In this paper we propose a mathematical model of bone remodeling with time delays of both osteoclast-derived paracrine signaling of tumor and tumor-derived paracrine signaling of osteoclast. The effects of time delays...In this paper we propose a mathematical model of bone remodeling with time delays of both osteoclast-derived paracrine signaling of tumor and tumor-derived paracrine signaling of osteoclast. The effects of time delays on the growth of tumor cells and bone system are studied in multiple myeloma-induced bone disease. In the case of small osteoclast-derived paracrine signaling, it is found that the growth of tumor cells slows down, the oscillation period of the ratio of osteoclasts to osteoblasts is extended with increasing time delay, and there is a competition between the delay and osteoclast-derived paracrine signaling. In the ease of large tumor-derived paraerine signaling, the tumor-derived paracrine signaling can induce a more significant decline in tumor growth for long time delay, and thus slowing down the progression of bone disease. There is an optimal coupling between the tumor-derived paracrine signaling of osteoclasts and time delay during the progressions of bone diseases, which suppresses the tumor growth and the regression of bone disease.展开更多
Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone...Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with(10 mg·kg-1sertraline in drinking water, n = 26) or without(control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.展开更多
Daily 20-mg and once-weekly 56.5-mg teriparatide（parathyroid hormone 1–34） treatment regimens increase bone mineral density（BMD） and prevent fractures, but changes in bone turnover markers differ between the two ...Daily 20-mg and once-weekly 56.5-mg teriparatide（parathyroid hormone 1–34） treatment regimens increase bone mineral density（BMD） and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.展开更多
The goal of this study is to analyze the statistics of the backscatter signal from bovine cancellous bone using a Nakagami model and to evaluate the feasibility of Nakagami-model parameters for cancellous bone charact...The goal of this study is to analyze the statistics of the backscatter signal from bovine cancellous bone using a Nakagami model and to evaluate the feasibility of Nakagami-model parameters for cancellous bone characterization. Ultrasonic backscatter measurements were performed on 24 bovine cancellous bone specimens in vitro and the backscatter signals were compensated for the frequency-dependent attenuation prior to the envelope detection. The statistics of the backscatter envelope were modeled using the Nakagami distribution. Our results reveal that the backscatter envelope mainly followed pre-Rayleigh distributions, and the deviations of the backscatter envelope from Rayleigh distribution decreased with increasing bone density. The Nakagami shape parameter(i.e., m) was significantly correlated with bone densities(R = 0.78–0.81, p < 0.001) and trabecular microstructures(|R| = 0.46–0.78, p < 0.05). The scale parameter(i.e.,?) and signal-to-noise ratio(SNR) also yielded significant correlations with bone density and structural features. Multiple linear regressions showed that bone volume fraction(BV/TV) was the main predictor of the Nakagami parameters,and microstructure produced significantly independent contribution to the prediction of Nakagami distribution parameters,explaining an additional 10.2% of the variance at most. The in vitro study showed that statistical parameters derived with Nakagami model might be useful for cancellous bone characterization, and statistical analysis has potential for ultrasonic backscatter bone evaluation.展开更多
The study was to investigate the role of pinhole single photon emission computed tomography (SPECT), the human pulmonary adenocarcinoma bone-seeking metastasis cell line SPC-A-1BM was used.These cells form typical ost...The study was to investigate the role of pinhole single photon emission computed tomography (SPECT), the human pulmonary adenocarcinoma bone-seeking metastasis cell line SPC-A-1BM was used.These cells form typical osteolytic bone metastases when inoculated into the arterial circulation of NIH-Beige-Nude-XD (BNX) mice via the left ventricle.In order to evaluate the irradiation impact of ^(99m)Tc-MDP versus X-ray on cells growth,we used six groups of SPC-A-1BM cells in our imaging scheme and irradiated by various doses of ^(99m)Tc-MDP (37,74,111, 370,740 MBq) and X-ray(40 kV,2 mA,6 s) respectively.The cell's number of each group was well recorded in different exposure time(4,8,12,24,48,72,96 hours).After that,SPC-A-1BM cells(1×106) were inoculated into the mice via left ventricle.We compared the results obtained with those different doses of ^(99m)Tc-MDP using pinhole SPECT and conventional X-ray skeletal surveys.The data show that the cell-survival number of 111 MBq group has insignificant difference with that of X-ray and the dose is adequate to have an ideal image.Besides,it is important that the chromosome of the cells in the group of 111 MBq showed no irradiation-related damages in our test.These results implied that ^(99m)Tc-MDP pinhole SPECT may provide another way other than conventional X-ray skeletal surveys in detecting bone metastasis of pulmonary adenocarcinoma in BNX mice.展开更多
Bone loss associated with musculoskeletal trauma or metabolic diseases often require bone grafting. The supply of allograft and auto-graft bones is limited. Hence, development of synthetic bone grafting materials is a...Bone loss associated with musculoskeletal trauma or metabolic diseases often require bone grafting. The supply of allograft and auto-graft bones is limited. Hence, development of synthetic bone grafting materials is an active area of research. Chitosan, extracted from chitin present in crawfish shells, was tested as a de-livery vehicle for osteoblasts in a 2-3 mm size defect model in rats. Twenty-seven male Lewis rats, divided into three groups with sacrifice intervals of 3, 6 &amp;9 months were used. In the experimental samples, a critical size defect was filled with chitosan bone graft paste and fixed with a plate, while in the operated control group, a critical size defect was repaired only by a plate (no paste was applied). An unoperated control group was also included. Bone growth was evaluated histologically by examining undecal-cified and decalcified stained sections. The fe-murs were also examined non-destructively by micro-computed tomography (礐T). Defects filled with chitosan bone graft paste demon-strated superior healing across all time periods compared to unfilled defects as examined by histology and micro-computed tomography. Crawfish chitosan has successfully been used as a cell delivery system for osteoblasts for use as a synthetic bone graft material.展开更多
Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications...Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.展开更多
Background: Chondrocytes in the growth plate(GP) undergo increases in volume during different cascades of cell differentiation during longitudinal bone growth. The volume increase is reported to be the most significan...Background: Chondrocytes in the growth plate(GP) undergo increases in volume during different cascades of cell differentiation during longitudinal bone growth. The volume increase is reported to be the most significant variable in understanding the mechanism of long bone growth.Methods: Forty-five postnatal Sprague-Dawley rat pups, 7-15 days old were divided into nine age groups(P7-P15). Five pups were allocated to each group. The rats were sacrificed and tibia and metatarsal bones were harvested. Bone lengths were measured after 0, 24, 48, and 72 hours of ex vivo incubation. Histology of bones was carried out, and GP lengths and chondrocyte densities were determined.Results: There were significant differences in bone length among the age groups after 0 and 72 hours of incubation. Histological sectioning was possible in metatarsal bone from all age groups, and in tibia from 7-to 13-day-old rats. No significant differences in tibia and metatarsal GP lengths were seen among different age groups at 0 and 72 hours of incubation. Significant differences in chondrocyte densities along the epiphyseal GP of the bones between 0 and 72 hours of incubation were observed in most of the age groups.Conclusion: Ex vivo growth of tibia and metatarsal bones of rats aged 7-15 days old is possible, with percentage growth rates of 23.87 ± 0.80% and 40.38 ± 0.95%measured in tibia and metatarsal bone, respectively. Histological sectioning of bones was carried out without the need for decalcification in P7-P13 tibia and P7-P15 metatarsal bone. Increases in chondrocyte density along the GP influence overall bone elongation.展开更多
It is commonly known that cortical bone exhibits viscoelastic-viscoplastic behavior which affects the biomechanical response when an implant is subjected to an external load. In addition, long term effects such as cre...It is commonly known that cortical bone exhibits viscoelastic-viscoplastic behavior which affects the biomechanical response when an implant is subjected to an external load. In addition, long term effects such as creep, relaxation and remodeling affect the success of the implant over time. Constitutive material models are commonly derived from data obtained in in vitro experiments. However during function, remodeling of bone greatly affects the bone material over time. Hence it is essential to include long term in vivo effects in a constitutive model of bone. This paper proposes a constitutive material model for cortical bone incorporating viscoelasticity, viscoplasticity, creep and remodeling to predict stress-strain at various strain rates as well as the behavior of bone over time in vivo. The rheological model and its parameters explain the behavior of bone subjected to longitudinal loading. By a proper set of model parameters, for a specific cortical bone, the present model can be used for prediction of the behavior of this bone under specific loading conditions. In addition simulation with the proposed model demonstrates excellent agreement to in vitro and in vivo experimental results in the literature.展开更多
This imaginary transformation from Sméagol to Gollum is a dramatization of the illusive repercussions of mechanical stress affecting bone. This paper presents the main ideas of mechanical stress and bone remodell...This imaginary transformation from Sméagol to Gollum is a dramatization of the illusive repercussions of mechanical stress affecting bone. This paper presents the main ideas of mechanical stress and bone remodelling from a novel’s perspective. The object of this study is to provide evidence for new ways to explore bone’s functional adaptation to mechanical stress made through the copious interpretation and integration of new and existing literature. It tackles the underlying biology of bone cells and how they detect and react to strain stimuli. The different types of mechanical demands in daily activities are sifted through and any misconceptions found fallible in literature are refined. A personal experience of a stress fracture is reviewed to parallel the implications that lead to the incident with the findings on the link between mechanical stress and bone remodelling. Some factors regarding age, gender and ethnicity and the interplay with mechanical stress influencing bone remodelling are considered. Brief overviews of three new medical novelties in bone healing are outlined, hoping that these interventions of proper medical techniques can be a change for the better: one from Gollum to Sméagol rather than vice versa.展开更多
The mechanical behaviour of trabecular bone is dependent on both the properties of individual trabeculae as well as their three-dimensional arrangement in space. In this study, nanoindentation was used to determine tr...The mechanical behaviour of trabecular bone is dependent on both the properties of individual trabeculae as well as their three-dimensional arrangement in space. In this study, nanoindentation was used to determine trabecular stiffness of bovine bone, both dehydrated and rehydrated. Values of 18.3 GPa and 14.3 GPa were obtained for dehydrated and rehydrated trabeculae respectively. These values were then used for finite element analysis where the mesh was generated directly from an X-ray microtomography dataset. The relationship between intrinsic tissue properties and apparent stiffness was explored. Moreover, the important role of collagen in bone micromechanics was demonstrated by complementing the study with Raman spectroscopy.展开更多
Live bone inherently responds to applied mechanical stimulus by altering its internal tissue composition and ultimately biomechanical properties, structure and function. The final formation may structurally appear inf...Live bone inherently responds to applied mechanical stimulus by altering its internal tissue composition and ultimately biomechanical properties, structure and function. The final formation may structurally appear inferior by design but complete by function. To understand the loading response, this paper numerically investigated structural remodeling of mature sheep femur using evolutionary structural optimization method (ESO). Femur images from Computed Tomography scanner were used to determine the elastic modulus variation and subsequently construct finite element model of the femur with stiffest elasticity measured. Major muscle forces on dominant phases of healthy sheep gait were imposed on the femur under static mode. ESO was applied to progressively alter the remodeling of numerically simulated femur from its initial to final design by iteratively removing elements with low strain energy density (SED). The computations were repeated with two different mesh sizes to test the convergence. The elements within the medullary canal had low SEDs and therefore were removed during the optimization. The SEDs in the remaining elements varied with angle around the circumference of the shaft. Those elements with low SED were inefficient in supporting the load and thus fundamentally explained how bone remodels itself with less stiff inferior tissue to meet load demand. This was in line with the Wolff’s law of transformation of bone. Tissue growth and remodeling process was found to shape the sheep femur to a mechanically optimized structure and this was initiated by SED in macro-scale according to traditional principle of Wolff’s law.展开更多
In this paper, the interferences of X-ray image noise on a bone age model, Xception model, were studied. We conduct a comparative experiment test according to the output performance of the neural network model using b...In this paper, the interferences of X-ray image noise on a bone age model, Xception model, were studied. We conduct a comparative experiment test according to the output performance of the neural network model using both the original image training and noise-added (Gaussian noise plus salt-pepper noise) training, and analyze the anti-interference ability of the Xception model, hoping to improve it through noise enhancement training and generalize the application ability of the model. The results show that the model trained with noise-added (Gaussian noise plussalt-pepper noise) images can make predictions that are more robust and less affected by the image disturbances, such as image noise.展开更多
背景:H型血管因其独特的功能为深入理解血管介导的骨代谢调控机制提供了新的视角和切入点。目的:探讨H型血管在不同骨骼疾病动物模型中的生成机制及对骨代谢的影响。方法:系统检索CNKI、维普、万方、PubMed、Scopus和Web of Science数...背景:H型血管因其独特的功能为深入理解血管介导的骨代谢调控机制提供了新的视角和切入点。目的:探讨H型血管在不同骨骼疾病动物模型中的生成机制及对骨代谢的影响。方法:系统检索CNKI、维普、万方、PubMed、Scopus和Web of Science数据库中2014年1月至2025年2月收录的H型血管相关中英文文献。剔除重复及不符合纳入标准的文献,对141篇涉及不同骨骼疾病动物模型中H型血管生成的文献进行系统分析。结果与结论:研究表明,H型血管在不同的骨骼疾病模型中表现出特定的生成机制和生物学功能。H型血管不仅在骨内血管生成中发挥重要作用,还与骨代谢密切相关,能够作为评估骨量水平的早期标志物。不同骨骼疾病动物模型中H型血管生成及作用不尽相同。在骨质疏松症、骨折、骨坏死等骨骼疾病中,通过促进H型血管表达,可显著改善血管重塑与骨再生能力;而在骨关节炎、骨肿瘤等恶性骨骼疾病中,选择性抑制H型血管表达则成为潜在的治疗干预策略。研究还揭示了多条关键信号通路在H型血管生成中的重要作用,如缺氧诱导因子1α/血管内皮生长因子、血小板源性生长因子BB、Wnt/β-catenin等,为理解血管介导的骨代谢调控机制提供了新的科学视角,同时为H型血管作为潜在治疗靶点的临床应用价值提供了重要理论基础。通过分析不同骨骼疾病动物模型中H型血管生成的作用,将为进一步深入探究人类骨关节疾病机制及治疗靶点提供重要依据。展开更多
Objective: The purpose of this study was to examine the relationships between osteoporosis knowledge, beliefs and calcium intake among college students. This study also examined perceived susceptibility, severity, ben...Objective: The purpose of this study was to examine the relationships between osteoporosis knowledge, beliefs and calcium intake among college students. This study also examined perceived susceptibility, severity, benefits, barriers and self-efficacy related to osteoporosis prevention. Participants: Seven hundred and ninety two (n = 792) men and women ages 17 - 31 of all ethnicities at a mid-western regional university in the US participated in the study. Methods: The Osteoporosis Knowledge Test, Osteoporosis Health Belief Scale, and Osteoporosis Preventing Behaviors Survey were utilized. Each of these tools were previously validated and found reliable. Correlation and multiple regression analyses were completed. Results: Participants did not perceive themselves as susceptible to osteoporosis and perceived minimal barriers to calcium intake. Their knowledge was minimal concerning alternate sources of calcium. Conclusions: Prevention programs should aim to increase osteoporosis knowledge of risk factors and osteoprotective behaviors and to decrease high-risk behaviors during college years when behavior changes can have the strongest impact on bone health.展开更多
Lower limb injures are frequently observed in passenger car traffic accidents.Previous studies of the injuries focus on long bone fractures by using either cadaver component tests or simulations of the long bone kinem...Lower limb injures are frequently observed in passenger car traffic accidents.Previous studies of the injuries focus on long bone fractures by using either cadaver component tests or simulations of the long bone kinematics,which lack in-depth study on the fractures in stress analysis.This paper aims to investigate lower limb impact biomechanics in real-world car to pedestrian accidents and to predict fractures of long bones in term of stress parameter for femur,tibia,and fibula.For the above purposes,a 3D finite element(FE) model of human body lower limb(HBM-LL) is developed based on human anatomy.The model consists of the pelvis,femur,tibia,fibula,patella,foot bones,primary tendons,knee joint capsule,meniscus,and ligaments.The FE model is validated by comparing the results from a lateral impact between simulations and tests with cadaver lower limb specimens.Two real-world accidents are selected from an in-depth accident database with detailed information about the accident scene,car impact speed,damage to the car,and pedestrian injuries.Multi-body system(MBS) models are used to reconstruct the kinematics of the pedestrians in the two accidents and the impact conditions are calculated for initial impact velocity and orientations of the car and pedestrian during the collision.The FE model is used to perform injury reconstructions and predict the fractures by using physical parameters,such as von Mises stress of long bones.The calculated failure level of the long bones is correlated with the injury outcomes observed from the two accident cases.The reconstruction result shows that the HBM-LL FE model has acceptable biofidelity and can be applied to predict the risk of long bone fractures.This study provides an efficient methodology to investigate the long bone fracture suffered from vehicle traffic collisions.展开更多
High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the h...High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep’s femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed in- creasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant No.11474117)
文摘In this paper we propose a mathematical model of bone remodeling with time delays of both osteoclast-derived paracrine signaling of tumor and tumor-derived paracrine signaling of osteoclast. The effects of time delays on the growth of tumor cells and bone system are studied in multiple myeloma-induced bone disease. In the case of small osteoclast-derived paracrine signaling, it is found that the growth of tumor cells slows down, the oscillation period of the ratio of osteoclasts to osteoblasts is extended with increasing time delay, and there is a competition between the delay and osteoclast-derived paracrine signaling. In the ease of large tumor-derived paraerine signaling, the tumor-derived paracrine signaling can induce a more significant decline in tumor growth for long time delay, and thus slowing down the progression of bone disease. There is an optimal coupling between the tumor-derived paracrine signaling of osteoclasts and time delay during the progressions of bone diseases, which suppresses the tumor growth and the regression of bone disease.
基金supported by a grant from the Musculoskeletal Transplant Foundation (JC)the National Institute of Health, the National Institute of Aging [NIH-NIA PO1-AG036675] (ME, WDH)+4 种基金in part by the Department of Veterans Affairs (VA Merit Award BX000333, ACL 1I01CX000930-01, WDH)funded through a training grant from the National Institutes of Health National Institute of Dental and Craniofacial Research [5T32DE017551]S.H. is funded through a fellowship from the National Institutes of Health National Institute of Dental and Craniofacial Research [5F32DE02471202]supported by the National Institutes of Health National Institute of General Medicine [P30GM103331]
文摘Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with(10 mg·kg-1sertraline in drinking water, n = 26) or without(control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.
文摘Daily 20-mg and once-weekly 56.5-mg teriparatide（parathyroid hormone 1–34） treatment regimens increase bone mineral density（BMD） and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11874289,11827808,11504057,11525416,and 81601504)the Fundamental Research Funds for the Central Universities
文摘The goal of this study is to analyze the statistics of the backscatter signal from bovine cancellous bone using a Nakagami model and to evaluate the feasibility of Nakagami-model parameters for cancellous bone characterization. Ultrasonic backscatter measurements were performed on 24 bovine cancellous bone specimens in vitro and the backscatter signals were compensated for the frequency-dependent attenuation prior to the envelope detection. The statistics of the backscatter envelope were modeled using the Nakagami distribution. Our results reveal that the backscatter envelope mainly followed pre-Rayleigh distributions, and the deviations of the backscatter envelope from Rayleigh distribution decreased with increasing bone density. The Nakagami shape parameter(i.e., m) was significantly correlated with bone densities(R = 0.78–0.81, p < 0.001) and trabecular microstructures(|R| = 0.46–0.78, p < 0.05). The scale parameter(i.e.,?) and signal-to-noise ratio(SNR) also yielded significant correlations with bone density and structural features. Multiple linear regressions showed that bone volume fraction(BV/TV) was the main predictor of the Nakagami parameters,and microstructure produced significantly independent contribution to the prediction of Nakagami distribution parameters,explaining an additional 10.2% of the variance at most. The in vitro study showed that statistical parameters derived with Nakagami model might be useful for cancellous bone characterization, and statistical analysis has potential for ultrasonic backscatter bone evaluation.
基金Supported by the Key Project for Basicl Research in Shanghai Science and Technology Commission,China (Grant No.071409011)
文摘The study was to investigate the role of pinhole single photon emission computed tomography (SPECT), the human pulmonary adenocarcinoma bone-seeking metastasis cell line SPC-A-1BM was used.These cells form typical osteolytic bone metastases when inoculated into the arterial circulation of NIH-Beige-Nude-XD (BNX) mice via the left ventricle.In order to evaluate the irradiation impact of ^(99m)Tc-MDP versus X-ray on cells growth,we used six groups of SPC-A-1BM cells in our imaging scheme and irradiated by various doses of ^(99m)Tc-MDP (37,74,111, 370,740 MBq) and X-ray(40 kV,2 mA,6 s) respectively.The cell's number of each group was well recorded in different exposure time(4,8,12,24,48,72,96 hours).After that,SPC-A-1BM cells(1×106) were inoculated into the mice via left ventricle.We compared the results obtained with those different doses of ^(99m)Tc-MDP using pinhole SPECT and conventional X-ray skeletal surveys.The data show that the cell-survival number of 111 MBq group has insignificant difference with that of X-ray and the dose is adequate to have an ideal image.Besides,it is important that the chromosome of the cells in the group of 111 MBq showed no irradiation-related damages in our test.These results implied that ^(99m)Tc-MDP pinhole SPECT may provide another way other than conventional X-ray skeletal surveys in detecting bone metastasis of pulmonary adenocarcinoma in BNX mice.
文摘Bone loss associated with musculoskeletal trauma or metabolic diseases often require bone grafting. The supply of allograft and auto-graft bones is limited. Hence, development of synthetic bone grafting materials is an active area of research. Chitosan, extracted from chitin present in crawfish shells, was tested as a de-livery vehicle for osteoblasts in a 2-3 mm size defect model in rats. Twenty-seven male Lewis rats, divided into three groups with sacrifice intervals of 3, 6 &amp;9 months were used. In the experimental samples, a critical size defect was filled with chitosan bone graft paste and fixed with a plate, while in the operated control group, a critical size defect was repaired only by a plate (no paste was applied). An unoperated control group was also included. Bone growth was evaluated histologically by examining undecal-cified and decalcified stained sections. The fe-murs were also examined non-destructively by micro-computed tomography (礐T). Defects filled with chitosan bone graft paste demon-strated superior healing across all time periods compared to unfilled defects as examined by histology and micro-computed tomography. Crawfish chitosan has successfully been used as a cell delivery system for osteoblasts for use as a synthetic bone graft material.
基金supported by NIAMS,of the National Institutes of Health,under award numbers R01AR062074 (to DJD) and R01AR060636 (to S-JL)the Harry Headley Charitable and Research Foundation,Punta Gorda,FL(to ELG-L)
文摘Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.
基金Ministry of Higher Education Malaysia,Grant/Award Number:FRGS/1/2012/SGO5/UPM/02/9
文摘Background: Chondrocytes in the growth plate(GP) undergo increases in volume during different cascades of cell differentiation during longitudinal bone growth. The volume increase is reported to be the most significant variable in understanding the mechanism of long bone growth.Methods: Forty-five postnatal Sprague-Dawley rat pups, 7-15 days old were divided into nine age groups(P7-P15). Five pups were allocated to each group. The rats were sacrificed and tibia and metatarsal bones were harvested. Bone lengths were measured after 0, 24, 48, and 72 hours of ex vivo incubation. Histology of bones was carried out, and GP lengths and chondrocyte densities were determined.Results: There were significant differences in bone length among the age groups after 0 and 72 hours of incubation. Histological sectioning was possible in metatarsal bone from all age groups, and in tibia from 7-to 13-day-old rats. No significant differences in tibia and metatarsal GP lengths were seen among different age groups at 0 and 72 hours of incubation. Significant differences in chondrocyte densities along the epiphyseal GP of the bones between 0 and 72 hours of incubation were observed in most of the age groups.Conclusion: Ex vivo growth of tibia and metatarsal bones of rats aged 7-15 days old is possible, with percentage growth rates of 23.87 ± 0.80% and 40.38 ± 0.95%measured in tibia and metatarsal bone, respectively. Histological sectioning of bones was carried out without the need for decalcification in P7-P13 tibia and P7-P15 metatarsal bone. Increases in chondrocyte density along the GP influence overall bone elongation.
文摘It is commonly known that cortical bone exhibits viscoelastic-viscoplastic behavior which affects the biomechanical response when an implant is subjected to an external load. In addition, long term effects such as creep, relaxation and remodeling affect the success of the implant over time. Constitutive material models are commonly derived from data obtained in in vitro experiments. However during function, remodeling of bone greatly affects the bone material over time. Hence it is essential to include long term in vivo effects in a constitutive model of bone. This paper proposes a constitutive material model for cortical bone incorporating viscoelasticity, viscoplasticity, creep and remodeling to predict stress-strain at various strain rates as well as the behavior of bone over time in vivo. The rheological model and its parameters explain the behavior of bone subjected to longitudinal loading. By a proper set of model parameters, for a specific cortical bone, the present model can be used for prediction of the behavior of this bone under specific loading conditions. In addition simulation with the proposed model demonstrates excellent agreement to in vitro and in vivo experimental results in the literature.
文摘This imaginary transformation from Sméagol to Gollum is a dramatization of the illusive repercussions of mechanical stress affecting bone. This paper presents the main ideas of mechanical stress and bone remodelling from a novel’s perspective. The object of this study is to provide evidence for new ways to explore bone’s functional adaptation to mechanical stress made through the copious interpretation and integration of new and existing literature. It tackles the underlying biology of bone cells and how they detect and react to strain stimuli. The different types of mechanical demands in daily activities are sifted through and any misconceptions found fallible in literature are refined. A personal experience of a stress fracture is reviewed to parallel the implications that lead to the incident with the findings on the link between mechanical stress and bone remodelling. Some factors regarding age, gender and ethnicity and the interplay with mechanical stress influencing bone remodelling are considered. Brief overviews of three new medical novelties in bone healing are outlined, hoping that these interventions of proper medical techniques can be a change for the better: one from Gollum to Sméagol rather than vice versa.
文摘The mechanical behaviour of trabecular bone is dependent on both the properties of individual trabeculae as well as their three-dimensional arrangement in space. In this study, nanoindentation was used to determine trabecular stiffness of bovine bone, both dehydrated and rehydrated. Values of 18.3 GPa and 14.3 GPa were obtained for dehydrated and rehydrated trabeculae respectively. These values were then used for finite element analysis where the mesh was generated directly from an X-ray microtomography dataset. The relationship between intrinsic tissue properties and apparent stiffness was explored. Moreover, the important role of collagen in bone micromechanics was demonstrated by complementing the study with Raman spectroscopy.
文摘Live bone inherently responds to applied mechanical stimulus by altering its internal tissue composition and ultimately biomechanical properties, structure and function. The final formation may structurally appear inferior by design but complete by function. To understand the loading response, this paper numerically investigated structural remodeling of mature sheep femur using evolutionary structural optimization method (ESO). Femur images from Computed Tomography scanner were used to determine the elastic modulus variation and subsequently construct finite element model of the femur with stiffest elasticity measured. Major muscle forces on dominant phases of healthy sheep gait were imposed on the femur under static mode. ESO was applied to progressively alter the remodeling of numerically simulated femur from its initial to final design by iteratively removing elements with low strain energy density (SED). The computations were repeated with two different mesh sizes to test the convergence. The elements within the medullary canal had low SEDs and therefore were removed during the optimization. The SEDs in the remaining elements varied with angle around the circumference of the shaft. Those elements with low SED were inefficient in supporting the load and thus fundamentally explained how bone remodels itself with less stiff inferior tissue to meet load demand. This was in line with the Wolff’s law of transformation of bone. Tissue growth and remodeling process was found to shape the sheep femur to a mechanically optimized structure and this was initiated by SED in macro-scale according to traditional principle of Wolff’s law.
文摘In this paper, the interferences of X-ray image noise on a bone age model, Xception model, were studied. We conduct a comparative experiment test according to the output performance of the neural network model using both the original image training and noise-added (Gaussian noise plus salt-pepper noise) training, and analyze the anti-interference ability of the Xception model, hoping to improve it through noise enhancement training and generalize the application ability of the model. The results show that the model trained with noise-added (Gaussian noise plussalt-pepper noise) images can make predictions that are more robust and less affected by the image disturbances, such as image noise.
文摘背景:H型血管因其独特的功能为深入理解血管介导的骨代谢调控机制提供了新的视角和切入点。目的:探讨H型血管在不同骨骼疾病动物模型中的生成机制及对骨代谢的影响。方法:系统检索CNKI、维普、万方、PubMed、Scopus和Web of Science数据库中2014年1月至2025年2月收录的H型血管相关中英文文献。剔除重复及不符合纳入标准的文献,对141篇涉及不同骨骼疾病动物模型中H型血管生成的文献进行系统分析。结果与结论:研究表明,H型血管在不同的骨骼疾病模型中表现出特定的生成机制和生物学功能。H型血管不仅在骨内血管生成中发挥重要作用,还与骨代谢密切相关,能够作为评估骨量水平的早期标志物。不同骨骼疾病动物模型中H型血管生成及作用不尽相同。在骨质疏松症、骨折、骨坏死等骨骼疾病中,通过促进H型血管表达,可显著改善血管重塑与骨再生能力;而在骨关节炎、骨肿瘤等恶性骨骼疾病中,选择性抑制H型血管表达则成为潜在的治疗干预策略。研究还揭示了多条关键信号通路在H型血管生成中的重要作用,如缺氧诱导因子1α/血管内皮生长因子、血小板源性生长因子BB、Wnt/β-catenin等,为理解血管介导的骨代谢调控机制提供了新的科学视角,同时为H型血管作为潜在治疗靶点的临床应用价值提供了重要理论基础。通过分析不同骨骼疾病动物模型中H型血管生成的作用,将为进一步深入探究人类骨关节疾病机制及治疗靶点提供重要依据。
文摘Objective: The purpose of this study was to examine the relationships between osteoporosis knowledge, beliefs and calcium intake among college students. This study also examined perceived susceptibility, severity, benefits, barriers and self-efficacy related to osteoporosis prevention. Participants: Seven hundred and ninety two (n = 792) men and women ages 17 - 31 of all ethnicities at a mid-western regional university in the US participated in the study. Methods: The Osteoporosis Knowledge Test, Osteoporosis Health Belief Scale, and Osteoporosis Preventing Behaviors Survey were utilized. Each of these tools were previously validated and found reliable. Correlation and multiple regression analyses were completed. Results: Participants did not perceive themselves as susceptible to osteoporosis and perceived minimal barriers to calcium intake. Their knowledge was minimal concerning alternate sources of calcium. Conclusions: Prevention programs should aim to increase osteoporosis knowledge of risk factors and osteoprotective behaviors and to decrease high-risk behaviors during college years when behavior changes can have the strongest impact on bone health.
基金supported by National Hi-tech Research and Development Program of China (863 Program,Grant No. 2006AA110101)"111 Program" of Ministry of Education and State Administration of Foreign Experts Affairs of China (Grant No. 111-2-11)+1 种基金General Motors Research and Development Center (Grant No. RD-209)Project of State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body,Hunan University,China (Grant No. 60870004)
文摘Lower limb injures are frequently observed in passenger car traffic accidents.Previous studies of the injuries focus on long bone fractures by using either cadaver component tests or simulations of the long bone kinematics,which lack in-depth study on the fractures in stress analysis.This paper aims to investigate lower limb impact biomechanics in real-world car to pedestrian accidents and to predict fractures of long bones in term of stress parameter for femur,tibia,and fibula.For the above purposes,a 3D finite element(FE) model of human body lower limb(HBM-LL) is developed based on human anatomy.The model consists of the pelvis,femur,tibia,fibula,patella,foot bones,primary tendons,knee joint capsule,meniscus,and ligaments.The FE model is validated by comparing the results from a lateral impact between simulations and tests with cadaver lower limb specimens.Two real-world accidents are selected from an in-depth accident database with detailed information about the accident scene,car impact speed,damage to the car,and pedestrian injuries.Multi-body system(MBS) models are used to reconstruct the kinematics of the pedestrians in the two accidents and the impact conditions are calculated for initial impact velocity and orientations of the car and pedestrian during the collision.The FE model is used to perform injury reconstructions and predict the fractures by using physical parameters,such as von Mises stress of long bones.The calculated failure level of the long bones is correlated with the injury outcomes observed from the two accident cases.The reconstruction result shows that the HBM-LL FE model has acceptable biofidelity and can be applied to predict the risk of long bone fractures.This study provides an efficient methodology to investigate the long bone fracture suffered from vehicle traffic collisions.
文摘High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep’s femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed in- creasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.
