Prof. Dr. Cristea Stefan

Ortopedie și traumatologie

Bucuresti, Hyperclinica Medlife

Osteoconductive bone substitutes as treatment of benign lytic lesions

Osteoconductive bone substitutes as treatment of benign lytic lesions Dragosloveanu Serban1, Cristea Stefan1, Zaharie Dan1
1 University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest,Romania
serbandrago@gmail.com
Keywords: bone substitutes, bone grafts, lytic lesions, tricalcium phosphate, hydroxyapatite
Abstract. Benign lytic lesions represent a frequent pathology in our clinic. Regarding therapy, we approach these benign tumors through curettage and filling the defects with bone grafting or bone substitutes like hydroxyapatite crystals and tricalcium phosphate.We want to evaluate the efficiency of both bone grafts and bone substitutes regarding bone consolidation, osseointegration and time until absorption for tricalcium phosphate and hydroxyapatite crystals combination. We analyzed 14 patients treated in our clinic through curettage and defect filling during the last three years: 9 patients’ beneficiated from bone grafting and for the other 5 we used a hydroxyapatite and tricalcium phosphate combination from the same supplier. Diagnoses were bone cyst, non-ossifying fibroma and giant-cell tumor. Therapeutic method was linked with bone graft availability. Followup was 24 months through periodical x-ray controls in our clinic. Bone consolidation was satisfactory in all cases with no defect collapse. In conclusion, bone substitutes like combinations of hydroxyapatite crystals and tricalcium phosphate are a useful and safe method for surgical treatment of strictly benign lytic tumors.
Introduction Lytic benign bone lesions are a frequent pathology in our clinic. Our treatment protocol regarding bone defects resulting from the lytic action of benign tumors or secondary to hip arthroplasty is curettage and filling with bone graft (autograft of allograft) or bone substitutes like hydroxyapatite crystals and tricalcium phosphate, depending on the dimension of the defect and graft accessibility [1]. In the scientific literature there is no consensus regarding the clinical results after the use of bone substitutes on mid to long term. Our method of treatment has proved itself useful in selected cases with a certain benign diagnosis. The question that we raise is the duration until full osseointegration compared to bone grafts, mechanic proprieties after integration until complete absorption [2, 3, 4]. In this study we plan to analyze the efficiency of bone substitutes like CERAFORM® (combination of tricalcium phosphate and hydroxyapatite) compared to bone grafts. It is very important for the postoperatory result to be optimal and the duration until satisfactory mechanical resistance to be shorter. Material and Methods We analyzed 14 patients treated in our clinic between 2010-2013 who beneficiated from filling of bone defects with bone grafts or bone substitutes like CERAFORM® (made by 35% tricalcium phosphate and 65% hydroxyapatite). The bone defects were small and medium and resulting from lytic action of benign tumors or secondary to hip arthroplasties and forming of cysts. Therapeutic method was influenced by bone graft availability from the bone bank. 9 patients had beneficiated from bone grafts and the other 5 patients from filling with CERAFORM®. Inclusion criteria to the study group were certain benign lytic lesions. Diagnosis was bone cyst, non-ossifying fibroma and giant-cell tumor. Follow-up was 24 months ± 1 month and for investigation we used X-ray controls and histopathology exams (in two cases). X-ray images were obtained using the same equipment and were done by the same operator. We calibrated the exposures using computer software for X-rays calibration, measurements and planning named Cedara I-View 6.3.2. We used the IRWIN scale (I: obvious margins, II: hazy margins, III: obvious incorporation) for classification and for bone
Key Engineering Materials Vol. 587 (2014) pp 422-426 © (2014) Trans Tech Publications, Switzerland doi:10.4028/www.scientific.net/KEM.587.422
All rights reserved. No part of contents of this paper may be reproduced or transmitted in any form or by any means without the written permission of TTP, www.ttp.net. (ID: 89.114.57.148-09/10/13,09:01:05)
biopsies we looked for bone neoformation, inflammatory response and fibrosis. Patients with large defects that affected bone structural resistance were excluded from the study. Statistical data was processed with IBM SPSS Statistics 20.0.0. In all cases we used curettage and filling with bone grafts of bone substitutes. The bone substitute that we used in all cases was CERAFORM®. We included in the study only the patients which complied with product indications [5, 6, 7, 8]. Results Average age was 39.4 years (variation between 12-67 years). Sex distribution was equal. Bone defects were on average 17.7cc (between 8-34cc). At the six month control patients with bone grafts have shown complete osseointegration, bone consolidation and lack of complications. At 12 months control patients treated with CERAFORM® bone substitute presented signs of osseointegration and lack of margins (IRWIN II and III). Bone consolidation was satisfactory for all patients. We encountered only one recurrence for one patient with giant-cell tumor diagnosis and bone grafting which needed another surgical intervention through curettage and filling with acrylic cement. At two years control we noticed low to none signs of hydroxyapatite absorption. Functional results were excellent. Regarding functional and clinical aspects we did not notice any differences between the two therapeutic methods. We have not encountered any fractures or any other forms of recurrences other than the one mentioned. Regarding the histopathology exam we noticed that bone formation has invaded the entire macroporous implant and forms a new cortical zone. The neoformed bone is very well vascularised with a large number of osteocytes and no fibrous interface is observed between the bone and the material. Age and sex distribution had no influence on the outcome. (p>0.05). We cannot draw a conclusion about size of bone defects and its influence on the final results, since we excluded any patients which did not comply with manufacturer`s indications.
Discussion Data from literature shows that bone substitutes have good bone integration, a fact confirmed also by our study. From literature two processes are important, osteoconduction and osseointegration. From the manufacturer`s info at six weeks in a spongy site, cone neoformation can be observed. Colonisation occurs by vascular and tissue invading the implant. The new bone is formed in direct contact with the surface of the ceramic without fibrousis [5, 9, 10, 11]. Osseointegration at 12 weeks shows that bone ingrowth reaches the center of holes and the macropores in the substitute are completely filled. Bone material contact is extensive and straight without fibrosis. The manufacturer claims that at 12 weeks fragmentation of the ceramic are observed but we did not achieve or noticed so early resorption. No inflammatory response or reaction was encountered or claimed [12, 13, 14, 15]. We noticed that on animal tests bone integration seems to be a little faster than in humans, with no bone integration until 9 months or later [16].
Key Engineering Materials Vol. 587 423

Case 1 – Benign lytic lesion Case 2- Bone cysts after failed total hip in the left calcaneus arthroplasty and revision surgery Figure 1. The radiological results in some relevant clinical cases
For a long time, bone grafts showed excellent results after successfully filling bone defects. The down-side of bone grafts is little availability due to reduced number of donors and high cost of prelevation and preparation. The main disadvantages of autografts are a longer surgery time, a new skin incision, an increase in pain level at the donor site which can recurrence even until 9 months and consuming a possible good bone graft for later use in more severe pathologies [17, 18, 19]. Disadvantages for bone substitutes like CERAFORM® are the fragility and low mechanical properties which limit its use for bone which are exposed to high levels of mechanical stress and torsion. Also, the osseointegration and gaining mechanical competence is slower than for bone grafts. A major advantage is a much lower cost and a large availability. From our study we can notice an almost complete local inflammatory reaction at bone-substitute lever, an excellent vascularization and the apparition of new bone formation [11]. Age and sex distribution do not appear to play an important role regarding osseointegration. Time period until disappear of lytic marginal signs is almost double for bone substitutes. We noticed a stage Irwin III bone integration for 4 patients and a stage II for the other. One patient presented a recurrence after a giant-cell tumor and needed reintervention and curettage and filling with acrylic bone cement. The histopathology exam showed osteoformation, satisfactory neovascularization, and lack of inflammatory reaction and filling of porous cells in the bone substitute. These findings are relevant for excellent results and bone-forming stimulation, without additional complications [17, 20, 21]. At the 2 years control, patients with bone grafts and no complication other than the one mentioned showed complete osseointegration with lytic signs. Those with CERAFORM® bone substitute presented discrete signs of hydroxyapatite absorption, but with certain signs of consolidation and integration.
Conclusions We noticed and excellent biocompatibility between bone substitutes and native bone; we have not encountered any adverse reactions or complications. Surgery time is reduced, with limitation of postoperatory pain compared to autografts; bone substitutes have a large availability and a lower cost and still represent a good choice for patients who refuse graft transplant for ethical reasons [22, 23, 24]. Synthetic bone substitutes like CERAFORM® (combinations of hydroxyapatite and tricalcium phosphate) are a useful and safe method for surgical treatment of strictly benign lytic tumors.
424 Bioceramics 25
References: [1]. Delloye C, Cnochaert C, Corbu N., Bone substitutes in 2003, an overview. ActaOrthopBelgica 69:1–8, 2003 [2]. Gouin F, Cappeli M., Aplications cliniques des céramiques phospho-calciques: Biomateriaux de substitution de l’oset du cartilage-. Cahiers d’einseignement de la SOFCOT. Expansion ScientifiqueFrancaise, 1996 [3]. Delecrin J, Takahasi S, Gouin F, Camps C, Passuti N., A synthetic porous ceramic as a bone graft substitute in the surgical management of scoliosis. Spine 25:563–569, 2000 [4]. Augereau B., Kysteanevrysmal. Tumeur set dystrophies benignes. In: Tomeno B, Forest M (eds) Les tumeur sosseuses de l’appareil locomoteur. Laboratoires UNICET, Paris, 1993 [5]. CERAFORM®: Technical description in Les substitutes osseux en 2005, surl’egide GESTO, p 44, 2005 [6]. Schwartz C, Lecestre P, Fraysinet P, Liss P., Bone Substitutes, Eur.J.OrthopSurgTraum. 9(3):161–165 , 1999 [7]. Botez P., Sirbu P., Simion L., Munteanu F., Antoniac I., Aplication of a biphasic macroporous synthetic bone substitutes CERAFORM®: clinical and histological results", Eur.J. OrthopSurgTrauma., 19 : 387-395, 2009 [8]. Botez P, Petcu I., Analyse des applications chez l’homme d’un substitute osseux a base de céramique biphasique (CERAFORM). Étude prospective préliminaire, 8e Congres de l’AOLF, Bucharest, 2002 [9]. Daculsi G, Passuti N., Effect of the macro porosity for osseous substitution of calcium phosphate ceramics, Biomater 11:86–88, 1990 [10]. Frayssinet P, Trouillet JL, Rouquet N, Autefage A, Delga C et al., Calcium phosphate porous ceramics osseointegration: the importance of a good definition of material specifications. Rev ChirOrthop 79, 1993. [11]. Yuan H, Kurashina K, De Brujin JD, Li Y, De Groot K, Zhang X (1999) A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics. Biomaterials 20:1799– 1806 [12]. Van Blitterswijk CA, Grote LL, Kuijpers W, DaemsWTh, De Grout K., Macrospore tissue ingrowths: a quantitative and qualitative study on hydroxyapatite ceramics. Biomateriaux 7:137–143 , 1986 [13]. Gourin F, Delécrin F, Passuti N, Touchait N, Poirier P, Bain JV, Comblement osseux par céramique phosphocalcique biphasée macroporeuse. A propos 23 cas., Revue Chir. Orthop. 81:59–65, 1995 [14]. Malard O, Bouler JM, Guicheux J, Heymann D, Pillet P, Coquard C, Daculsi G., Influence of biphasic calcium phosphate granulometry on bone ingrowth, ceramic resorbtion and inflamatory reactions. J Biomed Mater Res 46(1):103–111, 1999 [15]. Gautier O, Bouler JM, Aguado E, Legeros RZ, Pilet P, Daculsi G., Elaboration conditions influence physicochemical properties and in vivo bioactivity of macroporous biphasic ceramics. J Mater Sci Mater Med 10(4):199–204, 1999 [16]. Daculsi G, Passuti N, Martin S, Le Nihouanen IC, Brulliard V, Delécrin I, A comparative study of bioactive calcium phosphate ceramics after implantation in cancellous bone in the dog. Rev ChirOrthop 75:65–71, 1989 [17]. Saito M, Shimizu H, Beppu M, Takagi M., The role of ß-tricalcium phosphate in vascularized periosteum. J OrthopSci 5:275–282, 2000 [18]. Laurie SWS, Kaban LB, Mulliken LB, Murray IE, Donor-site morbidity after harvesting rib and iliac bone. PlastReconstrSurg 73:933–938, 1984 [19]. Summers BN, Eisenstein SM, Donor site pain from the ilium: A complication of lumbar spine fusion. J Bone Joint Surg 71-B:677–679, 1989 [20]. Nery EB, LeGeros RZ, Lynch ZL, Lee K., Tissue response to biphasic calcium phosphate ceramic with different ratios of HAIBTCP in periodontal osseous defects. J Periodont 63:729– 735, 1992
Key Engineering Materials Vol. 587 425
[21]. Khan Y, Yaszemski MJ, Antonios GM, Laurencin C, Tissue engineering of bone: material and matrix considerations. J Bone J Surg Am 90:36–42, 2008 [22]. D. Allison, A. Lindberg, B. Samimi, R. Mirzayan, L. Merendez, A Comparison of mineral bone graft substitutes for bone defects", US Oncology & Hematology [23]. Gianouddis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36 (Suppl 3): S20–S27 [24]. G. El-Adl, M. Mostafa, A. Enan, M. Ashraf, Biphasic ceramic bone substitute mixed with autogenous bone marrow in the treatment of cavitary ben