Key Laboratory of Medical Biomechanics and Materials of Heilongjiang Province, Harbin University of Science and Technology, Harbin 150080, P. R. China

E-mail Address: 413294724@qq.com

Search for more papers by this author

SONG CUI

https://orcid.org/0009-0000-9910-1474

Key Laboratory of Medical Biomechanics and Materials of Heilongjiang Province, Harbin University of Science and Technology, Harbin 150080, P. R. China

E-mail Address: 872445220@qq.com

Search for more papers by this author

, and

LINGBING XIA

https://orcid.org/0009-0001-6881-2342

Key Laboratory of Medical Biomechanics and Materials of Heilongjiang Province, Harbin University of Science and Technology, Harbin 150080, P. R. China

E-mail Address: lingbingxia@163.com

Search for more papers by this author

https://doi.org/10.1142/S0219519424400645Cited by:0 (Source: Crossref)

This article is part of the issue:

Special Issue: Application and Progress of Biomechanics in Medicine — Part III
Guest Editors: Esteban Peña Pitarch and Eddie Y. K. Ng

Abstract

Fracture is one of the most important health problems in people’s life. Millions of people have fractures every year. However, there is no unified standard for fracture healing in the clinic. Most definitions of complete fracture healing are subjective evaluations based on X-ray films. However, it is not reliable to evaluate the biomechanical strength of bone according to the number of callus on X-ray, and the imaging time of callus lags behind the actual callus, which is not conducive to the evaluation of early fracture healing time. In addition, although more and more fracture patients have achieved imaging healing after injury, the bone quality and bone strength of the whole body and local fracture have not returned to the normal level, and the probability of re-fracture has increased significantly, which has brought great pain to their families. Fracture healing is affected by many factors, such as age, fracture site, whether to fix the fracture site, and osteoporosis. Therefore, when evaluating the fracture healing status of patients, we should not only evaluate whether the fracture is healed but also evaluate its healing. By analyzing the previous research methods of fracture healing, in this paper, we systematically summarize the evaluation methods of fracture healing from the perspectives of computer tomography, ultrasound, bone density, biosensors, and biomechanics by analyzing previous research methods of fracture healing, aiming to provide reference for researchers in related fields.

Keywords:

1. Introduction

Fracture is a common and frequently occurring traumatic disease in clinics. Fracture healing is a physiological process of proliferation coordinated by multiple complex and continuous cellular and molecular events. However, different exogenous and endogenous factors may lead to delayed healing, bone nonunion, or pseudojoint.¹ The study of Li et al. pointed out that in the United States, about 7.9 million patients have fractures every year, of which up to 10% have impaired bone healing, resulting in delayed bone healing or bone nonunion.² Therefore, it is very important to monitor fracture healing.³ Although conventional X-ray film is still the most commonly used method to evaluate fracture and monitor subsequent healing process, ultrasonic measurement and biosensors are becoming an alternative method because of their advantages of being fast, portable, noninvasive, and radiation-free.^4,5 For the traditional image monitoring methods, on the one hand, they have radiation, causing secondary damage to the human body. On the other hand, they cannot accurately detect the early stage of fracture healing. In addition, the conclusions of these monitoring methods are subjective, without an accurate value, which is judged by the doctor’s experience, and physical methods are easy to produce the clinician’s subjective interpretation.⁶ X-ray tends to be similar. Inaccurate analysis leads to great differences among doctors. Computer-aided diagnosis can somewhat reduce the influence of subjective interpretation and improve the accuracy and reliability of diagnosis. The development of artificial intelligence and deep learning has significantly improved the performance of computer-aided diagnostic systems, enabling them to more accurately assist physicians in making diagnoses.⁷ The observation of early fracture healing is still a difficult and qualitative process for clinicians.^8,9 In the first 30 days after fracture, it becomes the acute healing stage of fracture healing, and the bone synthetic hardness in the acute healing stage changes significantly. However, due to the lack of mineralized tissue in the acute healing stage, standard radiography cannot monitor the early fracture healing process.¹⁰ After the occurrence of fracture, the final fracture incomplete healing or fracture nonunion is mostly caused by improper treatment in the early stage of fracture healing. It is very important to accurately evaluate the progress of healing by monitoring the early stage of fracture healing. Remove the bone plate prematurely, the fracture will not heal completely, and the risk of fracture will increase in the future. On the contrary, if the plate is not removed within a period after bone healing, the bone will overgrow, which makes it difficult to remove the plate and locking screw.^11,12,13,14 Research by Kussmaul et al.¹⁵ has demonstrated that the prompt detection and suitable management of wrist bone fractures can result in a successful healing rate exceeding 90%. Heckman et al. have shown that when early intervention is implemented to prevent delayed fracture healing, the economic burden can be greatly reduced.¹⁶ Most fractures heal through secondary or indirect healing, including three overlapping stages: inflammation (5–7 days), repair (4–40 days), and remodeling (months to years). Initial healing requires complete anastomosis of fracture fragments without gap or micro activity. Radiotherapy includes callus formation and blurred fracture lines in the repair stage, and there are some overlapping stages with reconstruction.¹⁷

2. Criteria of the Fracture Healing Process and Its Challenges in Clinical Practice

The process of fracture healing is influenced by various elements, including the specific bone affected, the fracture location, the initial degree of bone loss, the time after injury, the degree of soft tissue injury, and many patient factors, such as smoking, diabetes, and other systemic diseases.¹⁸ The medical criteria for determining fracture healing depends on many factors, encompassing physical assessments, radiological testing, and patient self-assessment. In physical examination, the most common include no pain or tenderness when loading at the fracture, no direct palpation pain, and weight-bearing ability.¹⁹ Radiographic evaluation mainly depends on X-rays: bridging fractures through bone, callus, or trabecular bone; bridging fractures at three of the four cortices; and the elimination of the fracture line or cortical continuity. Patients’ evaluation of the degree of pain at the fracture has increasingly become an important factor in doctors’ decision making.²⁰ Studies over the past few decades have shown that these three aspects of diagnosis (clinical, radiology, and patient grade) are consistently aligned. In addition, the biomechanical requirements of specific fracture sites also play a role.²⁰ The healing process varies in duration across different bone types and fracture types.

In the current study, a consensus among orthopedic practitioners regarding the clinical assessment and criteria for defining fracture healing remains elusive. Corrales et al.²¹ systematically reviewed the clinical research on the treatment of long bone fracture in three orthopedic journals, and summarized the definition standards of clinical fracture healing in 77 literatures, as shown in Table 1.

**Table 1. Commonly used definition standards of clinical fracture healing.**
Clinical criteria used to define fracture union	Number of articles ( $N = 77$ $N = 77$ )
1. No pain/tenderness when bearing weight	38 (49%)
2. No pain/tenderness on palpation/examination	30 (39%)
3. Ability to bear weight	14 (18%)
4. Ability to walk/perform activities of daily living with no pain	11 (14%)
5. Ability to walk/perform activities of daily living	9 (12%)
6. No residual pain at the fracture site	8 (10%)
7. No motion at the fracture site on examination	4 (5%)
8. Full range of motion at the adjacent joint	4 (5%)
9.“Clinically stable/asymptomatic”	2 (3%)
10. No residual warmth at the fracture site	1 (1%)
11. Full range of motion at the adjacent joint without pain	1 (1%)
12. Fracture stiffness measured mechanically	1 (1%)

In addition, Corrales et al. also evaluated the most commonly used fracture site criteria for fracture healing according to the literature review, as shown in Table 2.²¹

**Table 2. Most common criteria for assessing fracture union according to location of fracture.**
Fracture location	Proximal fracture		Shaft fracture		Distal fracture
Assessment method	Radiographic assessment	Clinical assessment	Radiographic assessment	Clinical assessment	Radiographic assessment	Clinical assessment
Femur	Bridging of the fracture site	No pain during weight-bearing	Bridging of the fracture site	No pain during weight-bearing	Bridging of the fracture site	No pain during weight-bearing
Tibia	Obliteration of fracture line	Ability to bear weight	Bridging of the fracture site	No pain during weight-bearing	Bridging of the fracture site	No pain during weight-bearing or ability to bear weight
Humerus	Obliteration of fracture line or bridging of fracture site	Ability to perform activities of daily living without pain, or no residual pain at the fracture site, the full range of motion at the adjacent joint	Bridging of the fracture site	No pain on palpation/examination	Bridging of the fracture site	No pain on palpation/examination
Forearm	—	—	Obliteration of fracture line	No pain on palpation/examination	—	—
Radius	—	—	—	—	Obliteration of fracture line or calcification of callus	No residual pain at the fracture site

Notes: The most common radiographic criteria (based on plain radiographs) and clinical definitions for fracture union are given. If more than one definition was used equally for a given region, all are listed. A dash indicates that none of the reviewed studies defined fracture union for that body region.

3. Evaluation Methods in the Process of Fracture Healing

The current research shows that there is still a lack of consensus among orthopedic doctors on the evaluation and definition of clinical fracture healing. The process of fracture healing is extremely complex and varied, and is influenced by a combination of systemic, local, and therapeutic factors. Different criteria and methods for evaluating fracture healing may be used in different clinical cases.

Fisher²⁰ and others reviewed the radiology technology in fracture healing monitoring. They discussed the monitoring methods of fracture healing from X-ray photography, computed tomography (CT), ultrasound, and nuclear medicine.²⁰ Later, an article published by Lu and others in 2020 focused on nonradioactivity in fracture healing monitoring. They discussed fracture healing from four aspects: acoustic emission, quantitative ultrasound, vibrational response, and osseointegrated implant.²² Based on previous studies, they discussed the monitoring of fracture healing from three aspects: Radiology, biomechanics, and intelligent implants.²³ In terms of Radiology, Team Bizzoca introduced it from four aspects: plain radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). Regarding biomechanics, Bizzoca discussed it from three aspects: radiostereometric analysis, virtual stress testing, and vibration testing.

Based on summarizing the previous studies, this paper will review the monitoring methods of fracture healing from five aspects: Radiology, acoustics, biomechanics, molecular biology, and biosensors. Radiologic assessment has the advantages of being intuitive, noninvasive, and efficient, but it also has the disadvantages of being dependent on physician experience and radiation risk. Biomechanical test directly correlates to mechanical stimulation during fracture healing. Howerver, specialized equipment and personnel are required for operation and analysis.²⁴ The BMD measurement technology can visualize and accurately reflect the degree of fracture healing. The biosensor enables real-time monitoring of biomechanical changes at the fracture site.

3.1. Evaluation of fracture healing by digital imaging technology

At present, imaging technology still plays a key role in helping orthopedic doctors make decisions and evaluate fracture healing. This section summarizes the monitoring methods of fracture healing and their advantages and disadvantages from the imaging perspective (Table 3).

**Table 3. Imaging monitoring mode.**
Monitoring mode	Study site\type	Research status	Advantage	Disadvantage
X-ray	Femur and clavicle	Mature technology	Mature technology, the main method of clinical application	The evaluation of early-stage healing is poor²⁵
Nuclear magnetic resonance	Acute fracture	It is often used to diagnose acute fractures and show bone marrow edema	Able to provide qualitative and quantitative data²⁶	Radiation; and metal implants will produce artifacts
Tractional CT	Joint fracture, complex fracture	Mature technology	Quantitative and volumetric measurements can be performed to evaluate the macro and microstructural properties.	Radiation; artifacts will occur when there are metal implants in the body
Dual-energy CT	Main parts of trabecular bone (such as vertebral body, pelvis, hip)	A popular research direction, mainly using virtual noncalcium maps to evaluate fracture healing	Image optimization and artifact reduction can improve the detection of subtle and occult fractures²⁷	Radiation; cortical bone abnormalities cannot be evaluated
Fault synthesis	Cortical bone	It can provide three-dimensional images of fracture sites	It provides more diagnostic information, low cost, and low radiation	Cannot accurately evaluate the differences in various imaging modes
Radioactive stereo technology	Femoral intertrochanteric fracture, femoral neck fracture	It is mostly used to evaluate the micro-injury of fracture healing^28,29	High precision and low radiation	Time consuming, high technical requirements, and high price for marker implantation³⁰

3.1.1. Evaluation of fracture healing by X-ray imaging

Due to the low cost, wide availability, and relatively low radiation of X-ray films, X-ray photography has always been the most commonly used technique to evaluate fracture healing. The formation and growth of callus, as well as its bridging to the fracture line are most easily detected in the imaging evaluation of fracture healing.³¹ It is particularly effective in the visualization of complex fractures, as it demonstrates the details of the fracture line and the damage to surrounding structures. Bhandari et al.²⁵ pointed out that correlation between X-ray plain film healing evaluation and biomechanical and histological data is poor. In addition, X-ray films need to be exposed to ionizing radiation when evaluating fracture healing.³² A new scoring system was proposed in a recent study by Crompton et al.,³³ who conducted a retrospective 5-year pilot study on femoral fractures in children under three years old. Radiographs were scored according to subperiosteal new bone formation, callus, and remodeling. In the study, two radiologists scored the stage of fracture healing independently. The results show that the earliest subperiosteal new bone formation and callus formation in femoral fractures seems to lag behind the healing of birth-related clavicular fractures. The reconstruction of clavicular fracture occurred earlier than that of clavicular fracture. The power calculation for a single proportion, with a level of confidence of 95% and a margin of error of 5%, determined the number of femoral X-rays required for a decisive study (359). Harper et al.’s study,³⁴ which examined children with unintentional head trauma and with a known time interval since injury, along with a negative skeletal survey who had serial radiographic examinations, suggests that unexplained or multiple skull fractures in children under 24 months could stem from a single or multiple incidents of head injury.

However, the use of X-ray films is limited due to the exposure to X-ray radiation and its difficulty in accurately evaluating the early stage of fracture healing.

3.1.2. Computed tomography (CT) was used to evaluate fracture healing

Although computed tomography has high cost and radiation, it has become increasingly popular in the research of joint fractures, complex fracture types, and severe bone loss in recent years. The advantage of CT is that it can carry out quantitative and volumetric measurements to evaluate the macrostructure and microstructure characteristics of bone. However, the disadvantage is that metal implants in vivo will affect CT imaging and form metal artifacts, which makes the measurement results inaccurate. After CT evaluation of fracture healing, dual-energy CT and CT synthesis technology have emerged.^27,35 The capability of dual-energy CT to produce a virtual monochromatic energy spectrum confers it with a substantial edge over conventional CT in facilitating precise tissue composition analysis, minimizing artifacts, and optimizing image quality.²⁷

3.1.3. Evaluation of fracture healing by magnetic resonance imaging

MRI, a noninvasive technique, is instrumental in assessing tissue hydration levels. It is particularly valuable in the diagnosis of acute fractures because such injuries are characterized by increased local water content and bleeding due to microfractures in the trabecula.

Taha et al.²⁶ used noninvasive MRI and bone quantitative procedures to track bone regeneration and healing in rodents. Studies have shown that MRI is suitable for analyzing bone structure and yielding qualitative and quantitative insight without radiation exposure. The rat patellar tendon healing model shows that biomechanical stability is closely related to the development of new blood vessels in the injured tendon, which can be monitored and quantified by MRI.³⁶ Schmitz established a long-term intramedullary nail stabilized fracture model in mice and rats. This model accurately simulates the real scene of fracture and the long bone stabilization procedure commonly used in trauma surgery; it provides minimally invasive surgery and rapid weight-bearing ability. This research distinctly shows the benefits of utilizing high-resolution MRI along with volume analysis, which facilitates a more nuanced distinction between callus, bony structures, and various tissue types.³⁷

3.1.4. Radiostereometric analysis

Radiostereometric analysis (RSA) is a very accurate imaging method to evaluate the micro-motion of fracture. When using RSA technology, tantalum markers need to be implanted intraoperatively. Two ray images are obtained simultaneously in different planes to identify the previously implanted tantalum markers.³⁸ In treating femoral neck fracture, stable fixation of the fracture site is very important, but there are still some uncertainties about the best fixation method. Sami studied 16 patients with femoral fractures to analyze the feasibility of differential loading radio stereometric analysis (dl-rsa) in evaluating the initial stability of femoral neck internal fixation fractures.³⁹ The experimental study of Sami verified that dl-rsa can detect the presence of induced micro motion in femoral neck internal fixation fractures.³⁹ The limitation of the RSA method is that RSA is a time-consuming process, the technical requirements for marker implantation are very high, trained radiographers are needed to identify the implanted markers, and the price is expensive.³⁰ Vincent studied 16 patients with distal femoral fractures aged 22–89 to evaluate the micro-movement of the fracture block one year after the fixation of the distal femoral fracture. The study concluded that RSA can be used for reliable evaluation of distal femoral fracture healing. RSA showed differences in cases of healing and nonhealing for three months and was more consistent than traditional X-ray.²⁸ Andreas Ladurner experimented an experiment on pelvic ring injury in six patients. The fracture stability was evaluated by X-ray plain film and RSA measurement. Each patient was followed up at 2, 4, 6, 12, 26, 52, and 104 weeks after the operation, and was evaluated by Iowa pelvic score. The experimental results showed that at 104 weeks, the Iowa Pelvic Score (IPS) effect of four patients was excellent, one patient was good, and one patient was normal. Compared with RSA, the X-ray technique did not measure fracture displacement in these six patients. RSA can not only display fracture reduction but also accurately measure the displacement in all cases. Ladurner’s team demonstrated the limitations of plain films in evaluating stability and displacement during pelvic fracture healing. They also highlighted the superior accuracy of RSA in gauging the impact of stability and weight-bearing on fracture stability.²⁹

3.2. Acoustic evaluation of fracture healing

When using imaging to evaluate fracture healing, radiation is always generated, causing secondary injury to the human body. To avoid the harm of radiation, an increasing number of people are studying the use of acoustics to evaluate fracture healing. This section mainly summarizes the detection methods, advantages and disadvantages of fracture healing from the perspective of acoustics (Table 4).

**Table 4. Acoustic monitoring of fracture healing and its advantages and disadvantages.**
Monitoring mode	Site	Research status	Advantage	Disadvantage
Acoustic emission	Femur, cortical bone, trabecular bone	There are relatively few studies	It is very sensitive to micro-injury of fracture and can detect occult fracture⁴⁰	Most of them are only applicable to external fixation fractures, and some micro injuries have occurred when acoustic emission signals are monitored.
Ultrasonic	Femur and clavicle	At present, there are quantitative ultrasound, contrast-enhanced ultrasound, power Doppler ultrasound, and color Doppler ultrasound^21,22,41	Fracture healing and no radiation were detected earlier⁴² It is sensitive to the stiffness change of callus	The change in the aggregate shape of the callus could not be recognized.

3.2.1. Evaluation of fracture healing by acoustic emission

Acoustic emission is a type of transient elastic wave, which is a process of sudden release of strain energy during the formation of structural microdamage.⁴³ The criteria for fracture healing based on acoustic emission test are that there is no acoustic emission signal, and the estimated intensity is higher than body weight when fully loaded.⁴⁴ The acoustic emission technology proposed at present can only be a supplementary means of fracture healing monitoring. After years of development, studies have shown that acoustic emission is very sensitive in detecting bone microinjury, so it has a very useful potential application in detecting occult fracture and fracture healing monitoring. In addition, for cortical bone and trabecular bone with high anisotropy, acoustic emission has been proven to be effective in determining the mechanical properties of bone.⁴⁰

3.2.2. Evaluation of fracture healing by quantitative ultrasound

When ultrasound passes through the fracture site, different material properties of callus and cortical bone cause variations in the ultrasound’s wave velocity. These velocity changes can serve as a primary parameter for evaluating fracture healing. In addition, we can quantitatively measure the process of fracture healing by comparing the velocity values of fracture and intact bone. When using quantitative ultrasound technology, the geometric conditions along the propagation path will affect the transmission of ultrasound. As a result, the arrival velocity and ultrasonic velocity can only display surface information of the periosteal femoral region.²² Guided wave propagation has proved its potential in structural integrity monitoring due to its fast regional detection and minimum attenuation. In the study of Frederik Curvers, it is pointed out that when low-frequency ultrasound is used, less energy is absorbed, and the ability to penetrate tissue is stronger, but the image resolution is lower. When using high-frequency ultrasound, higher resolution can be obtained. Still, high-frequency ultrasound is absorbed more, and ultrasonic energy is dissipated into the surrounding soft tissue and bone marrow, leading to inaccurate imaging results.⁴⁵ One week after operation, newly formed calcified material can be detected in the bone defect using ultrasound imaging. Because ultrasound imaging can detect the fracture healing earlier, it is often used in early fracture healing. Ultrasound imaging is particularly useful for assessing fracture healing in superficial skeletal sites such as the tibia, ulna, and part of the radius. Bochud et al.⁴² proposed a new quantitative ultrasound method based on ultrasonic radiation force to evaluate fracture healing. This method can monitor the healing process of 80% of clavicular fractures. However, a limitation in the research is that the relationship between changes in wave velocity and bone mineral density has not been studied. Power doppler ultrasound has been applied to evaluate vascularization in the process of bone healing.⁴⁶ Studies have shown that compared with color Doppler ultrasound, power Doppler ultrasound has a stronger ability to detect neovascularization, so it is more often used in fracture healing monitoring.²¹ For contrast-enhanced ultrasound and power Doppler, contrast-enhanced ultrasound can quantitatively and qualitatively analyze the blood perfusion and neovascularization in the process of fracture healing. In contrast, the results of power Doppler can only provide qualitative analysis data.⁴¹ To solve the problem that reference samples need to be measured when using ultrasound to monitor fracture healing, Sorriento et al. proposed a monitoring model using the phase entropy of backscattered ultrasound signal to monitor the change of mineral content in bone-like materials for the first time.⁴⁷ Through in vitro experiments, they studied the performance of ultrasonic phase entropy in detecting alterations in bone mineral content such as hydroxyapatite and calcium carbonate. They also developed an innovative model that integrates phase entropy data with amplitude data. This indicator can distinguish the mineral concentration of most tests and shows a clear trend in particle concentration. The experimental results show that ultrasonic phase entropy can be used to monitor fracture healing.

3.3. Evaluation of fracture healing by vibration response

Biomechanical monitoring of fracture healing is also a hot research direction at present. Biomechanical monitoring of fracture healing is mainly through mechanical means. This section summarizes several biomechanical monitoring methods (Table 5).

**Table 5. Biomechanical monitoring methods.**
Monitoring mode	Site	Research status	Advantage	Disadvantage
Virtual stress test	Tibia	The CT scanning results were incorporated into the finite element model, the CT data were analyzed by computer, and the simulated load was used to test the bone failure²⁴	Effective prediction of fracture nonunion, malunion, and early evaluation of fracture healing⁴⁸	Only patients who underwent CT scans before removing the frame or instability were included, and the sample size was small and incomplete.
Vibration response	Internal fixation-Femur	Hot research directions mainly include the evaluation of fracture healing through fracture healing stiffness, internal fixation, integrated measurement sensors and wireless telemetry instruments, and intramedullary nail implants^49,50	It can reduce the degree of needle tract sepsis and joint stiffness, and enable the patient to return to normal function earlier.	Internal fixation causes the presence of plates or screws to interfere with vascular distribution and bone healing⁵¹
	External fixation-Tibia and femur	Hot research directions, the main technologies include in vitro experimental simulation of the healing process, thin-film sensing elements on external fixation screws, and white impulse excitation to quantify the percentage increment of the square of resonance frequency related to the change of fracture healing stiffness and the change of frequency response function to monitor the healing process⁵²	It is radiation-free and can effectively evaluate very complex tibial fractures	The mass load of soft tissue will affect the measurement results, and there is no reliable threshold to describe delayed fracture healing and nonunion^53,54,55,56

3.3.1. Loading and constraining

In the early stage, the study of vibration response to evaluate fracture healing was limited by technical factors. In recent years, with the progress of technology and the rapid development of new algorithms, people began to study the application of vibration response in evaluating fracture healing.⁵² Vibration response can evaluate fracture healing because the fracture stiffness gradually hardens with the healing process, and the vibration frequency is related to the fracture stiffness. Therefore, fracture healing can be indirectly evaluated by the frequency of fracture vibration when vibration shock is applied. In the study of Mattei’s team, the vibration response remained almost unchanged after the formation of woven bone, suggesting that the healing evaluation may be related to the relative changes of RFs.⁵⁷ The study of Ong et al. reported the possibility of evaluating femoral fracture healing with external fixation. Ong et al. proved that the healing state of the femur can be quantified by PVDF thin film sensing element attached to an external fixation nail and pulse excitation on external fixation. However, Ong et al. also pointed out that the mass load of soft tissue may affect the evaluation results when evaluating fracture healing.^53,54 In a study by Mattei, they quantitatively evaluated fracture healing through RFs, thus proving the effectiveness of vibration response in fracture healing monitoring.⁵⁵ In 2021, Mattei et al.⁵⁶ proposed a new fracture healing monitoring model. They monitored the healing process by analyzing the percentage increment of the square of resonance frequency (SFI) related to the change of fracture healing stiffness and the change of frequency response function. Mattei conducted a long-term healing monitoring (about nine months), very frequent tests (about two weeks apart), and also analyzed a single test configuration. The experimental results show that the vibration response mainly occurs in the transformation from soft callus to woven callus, and this response can effectively evaluate very complex tibial fractures. However, this experiment has limitations: it needs professional operators and lacks a reliable threshold for evaluating fracture nonunion and delayed healing.

3.3.2. Vibration response with internal fixations to evaluate fracture healing

Internal fixation is a common standard treatment for femoral fractures to correct alignment, provide mechanical stability, allow weight-bearing, and use the limbs in time for bone healing. Compared with external fixation, internal fixation can reduce needle tract sepsis and joint stiffness. So far, there have been a variety of internal fixation measurement methods to monitor fracture healing, including evaluating fracture healing through fracture healing stiffness, internal fixation integrated measurement sensor, and wireless telemetry instrument intramedullary nail implant.^49,50 Based on previous studies, Chiu et al. proposed a method to evaluate healing by measuring the dynamic response of the femur fixed with a plate and screw. This method uses dual sensors to reduce the impact of instrument impact on the measurement results, and this study also includes the mass load effect of soft tissue. The results show that this study provides a noninvasive method to evaluate bone healing cooperation using vibration analysis as a quantitative method, which allows further understanding of the potential to predict and prevent common fracture nonunion.⁵¹ However, Chiu et al. did not conduct in-depth clinical research, and some clinical trials are needed to verify the method further.

3.3.3. Virtual stress test

Virtual stress test provides a noninvasive assessment of bone strength. Virtual stress test incorporated the CT scan results of the patient’s fractured bone into the finite element model. Petfield’s research shows that by using computer to analyze CT data and simulate compression and torsion load to test bone failure, virtual stress test can effectively predict the risk of fracture nonunion and complications, that is, fracture and malunion.²⁴ Dailey et al. showed that the patient-specific virtual torsional stiffness was significantly correlated with healing time and was able to significantly distinguish between cases of delayed healing and the normal healing cohort. Moreover, the study also shows that low-dose CT scanning can provide quantitative and objective structural callus evaluation for virtual stress tests, reliably predict the healing time, and thus can evaluate fracture healing earlier.⁵⁸

3.4. Evaluation of fracture healing by quantitative measurement of bone mineral density (BMD)

Bone mineral density (BMD) refers to the density of bone minerals, which can directly reflect the quality of bone microstructure and strength. It depends on many factors, such as the degree of bone mineralization, the characteristics of bone collagen and bone matrix, and the metabolic transformation of bone. The healing process of bone is the recovery of bone structure and biomechanical properties. In monitoring the process of bone healing, the most important thing is to judge the bone strength. So far, the evaluation of the bone healing process still depends on manual monitoring of fracture strength and the formation and volume of bridging callus on X-ray film.²⁰ Ordinary X-ray has been proven to have a poor correlation with fracture strength, so it is not suitable to be used as the evaluation standard.⁴⁸ All patients with lumbar fractures adopted by Chinese scholars in the study have achieved imaging healing six months after fracture. Still, at this time, the bone mineral density of the whole body (both hips) and the bone mineral density of the fractured part (healthy vertebra) are still significantly lower than the baseline value, indicating that the bone quality and bone strength of the whole body and the fractured part of the patient have not returned to the normal level, Patients have a significantly increased risk of refracture. In the experiment of Stoffel et al., patients in the tibial group after bone grafting still have a large fracture area and need more extensive bone reconstruction after radiologic fracture healing and complete weight-bearing, which is also confirmed by this experiment.⁵⁹ This is because when the fracture heals, it will accelerate bone conversion, increase bone destruction and bone formation, and this high conversion rate will reduce the bone mineral density of the fracture part and even the whole body. At the same time, the pain and fixation after fracture will affect the bone metabolism of fracture patients, accelerate the rate of bone decomposition, and further lead to the loss of bone mass in the body.^59,60

According to an article by Kanis et al. in 2000, one in three women and one in five men will experience brittle fractures in adults over 50 years old, which is usually not found clinically.⁶² The research of Lespesailles et al.⁶³ shows that BMD measurement technology is one of the most important methods for fracture healing risk assessment. Dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) are the most commonly used tools for measuring bone mineral density. The following is a brief introduction and comparison of DXA and QCT.

3.4.1. Dual-energy X-ray absorption (DXA) was used to evaluate fracture healing

Dual-energy X-ray absorptiometry (DXA) is an internationally recognized standard tool for assessing the risk of brittle fracture. It is also recognized as the gold standard for detecting BMD. BMD measurement has been successfully applied to the evaluation of the bone healing process, a special form of bone lengthening.^61,63 The current DXA system includes a radiation source emitting two X-ray energy, a radiation detector, and a workbench supporting patients. Images and quantitative measurements of bone and soft tissue density were generated by software that evaluated the attenuation difference between two different energies.⁶⁴ DXA is a plane or two-dimensional bone mass measurement method. Since bone “depth” is not a factor, bone size can affect apparent bone mineral density. In essence, two vertebrae with the same bulk density can have different surface densities according to size.⁶⁵ The radiation of DXA is very low, which is equivalent to the natural background radiation received every day.⁶⁶ The most frequently measured parts are the lumbar spine and hip. The full table DXA system can measure bone mineral density in multiple parts (such as the lumbar spine, hip, and forearm). In contrast, the peripheral DXA system only measures peripheral bones, such as the forearm.⁶⁷ The full table DXA system is widely used in clinical practice and osteoporosis evaluation research. The lumbar spine and hip are the main parts of diagnosis and treatment decision making. DXA has good sensitivity and specificity in the diagnosis of vertebral fractures. This adaptation is called vertebral fracture assessment.

DXA is a safe and economical bone mineral density measurement method, which can not only evaluate the risk of fracture but also monitor the treatment response. World Health Organization (WHO) has identified DXA as the best measurement technique for evaluating bone mineral density in postmenopausal women. According to Thet-SCORE, this is the difference between the measured BMD and the average value of the young people to define osteoporosis^64,68 (Table 6), given the high incidence rate of osteoporosis and the incidence and mortality associated with brittle fracture. Bone mineral density measurement remains an important public health intervention. However, DXA technology is not widely used in fracture treatment. Peter Schwarzenberg and others mentioned in a review³⁰ in 2020 that DXA technology is used for osteoporosis screening and fracture risk assessment, but it is not widely used in fracture treatment. The research purpose of DXA is mainly to measure callus density, especially in large defects and limb extension. Although DXA technology has the advantages of wide availability and lower radiation dose than CT, DXA is not standardized in evaluating callus density and is easily disturbed by fixed hardware. In addition, the measurement result from this technology project the three-dimensional bone tissue density onto a two-dimensional plane, which can be difficult to effectively represent the three-dimensional spatial density of bone tissue. It is also difficult to distinguish between cancellous bone and cortical bone, and the application effect is limited.^30,67

**Table 6. WHO osteoporosis classification.⁶⁴**
Materials	T-score
Normal	>−1.0
Osteopenia	$< - 1.0, > - 2.5$ $< - 1.0, > - 2.5$
Osteoporosis	$< -$ $< -$ 2.5
Severe osteoporosis	$< -$ $< -$ 2.5 plus fragility fractures

3.4.2. Quantitative CT (QCT) was used to evaluate fracture healing

Quantitative CT (QCT) predicts bone healing by accurately measuring bone mineral density and body composition using clinical CT images after phantom calibration. As mentioned above, the DXA technique measures BMD in two dimensions, and the results are expressed in area density (g/cm²). QCT can measure volumetric bone mineral density without superimposing cortical bone and other tissues. The measurement results are in milligrams of hydroxyapatite calcium per cubic centimeter. Dailey et al. used virtual stress tests and low-dose CT scanning to provide quantitative and objective evaluation of callus structure and reliably predict the healing time in their experimental observation and research, to make it possible to diagnose poor healing early.⁴⁸ Although the commonly used measurement sites of DXA are the lumbar spine and hip, the spinal degeneration and abdominal aortic calcification may lead to the wrong discovery of bone mineral density increase in the measurement of two-dimensional BMD of lumbar spine by DXA. It is reported that the bone density measured by pa-dxa in patients with degenerative spondyloarthropathy with osteophytes in vertebral bodies and facets is significantly higher than that of patients with other diseases. In patients with osteophytes in vertebral bodies and facets, the bone density measured by pa-dxa is also significantly higher than that of patients with other diseases.⁴¹ In contrast, the most frequently measured part of QCT is the lumbar spine, which can avoid DXA overestimating BMD related to spinal degeneration, abdominal aortic calcification, and other sclerotic lesions (such as bone island). It may be more sensitive to the diagnosis osteoporosis.⁶⁷ Peter et al. summarized the research application of QCT technology for high-resolution imaging of trabecular microstructure and fracture callus, quantitative morphology and density analysis of callus, etc. QCT technology offers advantages such as lower cost and faster access speed compared to MRI. The disadvantages are higher cost and radiation than X-ray, and users need more training.³⁰ In addition, DXA equivalent projection BMD or T-score measurement of QCT scanning is an alternative method when a DXA scanner is not available. Still, QCT acquisition is generally not recommended solely for project analysis due to its substantially higher radiation exposure compared to DXA. Of course, in addition to osteoporosis, additional DXA may not be required for CT scans routinely obtained for diagnostic purposes. In general, the 2D projection calculated from the 3D-QCT dataset can not only provide real 3D-QCT parameters but also provide DXA equivalent evaluation. If both QCT and DXA are available and provide comparable information, DXA is favored to minimize radiation.⁶⁹ The International Commission on Radiation Protection has revised the organization weighting factor to describe the sensitivity of organizations to ionizing radiation. The effective dose for hip scans has been lowered by approximately 30% from past figures, while the effective dose for the lumbar spine is roughly the same. The radiation intensity of QCT of the spine or hip is about 50 to 100 times higher than that of DXA.

3.5. Application of biosensor in fracture healing evaluation

In recent years, with the continuous development of biosensors, researchers have begun to develop biosensors to provide information about the fracture healing process. Initially, the AO fracture monitor (AOFM) studied by AO Davos can continuously detect the fracture healing process in vivo for up to 8 months. AOFM serves as a biofeedback sensor system which gauges the deformation of implants when subjected to physiological stress.⁶⁹ Lin et al.⁷⁰ used the in vivo mouse fracture model to prove for the first time that the micro-instrumented implant provides a way for postoperative fracture monitoring, and used electrical impedance spectroscopy to track the healed tissue with high sensitivity. Borchani et al. studied the feasibility of using a piezoelectric floating grid sensor to monitor bone healing.⁴⁹ The sensor is directly integrated with the fixation device and obtains energy from microscale strain changes in the fixed structure.⁶⁷ The PFG sensor has seven linear logging channels for assessing bone healing progress. The authors demonstrate that piezoelectric floating grid sensors are capable of detecting and logging the dynamics of mechanical stress. In detail, they report that the number of sensor injection channels diminishes as the bone heals, so the recorded memory becomes unchanged when the bone heals.⁴⁹ By analyzing the memory, one can ascertain the bone’s healing status and decide if corrective surgery is necessary. These data assist in assessing the bone healing process, distinguishing different bone healing conditions, and determining the optimal time for removing fixation devices. In addition, Wolynski and others⁸ described the deployment of several ( $n = 5$ $n = 5$ ) implantable, flexible, wireless MEMS sensors on intramedullary nails to measure the biomechanical condition along the length of fracture fixation hardware during simulated healing of isolated sheep tibia.

The biosensors listed above are attached to orthopedic implants. In clinical experiments, they are currently used for in vitro fixed instrument monitoring, and parameters such as pressure at the target position in the human body can be used as an important diagnostic basis to monitor various types of serious potential medical conditions. Application of biosensors can provide more accurate data for complex fractures. Implantable commercial sensors can provide satisfactory accuracy and stability. However, patients need surgical removal after rehabilitation to avoid infection and other risks derived from long-term implantation. Many complications or troubles caused by these procedures force people to choose implantable sensors based on bioabsorbable materials.⁷¹ If properly designed, the whole equipment can be dissolved or absorbed without tracking after a certain control time. Hence, the necessity of removal surgery is eliminated.⁴⁹ At present, bioabsorbable sensors have been used as in vivo monitors, but their monitoring parameters take pressure as in vivo monitoring parameters in most of the searched articles because of the complex in vivo environment. Different fracture types and sites have brought great challenges to the design of such sensors. However, once a breakthrough is made, people can monitor their fracture healing status according to current events, which greatly reduces the burden on patients and the pressure on hospitals.

4. Discussion

This paper reviews the monitoring methods for fracture healing from five aspects: radiology, acoustics, biomechanics, molecular biology, and biosensors. Radiology technology still plays a crucial role in helping orthopedic doctors make decisions and evaluate fracture healing. It can assist doctors in observing the condition of the fracture site, but due to technological limitations, the detection accuracy of this method is difficult to guarantee. The method of using acoustics to evaluate the healing of fractures can solve the problem of secondary damage caused by X-ray radiation to the human body, but the detection accuracy of this method is also difficult to guarantee. Biomechanical monitoring is also a current research hotspot in fracture healing evaluation. This method mainly monitors the vibration response generated by mechanical means and is a noninvasive measurement method. This method has a good monitoring effect on the transformation process from cartilage callus to woven callus. The fracture evaluation method based on molecular biology quantitative measurement can detect the quality of bone microstructure and bone strength, and this method can assess the risk of bone healing to avoid the possibility of refracture. Biosensors monitor fracture healing information by implanting it into the patient’s fracture site. This method has high accuracy, but due to its invasive nature, it can cause damage to the human body. However, with the development of material and information technology, this evaluation method will be improved and more widely used.

By integrating different assessment methods into a more comprehensive assessment of fracture healing more comprehensive information and more accurate judgments can be provided.⁷² X-rays may be used first as an initial evaluation tool because they are quick, easy, and inexpensive. However, there is subjectivity, and interpretations may vary between observers.²¹ Next, depending on the X-ray findings and the patient’s specific situation, further assessment methods are chosen. DXA may be performed periodically to quantify changes in bone density at the fracture end to more accurately assess the degree of fracture healing. As noted by Kanis et al. in 2000, a significant number of fragility fractures in the elderly often go undetected,⁶² and a study by Lespesailles et al.⁶³ emphasized that bone mineral density (BMD) measurements are essential for assessing the risk of fracture healing. Based on the results of various assessment methods, physicians can more accurately determine the progression of fracture healing, and consequently, ascertain the necessary duration of treatment. A personalized physical therapy plan can be developed, including joint mobility training, plyometrics, etc., to promote fracture healing and restore the patient’s function.

Acknowledgment

The work described in this paper was supported in part by the National Natural Science Foundation of China (No. 61972117).

Conflict of Interest

The authors declare that they have no conflict of interest.

ORCID

Monan Wang https://orcid.org/0000-0003-0927-6487

Siyuan Zheng https://orcid.org/0009-0009-9589-2788

Su Gao https://orcid.org/0009-0008-0372-2830

Pengcheng Li https://orcid.org/0000-0002-9653-5194

Song Cui https://orcid.org/0009-0000-9910-1474

Lingbing Xia https://orcid.org/0009-0001-6881-2342

References

1. Potsika VT, Grivas KN, Gortsas T, Protopappas VC, Polyzos DK, Fotiadis DI, Boundary element simulation of ultrasonic backscattering during the fracture healing process, 2016 38th Annual Int Conf IEEE Engineering in Medicine and Biology Society (EMBC), pp. 2913–2916, 2016. Crossref, Google Scholar
2. Li Y, Liu D, Xu K, Ta D, Le LH, Wang W, Transverse and oblique long bone fracture evaluation by low order ultrasonic guided waves: A simulation study, BioMed Res Int 1 :3083141, 2017. Google Scholar
3. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A, Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025, J Bone Miner Res 22 :465–475, 2007. Crossref, Web of Science, Google Scholar
4. Huang Q, Xie B, Ye P, Chen Z, 3-D ultrasonic strain imaging based on a linear scanning system, IEEE Trans Ultrason, Ferroelectr, Freq Control 62 :392–400, 2015. Crossref, Web of Science, Google Scholar
5. Liu C, Xu F, Ta D, Tang T, Jiang Y, Dong J et al., Measurement of the human calcaneus in vivo using ultrasonic backscatter spectral centroid shift, J Ultrasound Med 35 :2197–2208, 2016. Crossref, Web of Science, Google Scholar
6. Schmickal T, von Recum J, Wentzensen, Stiffness measurement of the neocallus with the Fraktometer FM 100, Arch Orthop Trauma Surg 125 :653–659, 2005. Crossref, Google Scholar
7. Iqbal I, Shahzad G, Rafiq N, Mustafa G, Ma J, Deep learning-based automated detection of human knee joint’s synovial fluid from magnetic resonance images with transfer learning, IET Image Process 14 :1990–1998, 2020. Crossref, Web of Science, Google Scholar
8. Wolynski JG, Sutherland CJ, Demir HV, Unal E, Alipour A, Puttlitz CM et al., Utilizing multiple BioMEMS sensors to monitor orthopaedic strain and predict bone fracture healing, J Orthop Res 37 :1873–1880, 2019. Crossref, Web of Science, Google Scholar
9. Tan Y, Hu J, Ren L et al., A passive and wireless sensor for bone plate strain monitoring, Sensors (Basel) 17 :2635, 2017. Crossref, Web of Science, Google Scholar
10. Schmidhammer R, Zandieh S, Hopf R, Mizner I, Pelinka LE, Kroepfl A et al., Alleviated tension at the repair site enhances functional regeneration: The effect of full range of motion mobilization on the regeneration of peripheral nerves–histologic, electrophysiologic, and functional results in a rat model, J Trauma Acute Care Surg 56 :571–584, 2004. Crossref, Google Scholar
11. Bhavsar MB, Moll J, Barker JH, Bone fracture sensing using ultrasound pitch-catch measurements: A proof-of-principle study, Ultrasound Med Biol 46 :855–860, 2020. Crossref, Web of Science, Google Scholar
12. Moll J, Kexel C, Milanchian H, Bhavsar MB, Barker JH, Ultrasound bone fracture sensing and data communication: Experimental results in a pig limb sample, Ultrasound Med Biol 45 :605–611, 2019. Crossref, Web of Science, Google Scholar
13. Klosterhoff BS, Ghee Ong K, Krishnan L et al., Wireless implantable sensor for noninvasive, longitudinal quantification of axial strain across rodent long bone defects, J Biomech Eng 139 :1110041–1110048, 2017. Crossref, Web of Science, Google Scholar
14. Najafzadeh A, Serandi Gunawardena D, Liu Z, Tran T, Tam HY, Fu J et al., Application of fibre Bragg Grating sensors in strain monitoring and fracture recovery of human femur bone, Bioengineering (Basel) 7 :98, 2020. Crossref, Google Scholar
15. Kussmaul AC, Kuehlein T, Langer MF, Ayache A, Löw S, Unglaub F, The conservative and operative treatment of carpal fractures, Dtsch Arztebl Int, Forthcoming, arztebl-m2024, 2024. Google Scholar
16. Gilbreath J, IOM: The economics of better environmental health, Environ Health Perspect 115 :A80–A81, 2007. Crossref, Web of Science, Google Scholar
17. Marsell R, Einhorn TA, The biology of fracture healing, Injury 42 :551–555, 2011. Crossref, Web of Science, Google Scholar
18. Liu JX, Buza JA, Leucht P, Clinical aspects of fracture healing: An overview, Clin Rev Bone Miner Metab 13 :208–221, 2015. Crossref, Google Scholar
19. Morshed S, Current options for determining fracture union, Adv Med 2014 :708574, 2014. Crossref, Google Scholar
20. Fisher JS, Kazam JJ, Fufa D, Bartolotta RJ, Radiologic evaluation of fracture healing, Skelet Radiol 48 :349–361, 2019. Crossref, Web of Science, Google Scholar
21. Corrales LA, Morshed S, Bhandari M, Miclau T 3rd, Variability in the assessment of fracture-healing in orthopaedic trauma studies, J Bone Joint Surg Am 90 :1862–1868, 2008. Crossref, Google Scholar
22. Lu S, Vien BS, Russ M, Fitzgerald M, Chiu WK, Non-radiative healing assessment techniques for fractured long bones and osseointegrated implant, Biomed Eng Lett 10 :63–81, 2020. Crossref, Web of Science, Google Scholar
23. Bizzoca D, Vicenti G, Caiaffa V et al., Assessment of fracture healing in orthopaedic trauma, Injury 54 :S46–S52, 2020. Crossref, Google Scholar
24. Petfield JL, Hayeck GT, Kopperdahl DL, Nesti LJ, Keaveny TM, Hsu JR et al., Virtual stress testing of fracture stability in soldiers with severely comminuted tibial fractures, J Orthop Res 35 :805–811, 2017. Crossref, Web of Science, Google Scholar
25. Bhandari M, Guyatt GH, Swiontkowski MF, Tornetta P 3rd, Sprague S, Schemitsch EH, A lack of consensus in the assessment of fracture healing among orthopaedic surgeons, J Orthop Trauma 16 :562–566, 2002. Crossref, Web of Science, Google Scholar
26. Taha MA, Manske SL, Kristensen E, Taiani JT, Krawetz R, Wu Y et al., Assessment of the efficacy of MRI for detection of changes in bone morphology in a mouse model of bone injury, J Magn Reson Imaging 38 :231–237, 2013. Crossref, Web of Science, Google Scholar
27. Mallinson PI, Coupal TM, McLaughlin PD, Nicolaou S, Munk PL, Ouellette HA, Dual-energy CT for the musculoskeletal system, Radiology 281 :690–707, 2016. Crossref, Web of Science, Google Scholar
28. Galea VP, Botros MA, McTague MF et al., Radiostereometric analysis of stability and inducible micromotion after locked lateral plating of distal femur fractures, J Orthop Trauma 34 :e60–e66, 2020. Crossref, Web of Science, Google Scholar
29. Ladurner A, Callary SA, Mitra A et al., Radiostereometric analysis allows assessment of the stability and inducible displacement of pelvic ring disruptions during healing: A case series, J Clin Med 9 :3411, 2020. Crossref, Web of Science, Google Scholar
30. Schwarzenberg P, Darwiche S, Yoon RS, Dailey HL, Imaging modalities to assess fracture healing, Curr Osteoporos Rep 18 :169–179, 2020. Crossref, Web of Science, Google Scholar
31. Eastaugh-Waring SJ, Joslin CC, Hardy JRW, Cunningham JL, Quantification of fracture healing from radiographs using the maximum callus index, Clin Orthop Relat Res 467 :1986–1991, 2009. Crossref, Web of Science, Google Scholar
32. Akinmade A, Ikem I, Ayoola O, Orimolade E, Adeyeye A, Comparing ultrasonography with plain radiography in the diagnosis of paediatric long-bone fractures, Int Orthop 43 :1143–1153, 2019. Crossref, Web of Science, Google Scholar
33. Crompton S, Messina F, Klafkowski G, Hall C, Offiah AC, Validating scoring systems for fracture healing in infants and young children: Pilot study, Pediatr Radiol 51 :1682–1689, 2021. Crossref, Web of Science, Google Scholar
34. Harper NS, Eddleman S, Shukla K, Narcise MV et al., Radiologic assessment of skull fracture healing in young children, Pediatr Emerg Care 37 :213–217, 2021. Crossref, Web of Science, Google Scholar
35. Ha AS, Lee AY, Hippe DS, Chou SHS, Chew FS, Digital tomosynthesis to evaluate fracture healing: Prospective comparison with radiography and CT, Am J Roentgenol 205 :136–141, 2015. Crossref, Web of Science, Google Scholar
36. Stange R, Sahin H, Wieskotter B et al., In vivo monitoring of angiogenesis during tendon repair: A novel MRI-based technique in a rat patellar tendon model, Knee Surg, Sports Traumatol, Arthrosc 23 :2433–2439, 2015. Crossref, Web of Science, Google Scholar
37. Schmitz N, Timmen M, Kostka K, Hoerr V, Schwarz C, Faber C et al., A novel MRI compatible mouse fracture model to characterize and monitor bone regeneration and tissue composition, Sci Rep 10 :16238, 2020. Crossref, Web of Science, Google Scholar
38. Bojan AJ, Jonsson A, Granhed H, Ekholm C, Karrholm J, Trochanteric fracture-implant motion during healing - A radiostereometry (RSA) study, Injury 49 :673–679, 2018. Crossref, Web of Science, Google Scholar
39. Finnila S, Moritz N, Strandberg N, Alm JJ, Aro HT, Radiostereometric analysis of the initial stability of internally fixed femoral neck fractures under differential loading, J Orthop Res 37 :239–247, 2019. Crossref, Web of Science, Google Scholar
40. Rashid MS, Pullin R, The sound of orthopaedic surgery–the application of acoustic emission technology in orthopaedic surgery: A review, Eur J Orthop Surg Traumatol 24 :1–6, 2014. Crossref, Google Scholar
41. Yu W, Gluer CC, Fuerst T, Grampp S, Li J, Lu Y et al., Influence of degenerative joint disease on spinal bone mineral measurements in postmenopausal women, Calcified Tissue Int 57 :169–174, 1995. Crossref, Web of Science, Google Scholar
42. Bochud N, Vallet Q, Laugier P et al., Predicting bone strength with ultrasonic guided waves, Sci Rep 7 :43628, 2017. Crossref, Web of Science, Google Scholar
43. Lamy F, Takarli M, Angellier N, Dubois F, Pop O, Acoustic emission technique for fracture analysis in wood materials, Int J Fract 192 :57–70, 2015. Crossref, Web of Science, Google Scholar
44. Hirasawa Y, Takai S, Kim WC, Takenaka N, Yoshino N, Watanabe Y, Biomechanical monitoring of healing bone based on acoustic emission technology, Clin Orthop Relat Res 402 :236–244, 2002. Crossref, Google Scholar
45. Curvers F, Meschi N, Vanhoenacker A, Strijbos O, Van Mierlo M, Lambrechts P, Ultrasound assessment of bone healing after root-end surgery: Echoes back to patient’s safety, J Endod 44 :32–37, 2018. Crossref, Web of Science, Google Scholar
46. Jeon S, Jang J, Lee G et al., Assessment of neovascularization during bone healing using contrast-enhanced ultrasonography in a canine tibial osteotomy model: A preliminary study, J Vet Sci 21 :1, 2020. Crossref, Web of Science, Google Scholar
47. Sorriento A, Poliziani A, Cafarelli A, Valenza G, Ricotti L, A novel quantitative and reference-free ultrasound analysis to discriminate different concentrations of bone mineral content, Sci Rep 11 :301, 2021. Crossref, Web of Science, Google Scholar
48. Davis BJ, Roberts PJ, Moorcroft CI, Brown MF, Thomas PBM, Wade RH, Reliability of radiographs in defining union of internally fixed fractures, Injury 35 :557–561, 2004. Crossref, Web of Science, Google Scholar
49. Borchani W, Aono K, Lajnef N et al., Monitoring of postoperative bone healing using smart trauma-fixation device with integrated self-powered piezo-floating-gate sensors, IEEE Trans Biomed Eng 63 :1463–1472, 2016. Crossref, Web of Science, Google Scholar
50. Nemchand JL, Smart implant: The biomechanical testing of instrumented intramedullary nails during simulated callus healing using telemetry for fracture healing monitoring, Ph.D. Thesis, Brunel University London, 2015. Google Scholar
51. Chiu WK, Vien BS, Russ M, Fitzgerald M, Towards a non-invasive technique for healing assessment of internally fixated femur, Sensors (Basel). 19 :857, 2019. Crossref, Web of Science, Google Scholar
52. Mattei L, Longo A, Di Puccio F, Ciulli E, Marchetti S, Vibration testing procedures for bone stiffness assessment in fractures treated with external fixation, Ann Biomed Eng 45 :1111–1121, 2017. Crossref, Web of Science, Google Scholar
53. Ong WH, Chiu WK, Russ M, Chiu ZK, Extending structural health monitoring concepts for bone healing assessment, Fatigue Fract Eng Mater Struct 39(4) :491–501, 2016. Crossref, Web of Science, Google Scholar
54. Ong WH, Chiu WK, Russ M, Chiu ZK, Integrating sensing elements on external fixators for healing assessment of fractured femur, Struct Control Health Monit 23 :1388–1404, 2016. Crossref, Web of Science, Google Scholar
55. Mattei L, Di Puccio F, Marchetti S, Fracture healing monitoring by impact tests: Single case study of a fractured tibia with external fixator, IEEE J Transl Eng Health Med 7 :1–6, 2019. Crossref, Google Scholar
56. Mattei L, Di Fonzo M, Marchetti S, Di Puccio F, A quantitative and non-invasive vibrational method to assess bone fracture healing: A clinical case study, Int Biomech 8 :1–13, 2021. Crossref, Google Scholar
57. Mattei L, Di Puccio F, Marchetti S, In vivo impact testing on a lengthened femur with external fixation: A future option for the non-invasive monitoring of fracture healing? J R Soc Interface 15 :20180068, 2018. Crossref, Google Scholar
58. Dailey HL, Schwarzenberg P, Daly CJ, Boran SAM, Maher MM, Harty JA, Virtual mechanical testing based on low-dose computed tomography scans for tibial fracture a pilot study of prediction of time to union and comparison with subjective outcomes scoring, J Bone Joint Surg Am 101 :1193–1202, 2019. Crossref, Web of Science, Google Scholar
59. Stoffel K, Engler H, Kuster M, Riesen W, Changes in biochemical markers after lower limb fractures, Clin Chem 53 :131–134, 2007. Crossref, Web of Science, Google Scholar
60. Harada S, Rodan GA, Control of osteoblast function and regulation of bone mass, Nature 423 :349–355, 2003. Crossref, Web of Science, Google Scholar
61. Haseltine KN, Chukir T, Smith PJ, Jacob JT, Bilezikian JP, Farooki A, Bone mineral density: Clinical relevance and quantitative assessment, J Nucl Med 62 :446–454, 2021. Crossref, Web of Science, Google Scholar
62. Lespessailles E, Chappard C, Bonnet N, Benhamou CL, Imaging techniques for evaluating bone microarchitecture, Joint Bone Spine 73 :254–261, 2006. Crossref, Web of Science, Google Scholar
63. Tselentakis G, Owen PJ, Richardson JB, Kuiper JH, Haddaway MJ, Dwyer JS et al., Fracture stiffness in callotasis determined by dual-energy X-ray absorptiometry scanning, J Pediatr Orthop B 10 :248–254, 2001. Web of Science, Google Scholar
64. Kanis JA, Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report, WHO Study Group, Osteoporos Int 4 :368–381, 1994. Crossref, Web of Science, Google Scholar
65. Cagnoni C, Bibbo P, Gandolfi S, Iofrida M, Occhipinti M, Different approaches in the management of bone densitometry in clinical practice: Old certainties and room for improvement, Osteoporos Int 27 :S347–S348, 2016. Web of Science, Google Scholar
66. Damilakis J, Adams JE, Guglielmi G, Link TM, Radiation exposure in X-ray-based imaging techniques used in osteoporosis, Eur Radiol 20 :2707–2714, 2010. Crossref, Web of Science, Google Scholar
67. Li N, Li XM, Xu L, Sun WJ, Cheng XG, Tian W, Comparison of QCT and DXA: Osteoporosis detection rates in postmenopausal women, Int J Endocrinol 2013 :895474, 2013. Crossref, Web of Science, Google Scholar
68. El Maghraoui A, Roux C, DXA scanning in clinical practice, QJM 101 :605–617, 2008. Crossref, Web of Science, Google Scholar
69. Engelke K, Lang T, Khosla S, Qin L, Zysset P, Leslie WD et al., Clinical use of quantitative computed tomography (QCT) of the hip in the management of osteoporosis in adults: The 2015 ISCD Official Positions-Part I, J Clin Densitom 18 :338–358, 2015. Crossref, Web of Science, Google Scholar
70. Lin MC, Hu D, Marmor M et al., Smart bone plates can monitor fracture healing, Sci Rep 9 :2122, 2019. Crossref, Web of Science, Google Scholar
71. You Z, Wei L, Zhang M, Yang F, Wang X, Hermetic and bioresorbable packaging materials for MEMS implantable pressure sensors: A review, IEEE Sens J 22 :23633–23648, 2022. Crossref, Web of Science, Google Scholar
72. Abdelazeem MH, Cakir M, Erdogan O, Transoral endoscopic assisted reduction and internal fixation of mandibular condylar neck fractures with short condylar segment, J Cranio-Maxillofacial Surg 52 :914–921, 2024. Crossref, Web of Science, Google Scholar

Vol. 24, No. 09

Metrics

Downloaded 145 times

History

Received 10 March 2024

Accepted 10 August 2024

Published: 19 November 2024

Information

This is an Open Access article published by World Scientific Publishing Company. It is distributed under the terms of the Creative Commons Attribution 4.0 (CC BY) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Keywords

PDF download