Monitor Fracture Healing Research Articles

In silico re-foundation of strain-based healing assessment of fractures treated with an external fixator

In the last decades, the literature has demonstrated a renewed interest in finding quantitative and non-invasive techniques for the assessment of bone fractures, by replacing X-ray images. Many different approaches have been proposed from ultrasounds to vibrations.This study aims to numerically assess the foundation of a method firstly proposed in 70’ years, based on strain gauges measurements on external fixators for fracture healing monitoring. The theoretical basis consists in the load transfer from the fixator to the bone caused by the callus stiffening during healing. The feasibility is questioned since the level of fixator strain and its variation in invivo conditions should be high enough to be detectable by the sensors.A finite element model of a fractured tibia phantom treated with a monolateral external fixator was developed and validated experimentally. Then, this reference model was used to simulate bone healing and to investigate the sensitivity of virtual strain measurements to callus geometry and loading conditions.The analysis of load distribution among fixator components and their strain maps allowed to identify optimum strain gauges locations which resulted on the pins more distant from the callus, regardless of the simulated conditions. Even in the worst case of a very thin (3 mm) transverse callus in constrained compression conditions, the strain level (≈100 με/100 N) and its variation per week (-50 με/100 N/wk) resulted measurable in the first healing phase, before plateau conditions occurring after about 6 weeks from fixation.A thicker callus causes higher strain levels and can significantly improve measurements, whilst the callus orientation and the loading conditions have a minor effect. However, in case of a free compression loading, also the rods could provide useful indications if sensorized.The results support the method applicability in invivo conditions for the considered test case. Further investigations will be addressed to evaluate the effect of the fixator structure and configuration as well as of patient specific healing timing on the method sensitivity.

Evaluation of Femoral Bone Fracture Healing in Rats by the Modal Damping Factor and Its Correlation With Peripheral Quantitative Computed Tomography.

IntroductionMonitoring the progress of fracture healing is essential in order to establish the appropriate timing that ensures adequate bone strength for weight-bearing. In the present experimental study on a rat model of femoral fracture healing, the measurement of bone density and strength by peripheral quantitative computerized tomography (pQCT) was correlated with the modal damping factor (MDF) method.MethodsFour groups of 12 male six-month-old Wistar rats each were anesthetized and submitted to baseline femoral pQCT and MDF scanning, followed by aseptic midshaft osteotomy of the right femur which was fixed by a locking intramedullary nail technique. The animals were left to recover and re-scanned following euthanasia of each group after six, eight, 10, and 12 weeks, respectively. The parameters measured by the pQCT method were total bone mineral density (BMD) and polar strength strain index (SSIp).ResultsFracture healing progressed over time and at 12 weeks post-osteotomy there was no statistically significant difference between the osteotomized right and the control left femurs regarding MDF, BMD, and SSIp measurements. The highest correlations for the osteotomized femurs were observed between MDF and BMD (r = -0.647, P = 0.043), and between MDF and SSIp (r = -0.350, P = 0.321), at 10 weeks postoperatively. The high to moderate correlations between MDF and BMD, and between MDF and SSIp respectively, support the validity of MDF in assessing fracture healing.ConclusionsBased on our findings in this fracture healing animal model, the results from the MDF method are reliable and correlate highly with the total BMD and moderately with the SSI polar values obtained by the pQCT method of bone quality measurement. Further studies are needed which may additionally support that the MDF method can be an attractive portable alternative to monitor fracture healing in the community.

A novel MRI compatible mouse fracture model to characterize and monitor bone regeneration and tissue composition

Over the last years, murine in vivo magnetic resonance imaging (MRI) contributed to a new understanding of tissue composition, regeneration and diseases. Due to artefacts generated by the currently used metal implants, MRI is limited in fracture healing research so far. In this study, we investigated a novel MRI-compatible, ceramic intramedullary fracture implant during bone regeneration in mice. Three-point-bending revealed a higher stiffness of the ceramic material compared to the metal implants. Electron microscopy displayed a rough surface of the ceramic implant that was comparable to standard metal devices and allowed cell attachment and growth of osteoblastic cells. MicroCT-imaging illustrated the development of the callus around the fracture site indicating a regular progressing healing process when using the novel implant. In MRI, different callus tissues and the implant could clearly be distinguished from each other without any artefacts. Monitoring fracture healing using MRI-compatible implants will improve our knowledge of callus tissue regeneration by 3D insights longitudinal in the same living organism, which might also help to reduce the consumption of animals for future fracture healing studies, significantly. Finally, this study may be translated into clinical application to improve our knowledge about human bone regeneration.

Early Experience with the Trochanteric Fixation Nail-Advanced (TFN-A): A Descriptive Review of Thirty-Four Cases from a Single Center.

The Trochanteric Fixation Nail-Advanced (TFN-A) is offered as a "next-generation" solution to the ever-increasing incidence of pertrochanteric and intertrochanteric fractures. It aims to build upon the success of earlier-generation proximal femur implants, while at the same time attempting to address complications, like varus collapse, cut-out, implant failure and anterior cortical perforation/impingement. It also aims to provide the surgeon with flexibility by offering varied options under a single implant system. This descriptive study looked at the early outcomes of the TFN-A as used in a single trauma centre. It attempts to shed light on the question of whether the TFN-A is at least equivalent to more established proximal femur implants in terms of fixation while reducing complication rates. Thirty-four patients who underwent fixation using the TFN-A at a single centre from October 2016 to July 2018 were retrospectively reviewed for this study. All surgeries were done by experienced orthopaedic surgeons. The decision for cement augmentation of the femoral head element was made on a case-to-case basis. Radiographs of the hip, pelvis and femora were taken to monitor fracture healing and evaluate post-fixation neck-shaft angle (NSA)/varus collapse, cut-out/cut-through, implant failure and anterior cortical impingement/perforation. All thirty-four patients had neck-shaft angles within 5 degrees of the contralateral hip immediately post-surgery. Two patients had varus collapse > 5 degrees on follow-up but did not progress to cut-out. Two patients had broken distal locking screws, albeit their fractures healed uneventfully. There were four cases of cement augmentation with "retrograde filling", wherein most of the cement went into the femoral neck. No patients experienced distal anterior cortical impingement or perforation. All but one patient subsequently progressed to full weight-bearing. Early experience with the TFN-A appears to suggest that it is at least comparable to preceding proximal femur nail devices in terms of fixation. Absence of anterior cortical impingement or perforation suggests that the TFN-A shows promise in addressing this issue. The incidence of "retrograde cement filling" is a previously unreported point of interest for head-neck element augmentation which requires further study.

Monitoring of fracture healing. Update on current and future imaging modalities to predict union

Fracture nonunion causes considerable patient morbidity and an associated burden to society. Traditional reliance on radiographs to monitor union has limitations as bridging callus of long bone fractures can take three or more months to occur. Computed Tomographic (CT) scanning is becoming increasingly popular and can evaluate bridging callus in the late stages of healing to confirm union. The use of dynamic contrast enhanced Magnetic Resonance Imaging (MRI) and advances in nuclear imaging may yield benefits in the assessment of the infected nonunion. Emerging evidence supports the use of ultrasound to detect bridging callus prior to radiographic confirmation and it may be of use to predict patients at high risk of nonunion. This paper is part of a Supplement supported by The Osteosynthesis and Trauma Care Foundation (OTCF).

Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models

Longitudinal in vivo micro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0–6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups. The established longitudinal in vivo micro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinal in vivo micro-CT for healing-phase-specific monitoring of fracture repair in mice.

Numerical evaluation of the mechanical environment of a fractured long bone for osteoporotic and non-osteoporotic subjects.

Competent fracture healing monitoring requires an extensive knowledge of the evolution of the mechanical environment of the healing bone during daily-life activities such as walking. Fractures are caused due to a traumatic incidence, while low trauma or fragility fractures can also occur due to osteoporosis. It is expected that the mechanical behavior of healing bones differs among osteoporotic and non-osteoporotic subjects. This work presents finite element simulations of gait analysis considering a fractured long bone at the hematoma stage. The aim is to investigate the evolution of the mechanical environment of the femur for an osteoporotic and a non-osteoporotic subject. This is the first computational study providing quantitative information for the impact of osteoporosis on the mechanical environment of the femur. It was shown, that higher deformation and equivalent stress values are calculated for osteoporotic bones during a gait cycle, while the highest values were observed in the femoral head.

Fracture Healing Monitoring by Impact Tests: Single Case Study of a Fractured Tibia With External Fixator.

The correct evaluation of the healing process is important to define proper times of fixator dynamization and removal, avoiding refractures. Unfortunately, a quantitative healing assessment is not yet available in clinical practice. The aim of the paper is to prove the feasibility of the mechanical vibration method to assess bone healing in fractures treated with external fixation, in in vivo conditions. The case study was a patient with a tibial fracture treated with a monoaxial fixator. The healing process was monitored for three months through a series of five impact tests. The pins screwed into the bone were used both to excite and measure vibrations. Fracture healing was quantitatively assessed by estimating the resonant frequencies of the leg. The first frequency increased of about 4% per week during the observation period. After the hard callus formation (13 week), also other frequencies increased within the range 1%–6% per week. X-ray observations confirmed the healing progress and proved the method potentiality. In addition, the vibratory response of the leg after fixator removal was evaluated and resulted characterized by five modes in the bandwidth 0–1000 Hz. The results suggest that the vibratory response of a fractured bone treated with external fixation can be a promising indicator for quantitative healing monitoring. The mechanical vibration method could be helpful for reducing X-ray exposure of patients and could be performed more frequently, as desirable for obtaining more attentive monitoring.

Ultrasound Bone Fracture Sensing and Data Communication: Experimental Results in a Pig Limb Sample

Approximately 6.3 million fractures occur each year in the United States alone. Accurately monitoring the progression of fracture healing is essential to be able to advise patients when it is safe to return to normal activity. The most common method used to confirm and monitor fracture healing is the acquisition of multiple radiographic images over the many months required for healing. This imaging method uses large expensive equipment and exposes patients to high levels of ionizing radiation. In the study described here, we tested another technology for monitoring fracture healing that could minimize the need for multiple radiographic images. We tested a piezoelectric transducer fixed to the surface of a bone that uses electromechanical impedance spectroscopy to measure simulated fractures and transmits the measurement data to an acoustic receiver located externally on the skin surface.

Bone surface enhancement in ultrasound images using a new Doppler-based acquisition/processing method

Ultrasound (US) imaging has long been considered as a potential aid in orthopedic surgeries. US technologies are safe, portable and do not use radiations. This would make them a desirable tool for real-time assessment of fractures and to monitor fracture healing. However, image quality of US imaging methods in bone applications is limited by speckle, attenuation, shadow, multiple reflections and other imaging artifacts. While bone surfaces typically appear in US images as somewhat ‘brighter’ than soft tissue, they are often not easily distinguishable from the surrounding tissue. Therefore, US imaging methods aimed at segmenting bone surfaces need enhancement in image contrast prior to segmentation to improve the quality of the detected bone surface.In this paper, we present a novel acquisition/processing technique for bone surface enhancement in US images. Inspired by elastography and Doppler imaging methods, this technique takes advantage of the difference between the mechanical and acoustic properties of bones and those of soft tissues to make the bone surface more easily distinguishable in US images. The objective of this technique is to facilitate US-based bone segmentation methods and improve the accuracy of their outcomes. The newly proposed technique is tested both in in vitro and in vivo experiments. The results of these preliminary experiments suggest that the use of the proposed technique has the potential to significantly enhance the detectability of bone surfaces in noisy ultrasound images.

Fracture Healing Assessment Based on Impact Testing: In Vitro Simulation and Monitoring of the Healing Process of a Tibial Fracture with External Fixator

In clinical practice, bone healing is monitored with X-rays and manipulation. Its assessment is thus subjective, depending on the skills of the operator. Alternative and quantitative approaches have been proposed, generally based on the estimation of bone stiffness, which is known to increase with the healing process. The present study investigates the application of experimental modal analysis to fracture healing assessment focusing on fractures treated with an external fixator. The aim is to ascertain the capability of this approach to detect changes in the bone-callus stiffness as variations in the resonant frequencies despite the presence of the fixator, which might hide the bone response. In vitro tests were performed on a tibia phantom where the healing process was simulated creating three different types of callus surrogates, using glue and resin. The resonant frequencies of the phantom with screwed pins and of the phantom with the complete fixator were estimated. Results confirm an increase in the frequencies as the simulated bone-callus stiffness increases, encouraging the application of experimental modal analysis to fracture healing monitoring. This approach can offer remarkable advantages with respect to the actual standards: being non-invasive and quantitative, it would allow a more frequent healing monitoring.

Using impedance to track fracture healing rates in mice in vivo: A pilot study.

Fracture injuries are highly prevalent worldwide, with treatment of problematic fractures causing a significant burden on the U.S. healthcare system. Physicians typically monitor fracture healing by conducting physical examinations and taking radiographic images. However, nonunions currently take over 6 months to be diagnosed because these techniques are not sensitive enough to adequately assess fracture union. In this study, we display the utility of impedance spectroscopy to track different healing rates in a pilot study of an in vivo mouse tibia fracture model. We have developed small (56 μm) sensors and implanted them in an externally-stabilized fracture for twice-weekly measurement. We found that impedance magnitude increases steadily over time in healing mice but stalls in non-healing mice, and phase angle displays frequency-dependent behavior that also reflects the extent of healing at the fracture site. Our results demonstrate that impedance can track differences in healing rates early on, highlighting the potential of this technique as a method for early detection of fracture nonunion.

Implantable strain sensor to monitor fracture healing with standard radiography

Current orthopaedic clinical methods do not provide an objective measure of fracture healing or weight bearing for lower extremity fractures. The following report describes a novel approach involving in-situ strain sensors to objectively measure fracture healing. The sensor uses a cantilevered indicator pin that responds to plate bending and an internal scale to demonstrate changes in the pin position on plain film radiographs. The long lever arm amplifies pin movement compared to interfragmentary motion, and the scale enables more accurate measurement of position changes. Testing with a human cadaver comminuted metaphyseal tibia fracture specimen demonstrated over 2.25 mm of reproducible sensor displacement on radiographs with as little as 100 N of axial compressive loading. Finite element simulations determined that pin displacement decreases as the fracture callus stiffens and that pin motion is linearly related to the strain in the callus. These results indicate that an implanted strain sensor is an effective tool to help assess bone healing after internal fixation and could provide an objective clinical measure for return to weight bearing.

Transverse and Oblique Long Bone Fracture Evaluation by Low Order Ultrasonic Guided Waves: A Simulation Study.

Ultrasonic guided waves have recently been used in fracture evaluation and fracture healing monitoring. An axial transmission technique has been used to quantify the impact of the gap breakage width and fracture angle on the amplitudes of low order guided wave modes S0 and A0 under a 100 kHz narrowband excitation. In our two dimensional finite-difference time-domain (2D-FDTD) simulation, the long bones are modeled as three layers with a soft tissue overlay and marrow underlay. The simulations of the transversely and obliquely fractured long bones show that the amplitudes of both S0 and A0 decrease as the gap breakage widens. Fixing the crack width, the increase of the fracture angle relative to the cross section perpendicular to the long axis enhances the amplitude of A0, while the amplitude of S0 shows a nonmonotonic trend with the decrease of the fracture angle. The amplitude ratio between the S0 and A0 modes is used to quantitatively evaluate the fracture width and angles. The study suggests that the low order guided wave modes S0 and A0 have potentials for transverse and oblique bone fracture evaluation and fracture healing monitoring.

Effects of Eurycoma Longifolia on Fracture Healing of Androgen-Deficient Osteoporosis Model: A Micro Computed Tomograph Analysis

Micro computed tomography (micro-CT) imaging is a useful tool to monitor fracture healing in osteoporosis model. It creates a 3-D image of the fracture callus which can be analysed to assess bone parameters quantitatively. In this study, micro-CT was used to assess the fracture healing of orchidectomised rats, an androgen-deficient osteoporosis model. The effects of Eurycoma longifolia, a medicinal plant with pro-androgenic effects, on fracture healing were assessed. The rats were grouped into orchidectomised-control (ORX), sham-operated (SHAM), orchidectomised and injected with testosterone intramuscularly once weekly (TEN) and orchidectomised and daily oral gavage of Eurycoma longifolia (EL). Treatment duration was six weeks following bone fracture. Fracture was induced in the right tibia of all the rats. A total of 100 axial slices above and below fracture line were scanned with a micro-CT. The micro-CT analysis was able to detect significant difference in the fracture healing rate of ORX and TEN groups. The bridging cortices and fraction of mineralized tissue of the bridging cortices of the callous of ORX group was significantly lower than TEN group. No significant micro-CT changes were seen in the fracture healing of the EL group. The effect of EL on fracture healing was not demonstrable in orchidectomised rat model.

Boundary element simulation of ultrasonic backscattering during the fracture healing process.

Competent fracture healing monitoring and treatment requires an extensive knowledge of bone biology and microstructure. The use of non-invasive and non-radiating means for the monitoring of the bone healing process has gained significant interest in recent years. Ultrasound is considered as a modality which can contribute to the assessment of bone status during the healing process, as well as, enhance the rate of the tissues' ossification. This work presents boundary element simulations of ultrasound propagation in healing long bones to investigate the monitoring potential of backscattering parameters. The interaction of a plane wave at 100 kHz with the bone and the callus is examined by calculating the acoustic pressure and scattering amplitude in the backward direction. Callus is considered as a two-dimensional, non-homogeneous medium consisted of multiple layers with evolving material properties. It was shown that the backscattering parameters could potentially reflect the fracture healing progress.

An electronically instrumented internal fixator for the assessment of bone healing.

ObjectivesThe monitoring of fracture healing is a complex process. Typically, successive radiographs are performed and an emerging calcification of the fracture area is evaluated. The aim of this study was to investigate whether different bone healing patterns can be distinguished using a telemetric instrumented femoral internal plate fixator.Materials and MethodsAn electronic telemetric system was developed to assess bone healing mechanically. The system consists of a telemetry module which is applied to an internal locking plate fixator, an external reader device, a sensor for measuring externally applied load and a laptop computer with processing software. By correlation between externally applied load and load measured in the implant, the elasticity of the osteosynthesis is calculated. The elasticity decreases with ongoing consolidation of a fracture or nonunion and is an appropriate parameter for the course of bone healing. At our centre, clinical application has been performed in 56 patients suffering nonunion or fracture of the femur.ResultsA total of 39 cases of clinical application were reviewed for this study. In total, four different types of healing curves were observed: fast healing; slow healing; plateau followed by healing; and non-healing.ConclusionThe electronically instrumented internal fixator proved to be valuable for the assessment of bone healing in difficult healing situations. Cost-effective manufacturing is possible because the used electronic components are derived from large-scale production. The incorporation of microelectronics into orthopaedic implants will be an important innovation in future clinical care.Cite this article: B. Kienast, B. Kowald, K. Seide, M. Aljudaibi, M. Faschingbauer, C. Juergens, J. Gille. An electronically instrumented internal fixator for the assessment of bone healing. Bone Joint Res 2016;5:191–197. DOI: 10.1302/2046-3758.55.2000611.

Impedance spectroscopy to monitor fracture healing.

An estimated 7.9 million fracture injuries occur each year in the United States, of which a substantial fraction result in delayed or non-union. Current methods of monitoring fracture healing include taking x-rays and making clinical observations. However, x-ray confirmation of bone healing typically lags behind biologic healing, and physician assessment of healing is fraught with subjectivity. No standardized methods exist to assess the extent of healing that has taken place in a fracture. Without such knowledge, interventions to aid healing and prevent fracture non-union are often delayed, leading to increased morbidity and suffering to patients. We are developing an objective measurement tool that utilizes electrical impedance spectroscopy to distinguish between the various types of tissue present during the different stages of fracture healing. Preliminary measurements of cadaveric tissues reveal adequate spread in impedance measurements and differences in frequency response among different tissue types. Electrodes implanted in a simulated fracture created in an ex vivo cadaver model yield promising results for our system's ability to differentiate between the stages of fracture healing.

Time course of 25(OH)D3 vitamin D3 as well as PTH (parathyroid hormone) during fracture healing of patients with normal and low bone mineral density (BMD)

BackgroundUntil now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OH)D3 (Vitamin D) as well as PTH (Parathyroid Hormone) the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing.MethodsIn the presented study, we analyse the time course of 25(OH)D3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OH)D3 and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant.ResultsSerum levels of 25(OH)D3 showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study.ConclusionsThe time course of 25(OH)D3 and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for therapy and the monitoring of fracture healing.

English

Introduction In fractures, electrical properties are generated by the piezoelectric effect and cellular activity, initiate and augment healing. Monitoring these can result in the development a diagnostic tool for diagnosing delayed and early non-union of bones and may enable the clinician to change the line of treatment for decreasing the suffering time of the patient. This article summarizes 12 studies related to the electrical properties of bones for the monitoring of fracture healing. Materials and methods This experience has been used to develop a methodology comprising insulated fixators and measurement of electrical properties by an LCR (inductance, resistance and capacitance) meter at King George’s Medical University (KGMU). Inductance, conductance and impedance of the fractured and normal segments of fractured human tibia were monitored. Results Prospective data analysis was performed; this showed large variances. The patients were then stratified into two groups: (i) delayed union and (ii) normal union in a blinded manner. Analysis of data ensuring blinding was done separately. Conclusion Electrical properties are highly dependent on bone mineral density, temperature, structure and cross-sectional area of the bone. Skin and soft tissue are responsible for masking the electrical signals from bones measured in vivo. Therefore, at KGMU, insulated fixators were designed to prevent short circuit by rods and enable measurement from nothing else but the bone. Electrical properties of bones, can be used as a biomarker for monitoring fracture healing.