Voriconazole Is Cytotoxic at Locally Delivered Concentrations: A Pilot Study

Background

Fungal infections are rare but major problems when they involve orthopaedic implants. Preferred treatment in North America is two-staged: resection and then delayed reconstruction, with local delivery of an antifungal between stages. The effect of voriconazole, a hydrophobic antifungal, on local tissues and wound healing is unclear.

Questions/purposes

We asked: (1) Is voriconazole cytotoxic to fibroblasts or osteoblasts at target concentrations for local delivery? And (2) if cytotoxic, can fibroblasts or osteoblasts resume proliferation after voriconazole is removed?

Methods

We exposed 5000 fibroblasts or osteoblasts/well to voriconazole concentrations of 0, 1, 5, 10, 25, 100, 500, 1000, 5000, 10,000, and 20,000 μg/mL (n = 4 wells/concentration) in 24-well plates. At 3 and 7 days, cell growth was assessed with alamarBlue^® and light microscopy. After Day 7, exposure to voriconazole was stopped and incubation continued for 4 days in medium with no voriconazole. On Day 11, cell growth (recovery) was assessed with alamarBlue^® and light microscopy.

Results

Increasing voriconazole concentration to more than 100 μg/mL decreased osteoblast and fibroblast growth. Cell growth recovered after 7 days’ exposure to 1000 μg/mL or less.

Conclusions

Voriconazole is cytotoxic to osteoblasts and fibroblasts, but cell growth recovers over 4 days after exposure to 1000 μg/mL or less.

Clinical Relevance

Cytotoxicity seen from voriconazole to mouse osteoblasts and fibroblasts occurs at concentrations achievable clinically from local delivery. It may be prudent to limit the dose of voriconazole in antibiotic-loaded bone cement.     

Antimicrobial Distribution From Local Delivery Depends on Dose

Background

Tissue distribution after local delivery has been quantified over a period of 5 hours on 7-T MRI in a rabbit model using gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) as an antimicrobial surrogate; however, it is unknown how the Gd-DTPA load in a local depot will affect the duration of high-concentration Gd-DTPA in local tissues after surgical débridement.

Questions/purposes

We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery.

Methods

A 1-cm³ soft tissue dead space was created in the quadriceps of seven rabbits and filled with gadolinium-loaded bone cement. At 7, 14, and 33 days, the volume of tissue with a Gd-DTPA concentration of more than 14 μg/mL was calculated from T1-weighted images using 7-T MRI. Differences in volumes of distribution were analyzed with ANOVA.

Results

The volume of tissue with more than 14 μg/mL Gd-DTPA was much larger from higher gadolinium loads on Day 7 (p = 0.02) (2121 mm³ for 10 g and 665 mm³ for 1 g) and smaller with time for the 10-g formulation (2121 mm³ on Day 7 and 1241 mm³ on Day 14).

Conclusions

Volume of distribution and duration of Gd-DTPA after local delivery increased with increasing load in the cement and decreased with time.

Clinical Relevance

For local delivery, high antimicrobial concentrations would be expected in greater volumes of tissue, for longer durations, when higher antimicrobial loads are used.     

Enhanced migration of human bone marrow stromal cells in modified collagen hydrogels

Purpose

Collagen I hydrogels are widely used as scaffolds for regeneration of articular cartilage defects. We hypothesised that ingrowth might be improved by removing the superficial layer of a compressed hydrogel. The control group consisted of the original unmodified product.

Methods

The migration of human bone marrow stromal cells (hBMSCs) into the hydrogel was evaluated by confocal microscopy. We quantified the DNA concentration of the hydrogel for each group and time point and evaluated the chondrogenic differentiation of cells.

Results

After one week, the detectable amount of cells at the depth of 26–50 μm was significantly higher in the modified matrix (MM) than in the non-modified matrix (NM) (p = 0.011). The maximum depth of penetration was 75 μm (NM) and 200 μm (MM). After three weeks, the maximum depth of penetration was 175 μm (NM) and 200 μm (MM). Likewise, at a depth of 0–25 μm the amount of detectable cells was significantly higher in the MM group (p = 0.003). After 14 days, the concentration of DNA was significantly higher in the samples of the MM than in the control group (p = 0.000). Staining of histological sections and labelling with collagen II antibodies showed that a chondrogenic differentiation of cells in the scaffold can occur during in vitro cultivation.

Conclusions

Removing the superficial layer is essential to ensuring proper ingrowth of cells within the compressed hydrogel. Compressed hydrogels contribute better to cartilage regeneration after surface modification.     

Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial

Objective

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is clinically used to treat neutropenia. G-CSF also has non-hematopoietic functions and could potentially be used to treat neuronal injury. To confirm the safety and feasibility of G-CSF administration for acute spinal cord injury (SCI), we have initiated a phase I/IIa clinical trial of neuroprotective therapy using G-CSF.

Methods

The trial included a total of 16 SCI patients within 48 h of onset. In the first step, G-CSF (5 μg/kg/day) was intravenously administered for 5 consecutive days to 5 patients. In the second step, G-CSF (10 μg/kg/day) was similarly administered to 11 patients. We evaluated motor and sensory functions of patients using the American Spinal Cord Injury Association (ASIA) score and ASIA impairment scale (AIS) grade.

Results

In all 16 patients, neurological improvement was obtained after G-CSF administration. AIS grade increased by one step in 9 of 16 patients. A significant increase in ASIA motor scores was detected 1 day after injection (P < 0.01), and both light touch and pin prick scores improved 2 days after injection (P < 0.05) in the 10 μg group. No severe adverse effects were observed after G-CSF injection.

Conclusion

These results indicate that intravenous administration of G-CSF (10 μg/kg/day) for 5 days is essentially safe, and suggest that some neurological recovery may occur in most patients. We suggest that G-CSF administration could be therapeutic for patients with acute SCI.     

Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, part 1: a phase I and IIa clinical trial

Objective

Based on the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) on experimental spinal cord injury, we initiated a clinical trial that evaluated the safety and efficacy of neuroprotective therapy using G-CSF for patients with worsening symptoms of compression myelopathy.

Methods

We obtained informed consent from 15 patients, in whom the Japanese Orthopaedic Association (JOA) score for cervical myelopathy decreased two points or more during a recent 1-month period. G-CSF (5 or 10 μg/kg/day) was intravenously administered for five consecutive days. We evaluated motor and sensory functions of the patients and the presence of adverse events related to G-CSF therapy.

Results

G-CSF administration suppressed the progression of myelopathy in all 15 patients. Neurological improvements in motor and sensory functions were obtained in all patients after the administration, although the degree of improvement differed among the patients. Nine patients in the 10-μg group (n = 10) underwent surgical treatment at 1 month or later after G-CSF administration. In the 10-μg group, the mean JOA recovery rates 1 and 6 months after administration were 49.9 ± 15.1 and 59.1 ± 16.3%, respectively. On the day following the start of G-CSF therapy, the white blood cell count increased to more than 22,700 cells/mm³. It varied from 12,000 to 50,000 and returned to preadministration levels 3 days after completing G-CSF treatment. No serious adverse events occurred during or after treatment.

Conclusion

The results indicate that G-CSF administration at 10 μg/kg/day is safe for patients with worsening symptoms of compression myelopathy and may be effective for their neurological improvement.     

Is it Time for Cementless Hip Resurfacing?

Background

Metal-on-metal bearing with cemented femoral component and cementless acetabular fixation is the current standard in surface replacement arthroplasty (RSA) of the hip. Because of concerns about the long-term survivorship of cemented stems in conventional hip arthroplasty, it seems logical to achieve cementless fixation on the femoral side with RSA.

Questions/Purposes

The goals of this review were to evaluate clinical and radiological data reported from previously published cementless RSA series. In addition, we intend to review author’s preliminary experience with Conserve Plus cementless devices specifically assessing the clinical outcomes, the complications rate, the survivorship, and the metallic ions levels measured in follow-up.

Methods

A references search was done with PubMed using the key words “cementless hip resurfacing”, “cementless hip resurfacing prosthesis”, and “femoral cementless hip resurfacing”. Additionally, the clinical outcomes, the complications rate, the survivorship, and the metallic ions levels were measured in 94 cementless Conserve Plus^© devices in 90 patients (68 males and 22 females) with a mean age of 41.1 years (18–59). Mean follow-up was 13.1 months (8–16).

Results

No revision was performed during the observed follow-up. Neither radiological signs of loosening nor neck narrowing >10% were evident. Chromium and cobalt levels in whole blood samples rose respectively from 0.53 μg/l (0.1–1.7) to 1.7 μg/l (0.6–2.9) and from 0.54 μg/l (0.1–1.4) to 1.98 μg/l (0.1–2.8).

Conclusions

Cementless “fit and fill” femoral-side fixation, which seems to be potentially evolved and design-related, should be considered for future hip-resurfacing device generations.     

Long-term follow-up and metal ion trend of patients with metal-on-metal total hip arthroplasty

Purpose

Long-term studies are required to support the use of metal-on-metal (MoM) bearings in total hip arthroplasty (THA) given the concern about systemic metal ion release and reports of adverse local soft tissue reactions. The purpose of this study was to report the seven to 13-year clinical, radiographic, and metal ion results in patients following MoM THA.

Methods

We studied 163 prostheses after second-generation MoM THA between July 1997 and November 2003. Cobalt and chromium metal ions were collected using whole and analysed by inductively-coupled plasma-mass spectrometry.

Results

The mean follow-up was 8.87 years (range, 7–13 years). Four hips (2.5 %) were revised. The Kaplan-Meier survivorship was 91.3 % for revision for all causes, and 97.5 % when excluding the hips revised for a manufacturer’s defect. Median whole blood cobalt levels peaked at a value of 2.87 μg/L at four years (p < 0.0001 vs. pre-operative) and subsequently decreased to 2.0 μg/L after nine years (p = 0.002 vs. four years). Median chromium levels maximally increased up to 0.75 μg/L after five years (p < 0.0001 vs. pre-operative) and tended to decrease thereafter to values of 0.56 μg/L after seven years.

Conclusions

This seven to 13-year follow-up study indicates that the clinical and radiological results following MoM THA are satisfactory with low revision rates. Cobalt and chromium ion levels peaked at four and five years, respectively, and gradually decreased thereafter.     

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

Introduction

As a powerful bone-inducing cytokine, rhBMP-2 has been used as a bone graft substitute in combination with animal-derived collagen to achieve interbody or posterolateral spinal fusion. Successful interspinous process fusion using rhBMP-2 in combination with synthetic carrier materials would offer a safe, minimally invasive spinal fusion option for the treatment of spinal disorders. The aims of the present study were to achieve interspinous process fusion by implanting rhBMP-2-retaining degradable material instead of bone grafting and to evaluate efficacy for vertebral stabilization.

Materials and methods

A polymer gel (200 mg), β-tricalcium phosphate powder (400 mg), and rhBMP-2 (0, 30, 60 or 120 μg) were mixed to generate a plastic implant, which was then placed during surgery to bridge the L5–6 interspinous processes of 58 rabbits. Control animals received implants either without rhBMP-2 or with autogenous bone chips from the iliac crest. L5–6 vertebrae were recovered 8 weeks postoperatively. Interspinous process fusion was evaluated by radiography, biomechanical bending test, intradiscal pressure (IDP) measurement, and histology.

Results

In bending tests, strength of fusion was significantly greater in BMP60 and BMP120 groups than in sham, BMP0, BMP30 or autogenous bone groups. IDP at L5–6 was significantly reduced in BMP60 and BMP120 groups compared to sham, BMP0, BMP30, and autograft groups. Histologically, coronal sections of the fusion mass showed a bone mass bridging both spinous processes.

Conclusion

Solid interspinous process fusion was achieved in rabbit models by 8 weeks after implanting the biodegradable bone-inducing material. These results suggest a potential new less-invasive option without bone grafting for the treatment of lumbar disorders.     

The efficacy of immediate versus delayed antibiotic administration on bacterial growth and biofilm production of selected strains of uropathogenic Escherichia coli and Pseudomonas aeruginosa

Purpose

The treatment of urinary tract infections (UTI) with antibiotics is commonly used, but recurrence and antibiotic resistance have been growing and concerning clinicians. We studied whether the rapid onset of a protective biofilm may be responsible for the lack of effectiveness of antibiotics against selected bacteria.

Materials and Methods

Two established uropathogenic Escherichia coli strains, UTI89 and CFT073, and two Pseudomonas aeruginosa strains, PA01 and Boston-41501, were studied to establish a reliable biofilm formation process. Bacterial growth (BG) was determined by optical density at 600 nm (OD 600) using a spectrophotometer, while biofilm formation (BF) using crystal violet staining was measured at OD 550. Next, these bacterial strains were treated with clinically relevant antibiotics, ciprofloxacin HCl (200 ng/mL and 2 μg/mL), nitrofurantoin (20 μg/mL and 40 μg/mL) and ampicillin (50 μg/mL) at time points of 0 (T0) or after 6 hours of culture (T6). All measurements, including controls (bacteria -1% DMSO), were done in triplicates and repeated three times for consistency.

Results

The tested antibiotics effectively inhibited both BG and BF when administered at T0 for UPEC strains, but not when the antibiotic administration started 6 hours later. For Pseudomonas strains, only Ciprofloxacin was able to significantly inhibit bacterial growth at T0 but only at the higher concentration of 2 μg/mL for T6.

Conclusion

When established UPEC and Pseudomonas bacteria were allowed to culture for 6 hours before initialization of treatment, the therapeutic effect of selected antibiotics was greatly suppressed when compared to immediate treatment, probably as a result of the protective nature of the biofilm.     

Quantifying subtle but persistent peri-spine inflammation in vivo to submicron cobalt–chromium alloy particles

Purpose

We evaluated the consequences of cobalt–chromium alloy (CoCr) wear debris challenge in the peri-spine region to determine the inflammation and toxicity associated with submicron particulates of CoCr-alloy and nickel on the peri-spine.

Methods

The lumbar epidural spaces of (n = 50) New Zealand white rabbits were challenged with: 2.5 mg CoCr, 5.0 mg CoCr, 10.0 mg CoCr, a positive control (20.0 mg of nickel) and a negative control (ISOVUE-M-300). The CoCr-alloy and Ni particles had a mean diameter of 0.2 and 0.6 μm, respectively. Five rabbits per dose group were studied at 12 and 24 weeks. Local and distant tissues were analyzed histologically and quantitatively analyzed immunohistochemically (TNF-α and IL-6).

Results

Histologically, wear particles were observed in all animals. There was no evidence of toxicity or local irritation noted during macroscopic observations in any CoCr-dosed animals. However, Ni-treated control animals experienced bilateral hind leg paralysis and were euthanized at Day 2. Histopathology of the Ni particle-treated group revealed severe neuropathy. Quantitative immunohistochemistry demonstrated a CoCr-alloy dose-dependent increase in cytokines (IL-6, TNF-α, p < 0.05) at 12 and 24 weeks.

Conclusions

Subtle peri-spine inflammation associated with CoCr-alloy implant particles was dose dependent and persistent. Neuropathy can be induced by highly reactive Ni particles. This suggests peri-spine challenge with CoCr-alloy implant debris (e.g., TDA) is consistent with past reports using titanium alloy particles, i.e., mild persistent inflammation.     

Pravastatin suppresses matrix metalloproteinase expression and activity in human articular chondrocytes stimulated by interleukin-1β

Background

Matrix metalloproteinases are catabolic enzymes that play a key role in the articular cartilage degeneration evident in degenerative and inflammatory conditions of articular cartilage. The aim of this study is to assess the ability of pravastatin to modify matrix metalloproteinase (MMP) messenger RNA (mRNA) expression and enzyme activity in a culture of normal human chondrocytes stimulated by interleukin-1β.

Materials and methods

Normal human chondrocytes were stimulated with interleukin (IL)-1β for 6 h to induce MMP expression, simulating a catabolic state, and then treated with pravastatin (1, 5 and 10 μM) for a further 18 h before cell lysates and supernatants were harvested. Cells stimulated with IL-1β but not treated with pravastatin served as controls. Real-time polymerase chain reaction (PCR) was used to assess expression of MMP-3 and MMP-9 mRNA. MMP enzyme activity was assessed using a fluorescent MMP-specific substrate. Statistical analysis was performed using analysis of variance (ANOVA).

Results

MMP-3 and MMP-9 mRNA expression was reduced at all concentrations tested with statistically significant trends in reduction (p = 0.002 and <0.001, respectively). Analysis of culture supernatants revealed that pravastatin treatment led to a reduction in total MMP activity but not to a statistically significant degree (p = 0.07).

Conclusions

Treatment with pravastatin of stimulated human chondrocytes leads to significant down-regulation of selected MMP genes and a non-significant reduction in MMP enzyme activity. Our results provide further evidence that statins may have a role to play in future treatment of disease affecting articular chondrocytes.     

In Vitro Elution Characteristics of Vancomycin in a Composite Calcium Phosphate/Calcium Sulfate Bone Substitute

Background

Periprosthetic joint infection is a particularly difficult orthopedic problem, complicating a growing number of revision procedures. Joint debridement and systemic antibiotics are the mainstay of treatment, yet difficulty remains in maintaining a minimum inhibitory concentration of antibiotic at the localized site of infection.

Study Aims

This study analyzes the elution characteristics of a 40%bwt calcium phosphate–60%bwt calcium sulfate composite, at varying concentrations of vancomycin.

Methods

Four groups of varying concentrations of vancomycin (2.63%bwt, 5.13%, 9.76%, and 17.78%) were mixed with one pack of the composite cement. At designated time intervals up to 28 days, the antibiotic concentration was detected using fluorescence polarization immunoassay and the elution trends compared.

Results

The elution rate of each of the four groups decreased over time. At almost all of the intervals, the elution rates of the higher concentration groups were significantly higher than the lower concentration groups (P < 0.05).

Conclusions

Calcium sulfate reabsorbs over a prolonged period, producing porosity which allows for new bone ingrowth through occupation of osteoprogenitor cells and osteoblasts; while calcium phosphate acts as a long-term osteoconductive matrix.

Clinical Relevance

The results of this study suggest that vancomycin can be mixed affectively with a calcium sulfate/phosphate composite, both maintaining stability and eluting gradually over a clinically relevant period of time.     

Prosthetic radial head stem pull-out as a mode of failure: a biomechanical study

Purpose

Press-fit cementless radial head implant longevity relies on adequate bone ingrowth. Failed implant osseointegration remains a clinical concern and has been shown to lead to prosthetic failure. The purpose of this study was to test the hypothesis that implants with sufficient initial press-fit stability would be less likely to fail due to implant pull-out, as demonstrated by an increasing amount of energy required to remove the prosthesis from the canal.

Methods

Ten cadaveric radii were implanted with five sizes (6–10 mm in 1-mm increments) of grit-blasted, cementless radial head stems. A customised slap hammer was used to measure the energy required to remove each stem. Stem-bone micromotion was also measured.

Results

The suboptimally sized stem (Max − 1) (i.e. 1 mm undersized) required less energy (0.5 ± 0 J) to pull out than the optimally sized stem (Max) (1.7 ± 0.3 J) (p = 0.008). The optimally sized stem demonstrated greater initial stability (45 ± 7 μm) than the suboptimally sized stem (79 ± 12 μm) (p = 0.004).

Conclusions

This investigation demonstrates the importance of obtaining adequate press-fit stability for the prevention of radial head stem pull-out failure. These data add to the relatively scant knowledge in the literature regarding radial head biomechanics. The energy required to remove a prosthetic radial head ingrowth stem decreases in conjunction with diameter. The use of an inadequately sized stem increases the stem’s micromotion as well as the risk of prosthetic loosening due to pull-out.     

Etanercept treatment enhances clinical and neuroelectrophysiological recovery in partial spinal cord injury

Purpose

To investigate the effect of an anti-TNF-α agent (etanercept) on recovery processes in a partial spinal cord injury (SCI) model using clinical and electrophysiological tests.

Methods

Twenty-four New Zealand rabbits were divided into three groups: group 1 [SCI + 2 ml saline intramuscular (i.m.), n = 8], group 2 (SCI + 2.5 mg/kg etanercept, i.m., 2–4 h after SCI, n = 8) and group 3 (SCI + 2.5 mg/kg etanercept, i.m., 12–24 h after SCI, n = 8). Rabbits were evaluated before SCI, immediately after SCI, 1 week after, and 2 weeks after SCI, clinically by Tarlov scale and electrophysiologically by SEP.

Results

Tarlov scores of groups 2 and 3 were significantly better than group 1, 2 weeks after SCI. SEP recovery was significantly better in groups 2 and 3 than group 1, 2 weeks after SCI.

Conclusions

These results show that blocking TNF-α mediated inflammation pathway by an anti-TNF-α agent enhances clinical and electrophysiological recovery processes in partial SCI model.     

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells

Purpose

Many in vitro studies of the analysis of the lactoferrin (LF) effect on cells have been reported. However, no study has yet investigated the effect of LF on osteogenic differentiation of human adipose-derived stem cells (hADSCs). The aim of this study was to evaluate the effect of LF on osteogenic differentiation of human adipose stem cells.

Methods

The hADSCs were cultured in an osteogenic medium with 0, 10, 50 and 100 μg/ml LF, respectively. hADSC proliferation was analysed by Cell Counting Kit-8 (CCK-8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, von Kossa staining and real-time polymerase chain reaction (RT-PCR).

Results

Cell proliferation was significantly increased by LF in a dose-dependent manner from days 4 to 14. Cells cultured with 100 μg/ml LF presented a higher activity compared with the control. The deposition of calcium was increased after the addition of LF. The mRNA expression of type I collagen (COL-I), ALP, osteocalcin (OCN) and RUNX2 increased markedly as a result of LF treatment.

Conclusions

We have shown for the first time that LF could promote the proliferation and osteogenic differentiation of hADSCs, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.     

Liposomal Formulation Decreases Toxicity of Amphotericin B In Vitro and In Vivo

Background

Liposomal amphotericin B is locally delivered to treat fungal orthopaedic infections but little is known about local tissue toxicity, if any, that might be associated with local delivery.

Questions/purposes

(1) Is liposomal amphotericin B cytotoxic in vitro? (2) Is locally delivered liposomal amphotericin B toxic to tissue in vivo?

Methods

Mouse fibroblasts (BA LB/3T3 A31) and osteoblasts (MC3T3) were exposed to two formulations of amphotericin B (liposomal and deoxycholate) at concentrations of 0, 1, 5, 10, 100, 500, and 1000 μg/mL. Cell viability was determined by MTT assay after 1, 3, and 5 hours of exposure and a proliferation assay after 1, 4, and 7 days of exposure and then after 3 recovery days without drug. Tissue exposure occurred by local delivery of liposomal amphotericin B, 200 or 800 mg/batch antifungal-loaded bone cement (ALBC), or amphotericin B deoxycholate, 800 mg/batch ALBC in rat paraspinal muscles. White blood cell count (WBC) and serum amphotericin B levels were obtained on Days 1 and 3. Rats were euthanized at 2 and 4 weeks and semiqualitative histopathology was performed.

Results

Liposomal amphotericin B is cytotoxic in vitro but not toxic to tissues in vivo. All cells survived concentrations up to 1000 μg/mL for 5 hours, 100% ± 0%, but none survived ≥ 100 μg/mL for 7 days, 0% ± 0%. Fibrosis was seen adjacent to ALBC without inflammation or necrosis, indistinguishable from controls for both liposomal amphotericin B doses. Amphotericin B serum levels were all less than 1 µg/mL and WBC counts were all normal.

Conclusions

In vitro cytotoxicity to liposomal amphotericin B occurred but no adverse tissue reaction was seen in vivo.

Clinical Relevance

Local delivery of liposomal amphotericin B in ALBC was well tolerated by mouse tissue; however, clinical studies are needed to confirm this finding in humans.     

The accuracy and precision of radiostereometric analysis in monitoring tibial plateau fractures

Background and purpose

The application of radiostereometric analysis (RSA) to monitor stability of tibial plateau fractures during healing is both limited and yet to be validated. We therefore evaluated the accuracy and precision of RSA in a tibial plateau fracture model.

Methods

Combinations of 3, 6, and 9 markers in a lateral condyle fracture were evaluated with reference to 6 proximal tibial arrangements. Translation and rotation accuracy was assessed with displacement-controlled stages, while precision was assessed with dynamic double examinations. A comparison of error according to marker number and arrangement was completed with 2-way ANOVA models.

Results

The results were improved using more tantalum markers in each segment. In the fracture fragment, marker scatter in all axes was achieved by a circumferential arrangement (medial, anterior, and lateral) of the tantalum markers above the fixation devices. Markers placed on either side of the tibial tuberosity and in the medial aspect of the fracture split represented the proximal tibial reference segment best. Using 6 markers with this distribution in each segment, the translation accuracy (root mean square error) was less than 37 μm in all axes. The precision (95% confidence interval) was less than ± 16 μm in all axes in vitro. Rotation, tested around the x-axis, had an accuracy of less than 0.123° and a precision of ± 0.024°.

Interpretation

RSA is highly accurate and precise in the assessment of lateral tibial plateau fracture fragment movement. The validation of our center''s RSA system provides evidence to support future clinical RSA fracture studies.