|Year : 2017 | Volume
| Issue : 2 | Page : 155-160
Use of allogenic bone graft in the treatment of benign osteolytic bone lesion
OP Lakhwani1, Mohit Jindal2, Shashank Agarwal1, Keerty Garg3
1 Department of Orthopaedics, ESI-PGIMSR, New Delhi, India
2 Department of Orthopaedics, Kalpana Chawla Government Medical College, Karnal, Haryana, India
3 Department of Anaesthesia, Guru Nanak Medical College, Amritsar, Punjab, India
|Date of Web Publication||14-Nov-2017|
Department of Orthopaedics, Kalpana Chawla Government Medical College, Karnal, Haryana
Introduction: Management of benign osteolytic lesions of bone involve intralesional excision and filling of the bone defect. Allograft used as a filler in these lesions confer advantages of being available in sufficient quantity without the risk of donor site morbidity. However use of allografts may carry a potential risk of infection and has debatable osteogenic potential. This study used Allogenic Bone Graft using antibiotic impregnated allografts and adjuvants like bone marrowso as to address these shortcomings. Materials and Methods: Eight cases of benign osteolytic lesions were treated by intralesional curettage and bone grafting using allogenic bone graft. Appropiate surgical procedure for fixation was done wherever necessary. Five cases had Allogenic Bone Graft impregnated with vancomycin solution. Three cases had autogenic bone graft while 1 case used bone marrow as adjuvant. Outcome was assessed in terms of fracture healing, infection and osteointegration. Results: In all the cases adequate osteointegration and complete healing of the lesion was observed in all the cases with time period of healing closely matching that of complete osteointegration. There was no statistically significant difference in the duration of osteointegration and bone healing between vancomycin impregnated group vis a vis allograft used alone. Only one case developed infection who responded to Intravenous antibiotics. No failure was observed in this study was probably due to use of adjuvants in half of the cases. Discussion and Conclusion: Use of allogenic bone graft alongwith adjuvants (bone marrow and autologous bone graft) appears to be effective in treatment of benign lytic lesions. Healing rates may be attributed to use of osteogenic potentiators. Vancomycin impregnation of allograft appears to be a beneficial step in controlling the graft related infection and does not affect graft osteointegration and bone healing.
Keywords: Allografts, cystic lesions of bone, osteolytic bone lesions
|How to cite this article:|
Lakhwani O P, Jindal M, Agarwal S, Garg K. Use of allogenic bone graft in the treatment of benign osteolytic bone lesion. Trop J Med Res 2017;20:155-60
|How to cite this URL:|
Lakhwani O P, Jindal M, Agarwal S, Garg K. Use of allogenic bone graft in the treatment of benign osteolytic bone lesion. Trop J Med Res [serial online] 2017 [cited 2020 Apr 9];20:155-60. Available from: http://www.tjmrjournal.org/text.asp?2017/20/2/155/218208
| Introduction|| |
Management of benign osteolytic lesions of bone involves intralesional excision and filling of the bone defect., Various materials, such as autologous bone graft, allogenic bone graft (ABG),, synthetic materials including calcium phosphate and calcium hydroxyapatite, have been used with variable results. ABGs have got distinct advantages of being available in sufficient quantity without the risk of donor-site morbidity and do not warrant a second surgery for removal. However, a high risk of infection has been reported by Sethi et al. and Goel et al. using decalcified allograft for benign cystic lesions. ABGs also have limitation that they can serve only as scaffold and lack osteoinductive potential. Therefore, the present study was undertaken to address these shortcomings associated with the use of ABGs. To address the problem of infection associated with the use of ABG, gamma sterilization of the allograft was carried out prior to use in all patients. Vancomycin impregnation of ABG and use of osteogenic potentiators (autogenic bone graft and bone marrow aspirate) as adjuvants to ABG were also studied. The results were evaluated in terms of healing of lesion, osteointegration, and infection.
| Material and Methods|| |
The study was approved by the Institutional Ethical Committee of ESI-PGIMSR, Basaidarapur, Delhi, and all patients were fully informed and agreed to participate in the study. The inclusion criteria were histological confirmation of benign osteolytic bone lesion either by needle or incisional biopsy and having a minimum follow-up period of 6 months. Exclusion criteria were patients having any active osteoarticular infection at the concerned site. From 2011 to 2013, eight consecutive benign osteolytic lesions (three cases each of aneurysmal bone cysts [ABCs] and simple bone cysts and two cases of giant cell tumor [GCT]) were treated by intralesional curettage with a diamond burr and bone grafting using deep-freezed gamma-irradiated ABG. The tumor has been in the metaphyseal and epiphyseal areas of the bone. Appropriate surgical procedure for fixation was done wherever necessary.
The age range of the studied patients was from 14 to 43 years. Five cases (two cases each of simple bone cyst and GCT and one case of ABC) had ABG impregnated with vancomycin solution. Three cases (two cases of GCT and one case of simple bone cyst) had autogenic bone graft added as an adjuvant to the ABG while one patient of ABC had bone marrow aspirate added as an osteogenic potentiator. ([Table 1] showing the distribution of the patients as per varied indications of Benign Osteolytic lesions).
|Table 1: Showing the varied indications of benign osteolytic lesions wherein allogenic bone grafts were used|
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The institutional bone bank had bone grafts procured from consenting patients having undergone total hip and knee arthroplasty at the institute and stored them at −76°C for a minimum of 3 months before use. The gamma irradiation was achieved by administering a dose of 25 grays of radiation at an accredited center. The graft was manually morcelized to a fragment size of 0.4–0.6 cm and washed with plenty of sterile saline. The bacterial culture of the allograft was taken before implantation to ascertain sterility and was all negative. In cases where antibiotic impregnated graft was used, the morcelized bone graft was kept in 20 ml distilled water solution consisting of vancomycin 50 mg/ml for 1 h.
Patients were observed at 5 days for the 1st wound check, then 2 weeks postoperatively for suture removal, and again at 6 and 12 weeks. Particular attention was given to any sign of infection/inflammation. Radiographs were done every 4 weeks for initial 4 months and then at every 2 months till the completion of follow-up. Results were assessed in terms of cyst healing as defined by the Neer's criteria [Table 2], of osteointegration using criteria given by Slooff et al. [Table 3], and occurrence of infection according to the WHO surgical site infection (SSI) guidelines.
|Table 2: Neer's classification system for radiographic evaluation of cyst healing|
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|Table 3: Sloof's criteria for assessing osteointegration of allogenic bone grafts|
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| Results|| |
All the eight patients could be followed up for more than 6 months [Table 1]. The maximum follow-up period was of 17 months. None of the patients showed clinical or histological evidence of any immunological reaction.
Incorporation of bone graft was evaluated as per Sloof et al's. criteria. In all the cases, adequate osteointegration was observed. The earliest radiological sign of incorporation of allograft material was seen at about 10 weeks. Initially, the graft material was seen as having distinct radiodensity as compared to the host bone bed, but later, progressive homogeneity of the graft material with filling of the cavity and obliteration of margins of the original lesion was seen. For benign osteolytic lesions, the mean time of osteointegration in five patients where ABG was impregnated with vancomycin was 7.20 ± 1.64 months, while in three patients, where no such impregnation was carried out was slightly lesser at 5.33 ± 2.08 months but there was no statistical difference with P = 0.206.
Healing of lesion and recurrence
Complete healing of the lesion as assessed by Neer's staging system was observed in all the cases with time period of healing closely matching with that of complete osteointegration in all the cases. The overall mean time to heal in five patients where vancomycin impregnation of allograft was carried out was 7.62 ± 1.45 months and in three patients where no such impregnation was carried out was 6.93 ± 1.53 months. Both the time periods were comparable with P = 0.239. The time for adequate healing varied according to the nature of lesion with all the three cases of simple bone cyst healing earliest within an average period of 5.33 months and the three GCT cases taking the longest average duration of 8.33 months for adequate healing. The two cases of ABC cases took an average time of 6 months to heal completely. [Figure 1], [Figure 2], [Figure 3], [Figure 4] shows serial skiagrams of varied cases of benign osteolytic lesions showing adequate healing as per Neer's Criteria. No recurrence was reported in any of the benign osteolytic lesion cases treated. This study is not for the efficacy of ABG in tumor healing but about the versatility of its use when combined with different adjuvants.
|Figure 1: Serial skiagrams of a case of aneurysmal bone cyst proximal femur. (a) Preoperative skiagram showing the lytic lesion. (b) Postoperative skiagram showing the heterogeneous intensities of the allograft occupying the lesion as well as some extraosseously placed graft. (c) 5-month postoperative skiagram showing homogeneous intensity as of cortex with resorption of extraosseous graft. (d) 8-month postoperative skiagram showing adequate healing|
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|Figure 2: Serial skiagrams of a case of aneurysmal bone cyst proximal radius. (a) Preoperative skiagram showing the lytic lesion. (b) Postoperative skiagram showing the heterogeneous intensities of the allograft occupying the lesion as well as some extraosseously placed graft. (c) 5-month postoperative skiagram showing homogeneous intensity as of cortex with resorption of extraosseous graft, suggestive of adequate healing|
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|Figure 3: Serial skiagrams of a case of giant cell tumor proximal tibia. (a) Preoperative skiagram showing the lytic lesion. (b) 3-month postoperative skiagram showing the altered intensities of the allograft occupying the lesion. (c) 5-month postoperative skiagram showing homogeneous intensity as of cortex with resorption of extraosseous graft, suggestive of adequate healing|
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|Figure 4: Serial skiagrams of a case of 14-year-old male with aneurysmal bone cyst proximal humerus. (a) Preoperative anteroposterior view showing the cystic lesion. (b) 4-month postoperative view showing adequate osteointegration|
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SSI guideline was used to identify postoperative infection. Only one patient of ABC of the talus developed serous discharge first observed on the 5th postoperative day and cultures were sent in which Pseudomonas aeruginosa was identified. The patient was put on appropriate antibiotic therapy for about 3 weeks and there was no further clinical sign of infection. No other case developed any sign of infection.
| Discussion|| |
Earliest use of bone allografts for reconstruction had been made by Aubigne since 1966. In most experimental models, fresh allografts are associated with a rigorous inflammatory response as well as a specific immune response. However, deep frozen allografts are associated with decreased immunogenicity and no demonstrable change in initial mechanical properties as reported by Friedlander in 1987.
Spence et al. in 1969 implanted freeze-dried cancellous allografts in solitary bone cysts and obtained adequate healing in 55% of cases with partial healing in 9% and recurrence in 36% of cases. Kakiuchi et al. performed 75 implantations using decalcified human bone matrix gelatin and achieved complete healing in 68 cases with seven cases having recurrence of benign tumor. Sethi et al. in 1992 used decalcified ABG in GCT, simple and ABCs, fibrous dysplasia, and achieved complete healing in 65% of cases, with a recurrence rate of 6%. Similarly, Goel et al., 1992, reported successful allograft incorporation in 30 out of the total 35 cases of cystic bone lesions with one failure and four recurrences. Finkemeier in 2002 used morselized bone grafting in bone defects such as bone cysts, infective nonunions, and other reconstructive procedures. In the present case series, we used curettage with ABG in eight cases of lytic lesions and complete healing of the lesions was observed in all the cases. The better healing rate observed in this series may be attributed to the use of osteogenic potentiators such as autologous bone graft (in three cases) and bone marrow aspirate (in one case).
The period of incorporation varied within reasonable limits among different studies. Spence et al. reported a mean healing time of approximately 1 year. Kakiuchi et al. reported a time of 3–15 months in their series. Sethi et al. found age as an important factor in the time of incorporation of graft and found that in children the incorporation occurred relatively earlier at 6–9 months while incorporation occurred at a period of 9–15 months in adults. Goel et al. pointed toward variation in incorporation depending on the type of lesion with simple bone cysts having graft incorporation of around 3 months, ABCs between 3 and 6 months, and GCTs between 6 and 9 months. Spence et al. in a separate study involving the treatment of simple bone cyst using freeze-dried cortical allograft reported that inadequate filling of the lesion also adversely affected graft incorporation. In our case series, the time of healing of lesion and adequate osteointegration closely followed each other and varied according to the nature of lesion. In unicameral bone cysts, all the three cases showed incorporation of bone within 5 months. In ABCs, all the cases showed graft incorporation but the time period varied within 6 months and both cases of GCTs showed adequate osteointegration within 8 months.
Almost all studies reported some recurrence rates after curettage and bone grafting. Age of the patient, size, type of lesion, and adequacy of cavity filling by allograft are the factors seemingly affecting the recurrence rates. Glancy et al. in a study on cystic lesions in children reported complete healing in 80% of small volume cysts and 38% in large volume cavities. Spence et al. reported a recurrence rate of 36% in adult patients. Sethi et al. also concluded that small-sized cavities had better healing rates as compared to larger lesions. Goel et al. also reported a similar conclusion regarding the size of lesion and recurrence rates. In locally aggressive lesions, such as GCTs, recurrence rates vary from 27% to as high as 45%. In this case series, no recurrence has been observed which may be attributed to the use of osteogenic potentiators in half of the cases.
SSI associated with the use of ABG merits concern as shown by Ketonis et al. who carried out a study assessing bacteriological colonization of ABG and found a high risk of graft being colonized by microorganisms. Goel et al. found a higher rate (10.9%) of infection in benign cystic osseous lesions treated by curettage along with decalcified allogenic bone grafting as opposed to infection rate (9.5%) in series done by Campanacci et al. where treatment was only by curettage. The incorporation of antibiotic-loaded bone graft was first studied by Gudmundson in 1971 who showed that the presence of tetracycline locally markedly inhibited bone graft incorporation. Cancellous bone as a carrier for vancomycin has been studied in vitro by Witso et al. in 1999. Use of vancomycin is favored because of its physiochemical properties of hydrophilicity, heat stability, and efficacy against Staphylococcus species which is the most common cause of osteoarticular infection. Buttaro et al. in 2003 showed in an in vitro study that vancomycin if used in appropriate concentration (1 g dry vancomycin powder for 300 g of bone graft) will not affect osteointegration of ABG as the peak levels attained locally by such a use were higher than the minimum inhibitory concentration value of vancomycin for most susceptible organisms, but were 2000 times lower than the levels (10,000 μg/ml) associated with the death of osteoblasts. In the present series, one case (12.6%) out of the eight developed infection in the postoperative period and in this case nonvancomycin-impregnated allograft was used. None of the five cases where vancomycin-impregnated ABG was used showed any postoperative infection. As all the cases showed adequate graft uptake and cyst healing, no adverse effect of vancomycin on graft osteointegration and healing of lesion was observed in the present case series.
| Conclusion|| |
In the present case series, use of ABG per se or along with adjuvants (bone marrow aspirate and autologous bone graft) appears to be effective in the treatment of benign osteolytic lesions. Healing rates may be attributed to the use of osteogenic potentiators. Vancomycin impregnation of allograft appears to be beneficial in controlling the graft-related infection. Furthermore, it does not appear to affect the graft osteointegration and healing of the lesion as all the patients had complete healing of the lesion without any reported recurrence.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Chen F, Xia J, Wang S, Wei Y, Wu J, Huang G, et al.
Use of extended curettage with osteotomy and fenestration followed by reconstruction with conservation of muscle insertion in the treatment of Enneking stage II locally aggressive bone tumor of the proximal extremities: Resection and treatment of bone tumors. World J Surg Oncol 2013;11:54.
Eckardt JJ, Grogan TJ. Giant cell tumor of bone. Clin Orthop Relat Res 1986;(204):45-58.
Chigira M, Maehara S, Arita S, Udagawa E. The aetiology and treatment of simple bone cysts. J Bone Joint Surg Br 1983;65:633-7.
Spence KF, Sell KW, Brown RH. Solitary bone cyst: Treatment with freeze-dried cancellous bone allograft. A study of one hundred seventy-seven cases. J Bone Joint Surg Am 1969;51:87-96.
Kakiuchi M, Hosoya T, Takaoka K, Amitani K, Ono K. Human bone matrix gelatin as a clinical alloimplant. A retrospective review of 160 cases. Int Orthop 1985;9:181-8.
Altermatt S, Schwöbel M, Pochon JP. Operative treatment of solitary bone cysts with tricalcium phosphate ceramic. A 1 to 7 year follow-up. Eur J Pediatr Surg 1992;2:180-2.
Inoue O, Ibaraki K, Shimabukuro H, Shingaki Y. Packing with high-porosity hydroxyapatite cubes alone for the treatment of simple bone cyst. Clin Orthop Relat Res 1993;(293):287-92.
Sethi A, Agarwal K, Sethi S, Kumar S, Marya SK, Tuli SM, et al.
Allograft in the treatment of benign cystic lesions of bone. Arch Orthop Trauma Surg 1993;112:167-70.
Goel SC, Tuli SM, Singh HP, Sharma SV, Saraf SK, Srivastava TP, et al.
Allogenic decalbone in the repair of benign cystic lesions of bone. Int Orthop 1992;16:176-9.
Fernandez-Bances I, Perez-Basterrechea M, Perez-Lopez S, Nuñez Batalla D, Fernandez Rodriguez MA, Alvarez-Viejo M, et al.
Repair of long-bone pseudoarthrosis with autologous bone marrow mononuclear cells combined with allogenic bone graft. Cytotherapy 2013;15:571-7.
Neer CS, Francis KC, Johnston AD, Kiernan HA Jr., Current concepts on the treatment of solitary unicameral bone cyst. Clin Orthop Relat Res 1973;(97):40-51.
Slooff TJ, Huiskes R, van Horn J, Lemmens AJ. Bone grafting in total hip replacement for acetabular protrusion. Acta Orthop Scand 1984;55:593-6.
Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG. CDC definitions of nosocomial surgical site infections, 1992: A modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol 1992;13:606-8.
Merle D'Aubigné R, Méary R, Thomine JM. Resection in the treatment of bone tumors. Rev Chir Orthop Reparatrice Appar Mot 1966;52:305-24.
Friedlander GE, Bone Banking in Support of Reconstructive Surgery of the Hip. Current concepts review – Bone Grafts. J Bone Joint Surg 1987;69:786-90.
Finkemeier CG. Bone-grafting and bone-graft substitutes. J Bone Joint Surg Am 2002;84-A:454-64.
Spence KF Jr., Bright RW, Fitzgerald SP, Sell KW. Solitary unicameral bone cyst: Treatment with freeze-dried crushed cortical-bone allograft. A review of one hundred and forty-four cases. J Bone Joint Surg Am 1976;58:636-41.
Glancy GL, Brugioni DJ, Eilert RE, Chang FM. Autograft versus allograft for benign lesions in children. Clin Orthop Relat Res 1991;(262):28-33.
Ketonis C, Barr S, Adams CS, Hickok NJ, Parvizi J. Bacterial colonization of bone allografts: Establishment and effects of antibiotics. Clin Orthop Relat Res 2010;468:2113-21.
Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am 1987;69:106-14.
Gudmundson C. Oxytetracycline-induced fragility of growing bones. An experimental study in rats. Clin Orthop Relat Res 1971;77:284-9.
Witsø E, Persen L, Benum P, Aamodt A, Husby OS, Bergh K, et al.
High local concentrations without systemic adverse effects after impaction of netilmicin-impregnated bone. Acta Orthop Scand 2004;75:339-46.
Buttaro MA, González Della Valle AM, Piñeiro L, Mocetti E, Morandi AA, Piccaluga F, et al.
Incorporation of vancomycin-supplemented bone incorporation of vancomycin-supplemented bone allografts: Radiographical, histopathological and immunohistochemical study in pigs. Acta Orthop Scand 2003;74:505-13.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]