Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

The influence of locally applied granulocyte-colony stimulating factor on osteoporotic bone.

OBJECTIVES: The compromised capacity of bone healing in osteoporotic population renders a serious concern of patients and clinicians. This study aimed to investigate the influence of G-CSF on bone reconstruction using an osteoporotic animal model. MATERIALS AND METHODS: Sixty skeletal mature female Spraque-Dawley rats underwent bilateral ovariectomy (OVX) and were assigned into three groups (n = 20). Three months after OVX, defects of 5 mm in cranial and 2 mm in femur were surgically created on all the animals. The defects were left unfilled, filled with gelatin sponge (GS), or filled with granulocyte-colony stimulating factor (G-CSF) infused GS. Specimens were retrieved for histomorphometric and micro-CT analyses at weeks 1, 4, 8, and 12 after surgery. RESULTS: At early stage of week 1 to week 8, the histomorphometric and micro-CT analysis demonstrated more advanced bone formation in femur in the control group; by week 12, all groups achieved cortical closure. In cranial bone, more advanced bone formation was exhibited in G-CSF-treated group at both early and late stages, although this observation was not statistically significant. CONCLUSIONS: The results indicated that in osteoporotic bone, G-CSF may advance bone healing in cranial bone where spontaneous bone formation was insufficient.

Role of periodontal disease in bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats.

OBJECTIVE: This study aimed to investigate the role of progressive periodontal disease in inducing bisphosphonate-related osteonecrosis of the jaws (BRONJ) using an ovariectomized (OVX) rat model mimicking human intracortical remodeling process. MATERIALS AND METHODS: Thirty 12-week-old Spraque-Dawly (SD) female rats were randomly assigned into two groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, zoledronic acid (ZA) or vehicle control was administered intraperitoneally for 12 weeks. On the same day of injection, a cotton ligature was placed subgingivally around the first left lower molar to induce periodontitis. All animals were sacrificed 12 weeks after injection. The entire mandibles were harvested for micro-computed tomography (micro-CT) and histological examinations. RESULTS: Micro-CT examination showed that ligature placement caused significant alveolar bone loss both in ZA (0.63 ± 0.13 vs. 0.38 ± 0.06 mm, P < 0.001) and in control (0.88 ± 0.19 vs. 0.40 ± 0.06 mm, P < 0.001) groups. Whereas in the ZA group, bone loss was attenuated compared with the control group (P < 0.01); the bone mineral density in the ZA group (1.00 ± 0.02 g/cm(3)) was significantly higher than that in vehicle control group (0.96 ± 0.03 g/cm(3), P < 0.001). Histological examination found necrotic bone tissue with extensive, empty lacunae in two of 15 rats in ZA group, but in none of the control group. CONCLUSION: Bisphosphonates inhibit alveolar bone resorption in progressive periodontal disease, which might benefit the management of periodontitis, but increase the risk of developing BRONJ.

Skeletal site-specific response to ovariectomy in a rat model: change in bone density and microarchitecture.

OBJECTIVES: Ovariectomized (OVX) rat model has been widely used in osteoporosis-related studies. However, the discrepancies in age and skeletal sites being investigated make it difficult to compare the results from different studies. The purpose of this study was to provide information of systemic skeletal site-specific changes in a stable OVX rat model. MATERIAL AND METHODS: Thirty-three 6-month Spraque-Dawley female rats were used. Fifteen rats underwent ovariectomy, and fifteen received sham surgery. Three animals without any surgery were sacrificed at week 0 to serve as baseline. Three animals in the OVX and sham group, respectively, were euthanized at week 2, 4, 12, 24 and 36 post-surgery. Ten bone sites, including parietal bone, interparietal bone, maxilla, mandible, humerus, ulna, femur, tibia, lumber vertebra, and ilium, were subjected to micro-CT. RESULTS: Overall, long bones, lumber vertebra, and ilium showed similar trend of bone loss post-OVX, with tibia and femur suffered the most bone loss and spine the least (decreased by 75.0%, 70.4% and 36.6% in bone mineral density BMD at week 36 from base line, respectively). Upon OVX, jaw bones and cranial bones only showed a minor reduction in BMD (decreased by 1~3% from baseline) at week 36. Significant deterioration of trabecular structure was detected in long bones, lumber vertebra, and ilium post-OVX, while jaw bones remained relatively stable. CONCLUSIONS: This study for the first time assessed the systemic site-specific bone loss and microarchitecture changes in OVX rat model. It provided valuable information for selecting bone site and observation time in osteoporosis-related study.

A Deep-Learning Model for Diagnosing Fresh Vertebral Fractures on Magnetic Resonance Images.

BACKGROUND: The accurate diagnosis of fresh vertebral fractures (VFs) was critical to optimizing treatment outcomes. Existing studies, however, demonstrated insufficient accuracy, sensitivity, and specificity in detecting fresh fractures using magnetic resonance imaging (MRI), and fall short in localizing the fracture sites. METHODS: This prospective study comprised 716 patients with fresh VFs. We obtained 849 Short TI Inversion Recovery (STIR) image slices for training and validation of the AI model. The AI models employed were yolov7 and resnet50, to detect fresh VFs. RESULTS: The AI model demonstrated a diagnostic accuracy of 97.6% for fresh VFs, with a sensitivity of 98% and a specificity of 97%. The performance of the model displayed a high degree of consistency when compared to the evaluations by spine surgeons. In the external testing dataset, the model exhibited a classification accuracy of 92.4%, a sensitivity of 93%, and a specificity of 92%. CONCLUSIONS: Our findings highlighted the potential of AI in diagnosing fresh VFs, offering an accurate and efficient way to aid physicians with diagnosis and treatment decisions.

Performance evaluation of an AI-based preoperative planning software application for automatic selection of pedicle screws based on computed tomography images.

Introduction: Recent neurosurgical applications based on artificial intelligence (AI) have demonstrated its potential in surgical planning and anatomical measurement. We aimed to evaluate the performance of an AI planning software application on screw length/diameter selection and insertion accuracy in comparison with freehand surgery. Methods: A total of 45 patients with 208 pedicle screw placements on thoracolumbar segments were included in this analysis. The novel AI planning software was developed based on a deep learning model. AI-based pedicle screw placements were selected on the basis of preoperative computed tomography (CT) data, and freehand surgery screw placements were observed based on postoperative CT data. The performance of AI pedicle screw placements was evaluated on the components of screw length, diameter, and Gertzbein grade in comparison with the results achieved by freehand surgery. Results: Among 208 pedicle screw placements, the average screw length/diameters selected by the AI model and used in freehand surgery were 48.65 ± 5.99 mm/7.39 ± 0.42 mm and 44.78 ± 2.99 mm/6.1 ± 0.27 mm, respectively. Among AI screw placements, 85.1% were classified as Gertzbein Grade A (no cortical pedicle breach); among free-hand surgery placements, 64.9% were classified as Gertzbein Grade A. Conclusion: The novel AI planning software application could provide an accessible and safe pedicle screw placement strategy in comparison with traditional freehand pedicle screw placement strategies. The choices of pedicle screw dimensional parameters made by the model, including length and diameter, may provide potential inspiration for real clinical discretion.

Cortical Endplate Bone Density Measured by Novel Phantomless Quantitative Computed Tomography May Predict Cage Subsidence more Conveniently and Accurately.

OBJECTIVE: Previous studies have shown that bone mineral density (BMD) is a predictor of cage subsidence. Phantom-less quantitative computed tomography (PL-QCT) can measure volumetric bone mineral density (vBMD) of lumbar trabecular and cortical bone. The study of endplate vBMD (EP-vBMD) is important in predicting cage settlement after extreme lateral interbody fusion (XLIF). This study aimed to determine the risk factors for postoperative cage subsidence after XLIF, particularly focusing on the relationship between vBMD measured by automatic PL-QCT and cage subsidence. METHODS: Patients who underwent XLIF surgery from January 2018 to October 2020 with a minimum of 6 months of follow-up were retrospectively included. Cage subsidence was defined as >2 mm cage sinking on the adjacent endplate in follow-up imaging evaluation. Outcome measures were localized vBMDs included EP-vBMDs with different region of interest (ROI) heights measured by PL-QCT based on a customized muscle-fat algorithm. Shapiro-Wilk test, one-way ANOVA, Mann-Whitney test, Fisher exact test, univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were executed in this study. RESULTS: One hundred and thirteen levels of 78 patients were included in the analysis. The mean age was 65 ± 7.9 years for 11 males and 67 females. Cage subsidence occurred on 45 (39.8%) surgical levels. There was no significant difference in demographics, fused levels, or preoperative radiographic parameters. 1.25-mm EP-vBMD (0.991 [0.985,0.997], p = 0.004) and P-TB-vBMD (cage-positioned trabecular volumetric bone mineral density) (0.988 [0.977-0.999], p = 0.026) were cage-subsidence relevant according to univariate analysis. Low 1.25-mm EP-vBMD (0.992 [0.985, 0.999], p = 0.029) was an independent risk factor according to multifactorial analysis. CONCLUSION: Preoperative low EP-vBMD was an independent risk factor for postoperative cage subsidence after XLIF. EP-vBMD measured by most cortex-occupied ROI may be the optimal vBMD parameter for cage subsidence prediction.

Endplate volumetric bone mineral density biomechanically matched interbody cage.

Disc degenerative problems affect the aging population, globally, and interbody fusion is a crucial surgical treatment. The interbody cage is the critical implant in interbody fusion surgery; however, its subsidence risk becomes a remarkable clinical complication. Cage subsidence is caused due to a mismatch of material properties between the bone and implant, specifically, the higher elastic modulus of the cage relative to that of the spinal segments, inducing subsidence. Our recent observation has demonstrated that endplate volumetric bone mineral density (EP-vBMD) measured through the greatest cortex-occupied 1.25-mm height region of interest, using automatic phantomless quantitative computed tomography scanning, could be an independent cage subsidence predictor and a tool for cage selection instruction. Porous design on the metallic cage is a trend in interbody fusion devices as it provides a solution to the subsidence problem. Moreover, the superior osseointegration effect of the metallic cage, like the titanium alloy cage, is retained. Patient-specific customization of porous metallic cages based on the greatest subsidence-related EP-vBMD may be a good modification for the cage design as it can achieve biomechanical matching with the contacting bone tissue. We proposed a novel perspective on porous metallic cages by customizing the elastic modulus of porous metallic cages by modifying its porosity according to endplate elastic modulus calculated from EP-vBMD. A three-grade porosity customization strategy was introduced, and direct porosity-modulus customization was also available depending on the patient's or doctor's discretion.

Advances in 3D bioprinting technology for functional corneal reconstruction and regeneration.

Corneal transplantation constitutes one of the major treatments in severe cases of corneal diseases. The lack of cornea donors as well as other limitations of corneal transplantation necessitate the development of artificial corneal substitutes. Biosynthetic cornea model using 3D printing technique is promising to generate artificial corneal structure that can resemble the structure of the native human cornea and is applicable for regenerative medicine. Research on bioprinting artificial cornea has raised interest into the wide range of materials and cells that can be utilized as bioinks for optimal clarity, biocompatibility, and tectonic strength. With continued advances in biomaterials science and printing technology, it is believed that bioprinted cornea will eventually achieve a level of clinical functionality and practicality as to replace donated corneal tissues, with their associated limitations such as limited or unsteady supply, and possible infectious disease transmission. Here, we review the literature on bioprinting strategies, 3D corneal modelling, material options, and cellularization strategies in relation to keratoprosthesis design. The progress, limitations and expectations of recent cases of 3D bioprinting of artifial cornea are discussed. An outlook on the rise of 3D bioprinting in corneal reconstruction and regeneration is provided.

Current Biological Strategies to Enhance Surgical Treatment for Rotator Cuff Repair.

Rotator cuff tear is one of the most common shoulder problems encountered by orthopedic surgeons. Due to the slow healing process and high retear rate, rotator cuff tear has distressed millions of people all around the world every year, especially for the elderly and active athletes. This disease significantly impairs patients' motor ability and reduces their quality of life. Besides conservative treatment, open and arthroscopic surgery contributes a lot to accelerate the healing process of rotator cuff tear. Currently, there are many emerging novel treatment methods to promote rotator cuff repair. A variety of biological stimulus has been utilized in clinical practice. Among them, platelet-rich plasma, growth factors, stem cells, and exosomes are the most popular biologics in laboratory research and clinical trials. This review will focus on the biologics of bioaugmentation methods for rotator cuff repair and tendon healing, including platelet-rich plasma, growth factors, exosomes and stem cells, etc. Relevant studies are summarized in this review and future research perspectives are introduced.

Comparison of Vascular Morphometry in Jawbones and Long Bones: Micro-CT Study in a Rat Model Treated with Zoledronic Acid.

The study was aimed at investigating the effect of zoledronic acid on vascular morphometry in jawbones and long bones on a rat model. Twenty-four skeletal mature Sprague-Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla and a bone defect creation on the femur. After the surgical procedures, ZA or saline treatment was continued until sacrifice at week 2, week 4, and week 8 postoperatively. Vascular perfusion with MICROFIL was performed on all the animals. Micro-CT analysis demonstrated a tendency of decreased vessel density and vessel number in ZA-treated groups but no statistical difference. In conclusion, the neovessel formation is suppressed but not significantly by ZA treatment, indicating that angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

Skeletal Site-Specific Response of Jawbones and Long Bones to Surgical Interventions in Rats Treated with Zoledronic Acid.

Bisphosphonates (BPs) have been extensively used for management of bone diseases with pathologically high resorption. Despite the great clinical benefits, a severe complication known as medication-related osteonecrosis of the jaw (MRONJ) has been reported. It is found that most of the reported MRONJ cases were limited in the jawbones/craniofacial bones instead of long bones. The present study aims to investigate the differential bone response to surgical procedures between jawbones and long bones exposed to BPs. Forty-eight skeletal mature Sprague Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla, and a bone defect creation on the femur. After surgical procedures, ZA or saline treatment were continued until sacrifice at week 2, week 4, and week 8, post-operatively. The samples were subjected to micro-computerized tomography (micro-CT) and histological assessment. Osteonecrosis was only found in jawbones in ZA-treated rats. ZA-treated rats showed significantly higher bone mineral density with greater bone volume in all surgical sites than that in the controls. The length of exposure of ZA did not seem to affect trabecular microstructure, and it only showed higher bone volume and BMD with longer healing time which is expected in the healing process.

Effect of Granulocyte-Colony Stimulating Factor on Endothelial Cells and Osteoblasts.

OBJECTIVES: Some animal studies showed that granulocyte-colony stimulating factor (G-CSF) provides beneficial environment for bone healing. It has been well documented that endothelial cells and osteoblasts play critical roles in multiple phases of bone healing. However, the biological effects of G-CSF on these cells remain controversial. This study aimed to investigate the influence of G-CSF at various concentrations on endothelial cells and osteoblasts. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) were treated with G-CSF at 1000, 100, 10, and 0 ng/mL, respectively. The capacity of cell proliferation, migration, and tube formation of HUVECs was evaluated at 72, 8, and 6 hours after treatment, respectively. The capacity of proliferation, differentiation, and mineralization of hOBs was evaluated at 24 hours, 72 hours, and 21 days after treatment, respectively. RESULTS: HUVECs treated with 100 and 1000 ng/mL G-CSF showed a significantly higher value comparing with controls in migration assay (p < 0.001, p < 0.01, resp.); the group treated with 1000 ng/mL G-CSF showed a significantly lower value on tube formation. No significant difference was detected in groups of hOBs. CONCLUSIONS: G-CSF showed favorable effects only on the migration of HUVECs, and no direct influence was found on hOBs.

Impact of Actinomyces naeslundii on bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats with periodontitis.

Bisphosphonates-related osteonecrosis of the jaws (BRONJ) is a severe complication of BPs therapy with unknown pathogenesis. This study aimed to evaluate the impact of Actinomyces naeslundii (A. naeslundii) on the progression of BRONJ in ovariectomized (OVX) rat model with periodontal diseases. Sixty rats were randomly assigned into four groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, animals with periodontitis induced by ligature placement were administrated with normal saline (NS), NS &A. naeslundii inoculation, zolecdronic acid (ZA) and ZA &A. naeslundii inoculation for 12 weeks, respectively. Loads of total bacteria and A. naeslundii in the mouth were assessed by real time PCR. After sacrifice, the mandibles were harvested for micro-computed tomography (micro-CT) and histological examination. Real-time PCR demonstrated that A. naeslundii was not routinely found in the rats and ZA treatment did not promote its accumulation. Micro-CT examination disclosed that ligature placement induced significant alveolar bone loss, which was greatly attenuated by ZA treatment and aggravated by A. naeslundii. Histological assessment demonstrated that ZA treatment increased the risk of developing BRONJ-like disease but this condition was not worsen with the presence of A. naeslundii. Our study suggested that oral A. naeslundii inoculation aggravated periodontal disease but not BRONJ in our animal model.

Effect of ovariectomy on stimulating intracortical remodeling in rats.

OBJECTIVE: Technically primates and dogs represent ideal models to investigate diseases characterized by abnormal intracortical remodeling. High expenses and ethical issues, however, restrict the use of those animals in research. Rodent models have been used as alternatives instead, but their value is limited, if none, because these animals lack intracortical bone remodeling. This study aimed at investigating the effect of ovariectomy onto the stimulation of intracortical remodeling in rat mandibles. MATERIALS AND METHODS: Sixteen 12-week-old Spraque-Dawly (SD) female rats were randomly assigned into two groups, receiving either ovariectomy or sham operation. All the rats were sacrificed 18 weeks postoperatively. The entire mandibles were harvested for microcomputed tomography (micro-CT) and histomorphometric assessments. RESULTS: Micro-CT examination showed significantly decreased bone mineral density (0.95 ± 0.01 versus 1.01 ± 0.02 g/cm(3), P < 0.001) and bone volume (65.78 ± 5.45 versus 87.41 ± 4.12%, P < 0.001) in ovariectomy group. Histomorphometric assessment detected a sixfold increased intracortical bone remodeling as well as an increased bone modeling in mandibles of ovariectomized rats. CONCLUSION: For the first time, to the authors' knowledge, it was detected that ovariectomy stimulates intracortical remodeling in rat mandibles. This animal model might be of use to study various bone diseases associated with an abnormal intracortical remodeling process.

Comparison of reliability between the PUMC and Lenke classification systems for classifying adolescent idiopathic scoliosis.

STUDY DESIGN: Comparison of 2 radiographic scoliosis classification systems by multiple surgeons. OBJECTIVE: Compare the reliability of Peking Union Medical College (PUMC) and Lenke scoliosis classification systems and analyze their differences. SUMMARY OF BACKGROUND DATA: The PUMC classification is a newly reported system based on radiographic measurements with recent popularity, while the Lenke classification is widely accepted worldwide in surgical design. Both these classification systems have their own individual characteristics, hence it is necessary to compare their reliability. METHODS: Five scoliosis surgeons independently evaluated and classified presurgical radiographs of 62 adolescent idiopathic scoliosis patients based on the PUMC and Lenke classification systems on 2 separate occasions. Radiographs were cleaned before each evaluation. Inter- and intraobserver reliabilities were quantified using Kappa statistics. Data were compared using chi2 analysis. RESULTS: The PUMC classification's inter- and intraobserver percentage of agreement averaged to 91.0% (Kappa coefficient 0.896) and 90.2% (Kappa coefficient 0.892), respectively. While those of the Lenke curve type classification were 86.5% (Kappa coefficient 0.808) and 87.4% (Kappa coefficient 0.826). The PUMC classification from 10 individual measurements had 17 cases (27.4%) of disagreements, while in the Lenke curve type classification, 24 cases (38.7%) had disagreements. PUMC classification normally has discrepancies between type IIb, IIc, and IId, while Lenke classification has discrepancies in curve types 1 and 2. Out of 17 inconsistent PUMC curve type cases, 7 did not affect surgical fusion levels, while in the Lenke's only 2 out of 24 cases with discrepancies did not affect fusion range selection, with an obvious statistical difference. CONCLUSION: The reliability of both PUMC classification and Lenke curve type classification were categorized as good-to-excellent. PUMC classification is relatively simple, with less confusion among inter- and intraobservers, with corresponding surgical fusion guidance and planning. The mismatch of curve classification had less influence on PUMC's fusion range selection than Lenke's.