scholarly journals Study on the Mechanism of Qigu Capsule in Upregulating NF-κB/HIF-1α Pathway to Improve the Quality of Bone Callus in Mice at Different Stages of Osteoporotic Fracture Healing

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Peige Wang ◽  
Jie Ding ◽  
Guangyue Yang ◽  
Wen Sun ◽  
Hailing Guo ◽  
...  

Objective. The present study intends to investigate the effects and underlying molecular mechanism of Qigu Capsule (QG) on fracture healing in mice with osteoporosis. Methods. Ten-week-old female C57BL/6 mice were ovariectomized and three weeks later were evaluated for successful modeling. Then, all mice were prepared into models of transverse fracture in the right middle femoral shaft. Mice were treated daily using a gavage with normal saline (the NS group), Qigu Capsule (the QG group), or alendronate (the ALN group) postoperatively. Fracture callus tissues were collected and analyzed by X-ray, micro-CT, western blot (WB), and transmission electron microscope (TEM) on postoperation Day 14 (POD14), POD28, and POD42. Results. (1) X-ray results showed that on POD14, the QG group had the fracture healing score significantly higher than the NS and ALN groups, and on POD28, it had the fracture healing score higher than the NS group, suggesting that QG could promote fracture healing. (2) Micro-CT results showed that on POD14, the QG group had tissue bone density (TMD) significantly higher than the NS and ALN groups, and on POD28 and POD42, it had bone volume fraction, trabecular number, and TMD significantly higher than the NS group. (3) WB results showed that, compared with the NS group, the QG group had significantly increased expression of nuclear factor kappa-B (NF-κB), hypoxia-inducible factor-1α (HIF-1α), bone alkaline phosphatase (BALP), runt-related transcription factor 2 (Runx2), bone Gla protein (BGP) and collagen Iα1 (COLIα1) on POD14, significantly increased expression of NF-κB, HIF-1α, BALP and COLIα1 on POD28, and significantly increased expression of NF-κB, HIF-1α, and Runx2 on POD42. (4) TEM scanning results showed that, compared with the NS and ALN groups, the QG group had significantly increased numbers of autophagic vacuoles (AVs) in osteocytes on POD14, POD28, and POD42. Conclusion. QG could accelerate osteoporotic fracture healing by promoting bone formation and osteocyte autophagy, possibly through upregulating the NF-κB/HIF-1α signaling pathway.

2015 ◽  
Vol 22 (3) ◽  
pp. 273-282 ◽  
Author(s):  
Srinidhi Nagaraja ◽  
Hassan K. Awada ◽  
Maureen L. Dreher ◽  
John T. Bouck ◽  
Shikha Gupta

OBJECT The aim in this study was to quantify the effects of vertebroplasty on endplate subsidence in treated and adjacent vertebrae and their relationship to endplate thickness and underlying trabecular bone in elderly female spines. METHODS Vertebral compression fractures were created in female cadaveric (age range 51–88 years) thoracolumbar spine segments. Specimens were placed into either the control or vertebroplasty group (n = 9/group) such that bone mineral density, trabecular microarchitecture, and age were statistically similar between groups. For the vertebroplasty group, polymethylmethacrylate bone cement was injected into the fractured vertebral body under fluoroscopy. Cyclic compression (685–1370 N sinusoid) was performed on all spine segments for 115,000 cycles. Micro-CT scans were obtained before and after cyclic loading to quantify endplate subsidence. Maximum subsidence was compared between groups in the caudal endplate of the superior adjacent vertebra (SVcau); cranial (TVcra) and caudal (TVcau) endplates of the treated vertebra; and the cranial endplate of the inferior adjacent vertebra (IVcra). In addition, micro-CT images were used to quantify average endplate thickness and trabecular bone volume fraction. These parameters were then correlated with maximum endplate subsidence for each endplate. RESULTS The maximum subsidence in SVcau endplate for the vertebroplasty group (0.34 ± 0.58 mm) was significantly (p < 0.05) greater than for the control group (−0.13 ± 0.27 mm). Maximum subsidence in the TVcra, TVcau, and IVcra endplates were greater in the vertebroplasty group, but these differences were not significant (p > 0.16). Increased subsidence in the vertebroplasty group manifested locally in the anterior region of the SVcau endplate and in the posterior region of the TVcra and TVcau endplates (p < 0.10). Increased subsidence was observed in thinner endplates with lower trabecular bone volume fraction for both vertebroplasty and control groups (R2 correlation up to 62%). In the SVcau endplate specifically, these 2 covariates aided in understanding subsidence differences between vertebroplasty and control groups. CONCLUSIONS Bone cement injected during vertebroplasty alters local biomechanics in elderly female spines, resulting in increased endplate disruption in treated and superior adjacent vertebrae. More specifically, bone cement increases subsidence in the posterior regions of the treated endplates and the anterior region of the superior caudal endplate. This increased subsidence may be the initial mechanism leading to subsequent compression fractures after vertebroplasty, particularly in vertebrae superior to the treated level.


2018 ◽  
Vol 88 (5) ◽  
pp. 632-637 ◽  
Author(s):  
Kriangkrai Kraiwattanapong ◽  
Bancha Samruajbenjakun

ABSTRACT Objectives: To investigate the effects of light and heavy forces with corticotomy on tooth movement rate, alveolar bone response, and root resorption in a rat model. Materials and Methods: The right and left sides of 40 male Wistar rats were randomly assigned using the split-mouth design to two groups: light force with corticotomy (LF) and heavy force with corticotomy (HF). Tooth movement was performed on the maxillary first molars using a nickel-titanium closed-coil spring delivering either 10 g (light force) or 50 g (heavy force). Tooth movement and alveolar bone response were assessed by micro–computed tomography (micro-CT) at day 0 as the baseline and on days 7, 14, 21, and 28. Root resorption was examined by histomorphometric analysis at day 28. Results: Micro-CT analysis showed a significantly greater tooth movement in the HF group at days 7 and 14 but no difference in bone volume fraction at any of the observed periods. Histomorphometric analysis found no significant difference in root resorption between the LF and HF groups at day 28. Conclusions: Heavy force with corticotomy increased tooth movement at days 7 and 14 but did not show any difference in alveolar bone change or root resorption.


Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S375
Author(s):  
E. Perilli⁎ ◽  
A.M. Briggs ◽  
J.D. Wark ◽  
S. Kantor ◽  
I.H. Parkinson ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yuhui Chen ◽  
He Cao ◽  
Dawei Sun ◽  
Changxin Lin ◽  
Liang Wang ◽  
...  

Bone fracture is a global healthcare issue for high rates of delayed healing and nonunions. Although n-3 polyunsaturated fatty acid (PUFA) is considered as a beneficial factor for bone metabolism, only few studies till date focused on the effects of n-3 PUFAs on fracture healing. In this study, we investigated the effect of endogenous n-3 PUFAs on fracture healing by measuring femur fracture repair in bothfat-1transgenic mice and WT mice. Proximal femoral fracture model was established infat-1transgenic mice and WT mice, respectively, and then the fracture was analyzed by using X-ray, micro-computed tomography (micro-CT), and histological assessment at 7, 14, 21, 28, and 35 days after fixation. The results showed that compared with WT mice,fat-1mice exhibited acceleration in fracture healing through radiographic and histological analysis (18–21 days versus 21–28 days postfracture). Meanwhile, X-ray and micro-CT analysis that showed better remodeling callus formation were in thefat-1group compared to WT group. Furthermore, histological analysis revealed that endogenous n-3 PUFAs promoted local endochondral ossification and accelerated the remodeling of calcified calluses after fracture. In conclusion, the present study indicated that endogenously produced n-3 PUFAs promote fracture healing process and accelerate bone remodeling in mice, and supplementation of n-3 PUFAs was positively associated with fracture healing.


2016 ◽  
Vol 13 (114) ◽  
pp. 20150991 ◽  
Author(s):  
Patrik Christen ◽  
Friederike A. Schulte ◽  
Alexander Zwahlen ◽  
Bert van Rietbergen ◽  
Stephanie Boutroy ◽  
...  

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous.


2021 ◽  
Author(s):  
Ronald Man Yeung WONG ◽  
Simon Kwoon Ho CHOW ◽  
Ning TANG ◽  
Yik Lok CHUNG ◽  
James GRIFFITH ◽  
...  

Abstract BackgroundThere are more than 300,000 hip fractures yearly in the US with mortality rates of 20% within 1 year. The treatment of osteoporotic fractures is a major challenge as bone quality is poor, and healing is expected to delay due to the impaired healing properties with respect to bone formation, angiogenesis and mineralization. Enhancement of osteoporotic fracture healing and function is therefore critical as a major goal in modern fracture management. Previous pre-clinical studies have shown that low-magnitude high-frequency vibration (LMHFV) accelerates osteoporotic fracture healing. The objective of this study is to investigate the effect of LMHFV on accelerating trochanteric hip fracture healing and functional recovery.MethodsThis is a randomized, double-blinded, placebo-controlled clinical trial to evaluate the effect of LMHFV in accelerating trochanteric hip fracture healing. All fractures undergo cephalomedullary nail fixation. The primary outcome of this study is time to fracture healing by X-ray. Computed tomography (CT) and Dual-energy X-ray absorptiometry (DXA) will also be performed. Blood circulation at the fracture site will be assessed by dynamic perfusion magnetic resonance (MR). Clinical results include functional recovery by muscle strength, timed up and go test (TUG), quality of life questionnaire (SF-36), balancing, falls, and mortality. DiscussionPrevious animal studies have demonstrated LMHFV to improve both normal and osteoporotic fracture healing by accelerating callus formation and mineralization. The mechanical stimulation stimulates angiogenesis by significantly enhancing vascular volume and blood flow velocity. This is the first study to translate LMHFV to enhancing hip fracture healing clinically. Positive results would provide a huge impact in the recovery of hip fracture patients and save healthcare costs. Trial registrationClinicaltrials.gov, NCT04063891. Registered on August 21, 2019


2000 ◽  
Author(s):  
Mark J. Eichler ◽  
Chi Hyun Kim ◽  
Ralph Müller ◽  
X. Edward Guo

Abstract Age-related bone fractures are mostly influenced by trabecular bone sites. Trabecular bone constantly adapts its bone volume fraction (BV/TV) and orientation, and thus its mechanical properties, to mechanical usage. Therefore, understanding the trabecular bone adaptation process and its consequences will contribute to the better understanding of the etiology of age-related fractures. Micro-computed tomography (micro-CT) is a relatively new method to quantify the complex three-dimensional (3D) trabecular bone architecture [1,2]. Finite element computational studies can be performed on these 3D microstructural images by converting each image voxel into an element [3,4,5]. Image thresholding techniques to segment bone voxels from bone marrow voxels have a major impact on the results of these models. However, the influence of different types of thresholding techniques on the mechanical properties of bone has not been examined carefully.


2006 ◽  
Vol 129 (4) ◽  
pp. 481-486 ◽  
Author(s):  
Chi Hyun Kim ◽  
Henry Zhang ◽  
George Mikhail ◽  
Dietrich von Stechow ◽  
Ralph Müller ◽  
...  

Microimaging based finite element analysis is widely used to predict the mechanical properties of trabecular bone. The choice of thresholding technique, a necessary step in converting grayscale images to finite element models, can significantly influence the predicted bone volume fraction and mechanical properties. Therefore, we investigated the effects of thresholding techniques on microcomputed tomography (micro-CT) based finite element models of trabecular bone. Three types of thresholding techniques were applied to 16-bit micro-CT images of trabecular bone to create three different models per specimen. Bone volume fractions and apparent moduli were predicted and compared to experimental results. In addition, trabecular tissue mechanical parameters and morphological parameters were compared among different models. Our findings suggest that predictions of apparent mechanical properties and structural properties agree well with experimental measurements regardless of the choice of thresholding methods or the format of micro-CT images.


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