, Nilsonne U. Effect of the antineoplastic agent methotrexate on experimental heterotopic new bone formation in rats. Cancer Res. 1984; 44 1653-1656
20 Burchardt H, Glowczewskie Jr F P, Enneking W F. The effect of adriamycin and methotrexate on the repair of segmental cortical autografts in dogs. J Bone Joint Surg Am. 1983; 65 103-108
21 Canosa R, Gonzalez del Pino J. Effect of methotrexate in the biology of free vascularized bone grafts. A comparative experimental study in the dog. Clin Orthop Relat Res. 1994; 301 291-301
22 Nussenbaum B, Rutherford R B, Krebsbach P H. Bone regeneration in cranial defects previously treated with radiation. Laryngoscope. 2005; 115 1170-1177
23 Ehrhart N P, Hong L, Morgan A L, Eurell J A, Jamison R D. Effect of transforming growth factor-beta1 on bone regeneration in critical-sized bone defects after irradiation of host tissues. Am J Vet Res. 2005; 66 1039-1045
24 Schultze-Mosgau S, Lehner B, Rodel F et al.. Expression of bone morphogenic protein 2/4, transforming growth factor-beta1, and bone matrix protein expression in healing area between vascular tibia grafts and irradiated bone-experimental model of osteonecrosis. Int J Radiat Oncol Biol Phys. 2005; 61 1189-1196

Markus V KüntscherM.D. Ph.D.

Burn Center/Department of Plastic Surgery, Unfallkrankenhaus Berlin

Warener Str. 7, 12683 Berlin, Germany