Radiological and histological analysis of synthetic bone grafts in recurring giant cell tumour of bone: a retrospective study

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1 Journal of Orthopaedic Surgery 2010;18(1):63-7 Radiological and histological analysis of synthetic bone grafts in recurring giant cell tumour of bone: a retrospective study Hiroyuki Hattori, Hiroaki Matsuoka, Kengo Yamamoto Department of Orthopaedic Surgery, Tokyo Medical University, Tokyo, Japan ABSTRACT Purpose. To review the radiology and histology of synthetic bone grafts resected from patients with recurrent giant cell tumour (GCT) of bone. Methods. 22 patients underwent curettage and grafting for GCT of bone using autogenous cancellous bone mixed with apatite-wollastonite-containing glass ceramic (AWGC), hydroxyapatite (HA), or a mixture of HA and tricalcium phosphate (TCP). Patients were followed up every 3 to 6 months. Three men and 3 women aged 20 to 33 (mean, 27) years developed local recurrence. The mean interval from surgery to recurrence was 35 (range, 12 89) months. Specimens containing the recurring GCT of bone and the surrounding synthetic bone and new bone were evaluated. Results. No complication related to the use of the synthetic bone (such as toxicity, fracture or deformity) occurred. The synthetic bone incorporated well into the surrounding host bone, but was not completely absorbed. HA was more bioactive than AWGC in human bone. HA/TCP were more bioresorbable and osteoconductive in human bone than HA or AWGC. In most areas of AWGC grafts, intervening layers of fibrous connective tissue were seen between the granules and the bone. In most areas of HA grafts, the granules were completely surrounded by viable bone, with bone ingrowth into the pores of the granules, as well as venules and fibrous tissue ingrowth in the pores of portions of the grafts. Conclusion. A mixture of synthetic bone and autogenous cancellous bone is safe and useful for grafting after curettage for GCT of bone. Key words: apatite-wollastonite-containing glass ceramic; bone substitutes; giant cell tumor of bone; hydroxyapatitepolylactide INTRODUCTION Bone grafts can be divided broadly into autografts, allografts, and synthetic grafts. Autografts are osteogenic, osteoinductive, and osteoconductive because they consist of viable cells, matrix proteins, and bony matrix, respectively. 1 Bone defects are usually treated with autografts harvested from the Address correspondence and reprint requests to: Dr Hiroyuki Hattori, Department of Orthopaedic Surgery, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, , Japan. hiroyuki.hattori@jcom.home.ne.jp

2 64 H Hattori et al. Journal of Orthopaedic Surgery ilium, but the amount available is limited. Synthetic bones including apatite-wollastonite-containing glass ceramic (AWGC), hydroxyapatite (HA), and tricalcium phosphate (TCP) are biocompatible, bioactive, and osteoconductive. 2 5 They are useful and safe for filling of bone defects after tumour resection. 6 9 Histological analysis of these materials from human samples has been reported We reviewed the radiology and histology of grafted bone resected from patients with recurrent tumours. MATERIALS AND METHODS Between 1995 and 2005, 22 patients underwent curettage and grafting for giant cell tumours (GCT) of bone. The pseudocapsule was dissected circumferentially and excised completely. The entire intra-osseous lesion was curetted, followed by mechanical burring until the normal bone was exposed. The cavity was packed with mixtures of synthetic and autogenous cancellous bones. The synthetic bone used from 1995 to 2000 was AWGC (Cerabone; Nippon Electric Glass, Ohtsu, Japan) with porosity of 70%, pore size of 200 µm, and 900 to 1200ºC sintering temperature. The synthetic bone used from 2001 to 2005 was either pure HA (Apaceram; Asahi Optical, Tokyo, Japan) with porosity of 45%, pore size of 5 to 200 µm, and 1200ºC sintering temperature, or a mixture of HA and TCP (Ceratite; Chugai, Tokyo, Japan) in a ratio of 7:3 with porosity of 35%, pore size of 1 to 15 µm, and 1100ºC sintering temperature. Patients were followed up every 3 to 6 months. Increase in radiographic density of the radiolucent zone surrounding the grafted bone was recorded. Three men and 3 women aged 20 to 33 (mean, 27) years developed local recurrence in the proximal tibia (n=3), distal femur (n=2), and proximal fibula (n=1), which were all confirmed by magnetic resonance imaging. The mean interval from surgery to recurrence was 35 (range, 12 89) months. Three patients had AWGC grafts, 2 had HA grafts, and one had HA/TCP grafts. One patient with recurrence in the proximal fibula underwent en bloc resection without reconstruction. The remaining 5 patients underwent further curettage and grafting with synthetic bone or methylmethacrylate. Specimens containing the recurring GCT of bone and the surrounding synthetic bone and new bone were evaluated using paraffin sections of 3 µm stained with haematoxylin and eosin. RESULTS No complication related to the use of the synthetic bone (such as toxicity, fracture or deformity) occurred. The radiographic density of the grafted bone increased with time. Granules of the synthetic bone had attached to each other at the medullary side and extended cortically. The synthetic bone incorporated well into the surrounding host bone, but was not completely absorbed. Recurring tumours were typically located in the subchondral bone near the cortical window, and partially intruded into the absorbed synthetic bone (Fig. 1). Radiologically, most areas of AWGC grafts were hypointense, and granules were distinguishable as void signals on both T1- and T2-weighted images. Figure 1 Postoperative radiographs of the right proximal tibia in a 33-year-old woman: a clear margin between the bone and the hydroxyapatite granules immediately after surgery; the hydroxyapatite graft is homogenously incorporated 6 months later, with a diminishing margin; and (c) increased lucency at the superior edge of the hydroxyapatite graft, with evidence of infiltrating recurrent tumour.

3 Vol. 18 No. 1, April 2010 Synthetic bone grafts in recurring GCT of bone 65 Figure 2 The left distal femur in a 30-year-old man 27 months after surgery: the granules of the apatite-wollastonitecontaining glass ceramic graft are homogenously incorporated; a hypointense signal throughout the graft site in a T1- weighted image; (c) a hyperintense signal surrounding speckle void signals in a T2-weighted image. Figure 3 The right distal femur of a 30-year-old man 24 months after surgery: the granules of hydroxyapatite graft are homogenously incorporated; the centre of the graft is isointense and its surrounding is hypointense in a T1-weighted image; (c) the centre of the graft is hyperintense and its surrounding is hypointense in a T2-weighted image. The surrounding areas were isointense on T1- and hyperintense on T2-weighted images (Fig. 2). The centres of HA-containing grafts were isointense on T1- and hyperintense on T2-weighted images. The circumference was hypointense on both T1- and T2-weighted images, and the granules were indistinguishable (Fig. 3). Histologically, most areas of AWGC grafts showed intervening layers of fibrous connective tissue between the granules and the bone. Only a small portion of the graft interface was the newly formed lamellar with osteoblasts attached to the granules (Fig. 4). In most areas of HA grafts, however, the granules were completely surrounded by viable bone, with bone ingrowth into the pores of the granules, as well as venules, and fibrous tissue ingrowth into the pores of portions of the grafts (Fig. 5). Recurring tumour cells were in direct contact with the synthetic bone and extended into the pores. Large numbers of multinucleated giant cells surrounded the granules of synthetic bone (Fig. 6). DISCUSSION This retrospective study was not a comparative study of AWGC and HA. In patients with HA-containing grafts, the formation of osteons in the pores was evident, as was the ingrowth of the venules and fibrous tissue into the pores. In a study in which a porous HA

4 66 Journal of Orthopaedic Surgery H Hattori et al. Figure 4 Photomicrographs of the apatite-wollastonite-containing glass ceramic graft 12 months after surgery: an intervening layer of fibrous connective tissue between granules and the bone (H&E, x40); and newly formed lamellar bone containing osteoblasts is partially attached to the granule (H&E, x400). Figure 5 Photomicrographs of the hydroxyapatite graft 27 months after surgery: the granules are in direct contact to the viable bone (H&E, x80); and fibrous tissue is partially surrounded by granules, with the ingrowth of venules into the pores (H&E, x80). (c) Figure 6 Photomicrographs of recurring tumours (H&E, x80): tumour cells surround the granules and extend into the pores of the apatite-wollastonite-containing glass ceramic graft, and hydroxyapatite graft. Multinucleated giant cells surround the granules of the (c) hydroxyapatite and tricalcium phosphate mixture graft.

5 Vol. 18 No. 1, April 2010 Synthetic bone grafts in recurring GCT of bone 67 block was placed into the proximal tibial metaphysis of dogs, 3 at 12 months 66.5% of the implant surface was covered with bone ingrowth. AWGC was less bioactive than HA in human bone. Although AWGC was shown to contact newly formed bone directly in experimental animals, 2,4 in our study there were intervening layers of fibrous connective tissue between the granules and the bone, with different signal intensity from the bone trabeculae. HA/TCP were more bioresorbable and osteoconductive in human bone than HA or AWGC. Resorption of synthetic bone involves a solution-mediated process (the implant dissolves in physiologic solutions) and a cell-mediated process (phagocytosis). 11 Partial dissolution of the synthetic bone in the former process initiates the accumulation of phagocytic cells (macrophages or osteoclasts), which play a major role in resorption. In our study, accumulation of osteoclasts around the graft was not identified, but multinucleated giant cells were noted to surround the granules of the HA/TCP graft only. This suggests that HA/ TCP has a more aggressive cell-mediated process of resorption than HA or AWGC. Additionally, Cathepsin K, a cysteine protease, is expressed in both osteoclasts (responsible for the degradation of collagen matrix during bone remodelling) and multinucleated giant cells (responsible for osteolysis) in GCTs. 12 A variety of synthetic bone grafts have been used to promote new bone formation and structural support. They achieve mechanical strength immediately after grafting by stimulating osteoconduction. Most synthetic bones provide an osteoconductive lattice upon which host osteogenesis can take place. Autogenous cancellous bone should be added to provide osteoinductivity. Therefore, a mixture of synthetic bone and autogenous cancellous bone is preferable. REFERENCES 1. Bauer TW, Muschler GF. Bone graft materials. An overview of the basic science. Clin Orthop Relat Res 2000;371: Fujita H, Iida H, Ido K, Matsuda Y, Oka M, Nakamura T. Porous apatite-wollastonite glass-ceramic as an intramedullary plug. J Bone Joint Surg Br 2000;82: Holmes RE, Bucholz RW, Mooney V. Porous hydroxyapatite as a bone-graft substitute in metaphyseal defects. A histometric study. J Bone Joint Surg Am 1986;68: Teramoto H, Kawai A, Sugihara S, Yoshida A, Inoue H. Resorption of apatite-wollastonite containing glass-ceramic and beta-tricalcium phosphate in vivo. Acta Med Okayama 2005;59: Walsh WR, Vizesi F, Michael D, Auld J, Langdown A, Oliver R, et al. Beta-TCP bone graft substitutes in a bilateral rabbit tibial defect model. Biomaterials 2008;29: Matsumine A, Myoui A, Kusuzaki K, Araki N, Seto M, Yoshikawa H, et al. Calcium hydroxyapatite ceramic implants in bone tumour surgery. A long-term follow-up study. J Bone Joint Surg Br 2004;86: Ogose A, Hotta T, Kawashima H, Kondo N, Gu W, Kamura T, et al. Comparison of hydroxyapatite and beta tricalcium phosphate as bone substitutes after excision of bone tumors. J Biomed Mater Res B Appl Biomater 2005;72: Uchida A, Araki N, Shinto Y, Yoshikawa H, Kurisaki E, Ono K. The use of calcium hydroxyapatite ceramic in bone tumour surgery. J Bone Joint Surg Br 1990;72: Yamamoto T, Onga T, Marui T, Mizuno K. Use of hydroxyapatite to fill cavities after excision of benign bone tumours. Clinical results. J Bone Joint Surg Br 2000;82: Tachibana Y, Ninomiya S, Kim YT, Sekikawa M. Tissue response to porous hydroxyapatite ceramic in the human femoral head. J Orthop Sci 2003;8: Jarcho M. Calcium phosphate ceramics as hard tissue prosthetics. Clin Orthop Relat Res 1981;157: Lindeman JH, Hanemaaijer R, Mulder A, Dijkstra PD, Szuhai K, Bromme D, et al. Cathepsin K is the principal protease in giant cell tumor of bone. Am J Pathol 2004;165: