Bone Research Articles

Mechanical and in vitro study of 3D printed silk fibroin and bone-based composites biomaterials for bone implant application.

When treating orthopaedic damage or illness and accidental fracture, bone grafting remains the gold standard of treatment. In cases where this approach doesn't seem achievable, bone tissue engineering can offer scaffolding as a substitute. Defective and fractured bone tissue is extracted and substituted with porous scaffold structures to aid in the process of tissue regeneration. 3D bioprinting has demonstrated enormous promise in recent years for producing scaffold structures with the necessary capabilities. In order to create composite biomaterial inks for 3D bioprinting, three different materials were combined such as silk fibroin, bone particles, and synthetic biopolymer poly (ε-caprolactone) (PCL). These biomaterials were used to fabricate the two composites scaffolds such as: silk fibroin + bovine bone (SFB) and silk fibroin + bovine bone + Polycaprolactone (SFBP). The biomechanical, structural, and biological elements of the manufactured composite scaffolds were characterized in order to determine their suitability as a possible biomaterial for the production of bone tissue. The in vitro bioactivity of the two composite scaffolds was assessed in the simulated body fluids, and the swelling and degradation characteristics of the two developed scaffolds were analyzed separately over time. The results showed that the mechanical durability of the composite scaffolds was enhanced by the bovine bone particles, up to a specific concentration in the silk fibroin matrix. Furthermore, the incorporation of bone particles improved the bioactive composite scaffolds' capacity to generate hydroxyapatite in vitro. The combined findings show that the two 3D printed bio-composites scaffolds have the required mechanical strength and may be applied to regeneration of bone tissue and restoration, since they resemble the characteristics of native bone.

Enhancing Bone Healing through Localized Cold Therapy in a Murine Femoral Fracture Model.

Fracture healing, a critical and complex biological process, often presents challenges in clinical practice with the current standards failing to fully address the medical needs for rapid and effective recovery. In this work, a localized cold therapy is investigated as an alternative approach to expedite bone healing. We hypothesized that optimized cold application can enhance bone healing within a fracture model by inducing hypoxia, leading to accelerated angiogenesis along with improved osteogenesis. A short, localized cold exposure is directly applied to the fracture site over a four-week period in a mouse fracture model, aiming to assess its impact on bone formation through mechanisms of angiogenesis and osteogenesis. Our results revealed a significantly greater volume of new bone tissue and enhanced vascularity at the fracture site in the cold-treated group compared to controls. Calcified tissue histology analysis showed that the accelerated callus maturation and development of the vascular network following cold exposure were associated with an activity increase of alkaline phosphatase (ALP) and transient receptor potential vanilloid 1 (TRPV1). These biological changes were accompanied by a hypoxic environment induced during cold therapy. The study provides compelling evidence supporting the efficacy of intermittent cold therapy in accelerating fracture healing. These promising results highlight the need for further research in larger-scale studies and diverse fracture models, underlining the potential of cold therapy as a novel, non-invasive treatment strategy in orthopedic care.

ECM-Mimicking Strontium-Doped Nanofibrous Microspheres for Periodontal Tissue Regeneration in Osteoporosis.

Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr2+), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.

An Exploration of The Role of Osteoclast Lineage Cells in Bone Tissue Engineering.

Bone defects due to age, trauma, and surgery, which are exacerbated by medication side effects and common diseases like osteoporosis, diabetes, and rheumatoid arthritis, are a problem of epidemic scale. The present clinical standard for treating these defects includes autografts and allografts. While both treatments can promote robust regenerative outcomes, they fail to strike a desirable balance of availability, side effect profile, consistent regenerative efficacy, and affordability. This difficulty has contributed to the rise of bone tissue engineering (BTE) as a potential avenue through which enhanced bone regeneration could be delivered. BTE is founded upon a paradigm of using biomaterials, bioactive factors, osteoblast lineage cells (ObLCs), and vascularization to cue deficient bone tissue into a state of regeneration. Despite promising preclinical results, BTE has had modest success in being translated into the clinical setting. One barrier has been the simplicity of its paradigm relative to the complexity of biological bone. Therefore, this paradigm must be critically examined and expanded to better account for this complexity. One potential avenue for this is a more detailed consideration of osteoclast lineage cells (OcLCs). While these cells ostensibly oppose ObLCs and bone regeneration through their resorptive functions, myriad investigations have shed light on their potential to influence bone equilibrium in more complex ways through their interactions with both ObLCs and bone matrix. Most BTE research has not systematically evaluated their influence. Yet contrary to expectations associated with the paradigm, a selection of BTE investigations have demonstrated that this influence can enhance bone regeneration in certain contexts. Additionally, much work has elucidated the role of many controllable scaffold parameters in both inhibiting and stimulating the activity of OcLCs in parallel to bone regeneration. Therefore, this review aims to detail and explore the implications of OcLCs in BTE, and how they can be leveraged to improve upon the existing BTE paradigm.

Thermal, Surface, and Structure Analysis of Molybdenum substituted Bioactive Glass Ceramics SiO2-CaO- MoO3-P2O5

This study explores the incorporation of molybdenum oxide (MoO3) as a dopant in SiO2-CaO-P2O5 (BGC) glass-ceramics through a meticulously designed sol-gel synthesis process to optimize properties for regenerative medicine applications. Comprehensive characterization techniques, including thermal analysis (TGA/DSC), Raman spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR), elucidate the morphological and structural modifications induced by MoO3 doping. Results reveal that MoO3 affects the glass transition temperature, crystallization behavior, and surface morphology, leading to enhanced glass stability, crystallinity, and surface properties. The mechanical properties, such as fracture toughness, also significantly improved with MoO3 doping due to the formation of crystalline phases and densification of the material structure. Notably, the doping of MoO3 promotes the formation of CaMoO4 crystalline phases and influences the synthesis of hydroxyapatite—critical for bone tissue regeneration—when immersed in simulated body fluid (SBF). The study highlights the hydrophilic nature of the doped samples, facilitating bone development and cell adhesion, while also showing that increased MoO3 content reduces the rate of hydroxyapatite formation and material degradability. These findings demonstrate that MoO3 doping via the sol-gel method offers a promising approach for tailoring BGC glass-ceramics' properties, making them more suitable for regenerative medicine applications. This research underscores the potential of MoO3 in advancing biomaterial development for tissue engineering and implantology.

Employing novel biocompatible composite scaffolds with bioglass 58S and poly L-lactic acid for effective bone defect treatment.

Bioglass materials have gained significant attention in the field of tissue engineering due to their osteoinductive and biocompatible properties that promote bone cell differentiation. In this study, a novel composite scaffold was developed using a sol-gel technique to combine bioglass (BG) 58S with a poly L-lactic acid (PLLA). The physiochemical properties, morphology, and osteoinductive potential of the scaffolds were investigated by X-ray diffraction analysis, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The results showed that the SiO2-CaO-P2O5 system was successfully synthesized by the sol-gel method. The PLLA scaffolds containing BG was found to be osteoinductive and promoted mineralization, as demonstrated by calcium deposition assay, upregulation of alkaline phosphatase enzyme activity, and Alizarin red staining data. These in vitro studies suggest that composite scaffolds incorporating hBMSCs are a promising substitute material to be implemented in bone tissue engineering. The PLLA/BG scaffolds promote osteogenesis and support the differentiation of bone cells, such as osteoblasts, due to their osteoinductive properties.

Ribbing disease of the femur: a rare entity.

Ribbing disease is a rare benign bone dysplasia characterized by progressive cortical thickening of the diaphyses of long bones in adult patients. The literature provides limited insight into its natural radiological progression and anatomical distribution. Single-bone involvement is particularly uncommon, with prior cases exclusively affecting the tibia. This case report outlines the unique presentation of Ribbing disease in a 20-year-old male, localized to the left femur. The patient's history revealed intermittent left thigh pain persisting for more than 2 years, with no identifiable triggers or relief factors. Early radiographic imaging revealed no significant abnormalities, but subsequent imaging, conducted 1 year after the initial presentation, revealed focal fusiform widening and cortical thickening of the mid-diaphysis of the left femur. MRI further revealed circumferential cortical thickening with bone marrow edema, corroborated by CT, which revealed cortical thickening with near-complete obliteration of the intramedullary cavity. The patient was managed with nonsteroidal anti-inflammatory drugs and activity modifications. Misinterpretation of the radiographic findings of the osteoid osteoma led the patient to undergo radiofrequency ablation. This case highlights the challenges in diagnosing Ribbing disease and emphasizes the importance of considering it in the differential diagnosis of chronic limb pain. Continued reporting of cases contributes to enhancing our understanding and management of this rare skeletal dysplasia.

Gelatin Methacryloyl (GelMA) - 45S5 Bioactive Glass (BG) Composites for Bone Tissue Engineering: 3D Extrusion Printability and Cytocompatibility Assessment Using Human Osteoblasts.

3D extrusion printing has been widely investigated for low-volume production of complex-shaped scaffolds for tissue regeneration. Gelatin methacryloyl (GelMA) is used as a baseline material for the synthesis of biomaterial inks, often with organic/inorganic fillers, to obtain a balance between good printability and biophysical properties. The present study demonstrates how 45S5 bioactive glass (BG) addition and GelMA concentrations can be tailored to develop GelMA composite scaffolds with good printability and buildability. The experimental results suggest that 45S5 BG addition consistently decreases the compression stiffness, irrespective of GelMA concentration, albeit within 20% of the baseline scaffold (without 45S5 BG). The optimal addition of 2 wt % 45S5 BG in 7.5 wt % GelMA was demonstrated to provide the best combination of printability and buildability in the 3D extrusion printing route. The degradation decreases and the swelling kinetics increases with 45S5 BG addition, irrespective of GelMA concentration. Importantly, the dissolution in simulated body fluid over 3 weeks clearly promoted the nucleation and growth of crystalline calcium phosphate particles, indicating the potential of GelMA-45S5 BG to promote biomineralization. The cytocompatibility assessment using human osteoblasts could demonstrate uncompromised cell proliferation or osteogenic marker expression over 21 days in culture for 3D printable 7.5 wt % GelMA -2 wt % 45S5 BG scaffolds when compared to 7.5 wt % GelMA. The results thus encourage further investigations of the GelMA/45S5 BG composite system for bone tissue engineering applications.

Development of Ductile‐Sticky Bone Fillers from Biodegradable Hydrolyzed Wool‐Keratin and Silk Fibroin

AbstractIn the present study, a method is proposed for preparing novel ductile‐sticky materials that can be used as bone void fillers using hydrolyzed wool‐keratin (WK) and silk fibroin (SF). This methodology uses citric acid as a cross‐linking agent in preparing keratin paste (KP) owing to its non‐toxicity and plasticizing properties. The Keratin paste‐silk fibroin structure (KPSF) is obtained by adding SF, which possesses biocompatible and superior mechanical properties. Methanol treatment is employed on the KPSF mixture to convert the Silk I structure in the SF to Silk II, resulting in a water‐insoluble and tightly packed proteinaceous structure. The physicochemical properties of both bioscaffolds are investigated and discussed in detail by comparison. Based on the findings, the presence of SF in the KPSF structure contributed to properties such as flexibility and porosity. In ovo CAM analysis reveals that both materials exhibit proangiogenic properties and are biocompatible. KP and KPSF bioscaffolds can be converted into ductile‐sticky forms by adding water. It believes that these forms can easily apply to bone defect areas, particularly cavitary bone defects. Furthermore, KPSF bioscaffolds, with better mechanical properties, can be considered candidates for use in non‐load‐bearing bone tissue engineering applications.

A full-head model to investigate intra and extracochlear electric fields in cochlear implant stimulation

Objective. Despite the widespread use and technical improvement of cochlear implant (CI) devices over past decades, further research into the bioelectric bases of CI stimulation is still needed. Various stimulation modes implemented by different CI manufacturers coexist, but their true clinical benefit remains unclear, probably due to the high inter-subject variability reported, which makes the prediction of CI outcomes and the optimal fitting of stimulation parameters challenging. A highly detailed full-head model that includes a cochlea and an electrode array is developed in this study to emulate intracochlear voltages and extracochlear current pathways through the head in CI stimulation. Approach. Simulations based on the finite element method were conducted under monopolar, bipolar, tripolar (TP), and partial TP modes, as well as for apical, medial, and basal electrodes. Variables simulated included: intracochlear voltages, electric field (EF) decay, electric potentials at the scalp and extracochlear currents through the head. To better understand CI side effects such as facial nerve stimulation, caused by spurious current leakage out from the cochlea, special emphasis is given to the analysis of the EF over the facial nerve. Main results. The model reasonably predicts EF magnitudes and trends previously reported in CI users. New relevant extracochlear current pathways through the head and brain tissues have been identified. Simulated results also show differences in the magnitude and distribution of the EF through different segments of the facial nerve upon different stimulation modes and electrodes, dependent on nerve and bone tissue conductivities. Significance. Full-head models prove useful tools to model intra and extracochlear EFs in CI stimulation. Our findings could prove useful in the design of future experimental studies to contrast FNS mechanisms upon stimulation of different electrodes and CI modes. The full-head model developed is freely available for the CI community for further research and use.

Synthesis of Porous Bioceramic Scaffolds for Bone Tissue Engineering: Effects of Experimental Parameters

Synthesis of Porous Bioceramic Scaffolds for Bone Tissue Engineering: Effects of Experimental Parameters

In Situ Printing of Polylactic Acid/Nanoceramic Filaments for the Repair of Bone Defects Using a Portable 3D Device.

In situ 3D printing is attractive for the direct repair of bone defects in underdeveloped countries and in emergency situations. So far, the lack of an interesting method to produce filament using FDA-approved biopolymers and nanoceramics combined with a portable strategy limits the use of in situ 3D printing. Herein, we investigated the osseointegration of new nanocomposite filaments based on polylactic acid (PLA), laponite (Lap), and hydroxyapatite (Hap) printed directly at the site of the bone defect in rats using a portable 3D printer. The filaments were produced using a single-screw extruder (L/D = 26), without the addition of solvents that can promote the toxicity of the materials. In vitro performance was evaluated in the cell differentiation process with mesenchymal stem cells (MSC) by an alkaline phosphatase activity test and visualization of mineralization nodules; a cell viability test and total protein dosage were performed to evaluate cytotoxicity. For the in vivo analysis, the PLA/Lap composite filaments with a diameter of 1.75 mm were printed directly into bone defects of Wistar rats using a commercially available portable 3D printer. Based on the in vitro and in vivo results, the in situ 3D printing technique followed by rapid cooling proved to be promising for bone tissue engineering. The absence of fibrous encapsulation and inflammatory processes became a good indicator of effectiveness in terms of biocompatibility parameters and bone tissue formation, and the use of the portable 3D printer showed a significant advantage in the application of this material by in situ printing.

Natural Affinity Driven Modification by Silicene to Construct a "Thermal Switch" for Tumorous Bone Loss.

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.

Effect of Xanthohumol from Humulus lupulus L. Against Gouty Bone Damage in Arthritis of Rats Induced by Mono-sodium Urate.

Xanthohumol (XAN) is an isoprenyl flavonoid from Humulus lupulus L. known for beer brewing, and an osteoprotective agent due to its active improvement in bone loss of osteoporosis. This study was first time to investigate its effects on anti-gouty bone injury in rats of gouty arthritis (GA) induced by monosodium urate (MSU). Results showed that XAN could significantly exert anti-inflammatory activity by alleviating swelling degree of joints, reducing serum level of inflammatory factors, improving inflammatory injury and degrading the Markin's score in lesion joint. Meanwhile, XAN could also fight against gouty bone damage by improving pathological changes of bone tissue and parameters of bone micro-structure. Moreover, XAN could even promote bone formation by effectively enhancing expression of Runx2 and OPG, while inhibit bone resorption with depressing matrix metalloproteinase-9 (MMP-9), MMP-13 and CTSK expression, reducing RANKL secretion, and abating the ratio of RANKL/OPG. Therefore, it was the first time to reveal the mechanism of XAN against gouty bone injury via inhibiting RANKL/OPG/RANK signaling pathway. Above all, this study provided potential strategy for the treatment of GA, and further contributed to research and resource development for hops.

Research on the osteogenic properties of 3D-printed porous titanium alloy scaffolds loaded with Gelma/PAAM-ZOL composite hydrogels

Although titanium alloy is the most widely used endoplant material in orthopedics, the material is bioinert and good bone integration is difficult to achieve. Zoledronic acid (ZOL) has been shown to locally inhibit osteoclast formation and prevent osteoporosis, but excessive concentrations of ZOL exert an inhibitory effect on osteoblasts; therefore, stable and controlled local release of ZOL may reshape bone balance and promote bone regeneration. To promote the adhesion of osteoblasts to many polar groups, researchers have applied gelatine methacryloyl (Gelma) combined with polyacrylamide hydrogel (PAAM), which significantly increased the hydrogen bonding force between the samples and improved the stability of the coating and drug release. A series of experiments demonstrated that the Gelma/PAAM-ZOL bioactive coating on the surface of the titanium alloy was successfully prepared. The coating can induce osteoclast apoptosis, promote osteoblast proliferation and differentiation, achieve dual regulation of bone regeneration, successfully disrupt the balance of bone remodelling and promote bone tissue regeneration. Additionally, the coating improves the metal biological inertness on the surface of titanium alloys and improves the bone integration of the scaffold, offering a new strategy for bone tissue engineering to promote bone technology.

CT myelography by intrathecal injection of contrast medium though percutaneous administration route visualizes compressed cervical spinal cord in a mouse

BackgroundChronic compressive myelopathy (CCM) is a major cause of spinal cord disorders in the elderly, in which the spinal cord is compressed by bony or soft tissue structures. Although computed tomography myelography (CTM) has been clinically used for the diagnosis of CCM, a method of CTM in rodents remains to be developed. New methodA 50 μl Hamilton syringe attached to a disposable needle was percutaneously inserted into the subarachnoid space (cisterna magna) between the occipital bone and C1 lamina in an anesthetized adult mouse, followed by the injection of contrast medium and CT imaging. ResultsCTM clearly visualized the shape of the spinal cord of intact mice and tiptoe-walking Yoshimura (Twy) mice without any health issues. Comparison with existing method(s)Unlike histology, the current method functions in live mice, directly depicts the compressed spinal cord, and provides clinically related image information. Furthermore, the intrathecal administration of contrast medium through the percutaneous route makes CTM less invasive and takes less time than a conventional intrathecal injection method. ConclusionsThe CTM method used in the present study enables clear visualization of the shape of the dural sac and spinal cord and is useful when conducting experiments on CCM and other spinal diseases in rodents.

Impact of the SIK3 Pathway Inhibition on Osteoclast Differentiation via Oxidative Phosphorylation.

Maintenance of bone homeostasis and the balance between bone resorption and formation are crucial for maintaining skeletal integrity. This study sought to investigate the role of salt-inducible kinase 3 (SIK3), a key regulator in cellular energy metabolism, during the differentiation of osteoclasts. Despite osteoclasts being high energy-consuming cells essential for breaking down mineralized bone tissue, the specific function of SIK3 in this process remains unclear. To address this issue, we generated osteoclast-specific SIK3 conditional knockout mice and assessed the impact of SIK3 deletion on bone homeostasis. Our findings revealed that SIK3 conditional knockout mice exhibited increased bone mass and an osteopetrosis phenotype, suggesting a pivotal role for SIK3 in bone resorption. Moreover, we assessed the impact of pterosin B, a SIK3 inhibitor, on osteoclast differentiation. The treatment with pterosin B inhibited osteoclast differentiation, reduced the numbers of multinucleated osteoclasts, and suppressed resorption activity in vitro. Gene expression analysis demonstrated that SIK3 deletion and pterosin B treatment influence a common set of genes involved in osteoclast differentiation and bone resorption. Furthermore, pterosin B treatment altered intracellular metabolism, particularly affecting key metabolic pathways, such as the tricarboxylic acid cycle and oxidative phosphorylation. These results provide valuable insights into the involvement of SIK3 in osteoclast differentiation and the molecular mechanisms underlying osteoclast function and bone diseases.

Cortical thickness and childhood eating behaviors: differences according to sex and age, and relevance for eating disorders

PurposeThis study investigated the association between childhood eating behaviors and cortical morphology, in relation to sex and age, in a community sample.MethodsNeuroimaging data of 71 children (mean age = 9.9 ± 1.4 years; 39 boys/32 girls) were obtained from the Nathan Kline Institute-Rockland Sample. Emotional overeating, food fussiness, and emotional undereating were assessed using the Children’s Eating Behavior Questionnaire. Cortical thickness was obtained at 81,924 vertices covering the entire cortex. Generalized Linear Mixed Models were used for statistical analysis.ResultsThere was a significant effect of sex in the association between cortical thickness and emotional overeating (localized at the right postcentral and bilateral superior parietal gyri). Boys with more emotional overeating presented cortical thickening, whereas the opposite was observed in girls (p < 0.05). Different patterns of association were identified between food fussiness and cortical thickness (p < 0.05). The left rostral middle frontal gyrus displayed a positive correlation with food fussiness from 6 to 8 years, but a negative correlation from 12 to 14 years. Emotional undereating was associated with cortical thickening at the left precuneus, left middle temporal gyrus, and left insula (p < 0.05) with no effect of sex or age.ConclusionsLeveraging on a community sample, findings support distinct patterns of associations between eating behaviors and cortical thickness, depending on sex and age.

Stem Cells in Bone Tissue Engineering: Progress, Promises and Challenges.

Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pulp, hold immense potential in bone TE. Induced pluripotent stem cells and genetically modified stem cells can also be used. Proper manipulation of physical, chemical, and biological stimulation is crucial for their proliferation, maintenance, and differentiation. Stem cells contribute to osteogenesis, osteoinduction, angiogenesis, and mineralization, essential for bone regeneration. This review provides an overview of the latest developments in stem cell-based TE for repairing and regenerating defective bones.

Radiomics based on multiple machine learning methods for diagnosing early bone metastases not visible on CT images.

This study utilizes [99mTc]-methylene diphosphate (MDP) single photon emission computed tomography (SPECT) images as a reference standard to evaluate whether the integration of radiomics features from computed tomography (CT) and machine learning algorithms can identify microscopic early bone metastases. Additionally, we also determine the optimal machine learning approach. We retrospectively studied 63 patients with early bone metastasis from July 2020 to March 2023. The ITK-SNAP software was used to delineate early bone metastases and normal bone tissue in SPECT images of each patient, which were then registered onto CT images to outline the volume of interest (VOI). The VOI includes 63 early bone metastasis volumes and 63 normal bone tissue volumes. 126 VOIs were randomly distributed in a 7:3 ratio between the training and testing groups, and 944 radiomics features were extracted from every VOI. We established 20 machine learning models using 5 feature selection algorithms and 4 classification methods. Evaluate the performance of the model using the area under the receiver operating characteristic curve (AUC). Most machine learning models demonstrated outstanding discriminative capacity, with AUCs higher than 0.70. Notably, the K-Nearest Neighbors (KNN) classifier exhibited significant performance improvement compared to the other four classifiers. Specifically, the model constructed utilizing eXtreme Gradient Boosting (XGBoost) feature selection method integrated with KNN classifier achieved the maximum AUC, which is 0.989 in the training set and 0.975 in the testing set. Radiomics features integrated with machine learning methods can identify early bone metastases that are not visible on CT images. In our analysis, KNN is considered the optimal classification method.