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      Autologous mesenchymal stem cell (MSCs) transplantation for critical-sized bone defect following a wide excision of osteofibrous dysplasia

      case-report

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          Highlights

          • No recurrence of osteofibrous dysplasia at 84 week following a wide extraperiosteal excision.

          • The combination of autologous BM-MSCs, HA granules and BMP-2 successfully created new bone tissue.

          • The newly formed bone tissue filled in the gap of critical-sized bone defect and was able to improve the patient’s quality of life significantly.

          • No neoplastic, immunologic or other side-effects were noted at 84 weeks after autologous MSC transplantation.

          Abstract

          Introduction

          Osteofibrous dysplasia is a rare non-neoplastic disease that is almost exclusive to pediatric tibial diaphysis. Wide excision of the lesion is recommended to avoid recurrence. However, such radical surgery will results in large segmental bone defects that will require further extensive reconstructive surgery. We report a novel approach of treating bone defect by implementing the diamond concept of bone healing using autologous bone marrow derived mesenchymal stem cells (BM-MSCs).

          Presentation of case

          An eight-year-old Indonesian male presented with severe bowing deformity of the left lower leg. Radiographic and histological analysis confirmed the diagnosis of osteofibrous dysplasia. A wide excision of the defect was made leaving a critical-sized bone defect. A combination of autologous transplantation of 50 million BM-MSCs, hydroxyapatite (HA) granules, bone morphogenic protein 2 (BMP-2) and Djoko-Zarov hybrid circular external fixator was used to treat the defect. The outcomes measured were subjective complaints, functionality based on LEFS and radiological assessments.

          Discussion

          Radiographic assessments showed successful new bone tissue formation and integration of implanted HA granules. The external fixator was removed at 42 weeks after adequate callus formation and clinical stability was achieved. The patient underwent progressive functional improvements and reached a near normal functionality of 90% LEFS at 84 week. No therapy side effect or complication was reported.

          Conclusion

          Osteofibrous dysplasia was successfully excised without signs of recurrence after 84-week follow-up. Autologous transplantation of augmented BM-MSCs has successfully created new normal bone tissue without causing any side effect and had significantly improved the patient’s quality of life.

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          Most cited references20

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          The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network.

          The purpose of this study was to assess the reliability, construct validity, and sensitivity to change of the Lower Extremity Functional Scale (LEFS). The LEFS was administered to 107 patients with lower-extremity musculoskeletal dysfunction referred to 12 outpatient physical therapy clinics. The LEFS was administered during the initial assessment, 24 to 48 hours following the initial assessment, and then at weekly intervals for 4 weeks. The SF-36 (acute version) was administered during the initial assessment and at weekly intervals. A type 2,1 intraclass correlation coefficient was used to estimate test-retest reliability. Pearson correlations and one-way analyses of variance were used to examine construct validity. Spearman rank-order correlation coefficients were used to examine the relationship between an independent prognostic rating of change for each patient and change in the LEFS and SF-36 scores. Test-retest reliability of the LEFS scores was excellent (R = .94 [95% lower limit confidence interval (CI) = .89]). Correlations between the LEFS and the SF-36 physical function subscale and physical component score were r=.80 (95% lower limit CI = .73) and r = .64 (95% lower limit CI = .54), respectively. There was a higher correlation between the prognostic rating of change and the LEFS than between the prognostic rating of change and the SF-36 physical function score. The potential error associated with a score on the LEFS at a given point in time is +/-5.3 scale points (90% CI), the minimal detectable change is 9 scale points (90% CI), and the minimal clinically important difference is 9 scale points (90% CI). The LEFS is reliable, and construct validity was supported by comparison with the SF-36. The sensitivity to change of the LEFS was superior to that of the SF-36 in this population. The LEFS is efficient to administer and score and is applicable for research purposes and clinical decision making for individual patients.
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            Current approaches to experimental bone grafting.

            A number of osteogenic, osteoinductive, and osteoconductive substances currently are being investigated for use in bone repair. It is conceivable that a selected combination of osteogenic cells, osteoinductive factors, and osteoconductive matrices can be combined and fabricated into an implantable material custom-suited to particular clinical demands. Consequently, it is crucial that potential graft substances be experimentally characterized in terms of their precise contribution to the bone-forming mechanisms. In this article, the authors review current areas of research in the realm of experimental grafting, including the current understanding of materials that manifest osteogenic, osteoinductive, or osteoconductive properties.
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              Orthopaedic applications of bone graft & graft substitutes: a review.

              Treatment of delayed union, malunion, and nonunion is a challenge to the orthopaedic surgeons in veterinary and human fields. Apart from restoration of alignment and stable fixation, in many cases adjunctive measures such as bone-grafting or use of bone-graft substitutes are of paramount importance. Bone-graft materials usually have one or more components: an osteoconductive matrix, which acts as scaffold to new bone growth; osteoinductive proteins, which support mitogenesis of undifferentiated cells; and osteogenic cells, which are capable of forming bone in the appropriate environment. Autologous bone remains the "gold standard" for stimulating bone repair and regeneration, but its availability may be limited and the procedure to harvest the material is associated with complications. Bone-graft substitutes can either substitute autologous bone graft or expand an existing amount of autologous bone graft. We review the currently available bone graft and graft substitutes for the novel therapeutic approaches in clinical setting of orthopaedic surgery.
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                Author and article information

                Contributors
                Journal
                Int J Surg Case Rep
                Int J Surg Case Rep
                International Journal of Surgery Case Reports
                Elsevier
                2210-2612
                05 November 2015
                2015
                05 November 2015
                : 17
                : 106-111
                Affiliations
                [0005]Department of Orthopaedic and Traumatology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jl. Dipenogoro No. 71, Salemba, Jakarta Pusat 10430, Indonesia
                Author notes
                [* ]Corresponding author. ismailorthofkui@ 123456yahoo.co.id
                Article
                S2210-2612(15)00477-0
                10.1016/j.ijscr.2015.10.040
                4701811
                26599503
                c2ee4410-befe-4fbb-b9dd-0dcc4ca5e3da
                © 2015 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 14 July 2015
                : 28 October 2015
                : 31 October 2015
                Categories
                Case Report

                autologous mesenchymal stem cells,critical-sized bone defect,osteofibrous dysplasia,wide excision,bone morphogenetic protein 2,hydroxyapatite granules

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