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Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 32 - 32
1 Dec 2020
Kaymakoglu M Dede EC Korkusuz P Ozdemir E Erden ME Turhan E
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Adrenomedullin is a peptide hormone that has attracted attention with its proliferative and anti-apoptotic effects on osteoblasts in recent years. We investigated the effect of adrenomedullin on healing of the segmental bone defect in a rat model. 36 Wistar rats were randomly divided in six groups based on follow-up periods and administered dose of adrenomedullin hormone. In each group, a 2 mm bone defect was created at the diaphysis of radius, bilaterally. NaCl solution was administered to sham groups three times a week for 4 and 8 weeks, intraperitoneally. Adrenomedullin was administered to study groups three times a week; 15 µg-4 weeks, 15 µg-8 weeks, 30 µg-4 weeks and 30 µg-8 weeks, respectively. After euthanasia, the segmental defects were evaluated by histomorphometric (new bone area (NBA)) and micro-tomographic (bone volume (BV), bone surface (BS), bone mineral density (BMD)) analysis. Although 4 and 8 weeks 15 μg administered study groups had higher NBA values than the other study and control groups, histomorphometric analysis did not reveal any statistical difference between the control and study groups in terms of new bone area (p > 0.05). In micro-tomographic analysis, BV was higher in 15 μg – 4 weeks group than 30 μg – 4 weeks group (296.9 vs 208.5, p = 0.003) and BS was lower in 30 μg – 4 weeks than 4 week - control group (695.5 vs 1334.7, p = 0.005) but in overall, no significant difference was found between the control and study groups (p > 0.05). Despite these minor differences in histomorphometric and micro-tomographic criteria indicating new bone formation, BMD values of 15 µg-4 and −8 weeks study groups showed significant increase comparing with the control group (p = 0.04, p = 0.001, respectively). Adrenomedullin seemed to have a positive effect on BMD at a certain dose (15 µg) but it alone is not considered sufficient for healing of the defect with new bone formation. Further studies are needed to assess its effects on bone tissue trauma. This study was funded by Hacettepe University Scientific Research Projects Coordination Unit


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 4 - 4
1 Dec 2020
Tashmetov E Tuleubaev B Saginova D Koshanova A Rustambek I
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Introduction. Cancellous and cortical bone used as a delivery vehicle for antibiotics. Recent studies with cancellous bone as an antibiotic carrier in vitro and in vivo showed high initial peak concentrations of antibiotics in the surrounding medium. However, high concentrations of antibiotics can substantially reduce osteoblast replication and even cause cell death. Objectives. To determine whether impregnation with gentamycine impair the incorporation of bone allografts, as compared to allografts without antibiotic. Materials and method. Seventy two healthy rabbits (24 rabbits in each group) were used for this study. Bone defects (3-mm diameter, 10-mm depth) were created in the femur. Human femoral head prepared according to the Marburg bone bank system was used as bone allograft. In the experimental groups, in 1 group - the defects were filled with bone allografts, in 2 group – Perforated Gentamycin-impregnated bone allografts. The control group did not receive any filling. The animals were killed after 14, 30 and 60 days. Evaluations consisted of X-ray plain radiography, histology at 14-, 30- and 60-days post-surgery. Results. Active osteoblast activity and active formation of new bones were detected around the defect area in all groups, but the amount of new bone formation was greater in the experimental groups than the control group. We found no statistically significant differences in the rate of bone formation between 1 and 2 groups at 14, 30 and 60 days in any of the parameters studied. X-ray results showed no significant difference in bony callus formation around allografts in 1 and 2 groups. In contrast, no significant callus formation was observed in the control group. Conclusion. The use of gentamycin-impregnated bone allografts may be of value in procedures performed at the site of osteomyelitis which require a second stage reconstruction with impacted bone grafting techniques


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 35 - 35
7 Nov 2023
Tsang J Epstein G Ferreira N
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The Cierny and Mader classification assists with decision-making in the management of osteomyelitis by strafying the host status and the pathoanatomy of disease. However the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08– 8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistical significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_5 | Pages 2 - 2
23 Apr 2024
Tsang SJ Epstein G Ferreira N
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Introduction. The Cierny and Mader classification assists with decision-making by stratifying host status and the pathoanatomy of the disease. However, the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. Materials & Methods. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Results. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08–8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistically significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). Conclusions. This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 78 - 78
1 Oct 2022
Cacciola G Bruschetta A Meo FD Cavaliere P
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Aim. The primary endpoint of this study is to characterize the progression of bone defects at the femoral and tibial side in patients who sustained PJI of the knee that underwent two-stage revision with spacer implantation. In addition, we want to analyze the differences between functional moulded and hand-made spacers. Methods. A retrospective analysis of patients that underwent two-stage revision due to PJI of the knee between January 2014 and December 2021 at our institution. Diagnosis of infection was based on the criteria of the Muscoloskeletal Infection Society. The bone defect evaluation was performed intraoperatively based on the AORI classification. The basal evaluation was performed at the time the resection arthroplasty and spacer implantation surgery. The final evaluation was performed at the second-stage surgery, at the time of spacer removal and revision implant positioning. The differences between groups were characterized by using T-test student for continuous variables, and by using chi-square for categorical variables. A p-value < 0.05 was defined as significant. Results. Complete data of 37 two-stage TKAs revision were included in the study. An articulating moulded functional spacer was used in 14 (35.9%) cases, while a hand-made spacer was used in 23 (58.9%) cases. The average length of interval period (excluding the time for patients that retained the spacer) was 146.6 days. A bone defects progression based on the AORI classification was documented in 24 cases at the femoral side (61.6%), a bone defect progression was documented in 17 cases at the tibial side (43.6%), and a bone defect at both sides was documented in 13 cases (33.3%). A statistically significant greater bone defect progression at the tibial side was observed when hand-made spacers were used. A complication during the interval period was reported in five cases (12.8%) and postoperative complication was reported in 9 cases (23.1%). Conclusions. When comparing patients in which a functional articulating spacer was used, with patients in which static spacer was used, we reported a statistically significant reduced bone defect progression during the interval period at the femoral side only when moulded spacers were used. We observed a higher incidence of bone defect progression also at the tibial and both sides when hand-made spacers were used. This is the first study that documented the bone defect progression during two-stage revision of the knee, the results observed in this study are very encouraging


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_10 | Pages 38 - 38
1 Jun 2023
Hrycaiczuk A Biddlestone J Rooney B Mahendra A Fairbairn N Jamal B
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Introduction. A significant burden of disease exists with respect to critical sized bone defects; outcomes are unpredictable and often poor. There is no absolute agreement on what constitutes a “critically-sized” bone defect however it is widely considered as one that would not heal spontaneously despite surgical stabilisation, thus requiring re-operation. The aetiology of such defects is varied. High-energy trauma with soft tissue loss and periosteal stripping, bone infection and tumour resection all require extensive debridement and the critical-sized defects generated require careful consideration and strategic management. Current management practice of these defects lacks consensus. Existing literature tells us that tibial defects 25mm or great have a poor natural history; however, there is no universally agreed management strategy and there remains a significant evidence gap. Drawing its origins from musculoskeletal oncology, the Capanna technique describes a hybrid mode of reconstruction. Mass allograft is combined with a vascularised fibula autograft, allowing the patient to benefit from the favourable characteristics of two popular reconstruction techniques. Allograft confers initial mechanical stability with autograft contributing osteogenic, inductive and conductive capacity to encourage union. Secondarily its inherent vascularity affords the construct the ability to withstand deleterious effects of stressors such as infection that may threaten union. The strengths of this hybrid construct we believe can be used within the context of critical-sized bone defects within tibial trauma to the same success as seen within tumour reconstruction. Methodology. Utilising the Capanna technique in trauma requires modification to the original procedure. In tumour surgery pre-operative cross-sectional imaging is a pre-requisite. This allows surgeons to assess margins, plan resections and order allograft to match the defect. In trauma this is not possible. We therefore propose a two-stage approach to address critical-sized tibial defects in open fractures. After initial debridement, external fixation and soft tissue management via a combined orthoplastics approach, CT imaging is performed to assess the defect geometry, with a polymethylmethacrylate (PMMA) spacer placed at index procedure to maintain soft tissue tension, alignment and deliver local antibiotics. Once comfortable that no further debridement is required and the risk of infection is appropriate then 3D printing technology can be used to mill custom jigs. Appropriate tibial allograft is ordered based on CT measurements. A pedicled fibula graft is raised through a lateral approach. The peroneal vessels are mobilised to the tibioperoneal trunk and passed medially into the bone void. The cadaveric bone is prepared using the custom jig on the back table and posterolateral troughs made to allow insertion of the fibula, permitting some hypertrophic expansion. A separate medial incision allows attachment of the custom jig to host tibia allowing for reciprocal cuts to match the allograft. The fibula is implanted into the allograft, ensuring nil tension on the pedicle and, after docking the graft, the hybrid construct is secured with multi-planar locking plates to provide rotational stability. The medial window allows plate placement safely away from the vascular pedicle. Results. We present a 50-year-old healthy male with a Gustilo & Anderson 3B proximal tibial fracture, open posteromedially with associated shear fragment, treated using the Capanna technique. Presenting following a fall climbing additional injuries included a closed ipsilateral calcaneal and medial malleolar fracture, both treated operatively. Our patient underwent reconstruction of his tibia with the above staged technique. Two debridements were carried out due to a 48-hour delay in presentation due to remote geographical location of recovery. Debridements were carried out in accordance with BOAST guidelines; a spanning knee external fixator applied and a small area of skin loss on the proximal medial calf reconstructed with a split thickness skin graft. A revision cement spacer was inserted into the metaphyseal defect measuring 84mm. At definitive surgery the external fixator was removed and graft fixation was extended to include the intra-articular fragments. No intra-operative complications were encountered during surgeries. The patient returned to theatre on day 13 with a medial sided haematoma. 20ml of haemoserous fluid was evacuated, a DAIR procedure performed and antibiotic-loaded bioceramics applied locally. Samples grew Staphylococcus aureus and antibiotic treatment was rationalised to Co-Trimoxazole 960mg BD and Rifampicin 450mg BD. The patient has completed a six-week course of Rifampicin and continues on suppressive Co-Trimoxazole monotherapy until planned metalwork removal. There is no evidence of ongoing active infection and radiological evidence of early union. The patient is independently walking four miles to the gym daily and we believe, thus far, despite accepted complications, we have demonstrated a relative early success. Conclusions. A variety of techniques exist for the management of critical-sized bone defects within the tibia. All of these come with a variety of drawbacks and limitations. Whilst acceptance of a limb length discrepancy is one option, intercalary defects of greater than 5 to 7cm typically require reconstruction. In patients in whom fine wire fixators and distraction osteogenesis are deemed inappropriate, or are unwilling to tolerate the frequent re-operations and potential donor site morbidity of the Masqualet technique, the Capanna technique offers a novel solution. Through using tibial allograft to address the size mismatch between vascularised fibula and tibia, the possible complication of fatigue fracture of an isolated fibula autograft is potentially avoidable in patients who have high functional demands. The Capanna technique has demonstrated satisfactory results within tumour reconstruction. Papers report that by combining the structural strength of allograft with the osteoconductive and osteoinductive properties of a vascularised autograft that limb salvage rates of greater than 80% and union rates of greater than 90% are achievable. If these results can indeed be replicated in the management of critical-sized bone defects in tibial trauma we potentially have a treatment strategy that can excel over the more widely practiced current techniques


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 56 - 56
2 Jan 2024
Kaneko Y Minehara H Sonobe T Kameda T Sekiguchi M Matsushita T Konno S
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The Masquelet technique is a variable method for treating critical-sized bone defects, but there is a need to develop a technique for promoting bone regeneration. In recent studies of bone fracture healing promotion, macrophage-mesenchymal stem cell (MSC) cross-talk has drawn attention. This study aimed to investigate macrophage expression in the induced membrane (IM) of the Masquelet technique using a mouse critical-sized bone defect model. The study involved a 3-mm bone defect created in the femur of mice and fixed with a mouse locking plate. The Masquelet (M) group, in which a spacer was inserted, and the Control (C) group, in which the defect was left intact, were established. Additionally, a spacer was inserted under the fascia of the back (B group) to form a membrane due to the foreign body reaction. Tissues were collected at 1, 2, and 4 weeks after surgery (n=5 in each group), and immunostaining (CD68, CD163: M1, M2 macrophage markers) and RT-qPCR were performed to investigate macrophage localization and expression in the tissues. The study found that CD68-positive cells were present in the IM of the M group at all weeks, and RT-qPCR showed the highest CD68 expression at 1 week. In addition, there was similar localization and expression of CD163. The C group showed lower expression of CD68 and CD163 than the M group at all weeks. The B group exhibited CD68-positive cells in the fibrous capsule and CD163-positive cells in the connective tissue outside the capsule, with lower expression of both markers compared to the M group at all weeks. Macrophage expression in IM in M group had different characteristics compared to C group and B group. These results suggest that the IM differs from the fibrous capsules due to the foreign body reaction, and the macrophage-MSC cross-talk may be involved in Masquelet technique


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 24 - 24
1 Apr 2019
Hettich G Schierjott RA Schilling C Maas A Ramm H Bindernagel M Lamecker H Grupp TM
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Introduction. Acetabular bone defects are still challenging to quantify. Numerous classification schemes have been proposed to categorize the diverse kinds of defects. However, these classification schemes are mainly descriptive and hence it remains difficult to apply them in pre-clinical testing, implant development and pre-operative planning. By reconstructing the native situation of a defect pelvis using a Statistical Shape Model (SSM), a more quantitative analysis of the bone defects could be performed. The aim of this study is to develop such a SSM and to validate its accuracy using relevant clinical scenarios and parameters. Methods. An SSM was built on the basis of segmented 66 CT dataset of the pelvis showing no orthopedic pathology. By adjusting the SSM's so called modes of shape variation it is possible to synthetize new 3D pelvis shapes. By fitting the SSM to intact normal parts of an anatomical structure, missing or pathological regions can be extrapolated plausibly. The validity of the SSM was tested by a Leave-one-out study, whereby one pelvis at a time was removed from the 66 pelvises and was reconstructed using a SSM of the remaining 65 pelvises. The reconstruction accuracy was assessed by comparing each original pelvis with its reconstruction based on the root-mean-square (RMS) surface error and five clinical parameters (center of rotation, acetabulum diameter, inclination, anteversion, and volume). The influence of six different numbers of shape variation modes (reflecting the degrees of freedom of the SSM) and four different mask sizes (reflecting different clinical scenarios) was analyzed. Results. The Leave-one-out study showed that the reconstruction errors decreased when the number of shape variation modes included in the SSM increased from 0 to 20, but remained almost constant for higher numbers of shape variation modes. For the SSM with 20 shape variation modes, the RMS of the reconstruction error increased with increasing mask size, whereas the other parameters only increased from Mask_0 to Mask_1, but remained almost constant for Mask_1, Mask_2 and Mask_3. Median reconstruction errors for Mask_1, Mask_2, and Mask_3 were approximately 3 mm in Center of Rotation (CoR) position, 2 mm in Diameter, 3° in inclination and anteversion, as well as 5 ml in volume. Discussion. This is the first study analyzing and showing the feasibility of a quantitative analysis of acetabular bone defects using a SSM-based reconstruction method in the clinical scenario of a defect or implant in both acetabuli and incomplete CT-scans. Validation results showed acceptable reconstruction accuracy, also for clinical scenarios in which less healthy bone remains. Further studies could apply this method on a larger number of defect pelvises to obtain quantitative measures of acetabular bone defects


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 117 - 117
1 Nov 2018
Tazawa R Minehara H Matsuura T Kawamura T Uchida K Inoue G Shoji S Sakaguchi N Takaso M
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Segmental bone transport (SBT) with an external fixator has become a standard method for treatment of large bone defect. However, a long time-application of devices can be very troublesome and complications such as nonunion is sometimes seen at docking site. Although there have been several studies on SBT with large animal models, they were unsuitable for conducting drug application to improve SBT. The purpose of this study was to establish a bone transport model in mice. Six-month-old C57BL/6J mice were divided randomly into bone transport group (group BT) and an immobile control group (group EF). In each group, a 2-mm bone defect was created in the right femur. Group BT was reconstructed by SBT with external fixator (MouseExFix segment transport, RISystem, Switzerland) and group EF was fixed simply with unilateral external fixator (MouseExFix simple). In group BT, a bone segment was transported by 0.2 mm per day. Radiological and histological studies were conducted at 3 and 8 weeks after the surgery. In group BT, radiological data showed regenerative new bone consolidation at 8 weeks after the surgery, whereas high rate of nonunion was observed at the docking site. Histological data showed intramembranous and endochondral ossification. Group EF showed no bone union. In this study, experimental group showed good regenerative new bone formation and was similar ossification pattern to previous large animal models. Thus, the utilization of this bone defect mice model allows to design future studies with standardized mechanical conditions for analyzing mechanisms of bone regeneration induced by SBT


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 92 - 92
1 Feb 2020
Chun K Kwon H Kim K Chun C
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Purpose. The aim of this study was to compare the clinical outcomes of the revision TKA in which trabecular metal cones and femoral head allografts were used for large bone defect. Method. Total 53 patients who have undergone revision TKA from July 2013 to March 2017 were enrolled in this study. Among them, 24 patients used trabecular metal cones, and 29 patients used femoral head allografts for large bone defect. There were 3 males and 21 females in the metal cone group, while there were 4 males and 25 females in the allograft group. The mean age was 70.2 years (range, 51–80) in the femoral head allograft group, while it was 79.1 years (range, 73–85) in the metal cone group. Bone defect is classified according to the AORI classification and clinical outcomes were evaluated with Visual Analogue Scale (VAS), Hospital Special Surgery-score (HSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), and ROM. Operation time was also evaluated. We used radiographs to check complications such as migration or loosening. We took follow-up x-rays and 3D CT of the patients, to assess the mean bone union period. Shapiro-Wilk test was done to check normality and Student T-test and Mann Whitney U-test were done for comparison between two groups. Result. The mean follow-up period was 3 .75 years (Range; 2.1 ∼ 5.75). The pre-op scores did not show significant difference. The mean VAS in the allograft and trabecular metal cone groups was 2.1 ± 0.87 and 1.8 ± 0.53, respectively (p = 0.16). The mean HSS score were 76.3 ± 5.51 and 79.2 ± 4.12 respectively (p = 0.13) and the mean WOMAC scores were 15.1 ± 3.25 and 14.8 ± 3.31 respectively (p = 0.06), and the mean KOOS scores were 27.8 ± 4.77 and 25.5 ± 4.84, respectively (p = 0.07). The mean ROM ranges were 100.6 ± 17.54 and 101.3 ± 19.22, respectively (p = 0.09). But the mean operation time of the allograft and trabecular metal cone groups was 137 minutes (Range; 111–198) and 102minutes (Range; 93 −133) (p=0.02) respectively, which showed statistical significance. In follow-up x-rays, no migration or loosening of the implants, osteolysis and other complications were found in both groups. In follow-up 3D CT, osteointegration was seen at the trabecular metal cone site, host bone being interpreted to the host bone. The allograft group showed fibrous and stable union in follow-up 3D CT. Conclusion. According to this study, in case of revision TKA with large bone defect, using whether allograft or trabecular metal cones did not affect the clinical outcomes. However, operation time was significantly shorter in trabecular metal cone group, therefore, in patients with poor general condition along with severe underlying diseases, usage of trabecular metal cone would be a better choice to shorten operation time and ease postoperative care. Keywords. Revision TKA, metal cone, allograft, bone defect. For any figures or tables, please contact authors directly


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 50 - 50
1 Aug 2020
Woloszyk A Tuong K Tetsworth K Glatt V
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Treatment of segmental bone defects remains a major clinical problem, and innovative strategies are often necessary to successfully reconstruct large volumes of bone. When fractures occur, the resulting hematoma serves as a reservoir for growth factors and a space for cell infiltration, both crucial to the initiation of bone healing. Our previous studies have demonstrated very clear ultrastructural differences between fracture hematomas formed in normally healing fractures and those formed in segmental bone defects. However, there is little information available regarding potential differences in the underlying gene expression between hematomas formed in normal fractures, which usually heal by themselves, and segmental bone defects, which do not. Therefore, the aim of this study was to identify differences in gene expression within hematomas collected from 0.5 mm (normal fracture) and 5 mm (segmental bone defect) fracture sites during the earliest stages of bone healing. Osteotomies of 0.5 and 5 mm in the femur of Fisher 344 rats were stabilized with external fixators (RISystem AG). After 3 days the rats were sacrificed, and the fracture hematomas were collected for RNA-sequencing. Ingenuity pathway analysis (IPA) was used to identify upstream regulators and biological functions that were significantly enriched with differentially expressed genes from the RNA-sequencing analysis. Animal procedures were conducted following the IACUC protocol of the UT Health Science Center San Antonio. Key upstream regulators of bone formation were less active (e.g. TGFB1, FGF2, SMAD3) or even inhibited (e.g. WNT3A, RUNX2, BMP2) in non-healing defects when compared to normally healing fractures. Many upstream regulators that were uniquely enriched in healing defects were molecules recently discovered to have osteogenic effects during fracture healing (e.g. GLI1, EZH2). Upstream regulators uniquely enriched in non-healing defects were mainly involved in an abnormal modulation of hematopoiesis, revealing evidence of impaired maturation of functional macrophages and cytokines (e.g. IL3, CEBPE), both essential for successful bone healing. In addition, the enrichment pattern suggested a dysregulation of megakaryopoiesis (e.g. MRTFA, MRTFB, GATA2), which directly affects platelet production, and therefore fracture hematoma formation. Remarkably, the organization of the ECM was the most significantly enriched biological function in the normally healing fractures, and implies that the defect size directly affected the structural properties within the fracture hematoma. Conversely, genes encoding important ECM components (e.g. BGN, various collagens, IBSP, TNC), cell adhesion molecules, MMPs (MMP2), and TIMPs were all significantly downregulated in non-healing defects. Our most recent findings reveal new important key molecules that regulate defect size-dependent fracture healing. Combined with our previous results, which identified structural differences in fracture hematomas from both types of defects, current findings indicate that differential expression of genes is dictated by the structural properties of the hematomas formed during early fracture healing. Consequently, creating a bioscaffold that mimics the structure of normal fracture hematomas could be the first step towards developing new orthoregenerative treatment strategies that potentiate healing of large bone defects and non-healing fractures


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 91 - 91
1 Feb 2020
Chun K Kwon H Kim K Chun C
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Purpose. The aim of this study was to assess the clinical and radiological result of the usage of chip bone graft in non-contained type bone defect in primary or revision total knee arthroplasty patients. Subjects and Methods. We investigated 32 patients who had underwent primary or revision total knee arthroplasty from March, 2014 to February, 2017 in our hospital, who had non-contained type of defect. The mean age was 73.1 years. 5 of them were males, while 27 of them were females. 7 of them were primary total knee arthroplasty patients, while 25 of them were revision patients. 8 of them had chip bone graft used both in the femur and tibia. 9 of them had chip bone graft used only in the tibia. The other 15 had chip bone graft used only in the femur. Wire-mesh was used in the 9 patients who had chip bone graft used only in the medial side of the tibia. We used KOOS (Knee injury and osteoarthritis outcome score), HSS (Hospital for Special Surgery knee service rating system) and WOMAC scores to assess the clinical result, before the surgery and at the last follow-up. In addition, we had follow-up x-rays and 3D CT done for the patients to check the mean bone union period. In addition, overall radiologic imaging studies were used for complications such as loosening, osteolysis and lesions with radiolucency. Result. The Mean follow-up period was 2.7 years (range; 2.1 to 5). The Mean preoperative KOOS was 102.8 (range; 47 to 132), while it became 31.8 postoperatively (range; 20 to 45). The mean HSS was 13.1 (range; 6 to 35), while it became 35.9 postoperatively (range; 24 to 64). The mean WOMAC was 82.9 (range; 62 to 92), while it became 22.5 postoperatively (range; 13 to 30). According to follow-up x-ray and CT, the mean bone union period was 10.6 months (range: 10 to 13). In follow-up 3D CT of all cases, we could check cortical healing and new bone formation, seen as medium to high-attenuating conglomerate. The graft-host junction showed trabecular ingrowth, while the medullary canal showed fibrous ingrowth. Radiologically, there was no complication such as loosening, osteolysis, migration and radiolucent lines around the stems or cement mantles. In addition, there was no complication such as infection. Conclusion. Chip bone graft is not a commonly used method for bone defect in total knee arthroplasty. According to the result of the usage of chip bone graft in primary or revision total knee arthroplasty with non-contained type of bone defect, it showed favorable result for the subject patients. Therefore, we can consider it as one of the effective methods to manage non-contained bone defect in knee arthroplasty. Keywords. Revision TKA, chip bone graft, wire-mesh, non-contained bone defect. For any figures or tables, please contact authors directly


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 56 - 56
1 Apr 2018
Hettwer W
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Successful reconstruction of bone defects requires an adequate filling material that supports regeneration and formation of new bone within the treated defect in an optimal fashion. Currently available synthetic bone graft substitutes cannot fulfill all requirements of the highly complex biological processes involved in physiological bone healing. Due their unphysiologically asynchronous biodegradation properties, their specific foreign material-mediated side effects and complications and their relatively modest overall osteogenic potential, their overall clinical performance typically lags behind conventional bone grafts of human origin. However, defect- and pathology specific combination of synthetic bone graft substitutes exhibiting appropriate carrier properties with therapeutic agents and/or conventional bone graft materials allows creation of biologically enhanced composite constructs that can surpass the biological and therapeutic limits even of autologous bone grafts. This presentation introduces a bone defect reconstruction concept based on biological enhancement of optimal therapeutic agent-carrier composites and provides a rationale for an individual, requirement-specific adaptation of a truly patient-specific reconstruction of bone defects. It represents the pinnacle of the bone defect reconstruction pyramid, founded on the basic principles and prerequisites of complete elimination of the underlying pathology, preservation, augmentation or restoration of mechanical stability of the treated bone segment and creation of a biodegradable scaffold with adequate mechanical integrity. It summarises the current body of relevant experimental and clinical research, presents clinical case examples illustrating the various aspects of the proposed concept as well as early clinical results. The author hopes that the theoretical and conceptual framework provided, will help guide future research as well as clinical decision making with respect to this particular field


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_2 | Pages 63 - 63
1 Jan 2016
Ishii M Takagi M Kawaji H Tamaki Y Sasaki K
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Acetabular reconstruction of extensive bone defect is troublesome in revision total hip arthroplasty (rTHA). Kerboull or Kerboull type reinforcement acetabular device with allobone grafting has been applied since 1996. Clinical results of the procedure were evaluated. Patients. One hundred and ninety-two consecutive revision total hip arthroplasties were performed with allograft bone supported by the Kerboull or Kerboull type reinforcement acetabular device from 1996 to 2009. There were 23 men and 169 women. Kerboull plates were applied to 18 patients, and Kerboull type plates to 174. The mean follow up of the whole series was 8 years (4–18years). Surgical Technique. The superior bone defect was reconstructed principally by a large bulky allo block with plate system. Medial bone defect was reconstructed by adequate bone chips and/or sliced bone plates. After temporally fixation of bulky bone block with two 2.0mm K-wires, it was remodeled by reaming to fit the gap between host bone and plate, followed by fixation to the iliac bone by screws. Finally, residual space of the defect between host bone and the fixed plated was filled up with morselized cancellous bones, bone chips, and/or wedged bony fragments with impaction. This method was sufficiently applicable to AAOS Typeâ�, II, and III bone defects. In case of AAOS Typeâ�£, the procedure was also available after repairing discontinuation between distal and proximal bones by reconstrusion plate or allografting with tibial bone plates or sliced femoral head. Results. Nine patients (4.7%) required revision surgery (infection 5, breakage 3, and malalignment 1). The plate breakage was observed in 8 joints (4.2%). Three patients had no symptoms after the breakage. Three required revision, but the other cases were carefully observed without additional surgical intervention. Ten-year survival rate by Kaplan-Meier method was 96.6% when the endpoint was set revision by asceptic loosning. Conclusions. This study indicated that acetabular allograft reconstructions reinforced by Kerboull or Kerboull type acetabular device were able to recover bone stock with anatomic reconstruction of femoral head center, thus providing satisfactory clinical results in middle term period


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 11 - 11
1 Dec 2015
Grytsai M Linenko O Kolov G Tsokalo V Hordii A Sabadosh V Pecherskiy A
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This article is based on the analysis of surgical treatment peculiarities of 641 patients with post-osteomyelitis long bones defects. The average age of patients at the time of hospital admission was 32,4 ± 0,7 and ranged from 4 to 70 years. Most of them were people of active working age (476 (74.3%)) and male (523 (81.1%)). In this observation group 566 (88.3%) patients had the osteomyelitis process of the traumatic origin, including post-surgical (n = 155) and post-gunshot injuries (n = 13). Chronic hematogenous osteomyelitis was diagnosed in 75 (11.7%) patients. Most patients had lower extremity bones problems, including 444 tibia defects and 142 femoral bone defects. Much fewer patients had the osteomyelitis process of the upper extremity (humerus, radius, ulnar bone – 18, 19 and 18 respectively). Purulent necrotic process was accompanied by nonunion bone fragments in 160 (24%) patients, delayed union in 95 (14.6%) patients, false joint in 178 (27.6%) patients, segmental bone defect in 75 (11 5%) patients and bones union with edge defects and cavities in 143 (22.3%) patients. 340 (53%) patients were operated using the method of free bone grafting, and 301 (47%) patients were operated using the distraction method. The need to use the bilocal for external fixation on upper extremities occurs quite seldom (twice in our observations). Even when there is an upper extremity bone defect of several centimeters the preference should be given not to bilocal external fixation. When treating the lower extremities taking the above mentioned into consideration, segmental defects predominated, that is why the bilocal distraction-compression method of surgical treatment prevailed (98.6%). Thus, the main method of upper extremities long bones defects replacement is free bone grafting with segment fixation by the external fixation device, for lower extremities the is not-free main Ilizarov method, which allows to get positive results in 84.6% of patients with femoral bone problems and in 96.4% of tibia problems, mainly due to one-step treatment, directed simultaneously to inflammatory process elimination and maximum possible anatomical and functional restoration of the affected extremity


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_1 | Pages 78 - 78
1 Jan 2016
Cho W
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Introduction. The bone defect reconstruction is the first step of successful primary or revision TKA in case of large bone defect. If the defect is not reconstructed adequately, we can neither preserve knee joint function nor guarantee long survival of the implant. Allogeneic bone graft is known to be the treatment of choice in large defect. However the surgical technique is demanding and incorporation failure is constant issue of the allogeneic bone graft. We propose new bone defect reconstruction technique using multiple screws and cement. Material and method. From April 2012 to April 2014, 12 patients with large defect which could not be reconstructed with metal augment were involved in this study. The bone defect type was 10 cases of 2A and 2 cases of 2B according to AORI (Anderson Orthopedic Research Institute) classification. The defect was reconstructed with multiple screws and cementing technique by single surgeon (WS Cho). Average follow-up period was 15 months. (24 ∼ 1 month). Result. We analyzed 6 patients whose follow-up periods were more than 12 months. Average ROM was 107' and clinical scores were 86 by HSS, 93 by KS and 11 by WOMAC respectively. No complications such as infection and loosening were developed. Mean surgical time was 1 hour and 57 minutes. Conclusion. In short term follow-up, cementing technique using multiple screws can be a solution for large bone defect reconstruction


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 400 - 400
1 Apr 2004
Sato T Nakagawa A Umeda AH Terashima H
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Introduction: Filling bone defects with Polymethylmetaacrylate (PMMA) has been a easy, safe and reliable technique for past four decade. Newly developed Calcium Phosphate Paste (CPP) is a mixture of alpfa Tri Calcium Phsphate (TCP), Tetra Calcium Phosphate, Calcium Hydrogen Phosphate and Hydroxyapatite. This paste hardens in 10 minutes and its stffness increases to 80Mpa in seven days. It generates no heat, no gas and requires no organic solvents. In process of hardening, the TCP structure changes to Hydroxyapatite. Materials and methods: We have used CPP in two TKA cases associate with bone defect, and 14 fracture cases. In a MRSA infected revision TKA case, reconstruction was performed with PMMA-VCM articulated spacers, and they was fixed to bone with CPP-VCM. MRSA infection has been well controlled and weight bearing could be done in 10 days after surgery. In another TKA case, large bone necrosis in femoral condyle was filled with CPP and Cementless inplant were placed on it. Seven days later, this patient could walk with a cane. Results: CPP filled in bones were not absorbed for a year, and exess CPP in soft tissue were absorbed in several weeks. In 16 cases no side effects were observed during as long as one year. Conclusion: Handling CPP is much easier than Hydroxyapatite brick or granule. CPP can be useful for total joint arthroplasty, especially in large bone defect or infected cases. It can replace a part of PMMA as a bone cement for implants in the near future


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 71 - 71
1 Apr 2018
Tai IC Wang YH Ho ML
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In therapeutic bone repairs, autologous bone grafts, conventional or vascularized allografts, and biocompatible artificial bone substitutes all have their shortcomings. Tissue engineering may be an alternative for cranial bone repair. Titanium (Ti) and its alloys are widely used in many clinical devices because of perfect biocompatibility, highly corrosion resistance and ideal physical properties. An important progress in treating bone defects has been the introduction of bone morphogenetic proteins (BMPs), specifically BMP-2. The proteins induce osteogenic cell differentiation in vitro, as well as bone defect healing in vivo. In this study, we fabricated the titanium plate with dioxide creating by microarc oxidation (MAO) and then electronic deposition of Ca.P that can carrier recombinant human bone morphogenetic protein-2 (rhBMP-2) to enhance osteogenesis in vitro and bone formation in vivo. The rhBMP-2 was controlled released from MAO-Ca.P-rhBMP2 implant was maintain within 35days longer than Ti without MAO modification group and without CaP electronic deposition group. In addition, the in vitro results revealed that the bioactivity of rhBMP-2 released from MAO-Ca.P-rhBMP2 implant with an ideal therapeutic dose was well maintained. In vivo, the critical-sized defect (20-mm diameter) of New Zealand White rabbits was used to experiment. We concluded that sustained controlled-release of rhBMP-2 above a therapeutic dose could induce osseointegration between the implant and surrounding bone the rate of bone formation into the implant and produce neovascularization. Our study combined the concept of osteoconductive and osteoinductive to do the bone tissue regeneration


In severe cases of total knee & hip arthroplasty, where off-the-shelf implants are not suitable (i.e., in cases with extended bone defects or periprosthetic fractures), 3D-printed custom-made knee & hip revision implants out of titanium or cobalt-chromium alloy represent one of the few remaining clinical treatment options. Design verification and validation of such custom-made implants is very challenging. Therefore, a methodology was developed to support surgeons and engineers in their decision on whether a developed design is suitable for the specific case. A novel method for the pre-clinical testing of 3D-printed custom-made knee implants has been established, which relies on the biomechanical test and finite element analysis (FEA) of a comparable clinically established reference implant. The method comprises different steps, such as identification of the main potential failure mechanism, reproduction of the biomechanical test of the reference implant via FEA, identification of the maximum value of the corresponding FEA quantity of interest at the required load level, definition of this value as the acceptance criterion for the FEA of the custom-made implant, reproduction of the biomechanical test with the custom-made implant via FEA, decision making for realization or re-design based on the acceptance criterion is fulfilled or not. Exemplary cases of custom-made knee & hip implants were evaluated with this new methodology. The FEA acceptance criterion derived from the reference implants was fulfilled in both custom-made implants and subsequent biomechanical tests verified the FEA results. The suggested method allows a quantitative evaluation of the biomechanical properties of custom-made knee & hip implant without performing physical bench testing. This represents an important contribution to achieve a sustainable patient treatment in complex revision total knee & hip arthroplasty with custom-made 3D printed implants in a safe and timely manner


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 113 - 113
1 Mar 2010
Maruyama M Kitagawa K Ono S Tensho K
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A seventy-one-years old, female, has been treated by hemodialysis from 1977 due to renal failure. In April 19, 1985, she had Charnley Low Friction Arthroplasty for right hip joint. She often felt mild pain on the joint from 2000. Radiograph showed central migration of the socket and huge cystic bone defect of the acetabulum surrounded by thin cortical bone like an egg-shell form. Tear drop (acetabular floor) was diminished due to massive bone destruction or severe osteolysis. CT showed that the diameter of the cavity was approximately 10 cm. In March 1, 2002, the socket was upside down and moving freely in the cavity. The patient could not weight-bear on right lower extremity but walk without two crutches. Hemiarthroplasty for her left hip joint (contra-lateral side) was done in June 26, 2006, due to femoral neck fracture. Because of continuous right hip joint pain and walking disturbance, she underwent revision surgery in May 20, 2008. At the surgery, the cavity was empty except for the socket and fibrous tissue. Impaction grafting by using morselized allograft including porous and solid hydroxyapatite granules (100 g and 40 g each) was done after the socket and the tissue were extracted. A custom made all polyethylene socket (73 × 68 mm in diameter) was fixed by polymethylmetacrylate bone cement. Postoperative course was uneventful. She can walk with one crutch and ride on/off a vehicles without help four months postoperatively. It is often difficult to reconstruct acetabulum with large bone defect in revision total hip arthroplasty. Especially, almost of support rings with hook cannot be applied in the case that the tear drop is destructive or absorbed. Impaction bone grafting is commonly used for reconstruction of bone defect in revision surgery. However, the extremely thick graft for large bone defect is at risk of collapsing lead to implant migration. The socket used in the case was custom made jumbo type to reduce the thickness of impaction grafting. It seems to be one of resolution to use the custom made jumbo socket for the case with large defect of acetabulum in revision total hip Arthroplasty