Purpose: Micro-CT is efficient, non-destructive, and accurate for qualitative and quantitative studies of bone microarchitecture during fracture healing. A cell-based vascular endothelial growth factor (VEGF) gene delivery system can increase fracture healing. Three dimensional structural variation of new bone formation in rabbit fracture segmental defects was studied with micro-CT to determine how VEGF affects these microarchitectural differences for bone healing in various periods.

Method: All animal procedures were approved by the Animal Care Committee at St. Michael’s hospital. Ten millimeter segmental bone defects were treated by local injection with cell-based VEGF gene transfer (n=15), or control group with fibroblasts alone or saline only (n=15), to stimulate differences in bone healing. The animals were sacrificed and fracture healing specimens collected at 4, 8 and 12 weeks post surgery. The region of interest (ROI) was set where the segmental defect was located, and was selected for analysis from the recognizable margins of the original defect. To describe the topographic pattern of bone healing, the ROI was divided into three areas of equal volume: proximal, middle and distal. The new bone formation and mineralization at the defect sites were evaluated by bone structural parameters from the 3-D reconstruction of micro-CT.

Results: Macroscopic evaluation of the interfragmentary section from reconstructed micro CT scans, in the VEGF treated rabbits, showed abundant fragmentary bone filling the gap of the osteotomy at 4 weeks and abundant callus bridging the gap at 8 and 12 weeks. In the control group, only small amounts of sparsely formed bone were seen in the gap at 4 weeks. In the control group, the regenerate bone was ovoid around the bone sites and a big gap remained in the segmental bone defects at 8 and 12 weeks. The bone healing micro-structural differences between the two groups varied with the period of treatment, with more differences seen at 4 than 8 or 12 weeks.

Conclusion: Cell-based VEGF gene therapy enhances fracture healing of segmental defects, and this effect is best seen in the early period following defect creation.

Purpose: The mechanical behavior of human scapholunate ligaments is not described well in the literature regarding torsion. Presently, intact scapholunate specimens were mechanically tested in torsion to determine if any tensile forces were generated as a result.

Method: Scapholunate specimens (n=19) were harvested and inspected visually. Scaphoid and lunate bones were potted in square chambers using epoxy cement. The interposing ligaments remained exposed. Specimens were mounted in a specially designed test jig and remained at a fixed axial length during testing. Using angular displacement control, ligaments were subjected to a torsional motion regime that included cyclic preconditioning (25 cycles, 1 Hz, triangular wave, 5 deg max), ramp-up to 15 deg at 180 deg/min, stress relaxation for 120 sec duration, ramp-down to 0 angulation at 180 deg/min, rest period for 5–10 minutes, and torsion-to-failure at 180 deg/min. Torque and axial tension were monitored simultaneously.

Results: Tests showed a coupled linear relationship between applied torsion and the resultant tensile forces generated for the ligament during ramp-up (Torsion/Tension Ratio = 38.86 +/− 29.00 mm, Linearity Coefficient R-squared = 0.89 +/− 0.15, n=19), stress relaxation (Ratio = 23.43 +/− 15.84 mm, R-squared = 0.90 +/− 0.09, n=16), and failure tests (Ratio = 38.81 +/− 26.39 mm, R-squared = 0.77 +/− 0.20, n=16). No statistically significant differences were detected between the Torsion/Tension ratios (p=0.13) or between the linearity (R-squared) of the best-fit lines (p> 0.085).

Conclusion: A strong linear relationship between applied torsion and resulting tensile forces for the ligament was exhibited during all testing phases. This may suggest that there is interplay between torsion and tension in both the stabilization of the scapholunate ligament during normal physiological motion and during resistance to injury processes. This is the first report in the literature of the coupling of torsion with tension for the scapholunate ligament.

Purpose: The choice of irrigating fluid and delivery pressure remains controversial. Identifying surgeons’ preferences in techniques and the rationale for their choices may aid in focusing educational activities to the orthopaedic community as well as planning future clinical trials. Our objective was to clarify current opinion with regard to the irrigation of open fracture wounds.

Method: We mailed and delivered a cross-sectional survey using a sample-to-redundancy strategy to members of the Canadian Orthopaedic Association and attendees of an international fracture course (AO, Davos, Switzerland) to examine surgeons’ preferences in the initial management of open fracture wounds.

Results: Of the 1,764 surgeons who received the questionnaire, 984 (55.8%) responded. In the management of open wounds, most surgeons surveyed, 676 (70.5%), favoured normal saline alone, however 16.8% used Bacitracin. Many surgeons, 695 (71%) used low pressures when delivering the irrigating solution to the wound, however variation exists in what constituted high versus low pressure lavage. Surgeons supported the need for a clinical trial evaluating outcomes following both the use of different irrigating solutions as well as irrigating pressures [803 (84.8%) and 730 (77.6%) respectively].

Conclusion: The majority of surgeons favour both normal saline and low pressure lavage for the initial management of open fracture wounds.

Purpose: We conducted the first, multicentre, prospective cohort study to define the incidence of symptomatic venous thromboembolism (VTE) in patients with tibia and ankle fractures treated conservatively and relatively minor lower leg fractures. The reported incidence of deep vein thrombosis (DVT) using routine venography in patients with lower leg injury requiring cast immobilization is approximately 20–40%, which has lead to the routine use of anticoagulant prophylaxis for several weeks in many such patients. However the vast majority of venographically-detected DVTs are asymptomatic, distal thrombi whose clinical relevance is uncertain. Therefore venography is not the best outcome measure to assess the burden of clinically important VTE.

Method: Consecutive patients with tibia and fibula fractures (treated non-operatively) and patella and foot fractures, (treated operatively or conservatively) were assessed for eligibility at 5 Ontario hospitals. Patients were enrolled after informed consent within 96 hours of injury and were followed prospectively, by telephone, at 2, 6 and 12 weeks. Those with major trauma, active cancer, and previous VTE were excluded. Thromboprophylaxis was not allowed. Education regarding symptoms of VTE was provided at study entry and patients were asked about VTE symptoms at follow up. Suspected VTE was investigated in a standardized manner.

Results: From August 2002 to June 2005, 1200 patients were enrolled from 2446 consecutively screened patients. 98% of patients completed 3-month follow-up. The mean age was 45 years (16 to 93) and 60% were female. The most common fractures were fibular (39%) and most injuries were caused by falls (75%). 99 % of these fractures were unilateral. Most fractures did not require surgical repair (93%), and 82% of patients were immobilized by cast or splint for an average of 42 ±32 days. Overall, 7 patients had symptomatic, objectively confirmed VTE (2 proximal DVT, 3 calf DVT, 2 PE) with no fatal PE – an incidence of 0.6 % (95% CI 0.2 to 1.2).

Conclusion: Symptomatic VTE is an infrequent complication after these fractures without thromboprophylaxis. Therefore routine thromboprophylaxis is neither warranted, nor likely to be cost-effective in these patients. This study also highlights the significant discrepancy between clinical endpoint studies and studies using venography.

Purpose: Vascular Endothelial Growth Factor (VEGF) is vital for both angiogenesis and osteogenesis. The aim of this study was to investigate the effect of cell based VEGF gene delivery on the proliferation and mineralization of rabbit osteoblasts in vitro.

Method: Primary cultured rabbit osteoblasts were divided into four groups (each n=6). In Group I, osteoblasts were transfected with pcDNA3.1-VEGF; in Group II, osteoblasts were transfected with pcDNA-Efficiency Green Fluorescent Protein (EGFP); in Group III, osteoblasts were treated with the supernatant of fibroblasts that were transfected with VEGF genes; and in Group IV, osteoblasts were treated with the supernatant of fibroblasts that were transfected with EGFP. The cells were cultured in a-EME with 10% FBS, 2% penicillin/streptomycin with or without 10-^7 M dexamethasone and 50μg/ml L-ascorbic acid for 28 days. In the last 4 days, the cells were stimulated to initiate calcium mineralized nodule formation by adding 10 mM B-glycerophosphate. They were stained by the Von Kossa technique so that the number and the area of the nodules could be assessed by an imaging analysis system.

Results: The cells transfected by VEGF were indicated by the EGFP marked cells under a fluorescent microscope. There was a significant difference in the total nodule area (mean 18.38 mm² SE 3.73 and 5.07 mm² SE 0.55, p< 0.05) and count (mean 18.67 SE 3.22 and 2.17 SE 0.40, p< 0.001) between Group I and Group II (ANOVA, SPSS). More unmineralized and smaller nodules were found in Group III and Group IV. However, the nodules in Group III covered greater areas with dark brown staining in the cell culture dishes when compared with Group IV.

Conclusion: The observations indicate that cell based VEGF gene delivery has a positive effect on the proliferation and mineralization of osteoblasts. The greatest effect is seen with direct transfection of osteoblast cells. Cell-based VEGF gene therapy may be used to promote fracture healing.

Femur fractures are a complication of hip arthroplasty. When the stem is well fixed, fracture fixation is the preferred treatment option. Numerous fixation methods have been advocated, using plates and/or allograft struts. The study was conducted to determine the biomechanical characteristics of three constructs currently used for fixation of these fractures.

Vancouver type B1 periprosthetic femur fractures were created distal to a cemented hip stem implanted in third generation composite femurs. The fractures were fixed with one of three constructs: 1- A non-locking plate and allograft strut (NLP-A) 2- A locking plate and allograft strut (LP-A) 3- A locking plate alone. (LP) The struts were held in place with cables. There were five specimens in each group. Following fixation, the constructs underwent sinusoidal cyclic loading from 200 to 1200 N for 100000 cycles. Stiffness of the constructs was determined in bending, torsion and axial compression before and after cyclic loading. Axial load to failure was also determined.

Overall, cyclic loading had little effect on the mechanical properties of these constructs. The two constructs with allografts were significantly stiffer in coronal plane bending than the construct consisting of only a locking plate. There were no significant differences in axial or torsional stiffness between the constructs. Load to failure of the NLP-A (4095 N) and LP-A (4007 N) constructs was significantly greater than the LP construct (3398 N) (p=0.023 and p=0.044 respectively).

All three constructs tested retained their mechanical characteristics following 100000 cycles of loading. Our initial concerns that the cables holding the allograft strut would loosen appear unfounded. Allograft strut-plate constructs are stiffer in bending and have a higher load to failure than a stand-alone locking plate. When an allograft plate construct is chosen, locking screws provide no mechanical advantage in this experimental model.

Early fracture stabilization has been shown to reduce morbidity and mortality in the patient who is multiply injured. Controversy exists in terms of managing multiple trauma patients who sustain thoracic injuries along with femoral shaft fractures. The purpose of the present study was to determine whether the presence and treatment of femoral shaft fractures increases morbidity in patients with pulmonary contusions and to determine the effect of patient and surgical factors on outcome.

Patients that suffered chest injuries between January 1987 and April 2006 were identified from the prospectively collected trauma databases at two hospitals. Patient records were reviewed to verify all data. The diagnosis of pulmonary contusion was confirmed with radiologic or post-mortem investigations. All relevant patient and surgical data was collected. Exclusion criteria included severely injured patients (head/abdomen AIS> 3), age sixty years, death twenty-four hours after injuries occurred.

A total of 1190 patients with confirmed pulmonary contusions met inclusion criteria; there were 113 femoral shaft fractures (five bilateral). Patients in both the isolated pulmonary contusion and pulmonary contusion with femoral fracture had similar injury severity scores (ISS) and demographic information. Fractures were reduced with intramedullary nailing in 88% of cases. Mean age was thirty-five years. There were significantly more incidences of fat embolism syndrome and acute lung injury (ALI) in patients with femoral factures (twenty-four hours following the injury had significantly greater risk of developing ARDS (p< 0.05).

The presence of femoral shaft fractures in patients with pulmonary contusions increases the duration of admittance to hospital and can lead to higher rates of fat embolism syndrome and ALI, however it does not appear to impact overall mortality or contribute to the development of other common respiratory complications. Early reduction of shaft fractures is encouraged to further decrease complications.

Fat embolism syndrome (FES) is a potentially lethal condition commonly seen in poly-traumatised patients, particularly those with multiple long-bone fractures. Treatment has centered around supportive care and early fracture fixation. Several clinical small trials have suggested corticosteroids benefit patients with FES but its use remains controversial. Our objective was to determine the effect of corticosteroids in preventing FES in patients with multiple long-bone fractures.

We conducted a meta-analysis of randomised trials, searching computerised databases for published studies from 1966–2006. Additionally, we performed hand searches of major orthopaedic journals, meeting proceedings, and texts. Our primary outcome was the rate of FES. Secondary outcomes included presence of hypoxia, petechiae, mortality, infection, and delayed union.

Of the one hundred and four studies identified, nine were potentially eligible, and only seven met all our eligibility criteria. From our pooled analysis of three hundred and eighty-nine patients, we found that corticosteroids reduced the risk of FES by 78% (95%CI: 43–92%, heterogeneity p-value=0.62, I2=10%) and that only eight patients needed to be treated (NNT=7.5) to prevent one case of FES (95%CI: five to thirteen patients). We did not find any significant differences in the rates of mortality, infection, or delayed union.

The current evidence suggests that the use of corticosteroids is beneficial in the prevention of fat embolism syndrome in patients with multiple long-bone fractures. The use of corticosteroids does not appear to significantly increase the risk of complications although a confirmatory large randomised trial is needed.

We sought to establish whether fibroblasts transfected ex vivo could be delivered via gelfoam impregnated with a solution of transfected cells to achieve local transgene expression in a fracture site.

A 10 millimeter segmental bone defect was created after 12 mm periosteal excision and plated in the middle one third of each rabbit tibia. Dermal tissues were obtained and fibroblasts were cultured with DMEM. Fibroblasts were labeled with CMTMR and 5x106 labeled fibroblasts in 1ml PBS with 1x1 cm? Impregnated gelfoam was placed into the fracture gap (n=2). Twenty four hours after cell injection, the rabbits were killed and specimens were harvested from the fractured leg. Using SuperFect (Qiagen Inc), the primary fibroblasts were transfected with pcDNA-VEGF which was generated with the full length coding sequence of the human VEGF gene. A convenient reporter gene, Efficiency Green Fluorescent Protein (EGFP), was used for monitoring transfection of VEGF by fluorescence intensity. Experimental rabbits received 5.0 X 106 VEGF transfected cells in 1 ml PBS via gelfoam at the fracture sites. The animals were sacrificed at seven days (n=4), fourteen days (n=4) and twenty-one days (n=4) post surgery and the fracture site specimens were collected for analysis.

The fluorescently labeled cells with CMTMR were found at the fracture site and surrounding tissues. It was demonstrated that the labeled cells were delivered into the fracture gap, bone marrow and muscle surrounding a segmental defect in the rabbit. In the VEGF group, visualised VEGF immunostaining (brown) was shown in the fracture site around the Gelfoam; as well VEGF was distributed at sites of endochondral ossification. Visible bone formation was shown: VEGF promoted new bone formation by VonKossa staining (dark) and produced numerous vessels by CD31 positive staining (brownish black). The VEGF protein was detected in and around the fracture by ELISA.

This data encourages the further development of genetic approaches using cell based VEGF gene transfer without viral vectors to promote fracture healing.

Gaining stable fixation in cases of recalcitrant non-unions can be challenging. These cases can be accompanied by a segmental bone defect and disuse osteopenia. One strategy to gain stable fixation is the use of allografts. Both cortical struts and intramedullary fibular allografts have been used for this purpose in the femur, tibia and humerus. The present study aims to compare the mechanical properties a locking plate, an intramedullary fibular strut allograft and a cortical strut allograft in a femur model of segmental bone defect.

A transverse mid-shaft osteotomy was performed in fifteen third generation large composite femurs. Twelve millimeters of bone was resected to create a segmental bone defect. Fixation was undertaken as follows: Construct F (Fibula): Lateral Non Locking plate and Intramedullary Fibula Allograft Construct LP (Locking Plate): Lateral Locking Plate Constrcut S (Strut): Lateral Non-Locking Plate and Medial Cortical Strut Allograft Axial, Torsional and Bending Stiffness as well as Load-to-Failure were determined using an Instron 8874 materials testing machine.

Overall, construct S was the stiffest, construct F intermediate and construct LP the least stiff. Specifically, the S construct was significantly (p< 0.05) stiffer than the two other constructs in the axial, coronal plane bending, sagital plane bending and torsional modes. Construct F was significantly stiffer than construct LP in the axial and coronal plane bending modes only. Both the S construct (6108 N) and the F construct (5344 N) had a greater Load-to-Failure than the LP construct (2855 N) (p=0.005 and 0.001 respectively).

The construct with a lateral non-locking plate and a medial allograft strut was stiffer and had a higher load-to-failure than the construct consisting of a stand-alone locking plate. An intramedullary fibular allograft with a lateral non-locking plate had intermediate characteristics. Other factors, such as anatomic and biologic considerations need to be considered before choosing one of the above constructs. The allograft procedures should only be used once soft tissue coverage has been obtained and any infection eradicated.

Thirty total hip replacements in twenty-eight patients in which a Zirconia/Polyethylene articulation was utilized were compared to a control group undergoing total hip replacement utilizing Cobalt-Chrome/Polyethylene articulation. These patients were matched for gender, BMI and pre-operative diagnosis.

At nine years after implantation there was no difference in the functional outcome between the two groups and no difference in liner wear rate on x-ray (Livermore technique). There was a 27% revision rate in the Zirconia group compared to the 11.5% revision rate in the Cobalt-Chrome group.

Bearing surfaces require long- term clinical follow-up to validate in vitro performance.

To determine the benefit of Zirconia on polyethylene versus cobalt-chrome on polyethylene in total hip articulation.

Zirconia offers no advantage over a cobalt-chrome head in decreasing in vivo polyethylene wear at ten- year follow-up.

Newer bearing surfaces require long- term clinical follow-up to validate in vitro laboratory performance.

All primary total hip replacements at this institution are entered prospectively in a database and are assessed on an annual basis. All patients in this study were followed for a mean of nine years with a range of six to thirteen years.

Thirty cementless total hip arthroplasties were performed in twenty-eight patients utilizing a Zirconia head coupled with a polyethylene acetabular component. Twenty-six hips have been followed for a mean of nine years. These were matched to a control group of twenty-six hips in twenty-six patients utilizing a cobalt-chrome head coupled with an identical polyethylene liner followed for a mean of ten years (range five to fourteen years). There was no functional difference in outcome at nine years between the two groups utilizing the Livermore technique there was no difference in the liner wear rate between the two patient groups. However, seven hips (27%) of the Zirconia group required revision due to loosening and/or extensive osteolysis around the cup and only three hips (11.5%) required revision in the cobalt-chrome group. Our study demonstrates that although changes in component designs and materials may offer theoretical advantages over current components their effect in vivo remains questionable.

This study (n=126, mean age=68.8 years, males=62) evaluated pre-operative WOMAC pain and physical function, age, gender, general health status, revision severity classification, number of revisions, comorbidity and unilateral vs. bilateral surgery as predictors of WOMAC pain and physical function at twenty-four months post revision hip arthroplasty. Pain improved from 9.3 to 3.6 and physical function improved from 35.4 to 17.1. No factors were predictive of patient function. Decreased pain was predicted by less pain pre surgery (p=0.01) and being male (p=0.04).

To determine if pre-operative WOMAC pain and physical function, age, gender, general health status (SF-36), revision severity classification, number of revisions, comorbidity and unilateral vs. bilateral surgery are predictive of WOMAC pain and physical function at twenty-four months post revision hip arthroplasty.

Physical function at twenty-four months is not independently predicted by the pre-treatment factors evaluated in this study. Male patients with less pain pre surgery and little comorbidity have less pain post surgery.

With the exception of pre-treatment pain, the pre-treatment factors tested in this study provide minimal guidance in identifying factors that might be modified to enhance patient outcome.

This prospective cohort study included one hundred and twenty-six patients (mean age=68.8 years, males: females=62:64) who had revision for other than infection or peri-prosthetic fracture. On average from pre-surgery to twenty-four months post-surgery, WOMAC pain improved 9.3 to 3.6 and physical function improved from 35.4 to 17.1. In univariate analysis (t-test, p< 0.05), males tended to have better function (19.6 vs. 14.7) and reported less pain (4.4 vs. 2.8). No other factors were significant in univariate analysis. None of the a priori factors noted above were independently predictive of patient function at twenty-four months in the multivariate model (F=2.06, p=0.04, R²=0.16). Decreased pain with activity at twenty-four months independently was predicted by having less pain pre surgery (p=0.01), being male (p=0.04) and having fewer comorbidities (p=0.07) in the multi-variate model (F=2.9. p=0.004, R²=0.21).

Funding: This work was supported by a grant from The Arthritis Society