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Progression of fracture healing can be reliably measured by means of implant deformation in lower limbs.
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Smart sensor devices will be able to deliver such information through autonomous remote monitoring to support therapeutic decision making.
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Improved feedback on the healing progression holds the potential to accelerate recovery by more patient-specific fracture care.
Abstract
The assessment of fracture healing is still marked by a subjective and diffuse outcome due to the lack of clinically available quantitative measures. Without reliable information on the progression of healing and uniform criteria for union and non-union, therapeutic decision making, e.g. regarding the allowed weight bearing, hinges on the experience and the subjective evaluation of physicians. Already decades ago, fracture stiffness has been identified as a valid outcome measure for the maturity of the repair tissue. Despite early promising results, so far no method has made its way into practice beyond clinical studies. However, with current technological advancements and a general trend towards digital health care, measuring fracture healing seems to regain momentum. New generations of instrumented implants with sensoring capabilities, often termed as "smart implants", are under development. They target X-ray free and timely provision of reliable feedback upon the mechanical competence of the repair tissue and the healing environment to support therapeutic decision making and individualized after-care. With the gained experience from these devices, the next generations of smart implants may become increasingly sophisticated by internally analyzing the measured data and suggesting adequate therapeutic actions on their own.
Generally, fracture healing following internal fixation is a robust process and broken bones may consolidate within a few weeks under optimal conditions. Yet, the individual course of healing varies greatly, depending on many factors such as anatomical site of the fracture, comorbidities, and fracture pattern. Mechanobiological research made a substantial impact on the improvement of osteosynthesis implants in the past decades. Recognizing the importance of interfragmentary micromotion for secondary healing and the preservation of blood supply, bridge plating and less invasive procedures with indirect reduction have become standard of care [
Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new balance between stability and biology.
Comparison of minimally invasive percutaneous plate osteosynthesis with open reduction and internal fixation for treatment of extra-articular distal tibia fractures.
]. Nevertheless, healing complications in lower limb fractures still occur in approximately 5–10% of cases and go along with drastically reduced quality of life for the patients, increased morbidity and significant health care costs with socioeconomic burden [
Despite the importance of early mobilization in terms of fracture stimulation and return to function, surgeons remain hesitant with regard to early weight bearing due to concerns regarding failure of the fixation and non-union [
2010 mid-America Orthopaedic Association Physician in Training Award: healing complications are common after locked plating for distal femur fractures.
] suggested that healing complications with locking plate constructs may be rather associated by understimulation of the fracture due to overly stiff fixation or conservative mobilization, whereas implant failures following fixation overload occur less often. This discrepancy may be attributed to the fact that reliable measures for assessing the healing status and the mechanical environment present at the fracture site are missing.
Given the lack of adequate alternatives, plain radiography and clinical examination remain standard of care, despite its known health threats due to X-ray exposure and limitations including non-standardized diagnostic criteria, limited inter-rater reliability and questionable correlation with mechanical properties of the callus tissue [
]. Different concepts such as the maximum callus index or RUST score have been suggested to identify the most relevant radiological criteria and standardize their evaluation in order to increase reliability and establish mutually agreed definitions as to when a fracture is considered as healed [
]. Recognizing a certain improvement of inter- and intraobserver reliability achieved by such scores, they nevertheless remain a subjective assessment method and rely on a very limited data basis of only a few images per healing cycle. The subsequent sections describe the evolution of indirect fracture healing assessment concepts based on implant load and elaborate how such smart implants may impinge on the aftercare of fracture patients in future. The references were selected following a keyword-based literature search on the most important databases without claiming completeness. In particular, different measurement principles such as ultrasound or electrical impedance spectroscopy were omitted.
Callus stiffness measurements – early attempts
While seeking an objective measure of fracture healing during the past decades, considerable effort has been put into measuring stiffness of the repair tissue.
Most of the early attempts have focused on direct or indirect measurements in patients treated with external fixators. External fixators offer the possibility to directly measure fracture stiffness upon removal of the connection rod or in an indirect approach (Fig. 1) by attaching additional measurement equipment, e.g. goniometers or a strain gage transducer clamp, noninvasively to the fixation hardware [
] directly equipped the fixation rods of external fixators with strain gauges, being one of the first to introduce instrumented implants.
Fig. 1Principle of indirect bone healing measurement. Left: Implant strain reduces with fracture consolidation. Strain is already considerably diminished at early healing stage (here cartilage-like tissue simulated in the fracture gap b), Young's modulus 10 MPa). Right: Experimental correlation between implant deflection measured with strain-gage based healing sensors and the interfragmentary displacement. Prediction of fracture motion from implant loading seems possible. Simulation taken from "OSapp" software (Varga and Mischler, AO Research Institute Davos, unpublished).
] proposed a bending stiffness of 15 N/mm as biomechanical definition for healing, after which removal of the fixation and full weight bearing is considered safe [
]. Overall, there is a broad evidence that fracture stiffness is a valid indicator for the progression of healing. Several groups could show the capability of their measurement systems to distinguish different healing patterns such as normal and slow healing, delayed union or non-responders [
. Moreover, results suggested that stiffness measurements are especially sensitive to early stages of healing, whereas radiographs tend to reflect strength of the repair tissue better at the later stages of healing [
External fixation plays a minor role in today's fracture treatment where the vast majority of lower limb fractures is treated by internal fixation. Thus, the need for determining the timepoint of union i.e. whether the bone is strong enough for hardware removal has become less pressing. In fact, a method to steer weight bearing recommendations and detect the onset of healing as an early indicator predicting the likely course of the healing process is clinically of highest importance.
Current telemetric sensor devices - towards smart implants
In spite of promising results in the research space, the clinical feasibility of these early measurement devices was not given. A first telemetric measurement on an osteosynthesis plate was reported by Sommelet et al. [
] in 1976. Following the technological advances, recent approaches increasingly feature miniaturized sensors and integration of telemetric data transmission, facilitating the assessment of healing parameters from internal fixators [
] by correlating the implant strain with an externally applied load. An instrumented locking plate has been applied in more than 50 clinical cases so far and contributed in preventing reoperation in slowly healing fractures [
] introduced locking plates equipped with MEMS sensors as an alternative strain sensor and could demonstrate a reduction in the sensor's resonance response frequency with progressing bony consolidation. Externally powered systems typically require a reader device that supplies energy to the sensor for the measurement and wireless transmission of the respective data via electromagnetic fields. This allows the design of miniature measurement systems that can be integrated in the fixation hardware. Considering a clinical routine application, readings with such systems are distinct snapshot measurements that most likely require a hospital visit. Patient-operated measurements in a home-care environment would allow more frequent data acquisition and remote monitoring but might be difficult from a handling perspective. Increasing the feedback frequency of fracture healing assessment is, however, considered crucial for timely diagnosis and adequate adaptation of the post-operational treatment.
Measurements based on passive sensor devices are limited to short snippets and require the reader device to be kept in close proximity. Since the measurement is highly dependent on the degree of patient loading (which varies considerably), an external load reference is necessary to determine a single stiffness value. It also restricts the possibilities for continuous data acquisition during daily activities. Schmickal et al. [
] extended an existing measurement device for external fixators (Fraktometer FM 100) with a portable data acquisition system for permanent monitoring and demonstrated its potential to get more detailed feedback on the healing progression and early detection of complications. Similarly, an implantable monitoring system with internal power supply has been proposed by Windolf et al. [
]. The instrumented bone plate provides continuous and wireless monitoring of interfragmentary motion throughout the day, thereby capturing patient activity and the mechanical environment at the fracture site. Statistical processing of the daily raw data enables averaging out the influence of physiological loading variances and hence renders an external load reference void. The gained simplicity allowing for remote monitoring and the continuous recording of the fracture activity profile are believed to be the key distinguishing factors of this concept over passive approaches.
Meanwhile, the monitoring system has been adapted for external fixators and was applied in 20 clinical cases (unpublished data, Fig. 2). The studies confirmed the capability of the device to monitor fracture activity and elasticity of the repair construct under functional loading over several months in a demanding clinical setting (infection patients with delayed healing and complex external fixator configurations). Maintaining the measuring concept, the device is, after some early attempts [
], continually developed into an implantable sensor system that is attachable to standard locking plates measuring implant deflection under natural weight bearing (Figs. 2, and 3). The sensor unit operates autonomously. The recorded parameters are synchronized daily to a cloud server via a smartphone. The design of such actively powered sensor devices decouples data acquisition from data transmission and largely eliminates the need for any active user interaction and hence decreases the risks associated with poor patient compliance.
Fig. 2Sensor prototypes attached to a strut of an external fixator (left, clinical trial) and a standard locking plate for implantation (right, animal study) . The sensor measures implant loading continuously and transmits data to the patient's smartphone.
Fig. 3Exemplary implant load progression from a sensor device attached to a locking compression plate in a 3-mm sheep tibia osteotomy model (continuous measurement). Callus formation sequence from weekly X-rays correlates with the curve drop. However, two weeks post-operative the implant load already dropped by approx. 40%, while at the same time barely any callus formation is visible on the radiograph. Top right: Loading event histogram of an arbitrary measurement day (day 17) broken down into interfragmentary displacement bins and time distribution over the day cycle – potential data to individualize rehabilitation protocols.
In addition, permanent monitoring of the actual mechanical environment during natural weight bearing could reveal valuable information regarding the optimum stimulation of the repair tissue and the effective implant stresses due to patient activity [
]. Using such knowledge, rehabilitation protocols may be individually tailored by steering weight bearing and patient activity to promote timely healing and early return to function with, at the same time, reduced risk for implant failure (Fig. 3). The major obstacles hampering the introduction of implantable sensor systems into clinics are considerable regulatory hurdles (due to an increased risk profile) and the misfit to current reimbursement schemes and the journey to adapt them.
The future – closing the loop with active implants
The expression "smart implant" is more and more associated with telemetric sensor devices [
]. Even though none of the proposed solutions has made it to commercial clinical application yet, there is only little doubt that such instrumented implants will make their way to the market in the near future [
] predicted that smart technology will reach the orthopedics market in four waves, starting with "Smart Tools in the OR", which have already arrived in clinics, followed by "Smart Diagnostics on Demand" (raw sensor data accessed and interpreted by physician) and "Smart Diagnostics by Exception" (alerts coming via push notifications from implants directly). The final wave designated as "Treatment by Exception" means that eventually the implants not only diagnose, but actually trigger the according treatment. Similarly, we believe the current developments only mark the starting point in the field of smart implants for fracture healing assessment. The current concepts of instrumented implants reveal so far clinically inaccessible data regarding the maturity of the repair tissue. Utilizing modern technologies, these data can be generated at high frequencies or even in real-time and enable remote monitoring. This offers new opportunities for more reliable assessment of healing and supports evidence-based decision making throughout the course of healing.
Nevertheless, surgeons will need time to familiarize with the novel measures and gain confidence in the provided data. Ultimately, smart implants should not only be an amendment to current methods but replace current standards like plain radiographs or computed tomography to a significant proportion, thereby minimizing radiation exposure and reducing dispensable follow up visits.
Upcoming smart implants will likely integrate different measurement parameters beyond the here outlined devices assessing the mechanical competence of a fracture. Other groups for example investigate the use of electrochemical sensors to measure oxygen saturation [
In the long run, implants must earn their designation of being "smart" by not only delivering but also analyzing data, in order to recognize normal or aberrant patterns on their own and if indicated, alarm the physicians proactively. Even if the rendered data of novel devices is accessible at any time, the physician's resources to review the information from remote is limited, especially in the absence of dedicated healthcare reimbursement codes. Hence, pre-assessment and filtering of the raw data must be delegated to the smart implant system.
Anonymized clinical sensor data will serve as a basis to characterize different healing patterns and derive uniform definitions for union and indicators of abnormal healing. Correlation of the recorded parameters with additional details such as fracture pattern, implant configuration or comorbidities will help to better understand how internal and external factors impact the course of healing. Knowing how to optimally tune the healing environment to best support fracture consolidation lays the foundation for the highest level of smart implants: intelligent implants that can actively influence the healing environment e.g. by changing their stiffness [
]. Providing a closed loop control, we envision an implant that could install adequate healing conditions patient-specifically throughout the healing period and only require a physician's intervention in extraordinary situations.
Obviously, evidence must be collected to demonstrate these clinical benefits can actually be achieved and justify the potentially significant surcharge of smart implants. Besides, it must be taken into consideration that not only the mechanical environment, but also biological factors play a role in the outcome of fracture healing and that there might not be straightforward corrective actions for each individual case.
Conclusion
Current fracture healing assessment lacks means to reliably and objectively determine the progression of fracture consolidation. The loading of the fixation hardware has been identified as a valid surrogate measure for the maturity of the repair tissue. Compared to the early measurement systems, recent concepts feature miniaturized and low-power sensor devices that can smoothly integrate with currently used internal fixators and provide wireless communication, which enhances their potential for clinical translation.
Beyond the ability to determine the current state of fracture healing for timely therapeutic decision making, in particular actively powered sensor concepts additionally bear the potential to continuously monitor the mechanical healing environment and the state of the fixation hardware in real-time in a home-care setting. This opens further possibilities for patient-specific rehabilitation and enhancement of fracture healing.
The journey towards truly smart implants is, however, far from complete. By learning from the experience with the first generation of instrumented implants, future devices will apply computational intelligence to evaluate the recorded parameters from different sensors autonomously and eventually maybe even trigger the required therapeutic actions on their own.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new balance between stability and biology.
Comparison of minimally invasive percutaneous plate osteosynthesis with open reduction and internal fixation for treatment of extra-articular distal tibia fractures.
2010 mid-America Orthopaedic Association Physician in Training Award: healing complications are common after locked plating for distal femur fractures.
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