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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 4  |  Issue : 1  |  Page : 20-25

Effectiveness of the management of bony articular collapse with bony defects in tibial plateau fractures with the use of genex: An absorbable calcium composite synthetic bone graft


Department of Trauma and Orthopaedics, Hull Royal Infirmary, Hull, England

Date of Web Publication3-May-2018

Correspondence Address:
Mr. Hemant Sharma
Hull Royal Infirmary, Hull
England
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jllr.jllr_9_17

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  Abstract 


Background: Synthetic grafts containing calcium sulfate and calcium phosphate are used to manage defects and support the articular surface in the management of periarticular fractures. GeneX is a synthetic graft that contains beta-tricalcium phosphate and calcium sulfate. Objectives: This study's aim was to assess the maintenance of elevated articular segments in tibial plateau fractures grafted with a synthetic calcium composite graft. Methods: Patients who received a single synthetic calcium composite graft intraoperatively at a single Level 1 Major Trauma Centre were identified. Case notes and radiographic images were reviewed to assess articular collapse, mode of fixation, maintenance of the articular surface, and reoperation rates. All intra-articular segments were elevated, graft applied, and combination of implant (circular frame/plate) were used for definitive fixation along with raft screws. There were forty tibial plateau with average preoperative collapse of 13.12 mm (2.2−50). Modes of definitive fixation: frame and raft screw technique 19, plate 18, and screws alone 3. Results: Two (5%) had postoperative collapse after anatomical reduction intraoperatively (one plate and one circular frame). Five demonstrated inadequate reduction intraoperatively, three circular frames, and 2 plates as definitive mode of stabilization. Four maintained inadequate reduction at final X-ray but one collapsed postoperatively. Of those with collapse, final average was 4.2 mm (3−5.3). Five patients required secondary surgery and none directly attributable to the synthetic graft. Conclusions: The use of the synthetic graft GeneX with subchondral raft screws along with circular frame or plate appears to be safe and effective in providing support to elevated intra-articular fractures and provides satisfactory outcomes in tibial plateau fractures.

Keywords: Circular frame, Gene-X, periarticular fractures, synthetic graft, tibial plateau fractures


How to cite this article:
Lowery K, Chatuverdi A, Blomfield M, Sharma H. Effectiveness of the management of bony articular collapse with bony defects in tibial plateau fractures with the use of genex: An absorbable calcium composite synthetic bone graft. J Limb Lengthen Reconstr 2018;4:20-5

How to cite this URL:
Lowery K, Chatuverdi A, Blomfield M, Sharma H. Effectiveness of the management of bony articular collapse with bony defects in tibial plateau fractures with the use of genex: An absorbable calcium composite synthetic bone graft. J Limb Lengthen Reconstr [serial online] 2018 [cited 2018 Sep 20];4:20-5. Available from: http://www.jlimblengthrecon.org/text.asp?2018/4/1/20/231791


  Introduction Top


Periarticular fractures of the proximal tibia remain a challenge to the orthopedic surgeon. The surgical management requires an anatomical reduction of the joint surface, stable fixation, and limb alignment to allow early rehabilitation and to minimize the development of arthritis.[1] These fractures are complex, and by the nature of the fracture configuration, once the joint surface is reconstructed, it often leaves a void underneath. Bone graft is often used to fill this space, to help maintain alignment through its use as a mechanical scaffold and provides a structure for new cells to form new bone in the healing process. Bone graft substitutes are widely used with various applications. They can be categorized into two main types, biological or synthetic.[2] Synthetic graft substitutes are broadly categorized into two groups, osteoinductive or osteoconductive.[2] They should ideally be biomechanically similar in properties to that of the bone to provide structural support and have a similar modulus of elasticity. They should be biocompatible, demonstrate minimal fibrotic reaction, and undergo remodeling.[3]

GeneX (Biocomposites, Keele, UK) is a commercially available synthetic graft which contains Beta-tri-calcium phosphate and calcium sulfate. It is a biphasic absorbable, osteoconductive (scaffold) putty, which can be injected subchondrally under the elevated intra-articular segment, thereby providing support, preventing collapse, and stimulating bone regrowth.[4] This composite has been manufactured through a proprietary process called zeta potential control, thus producing a bioactive material through the negative charges on the surface of the composite.[4]

This is a retrospective study, in which the aim was to assess the effectiveness of a single synthetic calcium composite graft (GeneX) in maintaining the position of elevated articular segments in tibial plateau fractures treated in a single level 1 major trauma centre (MTC).


  Methods Top


Forty patients were identified. All were over 16-year-old and had sustained an acute periarticular proximal tibial fracture that required surgical intervention with bone grafting. This was a retrospective study and before commencement, the appropriate ethical approval was obtained from the Local Ethics Review Board.

The inclusion criterion used was any patient who sustained an acute periarticular fracture of the proximal tibia that had undergone surgical fixation with the adjunctive use of a synthetic bone graft substitute. The exclusion criterion was any patient under the age of 16.

All patients had undergone either fixation with a circular frame, plating, or the use of screws alone. Raft screw technique was used as an adjunct to the frame or plate if required. All patients had the calcium composite graft used intraoperatively to provide structural support and provide osteogenic stimulus to fill defects once the articular congruity had been restored. All plateau fractures treated with plating were reduced under direct vision. Almost all plateau fractures treated with circular frame were reduced with radiological intraoperative guidance with indirect reduction.

The surgeries were performed within a single department at a Level 1 MTC. The calcium composite synthetic graft was used in accordance with the manufacturers' guidelines.

The postoperative regimen and rehabilitation were at the discretion of the operating surgeon and the team responsible for the care of that individual. Therefore, this was not specifically looked at in the context of this study.

The case notes and radiographic images were obtained. The pre- and intra-operative fluroscopic images and all postoperative images were analyzed for fracture type, the amount of articular collapse at the time of presentation, adequate restoration of the articular congruity, and any collapse seen in the postoperative period until union. Any further surgical procedures were also determined. The radiographic analysis was performed by two different individuals who were not involved directly in the surgical procedures and an average for each measurement was obtained for analysis. Analysis involved measurements taken on routine anteroposterior (AP) and lateral radiographs obtained during clinical follow-up. These were validated and checked for accuracy by the senior author. Greater than 2 mm was used as a marker for evidence of collapse on plain radiographs.

The primary outcome measures for this study are to assess the effectiveness of the calcium sulfate graft in fracture management as a bone graft substitute. We measured time to union and the maintenance of radiological alignment with respect to the use of the graft as a supporting scaffold. The secondary outcome measures were secondary surgery related to the use of the graft. Forty periarticular proximal tibial fractures were identified. All required elevation of an articular segment and application of the calcium composite graft. Following elevation, patients underwent plate fixation, circular frame, or screws only. [Figure 1] demonstrates elevation of an articular segment with circular frame application. [Figure 2] demonstrates fixation with screws alone.
Figure 1: (a and b) Fracture configuration shown on CT, (c) Elevation of articular surface, (d and e) Application of frame with GeneX application, (f) Following frame removal demonstrating maintenance of articular surface

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Figure 2: Fixation with screws

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Ethical approval

This study has been approved by the appropriate Ethical Committee and has therefore been performed in accordance with the pertinent ethical guidelines.


  Results Top


Fracture type and fixation method

The fractures were classified using the Müller AO classification. Analysis was performed to determine if there were any differences in the amount of articular collapse with the different fracture configurations according to the AO classification. An ANOVA statistical analysis was performed which resulted in P = 0.27 showing no statistical differences between the groups. There were 5-41B2, 17-41B3, 4-41C1, 2-41C2, and 12-41C3. There were no preoperative images to calculate the amount of articular collapse in two patients. The fixation methods used were frame and raft screw technique (19), plate (18), and screws alone (3).

Articular collapse

The mean preoperative joint depression was 13.12 mm (range 2−50 mm). Intraoperatively, all but five were restored anatomically, as assessed on the images obtained intraoperatively. Postoperatively, two (5%) patients demonstrated articular collapse, a 41B3 and 41C3, both had undergone plate fixation. Both of these patients underwent further surgical procedures unrelated to the articular collapse or the graft. A further five (12.5%) patients demonstrated articular incongruity on radiographs due to inadequate reduction intraoperatively (three circular frame and 2 plates). Four patients maintained the position on final X−rays, but one patient had further collapse on postoperative X-rays. One of these patients demonstrated collapse associated with a nonunion. This patient underwent bone marrow aspirate concentrate (BMAC) and went on to achieve union with no further surgical intervention needed. In all cases, it was felt on the radiographic images that the graft had been placed within the defect but not sufficiently subchondral to obtain the structural support that the graft offers to the elevated segment [Figure 3]. Overall 17.5% of cases demonstrated articular incongruity on radiographic analysis in the period from surgical intervention until radiographic union, three (7.5%) patients demonstrated collapse of the articular segment from the position achieved intraoperatively, none however required further surgery related to the use of GeneX or the articular surface collapse. The final average articular incongruity of those surfaces which had undergone collapse was 4.2 mm (3−5.3).
Figure 3: Postoperative collapse of articular surface (a) fracture configuration, (b and c) Intra-operative views following frame application and elevation of articular surface, (d-f) Demonstrating collapse of articular surface

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Union

Within this study period, all patients went onto union. Union was established radiologically and clinically. Radiological assessment evaluated healing of three cortices, clinical, the absence of pain or tenderness over the fracture site. In the circular frame group, all underwent two-stage reloading process before removal. The first stage involved loosening of threaded rods and the second stage removal of the threaded rods and functional loading. This aided in confirmation of union clinically. Clinical union was determined from medical records. The mean time to union was 188 days (range: 55−522 days), one patient is not included in the calculation as he were transferred back to the referring hospital; however, he has gone on to unite satisfactorily resulting in a 100% union rate. One patient required an additional procedure of BMAC injection and bone grafting to achieve union but following this went onto unite satisfactorily.

Further surgery/complications

There was one complication associated with the application of the graft, wound leakage postoperatively with full resolution, and satisfactory healing. Other complications noted were four pin site infections, one superficial abscess which resolved with intravenous antibiotics, and one arterial injury intraoperatively requiring vascular intervention. Five patients required secondary surgery, none directly attributable to the use of the graft. One had a circular frame which lost position and following collapse the whole frame was revised and articular segment re-elevated. Another underwent BMAC injection and bone grafting and went on to unite. Another patient maintained the elevated articular segment (following fixation with plate) but collapsed in the metaphyseal region and developed a malunion, requiring periarticular osteotomy and correction of the deformity. One patient healed satisfactorily but developed a deep infection and requested and underwent amputation. The remaining patient had removal of hardware due to late infection. The patient had sustained a laceration near to the old incision site which went on to develop infection of the underlying metalwork. Following removal, the patient had a full recovery.


  Discussion Top


Periarticular fractures of the proximal tibia frequently involve depressed segments which require surgical stabilization. With elevation of these segments, there is a subchondral void which requires grafting.

The findings of this study suggest that the use of this synthetic calcium composite synthetic graft is safe and effective as a bone graft substitute. The majority of patients in this study achieved satisfactory union and one patient required an additional bone grafting procedure. Regarding the maintenance of the articular congruity, although 7.5% did demonstrate >2 mm collapse from position achieved none of these patients required any further intervention.

The limitations in this study were the small number of patients involved and the retrospective nature of the study. The authors also appreciate that this study did not evaluate the functional outcomes or patient satisfaction. The study compared different modes of fixation by different surgeons. This study involved all the patients operated on in the treating hospital that used GeneX. The surgery was carried out by different surgeons and therefore technique and rehabilitation differed, as did the follow-up radiograph timings. However, the aim and focus of this study were to assess the effectiveness of a single synthetic calcium composite graft (GeneX) in its role as a graft in its structural and osteogenic capacities, analyzed radiologically.

In the evaluation and analysis of the radiographs, only standard AP and lateral views were obtained. The authors accept that this was not ideal, but this maintained the consistency in the study to evaluate collapse seen in the postoperative period until union. A proportion of the patients studied had comminuted fractures and therefore it was not always possible to reduce anatomically. The authors feel this is more related to fracture anatomy than actual surgical technique. Although our aim was to reduce articular surfaces anatomically, there is evidence that small articular incongruity is well tolerated, as long as the alignment has been restored and there was no valgus instability.[5],[6] A study looking at contact stresses within the joint at the point of incomplete reduction using Fujifilm analysis demonstrated that peak pressures locally at the site of incongruity were only 75% greater than the anatomical pressures. The authors concluded that the articular incongruity of magnitudes 5−10 mm are probably within long-term tolerance of an articular joint provided they occur in small portions of the joint.[7]

Another limitation in this study was that the postoperative regimen in this study was at the discretion of the operating surgeon. The weight-bearing status of the individual patients was not analyzed in this study. Generally, patients who underwent circular frame fixation were allowed to weight bear earlier; however, the authors cannot comment on the relationship to this collapse of the articular surface. However, the literature demonstrates that weight bearing may not have a large effect on fracture collapse following surgical intervention. AO recommendations following surgical fixation of tibial plateau fractures emphasize non-weight bearing or partial weight bearing for 10−12 weeks following surgery.[8] A recent study, however, demonstrated that a large number of surgeons do not follow these guidelines and are allowing earlier weight bearing.[9] In one study, it has been demonstrated that the peak joint reaction force in the knee during walking was not associated with excessive migration of the fracture fragments. The authors demonstrated that, during the stance phase, the force passing through the joint had a positive association with fracture migration but was not sufficient to exceed the elastic limit of the fracture construct. They comment that immediate weight bearing may be a safe option.[10] Another study has demonstrated that early weight bearing did not produce depression more than 2 mm.[11]

Synthetic bone grafts containing calcium phosphate have been used with success to maintain the articular congruity.[12],[13],[14] Autografts have both osteoconductive and osteoinductive properties; however, they do not have the mechanical stability to allow early postoperative weight bearing.[15] Calcium phosphate and calcium sulfate containing compounds have been shown to provide an immediate structural support with osteoinductive properties.[15] Calcium phosphate is known to be osteoconductive. The calcium phosphate allows cells such as osteoblasts to attach to it and proliferate and differentiate.[16] Osteoblasts produce collagen Type 1, osteoid, matrix proteins, and alkaline phosphatase which are all involved in the regulation and formation of bone.[17] However, it is not osteoinductive and therefore compounds such as beta-tricalcium phosphate are combined to provide these osteoinductive properties.[4] Combining calcium sulfate and calcium phosphate containing materials provides osteoconductive and mechanical support.[18] One school of thought is that voids created by elevation of articular fragments, do not need to be filled; however, the authors feel that subchondral support after elevating the fragments, decreases the risk of collapsing.[19] This is particularly relevant in comminuted fractures, where implant support can be precarious.

GeneX (Biocomposites) is a synthetic graft which contains beta-tricalcium phosphate and calcium sulfate with a negative zeta potential. GeneX is engineered to deliver both bioactive and biphasic properties.[4] The calcium sulfate acts as a barrier to prevent initial soft tissue in-growth and the beta-tricalcium phosphate acting as a scaffold. The negatively charged surface chemistry increases concentrations of key markers of osteoblast activity.[4]

Studies demonstrating the use of calcium phosphate containing bone graft substitutes have demonstrated good results in maintenance of the articular reduction.[12],[13],[14] Welch et al. demonstrated in a goat model that a calcium phosphate (Alpha-BSM) displayed sufficient mechanical properties within defects to prevent fragment subsidence with immediate postoperative weight bearing. It was shown to demonstrate significantly less subsidence than autologous graft in comparison. The authors suggested that calcium phosphate cement may serve as an alternative to autologous bone graft.[14]

Keating et al. in a prospective study using calcium phosphate cement (Norian SRS) in tibial plateau fractures in combination with minimal internal fixation demonstrated satisfactory reduction in most and maintained this (84%). The authors concluded that the patients who collapsed tend to be elderly.[12] There were few complications and these were not attributed to the use of the cement.[5] Russel et al. also demonstrated a statistically significant rate of subsidence with autologous bone graft in a comparative study between autologous bone graft and calcium phosphate cement.[13]

Studies have looked into the zeta potential of bone and its relationship to the piezoelectric effect, and ability of biomaterials to bond with osteoblasts. One study demonstrated that the zeta potential analysis is an effective predictor of the attraction of biomaterials to bone and osteoblasts.[20] The authors looked at three biomaterials used in arthroplasty surgery, among these one of the materials studied was hydroxyapatite. They concluded that calcium phosphate ceramics are suitable for bone scaffold use in respect to osteoblast seeding and attachment to existing bone.[20] Another study reported on a case, in which a calcium composite material with zeta potential control (Fortoss Vital, Biocomposites) was implanted and utilized for maxillary sinus floor augmentation. The authors found it to be a promising biomaterial for osseointegration for dental implants although it is limited as the conclusion is based on a single case.[21]

Accurate placement of GeneX is critical in preventing the collapse of the elevated articular segment. GeneX is a moldable putty and can be placed precisely under the elevated segment to provide adequate support. Inability to place putty under the elevated intra-articular segment may lead to subsequent collapse, which may have contributed to the collapse seen in our study. Although this is not the only reason for collapse of elevated intra-articular segments, we believe that inadequate support under the elevated segment is an important factor.

The authors could not find any studies or reports for GeneX specifically on its uses in maintain articular restoration. There have been reported adverse effects with one paper showing a 16% complication rate with soft tissue inflammation.[22] However, our work finds no such complications associated with the use of GeneX, in a study of similar size. The indications for use differed as did the location of application. One study in a sheep vertebral body defect model studied the use of a calcium composite material (GeneX paste) in comparison to polymethylmethacrylate cement. They looked at computed tomography and histological analysis at 0, 8, 16, and 36 weeks after implantation. The authors demonstrated a superior result with the graft with extensive bone formation at 8 weeks and gradual incorporation of the graft. New bone formation was higher at 8, 16, and 36 weeks with almost complete regeneration by 36 weeks. The authors commented on further studies needed to assess the mechanical strength up to 8 weeks, Up to 8 weeks the cement was found to have increased compressive strength and stiffness in comparison to the graft.[23]


  Conclusions Top


This study demonstrates that the application of GeneX for periarticular proximal tibia defects after restoration of articular congruity is safe, effective, and provides adequate support. The authors would suggest that GeneX as a bone graft substitute is a useful adjunct in the treatment of these complex fractures.

Financial support and sponsorship

Three of the authors received a financial payment from Biocomposites Limited for their contribution to the study. Biocomposites had no participation in the study other than financial payment.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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12.
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Russell TA, Leighton RK, Alpha-BSM Tibial Plateau Fracture Study Group. Comparison of autogenous bone graft and endothermic calcium phosphate cement for defect augmentation in tibial plateau fractures. A multicenter, prospective, randomized study. J Bone Joint Surg Am 2008;90:2057-61.  Back to cited text no. 13
    
14.
Welch RD, Zhang H, Bronson DG. Experimental tibial plateau fractures augmented with calcium phosphate cement or autologous bone graft. J Bone Joint Surg Am 2003;85-A: 222-31.  Back to cited text no. 14
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Kulkarni S, Tangirala R, Malve SP, Kulkarni MG, Kulkarni VS, Kulkarni RM, et al. Use of a raft construct through a locking plate without bone grafting for split-depression tibial plateau fractures. J Orthop Surg (Hong Kong) 2015;23:331-5.  Back to cited text no. 19
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Smeets R, Kolk A, Gerressen M, Driemel O, Maciejewski O, Hermanns-Sachweh B, et al. Anew biphasic osteoinductive calcium composite material with a negative zeta potential for bone augmentation. Head Face Med 2009;5:13.  Back to cited text no. 21
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Friesenbichler J, Maurer-Ertl W, Sadoghi P, Pirker-Fruehauf U, Bodo K, Leithner A, et al. Adverse reactions of artificial bone graft substitutes: Lessons learned from using tricalcium phosphate geneX®. Clin Orthop Relat Res 2014;472:976-82.  Back to cited text no. 22
    
23.
Yang HL, Zhu XS, Chen L, Chen CM, Mangham DC, Coulton LA, et al. Bone healing response to a synthetic calcium sulfate/β-tricalcium phosphate graft material in a sheep vertebral body defect model. J Biomed Mater Res B Appl Biomater 2012;100:1911-21.  Back to cited text no. 23
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