Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area.

PubMed

Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

2016-01-01

Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications.

Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area

PubMed Central

Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

2016-01-01

Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications. PMID:27279797

Tendon healing in a bone tunnel. Part II: Histologic analysis after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep.

PubMed

Weiler, Andreas; Hoffmann, Reinhard F G; Bail, Hermann J; Rehm, Oliver; Südkamp, Norbert P

2002-02-01

Tendon-to-bone healing of soft-tissue grafts has been described to progress by the development of a fibrous interzone that undergoes a maturation process leading to the development of an indirect type of ligament insertion. Previous studies used extra-articular models or fixation far away from the joint line; thus, no data are available investigating tendon-to-bone healing of a soft-tissue graft fixed anatomically. Therefore, we studied the tendon-to-bone healing of the anatomic soft-tissue graft interference fit fixation in a model of anterior cruciate ligament (ACL) reconstruction in sheep. Animal study. Thirty-five mature sheep underwent ACL reconstruction with an autologous Achilles tendon split graft. Grafts were directly fixed with biodegradable poly-(D,L-lactide) interference screws. Animals were euthanized after 6, 9, 12, 24, and 52 weeks and histologic evaluations were performed. Undecalcified specimens were evaluated under normal and polarized light. Additionally, animals received a polychrome sequential labeling (tetracycline, xylenol orange, and calcein green) to determine bone growth per time under fluorescent light. Intratunnel histologic findings at 6 weeks showed a tendon-bone junction with only a partial fibrous interzone between the graft tissue and the surrounding bone. A mature intratunnel tendon-bone junction with a zone of fibrocartilage was found at 9 to 12 weeks. At the tunnel entrance site a wide regular ligamentous insertion site was seen in all specimens after 24 weeks. This insertion showed regular patterns such as the direct type of insertion of a normal ligament with a dense basophilic transition zone consisting of mineralized cartilage. A fibrous interzone between the graft tissue and the bone tunnel was only partially developed, which is in contrast to all previous studies in which nonanatomic fixation was used. Thus, it is reasonable to assume that the tendon-to-bone healing in the present study may progress partially by direct-contact healing without the development of a fibrous interzone. To our knowledge, this is the first report describing the development of a direct type of ligament insertion after ACL replacement with a soft-tissue graft. This is in contrast to previous studies reporting the development of an indirect type of insertion when using nonanatomic fixation far away from the joint line. Thus, histologic data strongly indicate that anatomic interference fit fixation is beneficial for tendon-to-bone incorporation by leading to the development of a direct type of ligament insertion.

Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance

PubMed Central

Stern, Tomer; Aviram, Rona; Rot, Chagai; Galili, Tal; Sharir, Amnon; Kalish Achrai, Noga; Keller, Yosi; Shahar, Ron; Zelzer, Elazar

2015-01-01

One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates. PMID:26241802

Genetic Expression in Cystic Fibrosis Related Bone Disease. An Observational, Transversal, Cross-Sectional Study.

PubMed

Ciuca, Ioana M; Pop, Liviu L; Rogobete, Alexandru F; Onet, Dan I; Guta-Almajan, Bogdan; Popa, Zoran; Horhat, Florin G

2016-09-01

Cystic fibrosis (CF) is the most frequent monogenic genetic disease with autosomal recessive transmission and characterized by important clinical polymorphism and significant lethal prospective. CF related bone disease occurs frequently in adults with CF. Childhood is the period of bone formation, and therefore, children are more susceptible to low bone density. Several factors like pancreatic insufficiency, hormone imbalance, and physical inactivity contribute to CF bone disease development. Revealing this would be important for prophylactic treatment against bone disease occurrence. The study was observational, transversal, with a cross-sectional design. The study included 68 children with cystic fibrosis, genotyped and monitored in the National CF Centre. At the annual assessment, besides clinical examination, biochemical evaluation for pancreatic insufficiency, and diabetes, they were evaluated for bone mineral density using dual energy X-ray absorptiometry (DXA). Twenty-six patients, aged over 10 years were diagnosed with CF bone disease, without significant gender gap. Bone disease was frequent in patients aged over 10 years with exocrine pancreatic insufficiency, carriers of severe mutations, and CF liver disease. CF carriers of a severe genotype which associates pancreatic insufficiency and CF liver disease, are more likely predisposed to low bone mineral density. Further studies should discover other significant influences in order to prevent the development of CF bone disease and an improved quality of life in cystic fibrosis children.

A longitudinal study of bone area, content, density, and strength development at the radius and tibia in children 4-12 years of age exposed to recreational gymnastics.

PubMed

Jackowski, S A; Baxter-Jones, A D G; Gruodyte-Raciene, R; Kontulainen, S A; Erlandson, M C

2015-06-01

This study investigated the long-term relationship between the exposure to childhood recreational gymnastics and bone measures and bone strength parameters at the radius and tibia. It was observed that individuals exposed to recreational gymnastics had significantly greater total bone content and area at the distal radius. No differences were observed at the tibia. This study investigated the relationship between exposure to early childhood recreational gymnastics with bone measures and bone strength development at the radius and tibia. One hundred twenty seven children (59 male, 68 female) involved in either recreational gymnastics (gymnasts) or other recreational sports (non-gymnasts) between 4 and 6 years of age were recruited. Peripheral quantitative computed tomography (pQCT) scans of their distal and shaft sites of the forearm and leg were obtained over 3 years, covering the ages of 4-12 years at study completion. Multilevel random effects models were constructed to assess differences in the development of bone measures and bone strength measures between those exposed and not exposed to gymnastics while controlling for age, limb length, weight, physical activity, muscle area, sex, and hours of training. Once age, limb length, weight, muscle area, physical activity, sex, and hours of training effects were controlled, it was observed that individuals exposed to recreational gymnastics had significantly greater total bone area (18.0 ± 7.5 mm(2)) and total bone content (6.0 ± 3.0 mg/mm) at the distal radius (p < 0.05). This represents an 8-21 % benefit in ToA and 8-15 % benefit to ToC from 4 to 12 years of age. Exposure to recreational gymnastics had no significant effect on bone measures at the radius shaft or at the tibia (p > 0.05). Exposure to early life recreational gymnastics provides skeletal benefits to distal radius bone content and area. Thus, childhood recreational gymnastics exposure may be advantageous to bone development at the wrist.

Skeletal responses to spaceflight

NASA Technical Reports Server (NTRS)

Morey-Holton, Emily R.; Arnaud, Sara B.

1991-01-01

The effect of gravity on the skeletal development and on the bone composition and its regulation in vertebrates is discussed. Results are presented from spaceflight and ground studies in both man and rat on the effect of microgravity on the bone-mineral metabolism (in both species) and on bone maturation and growth (in rats). Special attention is given to a ground-based flight-simulation rat model developed at NASA's Ames Research Center for studies of bone structure at the molecular, organ, and whole-body levels and to comparisons of estimated results with spaceflight data.

In vivo bone regeneration using a novel porous bioactive composite

NASA Astrophysics Data System (ADS)

Xie, En; Hu, Yunyu; Chen, Xiaofeng; Bai, Xuedong; Li, Dan; Ren, Li; Zhang, Ziru

2008-11-01

Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

Restrain of bone growth by estrogen-mimetic peptide-1 (EMP-1): a micro-computed tomographic study.

PubMed

Kasher, Roni; Bajayo, Alon; Gabet, Yankel; Nevo, Nava; Fridkin, Mati; Katchalski-Katzir, Ephraim; Kohen, Fortune; Bab, Itai

2009-06-01

Estrogen has a key role in the regulation of skeletal growth and maintenance of bone mass. Recently, we developed peptides having estrogen-like activity as potential estrogen-based new drugs. The aim of the present study was to evaluate the influence of long-term administration of the most efficacious of these peptides, the hexapeptide EMP-1 (VSWFFE), on bone mass and development. EMP-1 was injected daily to ovariectomized (OVX) and intact young, sexually mature female mice for 10 weeks. Whole femora, including the cartilaginous growth plates were analyzed by micro-computed tomography (microCT). We found that peptide EMP-1 restrains bone growth in OVX mice: it inhibited dramatically bone longitudinal growth (40%), and decreased femoral diaphyseal diameter. Peptide EMP-1 had no effect on bone growth in normal mice, and did not influence the OVX-induced bone loss. We then developed a new microCT methodology to evaluate uncalcified and calcified growth plate parameters. In the OVX mice, peptide EMP-1 reduced volume and thickness of the uncalcified growth plate, a possible cause for the inhibition of bone longitudinal growth. Peptide EMP-1 may be used as a lead compound for the development of drugs to treat acromegalic patients.

Silicon in broiler drinking water promotes bone development in broiler chickens.

PubMed

Sgavioli, S; de Faria Domingues, C H; Castiblanco, D M C; Praes, M F F M; Andrade-Garcia, Giuliana M; Santos, E T; Baraldi-Artoni, S M; Garcia, R G; Junqueira, O M

2016-10-01

Skeletal abnormalities, bone deformities and fractures cause significant losses in broiler production during both rearing and processing. Silicon is an essential mineral for bone and connective tissue synthesis and for calcium absorption during the early stages of bone formation. Performance was not affected by the addition of silicon. However, broilers receiving silicon showed a significant increase of phosphorus, zinc, copper, manganese and ash in the tibia. In conclusion, broiler performance was not impaired by adding the tested silicon product to the drinking water. In addition, bone development improved, as demonstrated by higher mineral and ash content. Further studies are required to determine the optimal concentration of silicon, including heat stress simulations, to better understand the effects of silicon on bone development.

The frequency of bone fractures among patients with chronic kidney disease not on dialysis: two-year follow-up.

PubMed

Figurek, Andreja; Vlatkovic, Vlastimir; Vojvodic, Dragan; Gasic, Branislav; Grujicic, Milorad

2017-12-01

Renal osteodystrophy is a severe complication of chronic kidney disease (CKD) that increases morbidity and mortality in these patients. Mineral and bone disorder starts early in CKD and affects the incidence of bone fractures. The aim of this study was to observe the frequency of diverse bone fractures in patients with CKD not on dialysis. This cohort study included 68 patients that were followed during the two-year period. The patients were divided into two cohorts: one that developed bone fractures and the other that did not. There were 35 (51.5%) men and 33 (48.5%) women. The mean age of patients ranged 62.88±11.60 years. During follow-up serum values of chronic kidney disease - mineral and bone indicators were measured. The methods of descriptive and analytical statistics were used in order to analyze obtained data. During this two-year follow-up seven patients developed bone fractures. Among them, females dominated (6 patients) compared to males (only 1 patient). The most common were fractures of forearm. The mean level of parathyroid hormone (PTH) at the beginning of the monitoring was higher in the group of patients with bone fractures (165.25 ± 47.69 pg/mL) in regard to another group (103.96 ± 81.55 pg/mL). After two-year follow-up, this difference became statistically significant at the level p < 0.05. Patients that developed bone fractures had higher FRAX (Fracture Risk Assessment) score compared to another group. In our study, about 10% of patients had bone fractures in the two-year follow-up period. Patients who developed fractures had a higher PTH level and FRAX score.

[Bone Cell Biology Assessed by Microscopic Approach. Assessment of bone quality using Raman and infrared spectroscopy].

PubMed

Suda, Hiromi Kimura

2015-10-01

Bone quality, which was defined as "the sum total of characteristics of the bone that influence the bone's resistance to fracture" at the National Institute of Health (NIH) conference in 2001, contributes to bone strength in combination with bone mass. Bone mass is often measured as bone mineral density (BMD) and, consequently, can be quantified easily. On the other hand, bone quality is composed of several factors such as bone structure, bone matrix, calcification degree, microdamage, and bone turnover, and it is not easy to obtain data for the various factors. Therefore, it is difficult to quantify bone quality. We are eager to develop new measurement methods for bone quality that make it possible to determine several factors associated with bone quality at the same time. Analytic methods based on Raman and FTIR spectroscopy have attracted a good deal of attention as they can provide a good deal of chemical information about hydroxyapatite and collagen, which are the main components of bone. A lot of studies on bone quality using Raman and FTIR imaging have been reported following the development of the two imaging systems. Thus, both Raman and FTIR imaging appear to be promising new bone morphometric techniques.

A New Method for Xenogeneic Bone Graft Deproteinization: Comparative Study of Radius Defects in a Rabbit Model.

PubMed

Lei, Pengfei; Sun, Rongxin; Wang, Long; Zhou, Jialin; Wan, Lifei; Zhou, Tianjian; Hu, Yihe

2015-01-01

Deproteinization is an indispensable process for the elimination of antigenicity in xenograft bones. However, the hydrogen peroxide (H2O2) deproteinized xenograft, which is commonly used to repair bone defect, exhibits limited osteoinduction activity. The present study was designed to develop a new method for deproteinization and compare the osteogenic capacities of new pepsin deproteinized xenograft bones with those of conventional H2O2 deproteinized ones. Bones were deproteinized in H2O2 or pepsin for 8 hours. The morphologies were compared by HE staining. The content of protein and collagen I were measured by the Kjeldahl method and HPLC-MS, respectively. The physical properties were evaluated by SEM and mechanical tests. For in vivo study, X-ray, micro-CT and HE staining were employed to monitor the healing processes of radius defects in rabbit models transplanted with different graft materials. Compared with H2O2 deproteinized bones, no distinct morphological and physical changes were observed. However, pepsin deproteinized bones showed a lower protein content, and a higher collagen content were preserved. In vivo studies showed that pepsin deproteinized bones exhibited better osteogenic performance than H2O2 deproteinized bones, moreover, the quantity and quality of the newly formed bones were improved as indicated by micro-CT analysis. From the results of histological examination, the newly formed bones in the pepsin group were mature bones. Pepsin deproteinized xenograft bones show advantages over conventional H2O2 deproteinized bones with respect to osteogenic capacity; this new method may hold potential clinical value in the development of new biomaterials for bone grafting.

A New Method for Xenogeneic Bone Graft Deproteinization: Comparative Study of Radius Defects in a Rabbit Model

PubMed Central

Lei, Pengfei; Sun, Rongxin; Wang, Long; Zhou, Jialin; Wan, Lifei; Zhou, Tianjian; Hu, Yihe

2015-01-01

Background and Objectives Deproteinization is an indispensable process for the elimination of antigenicity in xenograft bones. However, the hydrogen peroxide (H2O2) deproteinized xenograft, which is commonly used to repair bone defect, exhibits limited osteoinduction activity. The present study was designed to develop a new method for deproteinization and compare the osteogenic capacities of new pepsin deproteinized xenograft bones with those of conventional H2O2 deproteinized ones. Methods Bones were deproteinized in H2O2 or pepsin for 8 hours. The morphologies were compared by HE staining. The content of protein and collagen I were measured by the Kjeldahl method and HPLC-MS, respectively. The physical properties were evaluated by SEM and mechanical tests. For in vivo study, X-ray, micro-CT and HE staining were employed to monitor the healing processes of radius defects in rabbit models transplanted with different graft materials. Results Compared with H2O2 deproteinized bones, no distinct morphological and physical changes were observed. However, pepsin deproteinized bones showed a lower protein content, and a higher collagen content were preserved. In vivo studies showed that pepsin deproteinized bones exhibited better osteogenic performance than H2O2 deproteinized bones, moreover, the quantity and quality of the newly formed bones were improved as indicated by micro-CT analysis. From the results of histological examination, the newly formed bones in the pepsin group were mature bones. Conclusions Pepsin deproteinized xenograft bones show advantages over conventional H2O2 deproteinized bones with respect to osteogenic capacity; this new method may hold potential clinical value in the development of new biomaterials for bone grafting. PMID:26719896

The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments

PubMed Central

Aghajanian, Patrick; Hall, Susan; Wongworawat, Montri D.; Mohan, Subburaman

2016-01-01

Vitamin C is an important antioxidant and cofactor which is involved in the regulation of development, function and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures. PMID:26358868

Bone morphogenetic protein and bone metastasis, implication and therapeutic potential.

PubMed

Ye, Lin; Mason, Malcolm D; Jiang, Wen G

2011-01-01

Bone metastasis is one of the most common and severe complications in advanced malignancies, particularly in the three leading cancers; breast cancer, prostate cancer and lung cancer. It is currently incurable and causes severe morbidities, including bone pain, hypercalcemia, pathological fracture, spinal cord compression and consequent paralysis. However, the mechanisms underlying the development of bone metastasis remain largely unknown. Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and are pluripotent factors involved in the regulation of embryonic development and postnatal homeostasis of various organs and tissues, by controlling cellular differentiation, proliferation and apoptosis. Since they are potent regulators for bone formation, there is an increasing interest to investigate BMPs and their roles in bone metastasis. BMPs have been implicated in various neoplasms, at both primary and secondary tumors, particularly skeletal metastasis. Recently studies have also suggested that BMP signaling and their antagonists play pivotal roles in bone metastasis. In this review, we discuss the current knowledge of aberrations of BMPs which have been indicated in tumor progression, and particularly in the development of bone metastasis.

Modeling Vascularized Bone Regeneration Within a Porous Biodegradable CaP Scaffold Loaded with Growth Factors

PubMed Central

Sun, X; Kang, Y; Bao, J; Zhang, Y; Yang, Y; Zhou, X

2013-01-01

Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors. PMID:23566802

The use of rats and mice as animal models in ex vivo bone growth and development studies

PubMed Central

Abubakar, A. A.; Noordin, M. M.; Azmi, T. I.; Kaka, U.

2016-01-01

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine. Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2. PMID:27965220

Automated bone age assessment of older children using the radius

NASA Astrophysics Data System (ADS)

Tsao, Sinchai; Gertych, Arkadiusz; Zhang, Aifeng; Liu, Brent J.; Huang, Han K.

2008-03-01

The Digital Hand Atlas in Assessment of Skeletal Development is a large-scale Computer Aided Diagnosis (CAD) project for automating the process of grading Skeletal Development of children from 0-18 years of age. It includes a complete collection of 1,400 normal hand X-rays of children between the ages of 0-18 years of age. Bone Age Assessment is used as an index of skeletal development for detection of growth pathologies that can be related to endocrine, malnutrition and other disease types. Previous work at the Image Processing and Informatics Lab (IPILab) allowed the bone age CAD algorithm to accurately assess bone age of children from 1 to 16 (male) or 14 (female) years of age using the Phalanges as well as the Carpal Bones. At the older ages (16(male) or 14(female) -19 years of age) the Phalanges as well as the Carpal Bones are fully developed and do not provide well-defined features for accurate bone age assessment. Therefore integration of the Radius Bone as a region of interest (ROI) is greatly needed and will significantly improve the ability to accurately assess the bone age of older children. Preliminary studies show that an integrated Bone Age CAD that utilizes the Phalanges, Carpal Bones and Radius forms a robust method for automatic bone age assessment throughout the entire age range (1-19 years of age).

BONE PICTURE BOOK, A BOOK FOR STUDENTS USING THE ESS UNIT BONES.

ERIC Educational Resources Information Center

Elementary Science Study, Newton, MA.

THIS PICTURE BOOK WAS DEVELOPED FOR USE WITH THE ELEMENTARY SCIENCE STUDY UNIT ON "BONES." THE UNIT PROVIDES AN OPPORTUNITY TO DEVELOP MANY CONCEPTS ABOUT THE SKELETAL SYSTEM. NUMEROUS PHOTOGRAPHS ARE PROVIDED OF REPRESENTATIVES OF THE FIVE VERTEBRATE CLASSES AND SELECTED INVERTEBRATES. BOTH EXTANT AND EXTINCT MEMBERS ARE REPRESENTED.…

Long bone histology of the subterranean rodent Bathyergus suillus (Bathyergidae): ontogenetic pattern of cortical bone thickening.

PubMed

Montoya-Sanhueza, Germán; Chinsamy, Anusuya

2017-02-01

Patterns of bone development in mammals are best known from terrestrial and cursorial groups, but there is a considerable gap in our understanding of how specializations for life underground affect bone growth and development. Likewise, studies of bone microstructure in wild populations are still scarce, and they often include few individuals and tend to be focused on adults. For these reasons, the processes generating bone microstructural variation at intra- and interspecific levels are not fully understood. This study comprehensively examines the bone microstructure of an extant population of Cape dune molerats, Bathyergus suillus (Bathyergidae), the largest subterranean mammal endemic to the Western Cape of South Africa. The aim of this study is to investigate the postnatal bone growth of B. suillus using undecalcified histological sections (n = 197) of the femur, humerus, tibia-fibula, ulna and radius, including males and females belonging to different ontogenetic and reproductive stages (n = 42). Qualitative histological features demonstrate a wide histodiversity with thickening of the cortex mainly resulting from endosteal and periosteal bone depositions, whilst there is scarce endosteal resorption and remodeling throughout ontogeny. This imbalanced bone modeling allows the tissues deposited during ontogeny to remain relatively intact, thus preserving an excellent record of growth. The distribution of the different bone tissues observed in the cortex depends on ontogenetic status, anatomical features (e.g. muscle attachment structures) and location on the bone (e.g. anterior or lateral). The type of bone microstructure and modeling is discussed in relation to digging behavior, reproduction and physiology of this species. This study is the first histological assessment describing the process of cortical thickening in long bones of a fossorial mammal. © 2016 Anatomical Society.

Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft.

PubMed

Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

2016-04-20

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.

Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft

PubMed Central

Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

2016-01-01

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft. PMID:27104525

The development of curvature in the porcine radioulna

PubMed Central

Pantinople, Jess; McCabe, Kyle; Henderson, Keith; Milne, Nick

2017-01-01

Long bone curvature in animal limbs has long been a subject of interest and much work has explored why long bones should be curved. However, the ‘when’ and ‘how’ of curvature development is poorly understood. It has been shown that the rat tibia fails to attain its normal curvature if the action of muscles is removed early in life, but it is not clear if this is because the curvature fails to develop or if the bone becomes straighter without the action of muscles. No studies have examined the development of bone curvature in a normally developing quadruped, so this study tracks the course of curvature formation in the radioulna in a series of growing pigs. We also histologically examined the epiphyseal growth plates of these bones to determine if they contribute to the formation of curvature. In all three epiphyseal plates examined, the proliferative zone is thicker and more densely populated with chondrocytes on the cranial (convex) side than the caudal (concave) side. Frost’s chondral modelling theory would suggest that the cranial side of the bone is under more compression than the caudal side, and we conclude that this is due to the action of triceps extending the elbow by pulling on the olecranon process. These results support the idea that bone curvature is an adaptation to habitual loading, where longitudinal loads acting on the curved bone cause bending strains that counter the bending resulting from the habitual muscle action. PMID:28584714

The development of curvature in the porcine radioulna.

PubMed

Pantinople, Jess; McCabe, Kyle; Henderson, Keith; Richards, Hazel L; Milne, Nick

2017-01-01

Long bone curvature in animal limbs has long been a subject of interest and much work has explored why long bones should be curved. However, the 'when' and 'how' of curvature development is poorly understood. It has been shown that the rat tibia fails to attain its normal curvature if the action of muscles is removed early in life, but it is not clear if this is because the curvature fails to develop or if the bone becomes straighter without the action of muscles. No studies have examined the development of bone curvature in a normally developing quadruped, so this study tracks the course of curvature formation in the radioulna in a series of growing pigs. We also histologically examined the epiphyseal growth plates of these bones to determine if they contribute to the formation of curvature. In all three epiphyseal plates examined, the proliferative zone is thicker and more densely populated with chondrocytes on the cranial (convex) side than the caudal (concave) side. Frost's chondral modelling theory would suggest that the cranial side of the bone is under more compression than the caudal side, and we conclude that this is due to the action of triceps extending the elbow by pulling on the olecranon process. These results support the idea that bone curvature is an adaptation to habitual loading, where longitudinal loads acting on the curved bone cause bending strains that counter the bending resulting from the habitual muscle action.

Bone characteristics of late-term embryonic and hatchling broilers: bone development under extreme growth rate.

PubMed

Yair, R; Uni, Z; Shahar, R

2012-10-01

The development of broilers is an extreme example of rapid growth, increasing in weight from 40 g at hatch to 2,000 g 5 to 6 wk later. Such rapid growth requires a correspondingly fast development of the skeleton. Bone development is a genetically programmed process that is modified by epigenetic factors, mainly muscle-induced stresses and strains. In this study, we describe the temporal changes in bone morphology and material properties during the prehatch period [embryonic day (E) 14, E17, E19, E21] and posthatch d 3 and 7. The bones were examined for their weight, length, ash content, mechanical properties, and cortical structure. We show that the cross-sectional shape of the tibia and femur changes during the examination period from circular to elliptical. Additionally, the changes in bone properties are time-dependent and nonuniform: from E14 to E17 and from d 3 to 7, fast bone growth was noted, with major increases in both mechanical properties (stiffness, ultimate load, and energy to fracture) and geometric properties (cross-sectional area and thickness, medullary area, and moment of inertia). On the other hand, during the last days of incubation, most mechanical and geometric properties remain unchanged or even decrease. The reasons for this finding may relate to the hatching process but also to mineral shortage during the last days of incubation. This study leads to better understanding of bone development in ovo and posthatch in fast-growing broilers.

Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

PubMed

Gdowski, Andrew S; Ranjan, Amalendu; Sarker, Marjana R; Vishwanatha, Jamboor K

2017-09-01

The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

Additively manufactured metallic porous biomaterials based on minimal surfaces: A unique combination of topological, mechanical, and mass transport properties.

PubMed

Bobbert, F S L; Lietaert, K; Eftekhari, A A; Pouran, B; Ahmadi, S M; Weinans, H; Zadpoor, A A

2017-04-15

Porous biomaterials that simultaneously mimic the topological, mechanical, and mass transport properties of bone are in great demand but are rarely found in the literature. In this study, we rationally designed and additively manufactured (AM) porous metallic biomaterials based on four different types of triply periodic minimal surfaces (TPMS) that mimic the properties of bone to an unprecedented level of multi-physics detail. Sixteen different types of porous biomaterials were rationally designed and fabricated using selective laser melting (SLM) from a titanium alloy (Ti-6Al-4V). The topology, quasi-static mechanical properties, fatigue resistance, and permeability of the developed biomaterials were then characterized. In terms of topology, the biomaterials resembled the morphological properties of trabecular bone including mean surface curvatures close to zero. The biomaterials showed a favorable but rare combination of relatively low elastic properties in the range of those observed for trabecular bone and high yield strengths exceeding those reported for cortical bone. This combination allows for simultaneously avoiding stress shielding, while providing ample mechanical support for bone tissue regeneration and osseointegration. Furthermore, as opposed to other AM porous biomaterials developed to date for which the fatigue endurance limit has been found to be ≈20% of their yield (or plateau) stress, some of the biomaterials developed in the current study show extremely high fatigue resistance with endurance limits up to 60% of their yield stress. It was also found that the permeability values measured for the developed biomaterials were in the range of values reported for trabecular bone. In summary, the developed porous metallic biomaterials based on TPMS mimic the topological, mechanical, and physical properties of trabecular bone to a great degree. These properties make them potential candidates to be applied as parts of orthopedic implants and/or as bone-substituting biomaterials. Bone-substituting biomaterials aim to mimic bone properties. Although mimicking some of bone properties is feasible, biomaterials that could simultaneously mimic all or most of the relevant bone properties are rare. We used rational design and additive manufacturing to develop porous metallic biomaterials that exhibit an interesting combination of topological, mechanical, and mass transport properties. The topology of the developed biomaterials resembles that of trabecular bone including a mean curvature close to zero. Moreover, the developed biomaterials show an unusual combination of low elastic modulus to avoid stress shielding and high strength to provide mechanical support. The fatigue resistance of the developed biomaterials is also exceptionally high, while their permeability is in the range of values reported for bone. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biophotonics and Bone Biology

NASA Technical Reports Server (NTRS)

Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

2004-01-01

One of the more serious side effects of extended space flight is an accelerated bone loss. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.

A method of determining bending properties of poultry long bones using beam analysis and micro-CT data.

PubMed

Vaughan, Patrick E; Orth, Michael W; Haut, Roger C; Karcher, Darrin M

2016-01-01

While conventional mechanical testing has been regarded as a gold standard for the evaluation of bone heath in numerous studies, with recent advances in medical imaging, virtual methods of biomechanics are rapidly evolving in the human literature. The objective of the current study was to evaluate the feasibility of determining the elastic and failure properties of poultry long bones using established methods of analysis from the human literature. In order to incorporate a large range of bone sizes and densities, a small number of specimens were utilized from an ongoing study of Regmi et al. (2016) that involved humeri and tibiae from 3 groups of animals (10 from each) including aviary, enriched, and conventional housing systems. Half the animals from each group were used for 'training' that involved the development of a regression equation relating bone density and geometry to bending properties from conventional mechanical tests. The remaining specimens from each group were used for 'testing' in which the mechanical properties from conventional tests were compared to those predicted by the regression equations. Based on the regression equations, the coefficients of determination for the 'test' set of data were 0.798 for bending bone stiffness and 0.901 for the yield (or failure) moment of the bones. All regression slopes and intercepts values for the tests versus predicted plots were not significantly different from 1 and 0, respectively. The study showed the feasibility of developing future methods of virtual biomechanics for the evaluation of poultry long bones. With further development, virtual biomechanics may have utility in future in vivo studies to assess laying hen bone health over time without the need to sacrifice large groups of animals at each time point. © 2016 Poultry Science Association Inc.

The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body.

PubMed

Ramcharan, M A; Faillace, M E; Guengerich, Z; Williams, V A; Jepsen, K J

2017-03-01

How cortical and trabecular bone co-develop to establish a mechanically functional structure is not well understood. Comparing early postnatal differences in morphology of lumbar vertebral bodies for three inbred mouse strains identified coordinated changes within and between cortical and trabecular traits. These early coordinate changes defined the phenotypic differences among the inbred mouse strains. Age-related changes in cortical and trabecular traits have been well studied; however, very little is known about how these bone tissues co-develop from day 1 of postnatal growth to establish functional structures by adulthood. In this study, we aimed to establish how cortical and trabecular tissues within the lumbar vertebral body change during growth for three inbred mouse strains that express wide variation in adult bone structure and function. Bone traits were quantified for lumbar vertebral bodies of female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse strains from 1 to 105 days of age (n = 6-10 mice/age/strain). Inter-strain differences in external bone size were observed as early as 1 day of age. Reciprocal and rapid changes in the trabecular bone volume fraction and alignment in the direction of axial compression were observed by 7 days of age. Importantly, the inter-strain difference in adult trabecular bone volume fraction was established by 7 days of age. Early variation in external bone size and trabecular architecture was followed by progressive increases in cortical area between 28 and 105 days of age, with the greatest increases in cortical area seen in the mouse strain with the lowest trabecular mass. Establishing the temporal changes in bone morphology for three inbred mouse strains revealed that genetic variation in adult trabecular traits were established early in postnatal development. Early variation in trabecular architecture preceded strain-specific increases in cortical area and changes in cortical thickness. This study established the sequence of how cortical and trabecular traits co-develop during growth, which is important for identifying critical early ages to further focus on intervention studies that optimize adult bone strength.

Heterochronies in the cranial development of Asian tree frogs (Amphibia: Anura: Rhacophoridae) with different life histories.

PubMed

Vassilieva, A B

2017-03-01

The development of bony skull was studied in four species of Asian tree frogs (Rhacophoridae) with different life histories: biphasic development with free larval stage and direct development. In biphasic rhacophorids the sequence of the appearance of cranial bones generally followed the generalized pattern of craniogenesis, which was described for most studied anurans. In contrast, direct-developing species displayed some heterochronies in the formation of skull bones, namely, the accelerated formation of the anlagen of jaw and suspensorium bones. The obtained results support that the embryonization in amphibians is regularly accompanied by a heterochronic repatterning of craniogenesis, rather similar in different phyletic groups.

The development of a composite bone model for training on placement of dental implants

PubMed Central

Alkhodary, Mohamed Ahmed; Abdelraheim, Abdelraheim Emad Eldin; Elsantawy, Abd Elaleem Hassan; Al Dahman, Yousef Hamad; Al-Mershed, Mohammed

2015-01-01

Objectives It takes a lot of training on patients for both undergraduate to develop clinical sense as regards to the placement of dental implants in the jaw bones, also, the models provided by the dental implant companies for training are usually made of strengthened synthetic foams, which are far from the composition, and tactile sense provided by natural bone during drilling for clinical placement of dental implants. Methodology This is an in-vitro experimental study which utilized bovine femur bone, where the shaft of the femur provided the surface compact layer, and the head provided the cancellous bone layer, to provide a training model similar to jaw bones macroscopic anatomy. Both the compact and cancellous bone samples were characterized using mechanical compressive testing. Results The elastic moduli of the cancellous and cortical femur bone were comparable to those of the human mandible, and the prepared training model provided a more lifelike condition during the drilling and placement of dental implants. Conclusion The composite bone model developed simulated the macroscopic anatomy of the jaw bones having a surface layer of compact bone, and a core of cancellous bone, and provided a better and a more natural hands-on experience for placement of dental implants as compared to plastic models made of polyurethane. PMID:26309434

The development of a composite bone model for training on placement of dental implants.

PubMed

Alkhodary, Mohamed Ahmed; Abdelraheim, Abdelraheim Emad Eldin; Elsantawy, Abd Elaleem Hassan; Al Dahman, Yousef Hamad; Al-Mershed, Mohammed

2015-04-01

It takes a lot of training on patients for both undergraduate to develop clinical sense as regards to the placement of dental implants in the jaw bones, also, the models provided by the dental implant companies for training are usually made of strengthened synthetic foams, which are far from the composition, and tactile sense provided by natural bone during drilling for clinical placement of dental implants. This is an in-vitro experimental study which utilized bovine femur bone, where the shaft of the femur provided the surface compact layer, and the head provided the cancellous bone layer, to provide a training model similar to jaw bones macroscopic anatomy. Both the compact and cancellous bone samples were characterized using mechanical compressive testing. The elastic moduli of the cancellous and cortical femur bone were comparable to those of the human mandible, and the prepared training model provided a more lifelike condition during the drilling and placement of dental implants. The composite bone model developed simulated the macroscopic anatomy of the jaw bones having a surface layer of compact bone, and a core of cancellous bone, and provided a better and a more natural hands-on experience for placement of dental implants as compared to plastic models made of polyurethane.

Growth plate stress distribution implications during bone development: a simple framework computational approach.

PubMed

Guevara, J M; Moncayo, M A; Vaca-González, J J; Gutiérrez, M L; Barrera, L A; Garzón-Alvarado, D A

2015-01-01

Mechanical stimuli play a significant role in the process of long bone development as evidenced by clinical observations and in vivo studies. Up to now approaches to understand stimuli characteristics have been limited to the first stages of epiphyseal development. Furthermore, growth plate mechanical behavior has not been widely studied. In order to better understand mechanical influences on bone growth, we used Carter and Wong biomechanical approximation to analyze growth plate mechanical behavior, and explore stress patterns for different morphological stages of the growth plate. To the best of our knowledge this work is the first attempt to study stress distribution on growth plate during different possible stages of bone development, from gestation to adolescence. Stress distribution analysis on the epiphysis and growth plate was performed using axisymmetric (3D) finite element analysis in a simplified generic epiphyseal geometry using a linear elastic model as the first approximation. We took into account different growth plate locations, morphologies and widths, as well as different epiphyseal developmental stages. We found stress distribution during bone development established osteogenic index patterns that seem to influence locally epiphyseal structures growth and coincide with growth plate histological arrangement. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Anthropometric, densitometric and histometric investigations into the development of the femoral bone in human foetuses].

PubMed

Partyka, Cezary

2013-01-01

The purpose of this study was the estimation of foetal femoral bone development, based on anthropometric, densitometric and histometric examination. The study was done on 68 foetuses (31 female and 37 male) of various foetal ages (16-31 weeks of gestation). The specimens, ranging 16-31 weeks of gestation, were divided into 3 groups for better statistical analysis. After the left and right limb were removed from specimens each femoral bone was radiographed using a Microfocus 401 bone X-ray apparatus. Radiographs were digitized with an analogue camera and an A/D converter for transfer to a computer. Four measurements were taken for each bone: the total length of the shaft; the breadth of the proximal epiphysis; the breadth of the central part of the shaft; and the breadth of the distal epiphysis. After anthropometric research densitometric research was started within which BMC and BMD measurements were taken by a DPX-L osteodensitometer, Lunar, Wisconsin, USA, for tiny osseous structures. Mean values for results were calculated, and their correlation with the age and sex of the examined foetuses was described. The bones examined were cleared of soft tissues, and afterwards histological specimens were taken from the proximal epiphysis, the central part of the shaft, and the distal epiphysis for histometric study. The obtained histological images were saved on the computer, and processed using a special image analyser. During the experiment the surface area and circumference oftrabeculae of bone were calculated. The obtained values were used for estimating histometric indicators that describe the osseous structure of the proximal epiphysis, the central part of the shaft, and the distal epiphysis. Results of this research from certain parts of the femoral bone were described for the right and left limbs in correlation with the foetuses' age and sex. It has been stated that arbitrary diameters of foetal femoral bone are strongly and positively correlated with the total length of the femoral bone, CRL and the age of the examined foetuses. Anthropometric analysis of foetal femoral bones in the early stage of development do not indicate lateralization features. The mineral content of femoral bones (BMC) indicates a characteristic, positive correlation with foetal age, but the mineral density of foetal femoral bones (BMD) does not correlate with its development. The density of the femoral bone in human foetuses increases with age in all bone's parts and histometric parameters of foetal femoral bones show variability in terms of sex at an early stage of intrauterine development. Based on the given anthropometric densitometric and histometric data the occurrence of foetal dimorphism features has been analyzed in randomly chosen foetal groups. The cluster analysis and analysis of many other parameters of developing femoral bone revealed features of sexual dimorphism in selected groups of human foetuses.

Hypercholesterolemia Promotes an Osteoporotic Phenotype

PubMed Central

Pelton, Kristine; Krieder, Jaclynn; Joiner, Danese; Freeman, Michael R.; Goldstein, Steven A.; Solomon, Keith R.

2013-01-01

A role for hypercholesterolemia in the development of osteoporosis has been suggested in published reports. However, few studies contain direct evidence of a role for maintenance of cholesterol homeostasis in bone health. Using isocaloric high-fat/high-cholesterol and low-fat/no-cholesterol diets in a 4-month feeding study combined with micro computed tomography analysis, we demonstrated in two different mouse strains that mice with hypercholesterolemia lose cortical and trabecular bone in the femurs and vertebrae (bone mineral density was decreased on average by ≈90 mg/mL in the cortical vertebrae in one strain) and cortical bone in the calvariae (bone mineral density was decreased on average by ≈60 mg/mL in one strain). Mechanical testing of the femurs demonstrated that loss of bone in the mice with hypercholesterolemia caused changes in the mechanical properties of the bone including loss of failure load (failure load was decreased by ≈10 N in one strain) and energy to failure. Serologic and histomorphologic analyses suggested that hypercholesterolemia promotes osteoclastogenesis. These studies support a role for hypercholesterolemia in the development of osteoporosis and provide a model with which to test intervention strategies to reduce the effects of hypercholesterolemia on bone health. PMID:22770664

3D artificial bones for bone repair prepared by computed tomography-guided fused deposition modeling for bone repair.

PubMed

Xu, Ning; Ye, Xiaojian; Wei, Daixu; Zhong, Jian; Chen, Yuyun; Xu, Guohua; He, Dannong

2014-09-10

The medical community has expressed significant interest in the development of new types of artificial bones that mimic natural bones. In this study, computed tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic natural goat femurs. The in vitro mechanical properties, in vitro cell biocompatibility, and in vivo performance of the artificial bones in a long load-bearing goat femur bone segmental defect model were studied. All of the results indicate that CT-guided FDM is a simple, convenient, relatively low-cost method that is suitable for fabricating natural bonelike artificial bones. Moreover, PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to natural bone, good in vitro cell biocompatibility, biodegradation ability, and appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial bones could be potentially be of use in the treatment of patients with clinical bone defects.

Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds.

PubMed

Temple, Joshua P; Hutton, Daphne L; Hung, Ben P; Huri, Pinar Yilgor; Cook, Colin A; Kondragunta, Renu; Jia, Xiaofeng; Grayson, Warren L

2014-12-01

The treatment of large craniomaxillofacial bone defects is clinically challenging due to the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. The ability to regenerate new bone tissues that faithfully replicate the anatomy would revolutionize treatment options. Advances in the field of bone tissue engineering over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials and autologous cells. This approach combined with recent advances in three-dimensional (3D) printing technologies may soon allow the generation of large, bioartificial bone grafts with custom, patient-specific architecture. In this study, we use a custom-built 3D printer to develop anatomically shaped polycaprolactone (PCL) scaffolds with varying internal porosities. These scaffolds are assessed for their ability to support induction of human adipose-derived stem cells (hASCs) to form vasculature and bone, two essential components of functional bone tissue. The development of functional tissues is assessed in vitro and in vivo. Finally, we demonstrate the ability to print large mandibular and maxillary bone scaffolds that replicate fine details extracted from patient's computed tomography scans. The findings of this study illustrate the capabilities and potential of 3D printed scaffolds to be used for engineering autologous, anatomically shaped, vascularized bone grafts. © 2014 Wiley Periodicals, Inc.

Bone histological correlates of soaring and high-frequency flapping flight in the furculae of birds.

PubMed

Mitchell, Jessica; Legendre, Lucas J; Lefèvre, Christine; Cubo, Jorge

2017-06-01

The furcula is a specialized bone in birds involved in flight function. Its morphology has been shown to reflect different flight styles from soaring/gliding birds, subaqueous flight to high-frequency flapping flyers. The strain experienced by furculae can vary depending on flight type. Bone remodeling is a response to damage incurred from different strain magnitudes and types. In this study, we tested whether a bone microstructural feature, namely Haversian bone density, differs in birds with different flight styles, and reassessed previous work using phylogenetic comparative methods that assume an evolutionary model with additional taxa. We show that soaring birds have higher Haversian bone densities than birds with a flapping style of flight. This result is probably linked to the fact that the furculae of soaring birds provide less protraction force and more depression force than furculae of birds showing other kinds of flight. The whole bone area is another explanatory factor, which confirms the fact that size is an important consideration in Haversian bone development. All birds, however, display Haversian bone development in their furculae, and other factors like age could be affecting the response of Haversian bone development. Copyright © 2017 Elsevier GmbH. All rights reserved.

Greater access to fast-food outlets is associated with poorer bone health in young children.

PubMed

Vogel, C; Parsons, C; Godfrey, K; Robinson, S; Harvey, N C; Inskip, H; Cooper, C; Baird, J

2016-03-01

A healthy diet positively influences childhood bone health, but how the food environment relates to bone development is unknown. Greater neighbourhood access to fast-food outlets was associated with lower bone mass among infants, while greater access to healthy speciality stores was associated with higher bone mass at 4 years. Identifying factors that contribute to optimal childhood bone development could help pinpoint strategies to improve long-term bone health. A healthy diet positively influences bone health from before birth and during childhood. This study addressed a gap in the literature by examining the relationship between residential neighbourhood food environment and bone mass in infants and children. One thousand one hundred and seven children participating in the Southampton Women's Survey, UK, underwent measurement of bone mineral density (BMD) and bone mineral content (BMC) at birth and 4 and/or 6 years by dual-energy X-ray absorptiometry (DXA). Cross-sectional observational data describing food outlets within the boundary of each participant's neighbourhood were used to derive three measures of the food environment: the counts of fast-food outlets, healthy speciality stores and supermarkets. Neighbourhood exposure to fast-food outlets was associated with lower BMD in infancy (β = -0.23 (z-score): 95% CI -0.38, -0.08) and lower BMC after adjustment for bone area and confounding variables (β = -0.17 (z-score): 95% CI -0.32, -0.02). Increasing neighbourhood exposure to healthy speciality stores was associated with higher BMD at 4 and 6 years (β = 0.16(z-score): 95% CI 0.00, 0.32 and β = 0.13(z-score): 95% CI -0.01, 0.26 respectively). The relationship with BMC after adjustment for bone area and confounding variables was statistically significant at 4 years, but not at 6 years. The neighbourhood food environment that pregnant mothers and young children are exposed may affect bone development during early childhood. If confirmed in future studies, action to reduce access to fast-food outlets could have benefits for childhood development and long-term bone health.

Bone matrix calcification during embryonic and postembryonic rat calvarial development assessed by SEM-EDX spectroscopy, XRD, and FTIR spectroscopy.

PubMed

Henmi, Akiko; Okata, Hiroshi; Anada, Takahisa; Yoshinari, Mariko; Mikami, Yasuto; Suzuki, Osamu; Sasano, Yasuyuki

2016-01-01

Bone mineral is constituted of biological hydroxyapatite crystals. In developing bone, the mineral crystal matures and the Ca/P ratio increases. However, how an increase in the Ca/P ratio is involved in maturation of the crystal is not known. The relationships among organic components and mineral changes are also unclear. The study was designed to investigate the process of calcification during rat calvarial bone development. Calcification was evaluated by analyzing the atomic distribution and concentration of Ca, P, and C with scanning electron microscopy (SEM)-energy-dispersive X-ray (EDX) spectroscopy and changes in the crystal structure with X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Histological analysis showed that rat calvarial bone formation started around embryonic day 16. The areas of Ca and P expanded, matching the region of the developing bone matrix, whereas the area of C became localized around bone. X-ray diffraction and FTIR analysis showed that the amorphous-like structure of the minerals at embryonic day 16 gradually transformed into poorly crystalline hydroxyapatite, whereas the proportion of mineral to protein increased until postnatal week 6. FTIR analysis also showed that crystallization of hydroxyapatite started around embryonic day 20, by which time SEM-EDX spectroscopy showed that the Ca/P ratio had increased and the C/Ca and C/P ratios had decreased significantly. The study suggests that the Ca/P molar ratio increases and the proportion of organic components such as proteins of the bone matrix decreases during the early stage of calcification, whereas crystal maturation continues throughout embryonic and postembryonic bone development.

Computational biomechanics of bone's responses to dental prostheses - osseointegration, remodeling and resorption

NASA Astrophysics Data System (ADS)

Li, Wei; Rungsiyakull, Chaiy; Field, Clarice; Lin, Daniel; Zhang, Leo; Li, Qing; Swain, Michael

2010-06-01

Clinical and experimental studies showed that human bone has the ability to remodel itself to better adapt to its biomechanical environment by changing both its material properties and geometry. As a consequence of the rapid development and extensive applications of major dental restorations such as implantation and fixed partial denture (FPD), the effect of bone remodeling on the success of a dental restorative surgery is becoming critical for prosthetic design and pre-surgical assessment. This paper aims to provide a computational biomechanics framework to address dental bone's responses as a result of dental restoration. It explored three important issues of resorption, apposition and osseointegration in terms of remodeling simulation. The published remodeling data in long bones were regulated to drive the computational remodeling prediction for the dental bones by correlating the results to clinical data. It is anticipated that the study will provide a more predictive model of dental bone response and help develop a new design methodology for patient-specific dental prosthetic restoration.

Nanocomposites and bone regeneration

NASA Astrophysics Data System (ADS)

James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

2011-12-01

This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation

USDA-ARS?s Scientific Manuscript database

A major problem in patients with multiple myeloma is chemotherapy resistance, which develops in myeloma cells upon interaction with bone marrow stromal cells. However, few studies have determined the role of bone marrow adipocytes, a major component of stromal cells in the bone marrow, in myeloma ch...

Exercise training, menstrual irregularities and bone development in children and adolescents.

PubMed

Eliakim, Alon; Beyth, Yoram

2003-08-01

Weight bearing physical activity plays an important role in bone development. This is particularly important in children and adolescents since bone mineral density reaches about 90% of its peak by the end of the second decade, and because about one quarter of adult bone is accumulated during the two years surrounding the peak bone growth velocity. Recent studies suggested that the exercise-induced increase in bone mineralization is maturity dependent, and that there is a "window of opportunity" and a critical period for bone response to weight bearing exercise during early puberty and premenarchal years. This supports the idea that increase in physical activity during childhood and adolescence can prevent bone disorders (like osteoporosis) later in life. In contrast, strenuous physical activity may affect the female reproductive system and lead to "athletic amenorrhea". The prevalence of "athletic amenorrhea" is 4-20 times higher than the general population. As a consequence, bone demineralization may develop with increased risk of skeletal fragility, fractures, vertebral instability, and curvature. Menstrual abnormalities in the female athlete result from hypothalamic suppression of the spontaneous pulsatile secretion of gonadotropin releasing hormone. Recent studies suggested that reduced energy availability (increased energy expenditure with inadequate caloric intake) is the main cause of the central suppression of the hypothalamic pituitary-gonadal axis. Therefore, effort should be made to optimize the nutritional state of female athletes, and if not successful, to reduce the training load in order to prevent menstrual abnormalities, and deleterious bone effects in particular during the critical period of rapid bone growth.

The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

PubMed Central

Tsutsumimoto, Takahiro; Williams, Paul; Yoneda, Toshiyuki

2014-01-01

Neuroblastoma (NB), which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2). In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB. PMID:26909300

Inhibition of fetal bone development through epigenetic down- regulation of HoxA10 in obese rats fed high fat diet

USDA-ARS?s Scientific Manuscript database

Epidemiological studies show that maternal obesity during intrauterine and early postnatal life increases the risk of low bone mass and fracture later in life. Here, we show that bone development is inhibited in GED 18.5 embryos from rat dams made obese by feeding a high fat diet (HFD). Moreover, fe...

Development, validation and characterization of a novel mouse model of Adynamic Bone Disease (ABD).

PubMed

Ng, Adeline H; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

2014-11-01

The etiology of Adynamic Bone Disease (ABD) is poorly understood but the hallmark of ABD is a lack of bone turnover. ABD occurs in renal osteodystrophy (ROD) and is suspected to occur in elderly patients on long-term anti-resorptive therapy. A major clinical concern of ABD is diminished bone quality and an increased fracture risk. To our knowledge, experimental animal models for ABD other than ROD-ABD have not been developed or studied. The objectives of this study were to develop a mouse model of ABD without the complications of renal ablation, and to characterize changes in bone quality in ABD relative to controls. To re-create the adynamic bone condition, 4-month old female Col2.3Δtk mice were treated with ganciclovir to specifically ablate osteoblasts, and pamidronate was used to inhibit osteoclastic resorption. Four groups of animals were used to characterize bone quality in ABD: Normal bone controls, No Formation controls, No Resorption controls, and an Adynamic group. After a 6-week treatment period, the animals were sacrificed and the bones were harvested for analyses. Bone quality assessments were conducted using established techniques including bone histology, quantitative backscattered electron imaging (qBEI), dual energy X-ray absorptiometry (DXA), microcomputed tomography (microCT), and biomechanical testing. Histomorphometry confirmed osteoblast-related hallmarks of ABD in our mouse model. Bone formation was near complete suppression in the No Formation and Adynamic specimens. Inhibition of bone resorption in the Adynamic group was confirmed by tartrate-resistant acid phosphatase (TRAP) stain. Normal bone mineral density and architecture were maintained in the Adynamic group, whereas the No Formation group showed a reduction in bone mineral content and trabecular thickness relative to the Adynamic group. As expected, the No Formation group had a more hypomineralized profile and the Adynamic group had a higher mean mineralization profile that is similar to suppressed bone turnover in human. This data confirms successful replication of the adynamic bone condition in a mouse without the complication of renal ablation. Our approach is the first model of ABD that uses pharmacological manipulation in a transgenic mouse to mimic the bone cellular dynamics observed in the human ABD condition. We plan to use our mouse model to investigate the adynamic bone condition in aging and to study changes to bone quality and fracture risk as a consequence of over-suppressed bone turnover. Copyright © 2014 Elsevier Inc. All rights reserved.

Intracochlear pressure measurements to study bone conduction transmission: State-of-the art and proof of concept of the experimental Procedure

NASA Astrophysics Data System (ADS)

Borgers, Charlotte; van Wieringen, Astrid; D'hondt, Christiane; Verhaert, Nicolas

2018-05-01

The cochlea is the main contributor in bone conduction perception. Measurements of differential pressure in the cochlea give a good estimation of the cochlear input provided by bone conduction stimulation. Recent studies have proven the feasibility of intracochlear pressure measurements in chinchillas and in human temporal bones to study bone conduction. However, similar measurements in fresh-frozen whole human cadaveric heads could give a more realistic representation of the five different transmission pathways of bone conduction to the cochlea compared to human temporal bones. The aim of our study is to develop and validate a framework for intracochlear pressure measurements to evaluate different aspects of bone conduction in whole human cadaveric heads. A proof of concept describing our experimental setup is provided together with the procedure. Additionally, we also present a method to fix the stapes footplate in order to simulate otosclerosis in human temporal bones. The effectiveness of this method is verified by some preliminary results.

Monitoring the osseointegration process in porous Ti6Al4V implants produced by additive manufacturing: an experimental study in sheep.

PubMed

Kayacan, Mehmet C; Baykal, Yakup B; Karaaslan, Tamer; Özsoy, Koray; Alaca, İlker; Duman, Burhan; Delikanlı, Yunus E

2018-04-01

This study investigated the design and osseointegration process of transitive porous implants that can be used in humans and all trabecular and compact bone structure animals. The aim was to find a way of forming a strong and durable tissue bond on the bone-implant interface. Massive and transitive porous implants were produced on a direct metal laser sintering machine, surgically implanted into the skulls of sheep and kept in place for 12 weeks. At the end of the 12-week period, the Massive and porous implants removed from the sheep were investigated by scanning electron microscopy (SEM) to monitor the osseointegration process. In the literature, each study has selected standard sizes for pore diameter in the structures they use. However, none of these involved transitional porous structures. In this study, as opposed to standard pores, there were spherical or elliptical pores at the micro level, development channels and an inner region. Bone cells developed in the inner region. Transitive pores grown gradually in accordance with the natural structure of the bone were modeled in the inner region for cells to develop. Due to this structure, a strong and durable tissue bond could be formed at the bone-implant interface. Osseointegration processes of Massive vs. porous implants were compared. It was observed that cells were concentrated on the surface of Massive implants. Therefore, osseointegration between implant and bone was less than that of porous implants. In transitive porous implants, as opposed to Massive implants, an outer region was formed in the bone-implant interface that allowed tissue development.

ADRA2A is involved in neuro-endocrine regulation of bone resorption

PubMed Central

Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

2015-01-01

Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. PMID:25818344

Identification of DNA methylation changes associated with disease progression in subchondral bone with site-matched cartilage in knee osteoarthritis.

PubMed

Zhang, Yanfei; Fukui, Naoshi; Yahata, Mitsunori; Katsuragawa, Yozo; Tashiro, Toshiyuki; Ikegawa, Shiro; Lee, Ming Ta Michael

2016-09-30

Subchondral bone plays a key role in the development of osteoarthritis, however, epigenetics of subchondral bone has not been extensively studied. In this study, we examined the genome-wide DNA methylation profiles of subchondral bone from three regions on tibial plateau representing disease progression using HumanMethylation450 BeadChip to identify progression associated DNA methylation alterations. Significant differential methylated probes (DMPs) and differential methylated genes (DMGs) were identified in the intermediate and late stages and during the transition from intermediate to late stage of OA in the subchondral bone. Over half of the DMPs were hyper-methylated. Genes associated with OA and bone remodeling were identified. DMGs were enriched in morphogenesis and development of skeletal system, and HOX transcription factors. Comparison of DMGs identified in subchondral bone and site-matched cartilage indicated that DNA methylation changes occurred earlier in subchondral bone and identified different methylation patterns at the late stage of OA. However, shared DMPs, DMGs and common pathways that implicated the tissue reparation were also identified. Methylation is one key mechanism to regulate the crosstalk between cartilage and subchondral bone.

Identification of DNA methylation changes associated with disease progression in subchondral bone with site-matched cartilage in knee osteoarthritis

PubMed Central

Zhang, Yanfei; Fukui, Naoshi; Yahata, Mitsunori; Katsuragawa, Yozo; Tashiro, Toshiyuki; Ikegawa, Shiro; Lee, Ming Ta Michael

2016-01-01

Subchondral bone plays a key role in the development of osteoarthritis, however, epigenetics of subchondral bone has not been extensively studied. In this study, we examined the genome-wide DNA methylation profiles of subchondral bone from three regions on tibial plateau representing disease progression using HumanMethylation450 BeadChip to identify progression associated DNA methylation alterations. Significant differential methylated probes (DMPs) and differential methylated genes (DMGs) were identified in the intermediate and late stages and during the transition from intermediate to late stage of OA in the subchondral bone. Over half of the DMPs were hyper-methylated. Genes associated with OA and bone remodeling were identified. DMGs were enriched in morphogenesis and development of skeletal system, and HOX transcription factors. Comparison of DMGs identified in subchondral bone and site-matched cartilage indicated that DNA methylation changes occurred earlier in subchondral bone and identified different methylation patterns at the late stage of OA. However, shared DMPs, DMGs and common pathways that implicated the tissue reparation were also identified. Methylation is one key mechanism to regulate the crosstalk between cartilage and subchondral bone. PMID:27686527

The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development.

PubMed

Lappe, Joan M; Watson, Patrice; Gilsanz, Vicente; Hangartner, Thomas; Kalkwarf, Heidi J; Oberfield, Sharon; Shepherd, John; Winer, Karen K; Zemel, Babette

2015-01-01

Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear. The purpose of this study was to determine the effects of self-reported dietary calcium intake and weight-bearing physical activity on bone mass accrual across the five stages of pubertal development in a large, diverse cohort of US children and adolescents. The Bone Mineral Density in Childhood study was a mixed longitudinal study with 7393 observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray absorptiometry (DXA), physical activity and calcium intake by questionnaire, and pubertal development (Tanner stage) by examination for up to 7 years. Mixed-effects regression models were used to assess physical activity and calcium intake effects on BMC accrual at each Tanner stage. We found that self-reported weight-bearing physical activity contributed to significantly greater BMC accrual in both sexes and racial subgroups (black and nonblack). In nonblack males, the magnitude of the activity effect on total body BMC accrual varied among Tanner stages after adjustment for calcium intake; the greatest difference between high- and low-activity boys was in Tanner stage 3. Calcium intake had a significant effect on bone accrual only in nonblack girls. This effect was not significantly different among Tanner stages. Our findings do not support differential effects of physical activity or calcium intake on bone mass accrual according to maturational stage. The study demonstrated significant longitudinal effects of weight-bearing physical activity on bone mass accrual through all stages of pubertal development. © 2014 American Society for Bone and Mineral Research.

Study on 41Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

NASA Astrophysics Data System (ADS)

Shen, Hongtao; Pang, Fangfang; Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang; Pang, Yijun; Yang, Xianlin; Ruan, Xiangdong; Liu, Manjun; Xia, Chunbo

2015-10-01

The annual incidence of new cancer patients in China is about 2 million, 30-40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of 41Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague-Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl2 solution (containing 1.4 mg Ca and 5nCi 41Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for 41Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of 41Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 41Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

An Approach for Determining Quantitative Measures for Bone Volume and Bone Mass in the Pediatric Spina Bifida Population

PubMed Central

Horenstein, Rachel E.; Shefelbine, Sandra J.; Mueske, Nicole M.; Fisher, Carissa L.; Wren, Tishya A.L.

2015-01-01

Background The pediatric spina bifida population suffers from decreased mobility and recurrent fractures. This study aimed to develop a method for quantifying bone mass along the entire tibia in youth with spina bifida. This will provide information about all potential sites of bone deficiencies. Methods Computed tomography images of the tibia for 257 children (n=80 ambulatory spina bifida, n=10 non-ambulatory spina bifida, n=167 typically developing) were analyzed. Bone area was calculated at regular intervals along the entire tibia length and then weighted by calibrated pixel intensity for density weighted bone area. Integrals of density weighted bone area were used to quantify bone mass in the proximal and distal epiphyses and diaphysis. Group differences were evaluated using analysis of variance. Findings Non-ambulatory children suffer from decreased bone mass in the diaphysis and proximal and distal epiphyses compared to ambulatory and control children (P≤0.001). Ambulatory children with spina bifida showed statistically insignificant differences in bone mass in comparison to typically developing children at these sites (P>0.5). Interpretation This method provides insight into tibial bone mass distribution in the pediatric spina bifida population by incorporating information along the whole length of the bone, thereby providing more information than dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. This method can be applied to any population to assess bone mass distribution across the length of any long bone. PMID:26002057

Predicting Bone Mechanical Properties of Cancellous Bone from DXA, MRI, and Fractal Dimensional Measurements

NASA Technical Reports Server (NTRS)

Harrigan, Timothy P.; Ambrose, Catherine G.; Hogan, Harry A.; Shackleford, Linda; Webster, Laurie; LeBlanc, Adrian; Lin, Chen; Evans, Harlan

1997-01-01

This project was aimed at making predictions of bone mechanical properties from non-invasive DXA and MRI measurements. Given the bone mechanical properties, stress calculations can be made to compare normal bone stresses to the stresses developed in exercise countermeasures against bone loss during space flight. These calculations in turn will be used to assess whether mechanical factors can explain bone loss in space. In this study we assessed the use of T2(sup *) MRI imaging, DXA, and fractal dimensional analysis to predict strength and stiffness in cancellous bone.

Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

PubMed

Takahashi, Kuniyuki; Morita, Yuka; Ohshima, Shinsuke; Izumi, Shuji; Kubota, Yamato; Horii, Arata

2017-12-01

The temporal bone shows regional differences in bone development. The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.

Epigenetic regulation of fetal bone development and placental transfer of nutrients: progress for osteoporosis.

PubMed

Bocheva, Georgeta; Boyadjieva, Nadka

2011-12-01

Osteoporosis is a common age-related disorder and causes acute and long-term disability and economic cost. Many factors influence the accumulation of bone minerals, including heredity, diet, physical activity, gender, endocrine functions, and risk factors such as alcohol, drug abuse, some pharmacological drugs or cigarette smoking. The pathology of bone development during intrauterine life is a factor for osteoporosis. Moreover, the placental transfer of nutrients plays an important role in the building of bones of fetuses. The importance of maternal calcium intake and vitamin D status are highlighted in this review. Various environmental factors including nutrition state or maternal stress may affect the epigenetic state of a number of genes during fetal development of bones. Histone modifications as histone hypomethylation, histone hypermethylation, hypoacetylation, etc. are involved in chromatin remodeling, known to contribute to the epigenetic landscape of chromosomes, and play roles in both fetal bone development and osteoporosis. This review will give an overview of epigenetic modulation of bone development and placental transfer of nutrients. In addition, the data from animal and human studies support the role of epigenetic modulation of calcium and vitamin D in the pathogenesis of osteoporosis. We review the evidence suggesting that various genes are involved in regulation of osteoclast formation and differentiation by osteoblasts and stem cells. Epigenetic changes in growth factors as well as cytokines play a rol in fetal bone development. On balance, the data suggest that there is a link between epigenetic changes in placental transfer of nutrients, including calcium and vitamin D, abnormal intrauterine bone development and pathogenesis of osteoporosis.

Zebrafish skeleton development: High resolution micro-CT and FIB-SEM block surface serial imaging for phenotype identification

PubMed Central

Silvent, Jeremie; Akiva, Anat; Brumfeld, Vlad; Reznikov, Natalie; Rechav, Katya; Yaniv, Karina; Addadi, Lia; Weiner, Steve

2017-01-01

Although bone is one of the most studied living materials, many questions about the manner in which bones form remain unresolved, including fine details of the skeletal structure during development. In this study, we monitored skeleton development of zebrafish larvae, using calcein fluorescence, high-resolution micro-CT 3D images and FIB-SEM in the block surface serial imaging mode. We compared calcein staining of the skeletons of the wild type and nacre mutants, which are transparent zebrafish, with micro-CT for the first 30 days post fertilization embryos, and identified significant differences. We quantified the bone volumes and mineral contents of bones, including otoliths, during development, and showed that such developmental differences, including otolith development, could be helpful in identifying phenotypes. In addition, high-resolution imaging revealed the presence of mineralized aggregates in the notochord, before the formation of the first bone in the axial skeleton. These structures might play a role in the storage of the mineral. Our results highlight the potential of these high-resolution 3D approaches to characterize the zebrafish skeleton, which in turn could prove invaluable information for better understanding the development and the characterization of skeletal phenotypes. PMID:29220379

Minimizing Interpolation Bias and Precision Error in In Vivo μCT-based Measurements of Bone Structure and Dynamics

PubMed Central

de Bakker, Chantal M. J.; Altman, Allison R.; Li, Connie; Tribble, Mary Beth; Lott, Carina; Tseng, Wei-Ju; Liu, X. Sherry

2016-01-01

In vivo μCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered μCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling. PMID:26786342

Minimizing Interpolation Bias and Precision Error in In Vivo µCT-Based Measurements of Bone Structure and Dynamics.

PubMed

de Bakker, Chantal M J; Altman, Allison R; Li, Connie; Tribble, Mary Beth; Lott, Carina; Tseng, Wei-Ju; Liu, X Sherry

2016-08-01

In vivo µCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered µCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling.

Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

PubMed

Lennkh, C; de Zwaan, M; Bailer, U; Strnad, A; Nagy, C; el-Giamal, N; Wiesnagrotzki, S; Vytiska, E; Huber, J; Kasper, S

1999-01-01

Osteopenia is a well recognized medical complication of anorexia nervosa (AN). The mechanism of bone loss is not fully understood and there is uncertainty about its management. New markers of bone turnover have been developed. C-terminal type 1 propeptide (PICP) is a measure of bone formation and urinary pyridinolines such as deoxypyridinoline (DPYRX) and serum carboxyterminal crosslinked telopeptide (ICTP) are markers of bone resorption. The aim of this study was to examine these bone markers in patients with AN. Twenty female patients with AN and 12 healthy controls were included in the study. Bone mineral density (BMD) of AN patients was measured by dual energy X-ray absorptiometry (DEXA). Lumbar bone density was significantly reduced in the AN group compared to standardised values of thirty year old adults (t-score 83.2%, S.D. 12.1). Femoral neck bone density showed an even greater reduction (t-score 79.4%, S.D. 13.5). We found a significant negative correlation between femoral BMD and the duration of the illness. Femoral BMD correlated significantly with minimal body weight (r(16) = 0.504, p = 0.033). The markers of bone resorption were significantly higher in the patients with AN compared to the values of the control group (ICTP t(30) = -2.15, p = 0.04, DPYRX t(25) = -2.26, p = 0.033), whereas the markers of bone formation did not differ significantly between the groups. AN appears to be a low turn over state associated with increased bone resorption without concomitant bone formation. This pattern differs from osteopenia in menopausal women and should, therefore, lead to the development of specific therapeutic strategies in AN associated osteopenia. Hormone replacement therapy as well as calcium and vitamine D-supplementation are so far discussed controversially. Long-term treatment studies are warranted.

Androgens and bone health.

PubMed

Hansen, K A; Tho, S P

1998-01-01

Osteoporosis is one of the most common metabolic bone diseases in the adult population and its prevalence will continue to rise as our population grows older. In both sexes, hypogonadism is associated with accelerated loss of bone and development of osteoporosis. Adrenal and gonadal androgen levels decline with advancing age in both sexes. Androgens act by either directly binding to androgen receptors, or by aromatization of androgens to estrogens and subsequently interacting with estrogen receptors. Both pathways are important for skeletal health. Direct androgen binding to an androgen receptor may play a more important role in early skeletal development and determination of sexual dimorphic traits. While bone remodeling, which is important in maintaining healthy bone through life, is primarily stimulated by estrogen, studies in the rat and human support the complex action of androgens and estrogens in bone modeling and remodeling, and hence the development and maintenance of healthy bone. In postmenopausal females, the addition of androgens to hormone replacement therapy results in significant additional improvement in bone mineral density compared to estrogen replacement alone. Accumulating evidence indicate that androgens play an important role in the health of bone and the potential benefit of adding these agents to hormone replacement regimens.

Single-trabecula building block for large-scale finite element models of cancellous bone.

PubMed

Dagan, D; Be'ery, M; Gefen, A

2004-07-01

Recent development of high-resolution imaging of cancellous bone allows finite element (FE) analysis of bone tissue stresses and strains in individual trabeculae. However, specimen-specific stress/strain analyses can include effects of anatomical variations and local damage that can bias the interpretation of the results from individual specimens with respect to large populations. This study developed a standard (generic) 'building-block' of a trabecula for large-scale FE models. Being parametric and based on statistics of dimensions of ovine trabeculae, this building block can be scaled for trabecular thickness and length and be used in commercial or custom-made FE codes to construct generic, large-scale FE models of bone, using less computer power than that currently required to reproduce the accurate micro-architecture of trabecular bone. Orthogonal lattices constructed with this building block, after it was scaled to trabeculae of the human proximal femur, provided apparent elastic moduli of approximately 150 MPa, in good agreement with experimental data for the stiffness of cancellous bone from this site. Likewise, lattices with thinner, osteoporotic-like trabeculae could predict a reduction of approximately 30% in the apparent elastic modulus, as reported in experimental studies of osteoporotic femora. Based on these comparisons, it is concluded that the single-trabecula element developed in the present study is well-suited for representing cancellous bone in large-scale generic FE simulations.

Multiscale mechanobiology of de novo bone generation, remodeling and adaptation of autograft in a common ovine femur model.

PubMed

Knothe Tate, Melissa L; Dolejs, Scott; McBride, Sarah H; Matthew Miller, R; Knothe, Ulf R

2011-08-01

The link between mechanics and biology in the generation and the adaptation of bone has been studied for more than a century in the context of skeletal development and fracture healing. However, the interplay between mechanics and biology in de novo generation of bone in postnatal defects as well as healing of morcellized bone graft or massive cortical bone autografts is less well understood. To address this, here we integrate insights from our previously published studies describing the mechanobiology on both de novo bone generation and graft healing in a common ovine femoral defect model. Studying these effects in a common experimental model provides a unique opportunity to elucidate factors conducive to harnessing the regenerative power of the periosteum, and ultimately, to provide mechanistic insights into the multiscale mechanobiology of bone generation, remodeling and adaptation. Taken together, the studies indicate that, as long as adequate, directional transport of cells and molecules can be insured (e.g. with periosteum in situ or a delivery device), biological factors intrinsic to the periosteum suffice to bridge critical sized bone defects, even in the absence of a patent blood supply. Furthermore, mechanical stimuli are crucial for the success of periosteal bone generation and bone graft healing. Interestingly, areas of highest periosteal strain around defects correlate with greatest amounts albeit not greatest mineralization of newly generated bone. This may indicate a role for convection enhanced transport of cells and molecules in modulation of tissue generation by pluripotent cells that ingress into the defect center, away from the periosteum and toward the surface of the intramedullary nail that fills the medullary cavity. These insights bring us much closer to understanding the mechanobiological environment and stimuli that stimulate the proliferation and differentiation of periosteum-derived progenitor cells and ultimately drive the generation of new bone tissue. Furthermore, these insights provide a foundation to create virtual predictive computational models of bone mechanophysiology, to develop cell seeding protocols for scale up and manufacture of engineered tissues, to optimize surgical procedures, and to develop post-surgical therapies with the ultimate goal of achieving the best possible healing outcomes for treatment and/or reconstruction of postnatal bone defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development

PubMed Central

Kohn, Anat; Dong, Yufeng; Mirando, Anthony J.; Jesse, Alana M.; Honjo, Tasuku; Zuscik, Michael J.; O’Keefe, Regis J.; Hilton, Matthew J.

2012-01-01

The Notch signaling pathway has emerged as an important regulator of endochondral bone formation. Although recent studies have examined the role of Notch in mesenchymal and chondro-osteo progenitor cell populations, there has yet to be a true examination of Notch signaling specifically within developing and committed chondrocytes, or a determination of whether cartilage and bone formation are regulated via RBPjκ-dependent or -independent Notch signaling mechanisms. To develop a complete understanding of Notch signaling during cartilage and bone development we generated and compared general Notch gain-of-function (Rosa-NICDf/+), RBPjκ-deficient (Rbpjκf/f), and RBPjκ-deficient Notch gain-of-function (Rosa-NICDf/+;Rbpjκf/f) conditional mutant mice, where activation or deletion of floxed alleles were specifically targeted to mesenchymal progenitors (Prx1Cre) or committed chondrocytes (inducible Col2CreERT2). These data demonstrate, for the first time, that Notch regulation of chondrocyte maturation is solely mediated via the RBPjκ-dependent pathway, and that the perichodrium or osteogenic lineage probably influences chondrocyte terminal maturation and turnover of the cartilage matrix. Our study further identifies the cartilage-specific RBPjκ-independent pathway as crucial for the proper regulation of chondrocyte proliferation, survival and columnar chondrocyte organization. Unexpectedly, the RBPjκ-independent Notch pathway was also identified as an important long-range cell non-autonomous regulator of perichondral bone formation and an important cartilage-derived signal required for coordinating chondrocyte and osteoblast differentiation during endochondral bone development. Finally, cartilage-specific RBPjκ-independent Notch signaling likely regulates Ihh responsiveness during cartilage and bone development. PMID:22354840

Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins.

PubMed

Lanham, S A; Cagampang, F R; Oreffo, R O C

2014-12-01

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.

PubMed

Das Neves Borges, Patricia; Vincent, Tonia L; Marenzana, Massimo

2017-01-01

The degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods. OA was induced by destabilisation of the medial meniscus (DMM) in 10-week old male mice and disease assessed cross-sectionally from 1- to 20-weeks post-surgery. A novel approach was developed to automatically segment subchondral bone compartments into plate and trabecular bone in micro-CT scans of tibial epiphyses. Osteophyte volume, as assessed by shape differences using 3D image registration, and by measuring total epiphyseal volume was performed. Significant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 μm and the medial osteophyte grew by 0.124±0.028 μm3. Excellent agreement was found when automated measurements were compared with manual assessments. Our automated methods for assessing bone changes in murine periarticular bone are rapid, quantitative, and highly accurate, and promise to be a useful tool in future preclinical studies of OA progression and treatment. The current approaches were developed specifically for cross-sectional micro-CT studies but could be applied to longitudinal studies.

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis

PubMed Central

Vincent, Tonia L.; Marenzana, Massimo

2017-01-01

Objective The degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods. Methods OA was induced by destabilisation of the medial meniscus (DMM) in 10-week old male mice and disease assessed cross-sectionally from 1- to 20-weeks post-surgery. A novel approach was developed to automatically segment subchondral bone compartments into plate and trabecular bone in micro-CT scans of tibial epiphyses. Osteophyte volume, as assessed by shape differences using 3D image registration, and by measuring total epiphyseal volume was performed. Results Significant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 μm and the medial osteophyte grew by 0.124±0.028 μm3. Excellent agreement was found when automated measurements were compared with manual assessments. Conclusion Our automated methods for assessing bone changes in murine periarticular bone are rapid, quantitative, and highly accurate, and promise to be a useful tool in future preclinical studies of OA progression and treatment. The current approaches were developed specifically for cross-sectional micro-CT studies but could be applied to longitudinal studies. PMID:28334010

Development of PEGylated carboxylic acid-modified polyamidoamine dendrimers as bone-targeting carriers for the treatment of bone diseases.

PubMed

Yamashita, Shugo; Katsumi, Hidemasa; Hibino, Nozomi; Isobe, Yugo; Yagi, Yumiko; Kusamori, Kosuke; Sakane, Toshiyasu; Yamamoto, Akira

2017-09-28

In this study, we aimed to develop a polyethylene glycol (PEG)-conjugated third generation polyamidoamine (PAMAM) dendrimer with multiple carboxylic acids as a bone-targeting carrier for the treatment of bone diseases. We conjugated PAMAM backbones to various carboxylic acids [aspartic acid (Asp), glutamic acid (Glu), succinic acid (Suc), or aconitic acid (Aco)] to obtain four different types of carboxylic acid-modified PAMAMs. PEG was covalently bound to carboxylic acid-modified PAMAMs to obtain PEGylated carboxylic acid-modified PAMAMs. In a tissue distribution study, the amount of 111 In-labeled unmodified PAMAM taken up by the bone after intravenous injection in mice was 11.3%. In contrast, the dose of 111 In-labeled PEG(5)-Asp-PAMAM, PEG(5)-Glu-PAMAM, PEG(5)-Suc-PAMAM, or PEG(5)-Aco-PAMAM that accumulated in the bone after injection was approximately 46.0, 15.6, 22.6, and 24.5%, respectively. The bone clearance rates of 111 In-labeled PEGylated carboxylic acid-modified PAMAMs were proportional to their affinities to hydroxyapatite and Ca 2+ . An intra-bone distribution study showed that fluorescein isothiocyanate-labeled PEG(5)-Asp-PAMAM predominantly accumulated on eroded and quiescent surfaces, a pattern associated with the pathogenesis of bone diseases, such as rheumatoid arthritis and osteoporosis. Our findings indicate that PEG(5)-Asp-PAMAM is a promising drug carrier for efficient drug targeting to the bones. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a strain rate dependent material model of human cortical bone for computer-aided reconstruction of injury mechanisms.

PubMed

Asgharpour, Zahra; Zioupos, Peter; Graw, Matthias; Peldschus, Steffen

2014-03-01

Computer-aided methods such as finite-element simulation offer a great potential in the forensic reconstruction of injury mechanisms. Numerous studies have been performed on understanding and analysing the mechanical properties of bone and the mechanism of its fracture. Determination of the mechanical properties of bones is made on the same basis used for other structural materials. The mechanical behaviour of bones is affected by the mechanical properties of the bone material, the geometry, the loading direction and mode and of course the loading rate. Strain rate dependency of mechanical properties of cortical bone has been well demonstrated in literature studies, but as many of these were performed on animal bones and at non-physiological strain rates it is questionable how these will apply in the human situations. High strain-rates dominate in a lot of forensic applications in automotive crashes and assault scenarios. There is an overwhelming need to a model which can describe the complex behaviour of bone at lower strain rates as well as higher ones. Some attempts have been made to model the viscoelastic and viscoplastic properties of the bone at high strain rates using constitutive mathematical models with little demonstrated success. The main objective of the present study is to model the rate dependent behaviour of the bones based on experimental data. An isotropic material model of human cortical bone with strain rate dependency effects is implemented using the LS-DYNA material library. We employed a human finite element model called THUMS (Total Human Model for Safety), developed by Toyota R&D Labs and the Wayne State University, USA. The finite element model of the human femur is extracted from the THUMS model. Different methods have been employed to develop a strain rate dependent material model for the femur bone. Results of one the recent experimental studies on human femur have been employed to obtain the numerical model for cortical femur. A forensic application of the model is explained in which impacts to the arm have been reconstructed using the finite element model of THUMS. The advantage of the numerical method is that a wide range of impact conditions can be easily reconstructed. Impact velocity has been changed as a parameter to find the tolerance levels of injuries to the lower arm. The method can be further developed to study the assaults and the injury mechanism which can lead to severe traumatic injuries in forensic cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mechanical control of tissue-engineered bone.

PubMed

Hung, Ben P; Hutton, Daphne L; Grayson, Warren L

2013-01-31

Bone is a load-bearing tissue and physical forces play key roles in the development and maintenance of its structure. Mechanical cues can stimulate the expression of an osteogenic phenotype, enhance matrix and mineral deposition, and influence tissue organization to improve the functional outcome of engineered bone grafts. In recent years, a number of studies have investigated the effects of biophysical forces on the bone formation properties of osteoprogenitor cells. The application of physiologically relevant stimuli to tissue-engineered bone may be determined through observation and understanding of forces to which osteoblasts, osteoclasts, and osteocytes are exposed in native bone. Subsequently, these cues may be parameterized and their effects studied in well-defined in vitro systems. The osteo-inductive effects of three specific mechanical cues - shear stress, substrate rigidity, and nanotopography - on cells cultured in monolayer or in three-dimensional biomaterial scaffolds in vitro are reviewed. Additionally, we address the time-dependent effects of mechanical cues on vascular infiltration and de novo bone formation in acellular scaffolds implanted into load-bearing sites in vivo. Recent studies employing cutting-edge advances in biomaterial fabrication and bioreactor design have provided key insights into the role of mechanical cues on cellular fate and tissue properties of engineered bone grafts. By providing mechanistic understanding, future studies may go beyond empirical approaches to rational design of engineering systems to control tissue development.

Roles of Osteonectin in Breast Cancer Metastasis to Bone

DTIC Science & Technology

2005-05-01

directed cell motility. Some 18 of these other factors within the mineralized matrix of bone could be bone sialoprotein and thrombospondin. Bone... sialoprotein has been shown to increase MDA-MB-231 cell migration in an RGD-dependent manner [14]. Another study has demonstrated the chemoattraction of MDA... sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone. J Biol Chem, 1987. 262(20): p. 9702-8. 7. Dayhoff, M.O

Obesity-related changes in bone structural and material properties in hyperphagic OLETF rats and protection by voluntary wheel running

USDA-ARS?s Scientific Manuscript database

We conducted a study to examine how the development of obesity and the associated insulin resistance affect bone structural and material properties, and bone formation and resorption markers in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model. This was a 36-week study of sedentary, hyperphag...

Non-invasive assessment of bone quantity and quality in human trabeculae using scanning ultrasound imaging

NASA Astrophysics Data System (ADS)

Xia, Yi

Fractures and associated bone fragility induced by osteoporosis and osteopenia are widespread health threat to current society. Early detection of fracture risk associated with bone quantity and quality is important for both the prevention and treatment of osteoporosis and consequent complications. Quantitative ultrasound (QUS) is an engineering technology for monitoring bone quantity and quality of humans on earth and astronauts subjected to long duration microgravity. Factors currently limiting the acceptance of QUS technology involve precision, accuracy, single index and standardization. The objective of this study was to improve the accuracy and precision of an image-based QUS technique for non-invasive evaluation of trabecular bone quantity and quality by developing new techniques and understanding ultrasound/tissue interaction. Several new techniques have been developed in this dissertation study, including the automatic identification of irregular region of interest (iROI) in bone, surface topology mapping (STM) and mean scattering spacing (MSS) estimation for evaluating trabecular bone structure. In vitro results have shown that (1) the inter- and intra-observer errors in QUS measurement were reduced two to five fold by iROI compared to previous results; (2) the accuracy of QUS parameter, e.g., ultrasound velocity (UV) through bone, was improved 16% by STM; and (3) the averaged trabecular spacing can be estimated by MSS technique (r2=0.72, p<0.01). The measurement errors of BUA and UV introduced by the soft tissue and cortical shells in vivo can be quantified by developed foot model and simplified cortical-trabecular-cortical sandwich model, which were verified by the experimental results. The mechanisms of the errors induced by the cortical and soft tissues were revealed by the model. With developed new techniques and understanding of sound-tissue interaction, in vivo clinical trail and bed rest study were preformed to evaluate the performance of QUS in clinical applications. It has been demonstrated that the QUS has similar performance for in vivo bone density measurement compared to current gold-standard method, i.e., DXA, while additional information are obtained by the QUS for predicting fracture risk by monitoring of bone's quality. The developed QUS imaging technique can be used to assess bone's quantity and quality with improved accuracy and precision.

The peak bone mass concept: is it still relevant?

PubMed

Schönau, Eckhard

2004-08-01

The peak bone mass concept implies that optimal skeletal development during childhood and adolescence will prevent fractures in late adulthood. This concept is based on the observation that areal bone density increases with growth during childhood, is highest around 20 years of age and declines thereafter. However, it is now clear that strong bones in the youngster do not necessarily lead to a fracture-free old age. In the recent bone densitometric literature, the terms bone mass and bone density are typically used synonymously. In physics, density has been defined as the mass of a body divided by its volume. In clinical practice and science, "bone density" usually has a different meaning-the degree to which a radiation beam is attenuated by a bone, as judged from a two-dimensional projection image (areal bone density). The attenuation of a radiation beam does not only depend on physical density, but also on bone size. A small bone therefore has a lower areal bone density than a larger bone, even if the physical density is the same. Consequently, a low areal bone density value can simply reflect the small size of an otherwise normal bone. At present, bone mass analysis is very useful for epidemiological studies on factors that may have an impact on bone development. There is an ongoing discussion about whether the World Health Organization (WHO) definition of osteoporosis is over-simplistic and requires upgrading to include indices representing the distribution of bone and mineral (bone strength indices). The following suggestions and recommendations outline a new concept: bone mass should not be related to age. There is now more and more evidence that bone mass should be related to bone size or muscle function. Thus analyzed, there is no such entity as a "peak bone mass". Many studies are currently under way to evaluate whether these novel approaches increase sensitivity and specificity of fracture prediction in an individual. Furthermore, the focus of many bone researchers is shifting away from bone mass to bone geometry or bone strength. Bone mass is one surrogate marker of bone strength. Widely available techniques for measurement of bone mass, such as dual-energy X-ray absorptiometry, radiogrammetry, and computed tomography, can also be used to measure variables of bone geometry such as cortical thickness, cortical area, and moment of inertia.

Multi-frequency Axial Transmission Bone Ultrasonometer

PubMed Central

Tatarinov, Alexey; Egorov, Vladimir; Sarvazyan, Noune; Sarvazyan, Armen

2014-01-01

The last decade has seen a surge in the development of axial transmission QUS (Quantitative UltraSound) technologies for the assessment of long bones using various modes of acoustic waves. The condition of cortical bones and the development of osteoporosis are determined by numerous mechanical, micro-structural, and geometrical or macro-structural bone properties like hardness, porosity and cortical thickness. Such complex manifestations of osteoporosis require the evaluation of multiple parameters with different sensitivities to the various properties of bone that are affected by the disease. This objective may be achieved by using a multi-frequency ultrasonic examination The ratio of the acoustic wavelength to the cortical thickness can be changed by varying the frequency of the ultrasonic pulse propagating through the long bone that results in the change in composition of the induced wave comprised of a set of numerous modes of guided, longitudinal, and surface acoustic waves. The multi-frequency axial transmission QUS method developed at Artann Laboratories (Trenton, NJ) is implemented in the Bone Ultrasonic Scanner (BUSS). In the current version of the BUSS, a train of ultrasonic pulses with 60, 100, 400, 800, and 1200 kHz frequencies is used. The developed technology was tested on a variety of bone phantoms simulating normal, osteopenic, and osteoporotic bones. The results of this study confirm the feasibility of the multi-frequency approach for the assessment of the processes leading to osteoporosis. PMID:24206675

Clinical Features and Risk Factors of Skeletal-Related Events in Genitourinary Cancer Patients with Bone Metastasis: A Retrospective Analysis of Prostate Cancer, Renal Cell Carcinoma, and Urothelial Carcinoma.

PubMed

Owari, Takuya; Miyake, Makito; Nakai, Yasushi; Morizawa, Yosuke; Itami, Yoshitaka; Hori, Shunta; Anai, Satoshi; Tanaka, Nobumichi; Fujimoto, Kiyohide

2018-06-06

The objective of the present study was to report the incidence of skeletal-related events (SREs) and identify risk factors for SREs in patients with genitourinary cancer with newly diagnosed bone metastasis. This retrospective study included 180 patients with bone metastasis from prostate cancer (PCa; n = 111), renal cell carcinoma (RCC; n = 43), and urothelial carcinoma (UC; n = 26). Clinical factors at the time of diagnosis of bone metastasis were evaluated with Cox proportional hazards regression analysis to identify independent risk factors for SREs. During follow-up, 29 (26%) patients with PCa, 30 (70%) with RCC, and 15 (58%) with UC developed SREs. Treatment with bone-modifying agents (BMAs) before the development of SREs and within 6 months from the diagnosis of bone metastasis significantly delayed the time to first SRE as compared to nonuse of BMAs. Multivariate analysis identified type of primary cancer (PCa vs. RCC, PCa vs. UC), performance status, and bone pain as significant independent predictive risk factors for SREs. Treatment with BMAs significantly delayed the development of first SREs. The identified predictors of SREs might be useful to select patients who would benefit most from early treatment with BMAs. © 2018 S. Karger AG, Basel.

Quantitative assessment and characterization of glenoid bone loss in a spectrum of patients with glenohumeral osteoarthritis.

PubMed

Lombardo, D J; Khan, J; Prey, B; Zhang, L; Petersen-Fitts, G R; Sabesan, V J

2016-12-01

Eccentric posterior bone loss and associated glenoid retroversion represent challenges to glenoid placement during total shoulder arthroplasty. This bone loss can lead to poor stability and perforation of the glenoid during arthroplasty. The purpose of this study was to evaluate the morphology of glenoid bone loss for a spectrum of osteoarthritis patients using 3D computed tomography imaging and simulation software. This study included 29 patients with glenohumeral osteoarthritis treated with shoulder arthroplasty. Three-dimensional reconstruction of preoperative CT images was performed. Glenoid bone loss was measured at ten, vertically equidistant axial planes along the glenoid surface at four distinct anterior-posterior points on each plane. The images were fitted with modeled pegged glenoid implants to predict glenoid perforation. The 3D maps demonstrated greatest average bone loss posteriorly in the AP plane at the central axis of the glenoid in the SI plane. The average amount of bone loss was 3.85 mm. Walch A2 and B1 shoulders showed more central bone loss, while Walch B2 shoulders displayed more posterior and inferior bone loss. Patients with predicted peg perforation displayed significantly greater bone loss than those without predicted peg perforation (p = 0.037). Peg perforation was most common in Walch B2 shoulders occurring in the posterior direction involving the central and posterior-inferior peg. These data demonstrate an anatomic pattern of glenoid bone loss for different classes of glenohumeral arthritis. These findings can be used to develop various models of glenoid bone loss to guide surgeons, predict failures, and develop better glenoid implants. This study has been approved by the Cleveland Clinic IRB: Number 6235.

An Efficient and Reproducible Protocol for Distraction Osteogenesis in a Rat Model Leading to a Functional Regenerated Femur.

PubMed

Pithioux, Martine; Roseren, Flavy; Jalain, Christian; Launay, Franck; Charpiot, Philippe; Chabrand, Patrick; Roffino, Sandrine; Lamy, Edouard

2017-10-23

This protocol describes the use of a newly developed external fixator for distraction osteogenesis in a rat femoral model. Distraction osteogenesis (DO) is a surgical technique leading to bone regeneration after an osteotomy. The osteotomized extremities are moved away from each other by gradual distraction to reach the desired elongation. This procedure is widely used in humans for lower and upper limb lengthening, treatment after a bone nonunion, or the regeneration of a bone defect following surgery for bone tumor excision, as well as in maxillofacial reconstruction. Only a few studies clearly demonstrate the efficiency of their protocol in obtaining a functional regenerated bone, i.e., bone that will support physiological weight-bearing without fracture after removal of the external fixator. Moreover, protocols for DO vary and reproducibility is limited by lack of information, making comparison between studies difficult. The aim of this study was to develop a reproducible protocol comprising an appropriate external fixator design for rat limb lengthening, with a detailed surgical technique that permits physiological weight-bearing by the animal after removal of the external fixator.

Torsional and axial compressive properties of tibiotarsal bones of red-tailed hawks (Buteo jamaicensis).

PubMed

Kerrigan, Shannon M; Kapatkin, Amy S; Garcia, Tanya C; Robinson, Duane A; Guzman, David Sanchez-Migallon; Stover, Susan M

2018-04-01

OBJECTIVE To describe the torsional and axial compressive properties of tibiotarsal bones of red-tailed hawks (Buteo jamaicensis). SAMPLE 16 cadaveric tibiotarsal bones from 8 red-tailed hawks. PROCEDURES 1 tibiotarsal bone from each bird was randomly assigned to be tested in torsion, and the contralateral bone was tested in axial compression. Intact bones were monotonically loaded in either torsion (n = 8) or axial compression (8) to failure. Mechanical variables were derived from load-deformation curves. Fracture configurations were described. Effects of sex, limb side, and bone dimensions on mechanical properties were assessed with a mixed-model ANOVA. Correlations between equivalent torsional and compressive properties were determined. RESULTS Limb side and bone dimensions were not associated with any mechanical property. During compression tests, mean ultimate cumulative energy and postyield energy for female bones were significantly greater than those for male bones. All 8 bones developed a spiral diaphyseal fracture and a metaphyseal fissure or fracture during torsional tests. During compression tests, all bones developed a crushed metaphysis and a fissure or comminuted fracture of the diaphysis. Positive correlations were apparent between most yield and ultimate torsional and compressive properties. CONCLUSIONS AND CLINICAL RELEVANCE The torsional and axial compressive properties of tibiotarsal bones described in this study can be used as a reference for investigations into fixation methods for tibiotarsal fractures in red-tailed hawks. Although the comminuted and spiral diaphyseal fractures induced in this study were consistent with those observed in clinical practice, the metaphyseal disruption observed was not and warrants further research.

Development and evaluation of tetrapod-shaped granular artificial bones.

PubMed

Choi, Sungjin; Liu, I-li; Yamamoto, Kenichi; Igawa, Kazuyo; Mochizuki, Manabu; Sakai, Takamasa; Echigo, Ryosuke; Honnami, Muneki; Suzuki, Shigeki; Chung, Ung-il; Sasaki, Nobuo

2012-07-01

We have developed a novel form of granular artificial bone "Tetrabones" with a homogeneous tetrapod shape and uniform size. Tetrabones are four armed structures that accumulate to form the intergranular pores that allow invasion of cells and blood vessels. In this study we evaluated the physicochemical characteristics of Tetrabones in vitro, and compared their biological and biomechanical properties in vivo to those of conventional β-tricalcium phosphate (β-TCP) granule artificial bone. Both the rupture strength and elastic modulus of Tetrabone particles were higher than those of β-TCP granules in vitro. The connectivity of intergranular pores 100, 300, and 400 μm in size were higher in Tetrabones than in the β-TCP granules. Tetrabones showed similar osteoconductivity and biomechanical stiffness to β-TCP at 2 months after implantation in an in vivo study of canine bone defects. These results suggest that Tetrabones may be a good bone graft material in bone reconstruction. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fracture resistance behaviour of gamma-irradiation sterilized cortical bone protected with a ribose pre-treatment

NASA Astrophysics Data System (ADS)

Woodside, Carman Mitchell

Structural bone allograft reconstructions are often implemented to repair large skeletal defects. To ensure the biological safety of the patient, allograft material is routinely sterilized with gamma-irradiation prior to implantation. The sterilization process damages the tissue, specifically the collagen protein network, leading to severe losses in the mechanical properties of the bone. Our lab has begun developing a ribose pre-treatment that can protect bone from these harmful effects. The goals of the present study were to develop a method to measure the fracture toughness of bone, an important clinical failure mode, and implement it to determine the effectiveness of the ribose pre-treatment on fracture toughness. We have shown that the ribose pre-treatment is successful at protecting some of the original fracture toughness of sterilized bone, and that the connectivity of the collagen network is an important contributor to the fracture resistance of bone.

Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification.

PubMed

Osinga, Rik; Di Maggio, Nunzia; Todorov, Atanas; Allafi, Nima; Barbero, Andrea; Laurent, Frédéric; Schaefer, Dirk Johannes; Martin, Ivan; Scherberich, Arnaud

2016-08-01

: Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. Unlike bone marrow-derived stromal cells (also known as bone marrow-derived mesenchymal stromal/stem cells), adipose-derived stromal cells (ASC) have so far failed to form a bone organ by ECO. The goal of the present study was to assess whether priming human ASC to a defined stage of chondrogenesis in vitro allows their autonomous ECO upon ectopic implantation. ASC were cultured either as micromass pellets or into collagen sponges in chondrogenic medium containing transforming growth factor-β3 and bone morphogenetic protein-6 for 4 weeks (early hypertrophic templates) or for two additional weeks in medium supplemented with β-glycerophosphate, l-thyroxin, and interleukin1-β to induce hypertrophic maturation (late hypertrophic templates). Constructs were implanted in vivo and analyzed after 8 weeks. In vitro, ASC deposited cartilaginous matrix positive for glycosaminoglycans, type II collagen, and Indian hedgehog. Hypertrophic maturation induced upregulation of type X collagen, bone sialoprotein, and matrix metalloproteinase13 (MMP13). In vivo, both early and late hypertrophic templates underwent cartilage remodeling, as assessed by MMP13- and tartrate-resistant acid phosphatase-positive staining, and developed bone ossicles, including bone marrow elements, although to variable degrees of efficiency. In situ hybridization for human-specific sequences and staining with a human specific anti-CD146 antibody demonstrated the direct contribution of ASC to bone and stromal tissue formation. In conclusion, despite their debated skeletal progenitor nature, human ASC can generate bone organs through ECO when suitably primed in vitro. Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. This study demonstrated that expanded, human adult adipose-derived stromal cells can generate ectopic bone through ECO, as previously reported for bone marrow stromal cells. This system can be used as a model in a variety of settings for mimicking ECO during development, physiology, or pathology (e.g., to investigate the role of BMPs, their receptors, and signaling pathways). The findings have also translational relevance in the field of bone regeneration, which, despite several advances in the domains of materials and surgical techniques, still faces various limitations before being introduced in the routine clinical practice. ©AlphaMed Press.

Guiding bone formation in a critical-sized defect and assessments.

PubMed

Jannetty, Joseph; Kolb, Eric; Boxberger, John; Deslauriers, Richard; Ganey, Timothy

2010-11-01

Development of alternatives to autologous bone has been served by many hypotheses and developments. Favorable properties of synthetic materials used currently in bone grafting support tissue differentiation without shielding capacity for integrated modeling. Ideally, new materials provide tissue compatibility and minimize patient morbidity and are attractive because of potential for in situ delivery, isothermal polymerization, porous structure, and nontoxic chemistry. For application in cranial bone, ability for materials to be laid adjacent to brain and offer postsurgical protection without neural risk is a critical asset. Kryptonite Bone Cement (KBC) meets the property criteria for cranial bone repair with regard to adhesive, conductive, and biologic transparency and US Food and Drug Administration approval for cranial bone void repair. To better delineate the morphology effective in cranial bone repair, a comparison was made between KBC and BoneSource, another material approved for the same indication. After Institutional Animal Care and Use Committee approval, the study assessed 24 rabbits, each with 2 separate cranial implants, to evaluate integration and absorption of the biomaterial at defined time points of 12, 18, 24, and 36 weeks. The 36-week assessment demonstrated near-complete resorption/integration of the BoneSource graft material. Bone was present within the biomaterial as well as independent of contact. The KBC was similarly integrated throughout the mass of the material, and new bone was in contact with the grafting material and also seen as separate islands of new bone. The bone demonstrated lamellar bone architecture with clear trabecular morphology. At higher magnification, the bone architecture can be clearly delineated, and comparison between the graft fillers is not obvious relative to the bone that has formed. Despite microscopic similarities, the most striking difference was maintenance of scaffold anatomy during bone regeneration. Kryptonite Bone Cement meets the criteria described in the introduction; properties of biologic transparency, osteoconductivity, and ergonomic utility offer other potential uses in bone repair. Key tenets of bone tissue regeneration observed in this analysis included adequate cell differentiation and tissue support. Bone that formed demonstrated lamellar rather than woven bone to suggest response to loading strain rather than merely biochemical precipitation. Over the 36-week study, the graft showed progressive bioabsorbable potential with calibrated replacement.

Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling

PubMed Central

Zheng, Xi; Lee, Sun-Kyeong

2016-01-01

Abstract Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans. PMID:26670451

Development of Raman spectral markers to assess metastatic bone in breast cancer

PubMed Central

Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

2014-01-01

Abstract. Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk. PMID:24933683

Development of Raman spectral markers to assess metastatic bone in breast cancer

NASA Astrophysics Data System (ADS)

Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

2014-11-01

Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk.

Aggressive intraosseous lipoma of the intermediate phalanges of the thumb.

PubMed

Hashimoto, Kazuhiko; Nishimura, Shunji; Kakinoki, Ryosuke; Akagi, Masao

2018-07-01

Intraosseous lipomas occurring in the bones of the upper limbs are very rare. The tumor often occurs in long bones, especially the calcaneus. Usually patients with intraosseous lipomas present with mild clinical features. Thus far, bone destruction caused by the tumor has not been reported. The present study reported a case of an aggressive intraosseous lipoma that developed in the intermediate phalanges of the thumb. This is an extremely rare case with extraosseous development, which occurred at a rare site. A 47-year old woman presented to us with right thumb pain and swelling. Computed tomography and magnetic resonance imaging revealed a mass extending to the outer edge of the phalangeal bone. The patient was treated with surgery the remove the tumor. Artificial bone was used to refill the area due to the lack of cancellous bone. During the clinical management of lipomas, it is important to consider that intraosseous lipomas may spread out of the bone; moreover, the tumor should be removed immediately to help reduce the possibility of bone destruction.

[Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

PubMed

Wei, Xuelei; Dong, Fuhui

2011-12-01

To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

PubMed Central

Pawlak, Krystyna; Oksztulska-Kolanek, Ewa; Domaniewski, Tomasz; Znorko, Beata; Karbowska, Malgorzata; Citkowska, Aleksandra; Rogalska, Joanna; Roszczenko, Alicja; Brzoska, Malgorzata M.; Pawlak, Dariusz

2017-01-01

Background Disturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD. Methods Thirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites. Results Subtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry. Discussion In addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD. PMID:28439468

Quantitative computed tomography and cranial burr holes: a model to evaluate the quality of cranial reconstruction in humans.

PubMed

Worm, Paulo Valdeci; Ferreira, Nelson Pires; Ferreira, Marcelo Paglioli; Kraemer, Jorge Luiz; Lenhardt, Rene; Alves, Ronnie Peterson Marcondes; Wunderlich, Ricardo Castilho; Collares, Marcus Vinicius Martins

2012-05-01

Current methods to evaluate the biologic development of bone grafts in human beings do not quantify results accurately. Cranial burr holes are standardized critical bone defects, and the differences between bone powder and bone grafts have been determined in numerous experimental studies. This study evaluated quantitative computed tomography (QCT) as a method to objectively measure cranial bone density after cranial reconstruction with autografts. In each of 8 patients, 2 of 4 surgical burr holes were reconstructed with autogenous wet bone powder collected during skull trephination, and the other 2 holes, with a circular cortical bone fragment removed from the inner table of the cranial bone flap. After 12 months, the reconstructed areas and a sample of normal bone were studied using three-dimensional QCT; bone density was measured in Hounsfield units (HU). Mean (SD) bone density was 1535.89 (141) HU for normal bone (P < 0.0001), 964 (176) HU for bone fragments, and 453 (241) HU for bone powder (P < 0.001). As expected, the density of the bone fragment graft was consistently greater than that of bone powder. Results confirm the accuracy and reproducibility of QCT, already demonstrated for bone in other locations, and suggest that it is an adequate tool to evaluate cranial reconstructions. The combination of QCT and cranial burr holes is an excellent model to accurately measure the quality of new bone in cranial reconstructions and also seems to be an appropriate choice of experimental model to clinically test any cranial bone or bone substitute reconstruction.

Bone Growth, Mechanical Stimulus and IGF-1

DTIC Science & Technology

2006-10-01

suffer a bone fracture by the time they reach skeletal maturity. While strenuous physical activity and occupational hazards are key factors in the...females with low bone density. Ultimately, this information could be of great benefit to enhance musculoskeletal development and decrease the risk ...pathogenesis of these fractures , several studies indicate that teenagers who sustain fractures also have decreased bone mass. Therefore, the use of low

A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model.

PubMed

Ohno, Hiroaki; Kubo, Kazuo; Murooka, Hideko; Kobayashi, Yoshiko; Nishitoba, Tsuyoshi; Shibuya, Masabumi; Yoneda, Toshiyuki; Isoe, Toshiyuki

2006-11-01

In bone metastatic lesions, osteoclasts play a key role in the development of osteolysis. Previous studies have shown that macrophage colony-stimulating factor (M-CSF) is important for the differentiation of osteoclasts. In this study, we investigated whether an inhibitor of M-CSF receptor (c-Fms) suppresses osteoclast-dependent osteolysis in bone metastatic lesions. We developed small molecule inhibitors against ligand-dependent phosphorylation of c-Fms and examined the effects of these compounds on osteolytic bone destruction in a bone metastasis model. We discovered a novel quinoline-urea derivative, Ki20227 (N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N'-[1-(1,3-thiazole-2-yl)ethyl]urea), which is a c-Fms tyrosine kinase inhibitor. The IC(50)s of Ki20227 to inhibit c-Fms, vascular endothelial growth factor receptor-2 (KDR), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor beta were found to be 2, 12, 451, and 217 nmol/L, respectively. Ki20227 did not inhibit other kinases tested, such as fms-like tyrosine kinase-3, epidermal growth factor receptor, or c-Src (c-src proto-oncogene product). Ki20227 was also found to inhibit the M-CSF-dependent growth of M-NFS-60 cells but not the M-CSF-independent growth of A375 human melanoma cells in vitro. Furthermore, in an osteoclast-like cell formation assay using mouse bone marrow cells, Ki20227 inhibited the development of tartrate-resistant acid phosphatase-positive osteoclast-like cells in a dose-dependent manner. In in vivo studies, oral administration of Ki20227 suppressed osteoclast-like cell accumulation and bone resorption induced by metastatic tumor cells in nude rats following intracardiac injection of A375 cells. Moreover, Ki20227 decreased the number of tartrate-resistant acid phosphatase-positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats. These findings suggest that Ki20227 inhibits osteolytic bone destruction through the suppression of M-CSF-induced osteoclast accumulation in vivo. Therefore, Ki20227 may be a useful therapeutic agent for osteolytic disease associated with bone metastasis and other bone diseases.

ADRA2A is involved in neuro-endocrine regulation of bone resorption.

PubMed

Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

2015-07-01

Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Botulinum Toxin Induces Muscle Paralysis and Inhibits Bone Regeneration in Zebrafish

PubMed Central

Recidoro, Anthony M.; Roof, Amanda C.; Schmitt, Michael; Worton, Leah E.; Petrie, Timothy; Strand, Nicholas; Ausk, Brandon J.; Srinivasan, Sundar; Moon, Randall T.; Gardiner, Edith M.; Kaminsky, Werner; Bain, Steven D.; Allan, Christopher H.; Gross, Ted S.; Kwon, Ronald Y.

2016-01-01

Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions of bone formation (e.g., development, growth, and healing), yet the mechanisms of neuromuscular-bone crosstalk underlying these deficits have yet to be identified. Motivated by the emerging utility of zebrafish (Danio rerio) as a rapid, genetically tractable, and optically transparent model for human pathologies (as well as the potential to interrogate neuromuscular-mediated bone disorders in a simple model that bridges in vitro and more complex in vivo model systems), in this study we developed a model of BTx-induced muscle paralysis in adult zebrafish, and examined its effects on intramembranous ossification during tail fin regeneration. BTx administration induced rapid muscle paralysis in adult zebrafish in a manner that was dose-dependent, transient, and focal, mirroring the paralytic phenotype observed in animal and human studies. During fin regeneration, BTx impaired continued bone ray outgrowth, morphology, and patterning, indicating defects in early osteogenesis. Further, BTx significantly decreased mineralizing activity and crystalline mineral accumulation, suggesting delayed late-stage osteoblast differentiation and/or altered secondary bone apposition. Bone ray transection proximal to the amputation site focally inhibited bone outgrowth in the affected ray, implicating intra- and/or inter-ray nerves in this process. Taken together, these studies demonstrate the potential to interrogate pathological features of BTx-induced osteoanabolic dysfunction in the regenerating zebrafish fin, define the technological toolbox for detecting bone growth and mineralization deficits in this process, and suggest that pathways mediating neuromuscular regulation of osteogenesis may be conserved beyond established mammalian models of bone anabolic disorders. PMID:24806738

A novel three-dimensional bone chip organ culture.

PubMed

Kuttenberger, Johannes; Polska, Elzbieta; Schaefer, Birgit M

2013-07-01

The objective of this study was to develop a 3D bone chip organ culture model. We aimed to collect in vitro evidence of the ability of vital bone chips to promote new bone formation. We developed a 3D in vitro hypoxic bone chip organ culture model. Histology of the bone chips was performed before and after culture and immunohistochemistry after 3-week culture. The 3D culture supernatants were tested for the presence of pro-angiogenic growth factors, TGFβ1, GADPH, bone alkaline phosphatase, osteocalcin, osteonectin, osteopontin, bone sialoprotein and collagen type I. Histology after culture revealed bone chips in a matrix of fibrin remnants and a fibrous-appearing matter. Collagen type I- and IV-positive structures were also identified. Cells could be seen on the surface of the bone chips, with spindle-shaped cells bridging the bone chip particles. Pro-angiogenic growth factors and TGFβ1were detected in the 3D cell culture supernatants. The transcripts for osteocalcin, bone sialoprotein and collagen type I were revealed only via PCR. Our results indicate that bone chips in our 3D organ culture remain vital and may stimulate the growth of a bone-forming matrix. The use of autogenous bone chips for oral and maxillofacial bone augmentation procedures is widespread in clinical practice. The rationale for this is that if bone chips remain vital in vivo, they could provide an environment promoting new bone formation through growth factors and cells. This 3D culture method is an essential tool for investigating the behaviour of bone chips.

Advanced Ultrasonic Tomograph of Children's Bones

NASA Astrophysics Data System (ADS)

Lasaygues, Philippe; Lefebvre, Jean-Pierre; Guillermin, Régine; Kaftandjian, Valérie; Berteau, Jean-Philippe; Pithioux, Martine; Petit, Philippe

This study deals with the development of an experimental device for performing ultrasonic computed tomography (UCT) on bone in pediatric degrees. The children's bone tomographs obtained in this study, were based on the use of a multiplexed 2-D ring antenna (1 MHz and 3 MHz) designed for performing electronic and mechanical scanning. Although this approach is known to be a potentially valuable means of imaging objects with similar acoustical impedances, problems arise when quantitative images of more highly contrasted media such as bones are required. Various strategies and various mathematical procedures for modeling the wave propagation based on Born approximations have been developed at our laboratory, which are suitable for use with pediatric cases. Inversions of the experimental data obtained are presented.

Diversity of activity participation determines bone mineral content in the lower limbs of pre-pubertal children with developmental coordination disorder.

PubMed

Fong, S S M; Vackova, D; Choi, A W M; Cheng, Y T Y; Yam, T T T; Guo, X

2018-04-01

This study examined the relationships between activity participation and bone mineralization in children with developmental coordination disorder. Limited participation in physical, recreational, social, and skill-based and self-improvement activities contributed to lower bone mineral content. For improved bone health, these children should participate in a variety of activities, not only physical activities. Limited activity participation in children with developmental coordination disorder (DCD) may have a negative impact on bone mineral accrual. The objectives of this study were to compare bone mineralization and activity participation patterns of pre-pubertal children with DCD and those with typical development, and to determine the association between activity participation patterns and bone mineralization in children with DCD. Fifty-two children with DCD (mean age = 7.51 years) and 61 children with typical development (mean age = 7.22 years) participated in the study. Appendicular and total body (less head) bone mineral content (BMC) and bone mineral density (BMD) were evaluated by a whole-body dual-energy X-ray absorptiometry scan. Activity participation patterns were assessed using the Children's Assessment of Participation and Enjoyment (CAPE) questionnaire. Children with DCD had lower appendicular and total body BMCs and BMDs than children with typical development overall (p < 0.05). They also had lower CAPE total activity and physical activity diversity scores (p < 0.05). After accounting for the effects of age, sex, height, lean mass, and fat mass, the total activity diversity score remained independently associated with leg BMC in children with DCD, explaining 5.1% of the variance (p = 0.030). However, the physical activity diversity score was no longer associated with leg BMC (p = 0.090). Diversity of activity participation and bone mineralization were lower in pre-pubertal children with DCD. Decreased total activity participation diversity was a contributing factor to lower BMC in the legs of children with DCD.

Wnt and the Wnt signaling pathway in bone development and disease

PubMed Central

Wang, Yiping; Li, Yi-Ping; Paulson, Christie; Shao, Jian-Zhong; Zhang, Xiaoling; Wu, Mengrui; Chen, Wei

2014-01-01

Wnt signaling affects both bone modeling, which occurs during development, and bone remodeling, which is a lifelong process involving tissue renewal. Wnt signals are especially known to affect the differentiation of osteoblasts. In this review, we summarize recent advances in understanding the mechanisms of Wnt signaling, which is divided into two major branches: the canonical pathway and the noncanonical pathway. The canonical pathway is also called the Wnt/β-catenin pathway. There are two major noncanonical pathways: the Wnt-planar cell polarity pathway (Wnt-PCP pathway) and the Wnt-calcium pathway (Wnt-Ca2+ pathway). This review also discusses how Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists affect both the bone modeling and bone remodeling processes. We also review the role of Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists in bone as demonstrated in mouse models. Disrupted Wnt signaling is linked to several bone diseases, including osteoporosis, van Buchem disease, and sclerosteosis. Studying the mechanism of Wnt signaling and its interactions with other signaling pathways in bone will provide potential therapeutic targets to treat these bone diseases. PMID:24389191

Determining the Role of Sost and Sostdc1 During Fracture Healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yee, Cristal Sook Ngei

The bone is a dynamic organ, often changing throughout the course of the human lifespan with its continuous remodeling, laying down new bone and resorbing old bone. With age, the bone becomes increasingly porous and mechanically unstable, leading to the development of osteoporosis in some individuals. Elderly patients with osteoporosis are at an increased risk of fracturing their bones which contributes to a higher mortality rate. Recent studies have revealed that type 1 diabetic mellitus (T1DM) patients also have an osteoporotic bone phenotype and impaired fracture healing, independent of age. Currently, there is a lack of available treatments that canmore » improve impaired healing and directly enhance bone formation. Therefore, there is a great need for developing new therapies that can not only aid type 1 diabetic patients with osteoporosis to improve bone phenotype, but that could also aid patients with difficult or impaired fracture healing. In this thesis, I will be discussing the role of Wnt signaling and Sclerostin, a Wnt antagonist that negatively regulates bone formation, in the content of fracture repair.« less

Maxillofacial reconstruction using custom-made artificial bones fabricated by inkjet printing technology.

PubMed

Saijo, Hideto; Igawa, Kazuyo; Kanno, Yuki; Mori, Yoshiyuki; Kondo, Kayoko; Shimizu, Koutaro; Suzuki, Shigeki; Chikazu, Daichi; Iino, Mitsuki; Anzai, Masahiro; Sasaki, Nobuo; Chung, Ung-il; Takato, Tsuyoshi

2009-01-01

Ideally, artificial bones should be dimensionally compatible with deformities, and be biodegradable and osteoconductive; however, there are no artificial bones developed to date that satisfy these requirements. We fabricated novel custom-made artificial bones from alpha-tricalcium phosphate powder using an inkjet printer and implanted them in ten patients with maxillofacial deformities. The artificial bones had dimensional compatibility in all the patients. The operation time was reduced due to minimal need for size adjustment and fixing manipulation. The postsurgical computed tomography analysis detected partial union between the artificial bones and host bone tissues. There were no serious adverse reactions. These findings provide support for further clinical studies of the inkjet-printed custom-made artificial bones.

An animal model to evaluate skin-implant-bone integration and gait with a prosthesis directly attached to the residual limb

PubMed Central

Farrell, Brad J; Prilutsky, Boris I; Kistenberg, Robert S; Dalton, John F; Pitkin, Mark

2014-01-01

Background Despite the number of advantages of bone-anchored prostheses, their use in patients is limited due to the lack of complete skin-implant integration. The objective of the present study was to develop an animal model that would permit both detailed investigations of gait with a bone-anchored limb prosthesis and histological analysis of the skin-implant-bone interface after physiological loading of the implant during standing and walking. Methods Full-body mechanics of walking in two cats was recorded and analyzed before and after implantation of a percutaneous porous titanium pylon into the right tibia and attachment of a prosthesis. The rehabilitation procedures included initial limb casting, progressively increasing loading of implant, and standing and locomotor training. Detailed histological analysis of bone and skin ingrowth into implant was performed at the end of the study. Findings The two animals adopted the bone-anchored prosthesis for standing and locomotion, although loads on the prosthetic limb during walking decreased by 22% and 62%, respectively, 4 months after implantation. The animals shifted body weight to the contralateral side and increased propulsion forces by the contralateral hindlimb. Histological analysis of the limb implants demonstrated bone and skin ingrowth. Interpretation The developed animal model to study prosthetic gait and tissue integration with the implant demonstrated that porous titanium implants may permit bone and skin integration and prosthetic gait with a prosthesis. Future studies with this model will help optimize the implant and prosthesis properties. PMID:24405567

BONES, TEACHER'S GUIDE.

ERIC Educational Resources Information Center

Elementary Science Study, Newton, MA.

THIS GUIDE WAS DEVELOPED FOR USE WITH THE ELEMENTARY SCIENCE STUDY UNIT ON "BONES.""BONES" HAS BEEN TAUGHT IN THE FOURTH GRADE AND REQUIRES FROM 10 TO 25 LESSONS, DEPENDING ON THE NUMBER OF ACTIVITIES USED. THE GUIDE DOES NOT PROVIDE DETAILED INSTRUCTION FOR CONDUCTING CLASSES, BUT RATHER SOME POSSIBLE ACTIVITIES, AND LEAVES…

Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma

PubMed Central

Mohanty, Sindhu T.; Seckinger, Anja; Terry, Rachael L.; Pettitt, Jessica A.; Simic, Marija K.; Le, Lawrence M. T.; Kramer, Ina; Falank, Carolyne; Fairfield, Heather; Ghobrial, Irene M.; Baldock, Paul A.; Little, David G.; Kneissel, Michaela; Vanderkerken, Karin; Bassett, J. H. Duncan; Williams, Graham R.; Oyajobi, Babatunde O.; Hose, Dirk

2017-01-01

Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt antagonist that inhibits bone formation. We hypothesized that inhibiting sclerostin would prevent development of bone disease and increase resistance to fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1-eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was associated with a decrease in fracture resistance in the vertebrae. Treatment with anti-sclerostin antibody increased osteoblast numbers and bone formation rate but did not inhibit bone resorption or reduce tumor burden. Treatment with anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic bone lesions, and increased fracture resistance. Treatment with anti-sclerostin antibody and zoledronic acid combined increased bone mass and fracture resistance when compared with treatment with zoledronic acid alone. This study defines a therapeutic strategy superior to the current standard of care that will reduce fractures for patients with MM. PMID:28515094

Numerical simulation of stress amplification induced by crack interaction in human femur bone

NASA Astrophysics Data System (ADS)

Alia, Noor; Daud, Ruslizam; Ramli, Mohammad Fadzli; Azman, Wan Zuki; Faizal, Ahmad; Aisyah, Siti

2015-05-01

This research is about numerical simulation using a computational method which study on stress amplification induced by crack interaction in human femur bone. Cracks in human femur bone usually occur because of large load or stress applied on it. Usually, the fracture takes longer time to heal itself. At present, the crack interaction is still not well understood due to bone complexity. Thus, brittle fracture behavior of bone may be underestimated and inaccurate. This study aims to investigate the geometrical effect of double co-planar edge cracks on stress intensity factor (K) in femur bone. This research focuses to analyze the amplification effect on the fracture behavior of double co-planar edge cracks, where numerical model is developed using computational method. The concept of fracture mechanics and finite element method (FEM) are used to solve the interacting cracks problems using linear elastic fracture mechanics (LEFM) theory. As a result, this study has shown the identification of the crack interaction limit (CIL) and crack unification limit (CUL) exist in the human femur bone model developed. In future research, several improvements will be made such as varying the load, applying thickness on the model and also use different theory or method in calculating the stress intensity factor (K).

Cell interactions in bone tissue engineering.

PubMed

Pirraco, R P; Marques, A P; Reis, R L

2010-01-01

Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell-to-cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented.

Finite element study of human pelvis model in side impact for Chinese adult occupants.

PubMed

Ma, Zhengwei; Lan, Fengchong; Chen, Jiqing; Liu, Weiguo

2015-01-01

The occupant's pelvis is very vulnerable to side collision in road accidents. Finite element (FE) studies on pelvic injury help to design occupant protection devices to improve vehicle safety. This study was aimed to develop a highly biofidelic pelvis model of Chinese adults and assess its sensitivity to variations in pelvis cortical bone thickness, bone material properties, and loading conditions. In this study, 4 different FE models of the pelvis were developed from the computed tomography (CT) data of a volunteer representing the 50th percentile Chinese male. Two of them were meshed using entirely hexahedral elements with variable and constant cortical thickness distribution (the V-Hex and C-Hex models), and the others were modeled with hexahedral elements for cancellous bone and variable or constant thickness shell elements for cortical bone (the V-HS and C-HS models). In model developments, the semi-automatic multiblock meshing approach was employed to maintain the pelvis geometric curvature and generate a high-quality hexahedral mesh. Then, several simulations with postmortem human subjects (PMHS) tests were performed to obtain the most accurate model in predicting pelvic injury. Based on the most accurate model, sensitivity studies were conducted to analyze the effects of the cortex thickness, Young's modulus of the cortical and cancellous bone, impactor velocity, and impactor with or without padding on the biomechanical responses and injuries of pelvis. The results indicate that the models with variable cortical bone thickness can give more accurate predictions than those with constant cortical thickness. Both the V-Hex and V-HS models are favorable for simulating pelvic response and injury, but the simulation results of the V-Hex model agree with the tests better. The sensitivity study shows that pelvic response is more sensitive to alterations in the Young's modulus of cortical bone than cancellous bone. Compared to failure displacement, peak force is more sensitive to the cortical bone thickness. However, displacement is more sensitive to the Young's modulus of cancellous bone than peak force. The padding attached on the impactor plays a significant role in absorbing the impact energy and alleviating pelvic injury. The all-hex meshing method with variable cortical bone thickness has the highest accuracy but is time-consuming. The cortical bone plays a determining role in resisting pelvic fracture. Peak impact force appears to be a reasonable injury predictor for pelvic injury assessment. Some appropriate energy absorbers installed in the car door can significantly reduce pelvic injury and will be beneficial for occupant protection.

A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development

PubMed Central

Ducy, Patricia; Starbuck, Michael; Priemel, Matthias; Shen, Jianhe; Pinero, Gerald; Geoffroy, Valerie; Amling, Michael; Karsenty, Gerard

1999-01-01

The molecular mechanisms controlling bone extracellular matrix (ECM) deposition by differentiated osteoblasts in postnatal life, called hereafter bone formation, are unknown. This contrasts with the growing knowledge about the genetic control of osteoblast differentiation during embryonic development. Cbfa1, a transcriptional activator of osteoblast differentiation during embryonic development, is also expressed in differentiated osteoblasts postnatally. The perinatal lethality occurring in Cbfa1-deficient mice has prevented so far the study of its function after birth. To determine if Cbfa1 plays a role during bone formation we generated transgenic mice overexpressing Cbfa1 DNA-binding domain (ΔCbfa1) in differentiated osteoblasts only postnatally. ΔCbfa1 has a higher affinity for DNA than Cbfa1 itself, has no transcriptional activity on its own, and can act in a dominant-negative manner in DNA cotransfection assays. ΔCbfa1-expressing mice have a normal skeleton at birth but develop an osteopenic phenotype thereafter. Dynamic histomorphometric studies show that this phenotype is caused by a major decrease in the bone formation rate in the face of a normal number of osteoblasts thus indicating that once osteoblasts are differentiated Cbfa1 regulates their function. Molecular analyses reveal that the expression of the genes expressed in osteoblasts and encoding bone ECM proteins is nearly abolished in transgenic mice, and ex vivo assays demonstrated that ΔCbfa1-expressing osteoblasts were less active than wild-type osteoblasts. We also show that Cbfa1 regulates positively the activity of its own promoter, which has the highest affinity Cbfa1-binding sites characterized. This study demonstrates that beyond its differentiation function Cbfa1 is the first transcriptional activator of bone formation identified to date and illustrates that developmentally important genes control physiological processes postnatally. PMID:10215629

Bone metastases from breast cancer at the time or radical mastectomy as detected by bone scan. Eight-year follow-up.

PubMed

Sklaroff, R B; Sklaroff, D M

1976-07-01

Sixty-four women with Stage II breast cancer who had Sr85 bone scans at the time of radical mastectomy were followed for 8 years in a prospective study. Those women with positive scans had a slight, but statistically significant, increased incidence of metastic disease, particularly for metastases to bone.However, 40% of those women with positive bone scans and negative roentgenograms survived 8 years without evidence of any metastatic disease. Therefore, it has not been shown at this time that bone scans should be obtained in order to exclude bone metastasis before regional therapy for breast cancer is instituted. Also, a significant percentage of women with negative bone scans developed both bone and soft tissue metastases. As many as 30% of asymptomatic women with a history of breast cancer and positive bone scans and negative bone roentgenograms may still harbor disease in bone after 8 years.

Three-dimensional modeling and animation of two carpal bones: a technique.

PubMed

Green, Jason K; Werner, Frederick W; Wang, Haoyu; Weiner, Marsha M; Sacks, Jonathan M; Short, Walter H

2004-05-01

The objectives of this study were to (a). create 3D reconstructions of two carpal bones from single CT data sets and animate these bones with experimental in vitro motion data collected during dynamic loading of the wrist joint, (b). develop a technique to calculate the minimum interbone distance between the two carpal bones, and (c). validate the interbone distance calculation process. This method utilized commercial software to create the animations and an in-house program to interface with three-dimensional CAD software to calculate the minimum distance between the irregular geometries of the bones. This interbone minimum distance provides quantitative information regarding the motion of the bones studied and may help to understand and quantify the effects of ligamentous injury.

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

NASA Technical Reports Server (NTRS)

Cann, Christopher; Young, Donald R.

1976-01-01

Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

Hindlimb bone maturation during postnatal life in the Greater Rhea (Rhea americana, Aves, Palaeognathae): Implications for palaeobiological and zooarchaeological interpretations.

PubMed

Picasso, Mariana B J; Barbeito, Claudio Gustavo

2018-06-03

The objective of this study was to study the morphological pattern of bone maturation of the hindlimb bones of Rhea americana and find out how it can affect bone morphology after a taphonomic process. Juvenile specimens (n = 10) ranging from one month old to eight months old were studied. For comparison, bones from adults and juveniles from museum specimens (n = 4 and n = 6, respectively) were studied. In fresh bones, ossification centres were identified in the proximal and distal epiphyses of the tibiotarsi and in the proximal epiphysis of the tarsometatarsi, whereas the distal region of the femora and tarsometatarsi showed abundance of cartilage. The development and extension of the ossification centres of the tibiotarsi were different. In the proximal epiphysis, the centre presented less development with respect to the distal epiphysis. In the dry tibiotarsi, the proximal centre was absent and the distal one was well preserved. Both the fresh and dry juvenile tarsometatarsi presented unfused metatarsals and bulkier and wider aspect than the adult ones. The dry femora presented a noticeable excavation between condyles, whereas the dry tarsometatarsi showed the absence of the proximal epiphysis. The femora, tibiotarsi and tarsometatarsi possessed different traits of immaturity, which differentially affect the morphology of the preserved bones during a taphonomic process. © 2018 Blackwell Verlag GmbH.

The effect of tamoxifen on pubertal bone development in adolescents with pubertal gynecomastia.

PubMed

Akgül, Sinem; Derman, Orhan; Kanbur, Nuray

2016-01-01

During puberty, estrogen has a biphasic effect on epiphyses; at low levels, it leads to an increase in height and bone mass, whereas at high levels, it leads to closure of the epiphysis. Tamoxifen is a selective estrogen receptor modulator that has been used in the treatment of pubertal gynecomastia. Although it has not been approved for this indication, studies have shown it to be both successful and safe. In males, the peak of pubertal bone development occurs during Tanner stage 3-4, which is also when pubertal gynecomastia reaches its highest prevalence. Thus tamoxifen treatment could potentially effect pubertal bone development. The aim of this study was to assess the effects of tamoxifen on bone mineral density (BMD) and skeletal maturation when used for pubertal gynecomastia. We evaluated 20 boys with pubertal gynecomastia receiving tamoxifen for at least 4 months. BMD was measured with dual-energy X-ray absorptiometry. Z-score and absolute BMD (g/cm(2)) was determined at baseline and 2 months after completing tamoxifen treatment. Bone age and height was evaluated before treatment and again one year later. Using absolute BMD (g/cm(2)), the mean difference from baseline was significant between the two groups both at spine (p=0.002) and femur (p=0.001), but not with the Z-score. This result was attributed to the expected increase during puberty according to sex and age. No significant effect on skeletal maturation was found (p=1.112). We conclude that when pubertal bone development is concerned, tamoxifen is safe for the treatment of pubertal gynecomastia as neither bone mineralization nor growth potential was affected.

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

PubMed Central

Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

2015-01-01

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. PMID:25779879

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

PubMed

Chen, Shan; Grover, Monica; Sibai, Tarek; Black, Jennifer; Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

2015-05-01

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcutaneous Raman Spectroscopy of Bone

NASA Astrophysics Data System (ADS)

Maher, Jason R.

Clinical diagnoses of bone health and fracture risk typically rely upon measurements of bone density or structure, but the strength of a bone is also dependent upon its chemical composition. One technology that has been used extensively in ex vivo, exposed-bone studies to measure the chemical composition of bone is Raman spectroscopy. This spectroscopic technique provides chemical information about a sample by probing its molecular vibrations. In the case of bone tissue, Raman spectra provide chemical information about both the inorganic mineral and organic matrix components, which each contribute to bone strength. To explore the relationship between bone strength and chemical composition, our laboratory has contributed to ex vivo, exposed-bone animal studies of rheumatoid arthritis, glucocorticoid-induced osteoporosis, and prolonged lead exposure. All of these studies suggest that Raman-based predictions of biomechanical strength may be more accurate than those produced by the clinically-used parameter of bone mineral density. The utility of Raman spectroscopy in ex vivo, exposed-bone studies has inspired attempts to perform bone spectroscopy transcutaneously. Although the results are promising, further advancements are necessary to make non-invasive, in vivo measurements of bone that are of sufficient quality to generate accurate predictions of fracture risk. In order to separate the signals from bone and soft tissue that contribute to a transcutaneous measurement, we developed an overconstrained extraction algorithm that is based upon fitting with spectral libraries derived from separately-acquired measurements of the underlying tissue components. This approach allows for accurate spectral unmixing despite the fact that similar chemical components (e.g., type I collagen) are present in both soft tissue and bone and was applied to experimental data in order to transcutaneously detect, to our knowledge for the first time, age- and disease-related spectral differences in murine bone.

Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats.

PubMed

Folwarczna, Joanna; Pytlik, Maria; Zych, Maria; Cegieła, Urszula; Kaczmarczyk-Sedlak, Ilona; Nowińska, Barbara; Sliwiński, Leszek

2013-10-01

Caffeine, a methylxanthine present in coffee, has been postulated to be responsible for an increased risk of osteoporosis in coffee drinkers; however, the data are inconsistent. The aim of the present study was to investigate the effects of a moderate dose of caffeine on the skeletal system of rats with normal and decreased estrogen level (developing osteoporosis due to estrogen deficiency). The experiments were carried out on mature nonovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving caffeine once daily, 20 mg/kg p.o., for 4 wk. Serum bone turnover markers, bone mass, mass of bone mineral, calcium and phosphorus content, histomorphometric parameters, and bone mechanical properties were examined. Caffeine favorably affected the skeletal system of ovariectomized rats, slightly inhibiting the development of bone changes induced by estrogen deficiency (increasing bone mineralization, and improving the strength and structure of cancellous bone). Moreover, it favorably affected mechanical properties of compact bone. There were no significant effects of caffeine in rats with normal estrogen levels. In conclusion, results of the present study indicate that low-to-moderate caffeine intake may exert some beneficial effects on the skeletal system of mature organisms. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence

PubMed Central

2012-01-01

Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness. PMID:22834465

Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis.

PubMed

Ophoff, J; Venken, K; Callewaert, F; Boonen, S; Bouillon, R; Vanderschueren, D

2009-10-01

In this study, the role of disturbed bone mineral acquisition during puberty in the pathogenesis of osteoporosis was studied. To this end, a mouse model for senile and hypogonadal osteoporosis was used. Longitudinal follow-up showed that bone fragility in both models results from deficient bone build-up during early puberty. Male osteoporosis may result from impaired bone growth. This study characterizes the mechanisms of deficient peak bone mass acquisition in models for senile (SAMP6) and hypogonadal (orchidectomized SAMR1) osteoporosis. Bone mineral acquisition was investigated longitudinally in SAMP6 and orchidectomized SAMR1 mice (eight to ten animals per group) using peripheral quantitative computed tomography and histomorphometry. Additionally, the effects of long-term 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol (E2) replacement were studied. Statistical analysis was performed using ANOVA and Student's t test. SAMP6 mice showed an early (4 weeks) medullary expansion of the cortex due to impaired endocortical bone formation (-43%). Despite compensatory periosteal bone formation (+47%), cortical thickness was severely reduced in 20-week-old SAMP6 versus SAMR1. Orchidectomy reduced periosteal apposition between 4 and 8 weeks of age and resulted in high bone turnover and less trabecular bone gain in SAMP6 and SAMR1. DHT and E2 stimulated periosteal expansion and trabecular bone in orchidectomized SAMP6 and SAMR1. E2 stimulated endocortical apposition in SAMP6. Moreover, sex steroid action occurred between 4 and 8 weeks of age. Bone fragility in both models resulted from deficient bone build-up during early puberty. DHT and E2 improved bone mass acquisition in orchidectomized animals, suggesting a role for AR and ER in male skeletal development.

Low temperature setting polymer-ceramic composites for bone tissue engineering

NASA Astrophysics Data System (ADS)

Sethuraman, Swaminathan

Tissue engineering is defined as "the application of biological, chemical and engineering principles towards the repair, restoration or regeneration of tissues using scaffolds, cells, factors alone or in combination". The hypothesis of this thesis is that a matrix made of a synthetic biocompatible, biodegradable composite can be designed to mimic the properties of bone, which itself is a composite. The overall goal was to design and develop biodegradable, biocompatible polymer-ceramic composites that will be a practical alternative to current bone repair materials. The first specific aim was to develop and evaluate the osteocompatibility of low temperature self setting calcium deficient apatites for bone tissue engineering. The four different calcium deficient hydroxyapatites evaluated were osteocompatible and expressed the characteristic genes for osteoblast proliferation, maturation, and differentiation. Our next objective was to develop and evaluate the osteocompatibility of biodegradable amino acid ester polyphosphazene in vitro as candidates for forming composites with low temperature apatites. We determined the structure-property relationship, the cellular adhesion, proliferation, and differentiation of primary rat osteoblast cells on two dimensional amino acid ester based polyphosphazene films. Our next goal was to evaluate the amino acid ester based polyphosphazenes in a subcutaneous rat model and our results demonstrated that the polyphosphazenes evaluated in the study were biocompatible. The physio-chemical property characterization, cellular response and gene expression on the composite surfaces were evaluated. The results demonstrated that the precursors formed calcium deficient hydroxyapatite in the presence of biodegradable polyphosphazenes. In addition, cells on the surface of the composites expressed normal phenotype and characteristic genes such as type I collagen, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein. The in vivo study of these novel bone cements in a 5mm unicortical defect in New Zealand white rabbits showed that the implants were osteoconductive, and osteointegrative. In conclusion, the various studies that have been carried out in this thesis to study the feasibility of a bone cement system have shown that these materials are promising candidates for various orthopaedic applications. Overall I believe that these next generation bone cements are promising bone graft substitutes in the armamentarium to treat bone defects.

Secretome within the bone marrow microenvironment: A basis for mesenchymal stem cell treatment and role in cancer dormancy.

PubMed

Eltoukhy, Hussam S; Sinha, Garima; Moore, Caitlyn; Gergues, Marina; Rameshwar, Pranela

2018-05-31

The secretome produced by cells within the bone marrow is significant to homeostasis. The bone marrow, a well-studied organ, has multiple niches with distinct roles for supporting stem cell functions. Thus, an understanding of mediators involved in the regulation of stem cells could serve as a model for clinical problems and solutions such as tissue repair and regeneration. The exosome secretome of bone marrow stem cells is a developing area of research with respect to the regenerative potential by bone marrow cell, particularly the mesenchymal stem cells. The bone marrow niche regulates endogenous processes such as hematopoiesis but could also support the survival of tumors such as facilitating the cancer stem cells to exist in dormancy for decades. The bone marrow-derived secretome will be critical to future development of therapeutic strategies for oncologic diseases, in addition to regenerative medicine. This article discusses the importance for parallel studies to determine how the same secretome may compromise safety during the use of stem cells in regenerative medicine. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

A prospective study of change in bone mass with age in postmenopausal women.

PubMed

Hui, S L; Wiske, P S; Norton, J A; Johnston, C C

1982-01-01

For the first time a model for age-related bone loss has been developed from prospective data utilizing a new weighted least squares method. Two hundred and sixty-eight Caucasian women ranging in age from 50 to 95 were studied. A quadratic function best fit the data, and correcting for body weight and bone width reduced variance. The derived equation is: bone mass = (0.6032) (bone width) (cm) + (0.003059) (body weight) (kg) - (0.0163) (age - 50) + (0.0002249) (age - 50)2. Analysis of cross-sectional data on 583 Caucasian women of similar age showed a quadratic function with very similar coefficients. This quadratic function predicts an increase in bone mass after age 86, therefore 42 women over age 70 who had been followed for at least 2.5 yr were identified to test for this effect. of these, 13 had significantly positive regression coefficients of bone mass on age, and rate of change in bone width was positive in 40 of 42 individuals, of which 5 were significant. Since photon absorptiometry measures net changes on all bone envelopes, the most likely explanation for the observed changes is an early exponential loss of endosteal bone which ultimately slows or perhaps stops. There is a positive balance on the periosteal envelope which only becomes apparent in later years when the endosteal loss stops. These new statistical methods allow the development of models utilizing data collected at irregular intervals. The methods used are applicable to other biological data collected prospectively.

Embryonic development of Python sebae - I: Staging criteria and macroscopic skeletal morphogenesis of the head and limbs.

PubMed

Boughner, Julia C; Buchtová, Marcela; Fu, Katherine; Diewert, Virginia; Hallgrímsson, Benedikt; Richman, Joy M

2007-01-01

This study explores the post-ovipositional craniofacial development of the African Rock Python (Python sebae). We first describe a staging system based on external characteristics and next use whole-mount skeletal staining supplemented with Computed tomography (CT) scanning to examine skeletal development. Our results show that python embryos are in early stages of organogenesis at the time of laying, with separate facial prominences and pharyngeal clefts still visible. Limb buds are also visible. By 11 days (stage 3), the chondrocranium is nearly fully formed; however, few intramembranous bones can be detected. One week later (stage 4), many of the intramembranous upper and lower jaw bones are visible but the calvaria are not present. Skeletal elements in the limbs also begin to form. Between stages 4 (day 18) and 7 (day 44), the complete set of intramembranous bones in the jaws and calvaria develops. Hindlimb development does not progress beyond stage 6 (33 days) and remains rudimentary throughout adult life. In contrast to other reptiles, there are two rows of teeth in the upper jaw. The outer tooth row is attached to the maxillary and premaxillary bones, whereas the inner row is attached to the pterygoid and palatine bones. Erupted teeth can be seen in whole-mount stage 10 specimens and are present in an unerupted, mineralized state at stage 7. Micro-CT analysis reveals that all the young membranous bones can be recognized even out of the context of the skull. These data demonstrate intrinsic patterning of the intramembranous bones, even though they form without a cartilaginous template. In addition, intramembranous bone morphology is established prior to muscle function, which can influence bone shape through differential force application. After careful staging, we conclude that python skeletal development occurs slowly enough to observe in good detail the early stages of craniofacial skeletogenesis. Thus, reptilian animal models will offer unique opportunities for understanding the early influences that contribute to perinatal bone shape.

Handout on Health: Osteoporosis

MedlinePlus

... well, studies are comparing the effectiveness of different therapeutic approaches. Prevention Studies Researchers continue to explore the impact of nutritional status on bone health and fracture risk. Scientists are examining the impact of physical activity levels on bone health and are developing ...

Pre-existing periodontitis exacerbates experimental arthritis in a mouse model.

PubMed

Cantley, Melissa D; Haynes, David R; Marino, Victor; Bartold, P Mark

2011-06-01

Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid arthritis (RA) and that patients with periodontitis are at a greater risk of developing RA. The aim of this study was to develop an animal model to assess the relationship between pre-existing periodontitis and experimental arthritis (EA). Periodontitis was first induced in mice by oral gavage with Porphyromonas gingivalis followed by EA using the collagen antibody-induced arthritis model. These animals were compared with animals with periodontitis alone, EA alone and no disease (controls). Visual changes in paw swelling were assessed to determine clinical development of EA. Alveolar bone and joint changes were assessed using micro-CT, histological analyses and immunohistochemistry. Serum levels of C-reactive protein were used to monitor systemic inflammation. Mice with pre-existing periodontitis developed more severe arthritis, which developed at a faster rate. Mice with periodontitis only also showed evidence of loss of bone within the radiocarpal joint. There was also evidence of alveolar bone loss in mice with EA alone. The results of this study indicate that pre-existing periodontitis exacerbated experimental arthritis in a mouse model. © 2011 John Wiley & Sons A/S.

Construction of human induced pluripotent stem cell-derived oriented bone matrix microstructure by using in vitro engineered anisotropic culture model.

PubMed

Ozasa, Ryosuke; Matsugaki, Aira; Isobe, Yoshihiro; Saku, Taro; Yun, Hui-Suk; Nakano, Takayoshi

2018-02-01

Bone tissue has anisotropic microstructure based on collagen/biological apatite orientation, which plays essential roles in the mechanical and biological functions of bone. However, obtaining an appropriate anisotropic microstructure during the bone regeneration process remains a great challenging. A powerful strategy for the control of both differentiation and structural development of newly-formed bone is required in bone tissue engineering, in order to realize functional bone tissue regeneration. In this study, we developed a novel anisotropic culture model by combining human induced pluripotent stem cells (hiPSCs) and artificially-controlled oriented collagen scaffold. The oriented collagen scaffold allowed hiPSCs-derived osteoblast alignment and further construction of anisotropic bone matrix which mimics the bone tissue microstructure. To the best of our knowledge, this is the first report showing the construction of bone mimetic anisotropic bone matrix microstructure from hiPSCs. Moreover, we demonstrated for the first time that the hiPSCs-derived osteoblasts possess a high level of intact functionality to regulate cell alignment. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 360-369, 2018. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells.

PubMed

Hao, Sijie; Ha, Laura; Cheng, Gong; Wan, Yuan; Xia, Yiqiu; Sosnoski, Donna M; Mastro, Andrea M; Zheng, Si-Yang

2018-03-01

Bone metastasis occurs at ≈70% frequency in metastatic breast cancer. The mechanisms used by tumors to hijack the skeleton, promote bone metastases, and confer therapeutic resistance are poorly understood. This has led to the development of various bone models to investigate the interactions between cancer cells and host bone marrow cells and related physiological changes. However, it is challenging to perform bone studies due to the difficulty in periodic sampling. Herein, a bone-on-a-chip (BC) is reported for spontaneous growth of a 3D, mineralized, collagenous bone tissue. Mature osteoblastic tissue of up to 85 µm thickness containing heavily mineralized collagen fibers naturally formed in 720 h without the aid of differentiation agents. Moreover, co-culture of metastatic breast cancer cells is examined with osteoblastic tissues. The new bone-on-a-chip design not only increases experimental throughput by miniaturization, but also maximizes the chances of cancer cell interaction with bone matrix of a concentrated surface area and facilitates easy, frequent observation. As a result, unique hallmarks of breast cancer bone colonization, previously confirmed only in vivo, are observed. The spontaneous 3D BC keeps the promise as a physiologically relevant model for the in vitro study of breast cancer bone metastasis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New concept of 3D printed bone clip (polylactic acid/hydroxyapatite/silk composite) for internal fixation of bone fractures.

PubMed

Yeon, Yeung Kyu; Park, Hae Sang; Lee, Jung Min; Lee, Ji Seung; Lee, Young Jin; Sultan, Md Tipu; Seo, Ye Bin; Lee, Ok Joo; Kim, Soon Hee; Park, Chan Hum

Open reduction with internal fixation is commonly used for the treatment of bone fractures. However, postoperative infection associated with internal fixation devices (intramedullary nails, plates, and screws) remains a significant complication, and it is technically difficult to fix multiple fragmented bony fractures using internal fixation devices. In addition, drilling in the bone to install devices can lead to secondary fracture, bone necrosis associated with postoperative infection. In this study, we developed bone clip type internal fixation device using three- dimensional (3D) printing technology. Standard 3D model of the bone clip was generated based on computed tomography (CT) scan of the femur in the rat. Polylacticacid (PLA), hydroxyapatite (HA), and silk were used for bone clip material. The purpose of this study was to characterize 3D printed PLA, PLA/HA, and PLA/HA/Silk composite bone clip and evaluate the feasibility of these bone clips as an internal fixation device. Based on the results, PLA/HA/Silk composite bone clip showed similar mechanical property, and superior biocompatibility compared to other types of the bone clip. PLA/HA/Silk composite bone clip demonstrated excellent alignment of the bony segments across the femur fracture site with well-positioned bone clip in an animal study. Our 3D printed bone clips have several advantages: (1) relatively noninvasive (drilling in the bone is not necessary), (2) patient-specific design (3) mechanically stable device, and (4) it provides high biocompatibility. Therefore, we suggest that our 3D printed PLA/HA/Silk composite bone clip is a possible internal fixation device.

Computer-assisted analysis of cervical vertebral bone age using cephalometric radiographs in Brazilian subjects.

PubMed

Caldas, Maria de Paula; Ambrosano, Gláucia Maria Bovi; Haiter Neto, Francisco

2010-01-01

The aims of this study were to develop a computerized program for objectively evaluating skeletal maturation on cephalometric radiographs, and to apply the new method to Brazilian subjects. The samples were taken from the patient files of Oral Radiological Clinics from the North, Northeast, Midwest and South regions of the country. A total of 717 subjects aged 7.0 to 15.9 years who had lateral cephalometric radiographs and hand-wrist radiographs were selected. A cervical vertebral computerized analysis was created in the Radiocef Studio 2 computer software for digital cephalometric analysis, and cervical vertebral bone age was calculated using the formulas developed by Caldas et al.17 (2007). Hand-wrist bone age was evaluated by the TW3 method. Analysis of variance (ANOVA) and the Tukey test were used to compare cervical vertebral bone age, hand-wrist bone age and chronological age (P < 0.05). No significant difference was found between cervical vertebral bone age and chronological age in all regions studied. When analyzing bone age, it was possible to observe a statistically significant difference between cervical vertebral bone age and hand-wrist bone age for female and male subjects in the North and Northeast regions, as well as for male subjects in the Midwest region. No significant difference was observed between bone age and chronological age in all regions except for male subjects in the North and female subjects in the Northeast. Using cervical vertebral bone age, it might be possible to evaluate skeletal maturation in an objective manner using cephalometric radiographs.

Development of a Novel Synthetic Drug for Osteoporosis and Fracture Healing

DTIC Science & Technology

2012-09-01

application to chondrosarcoma , and preparation for bone fracture study. Body Aim 1: Development of salubrinal formulations and determination of...development of bone marrow derived cells, osteoclasts, osteoblasts, and chondrocytes. Application to chondrosarcoma : Besides osteoporosis and...osteoarthritis, we considered a potential application of salubrinal to skeletal malignancies. Approximately one-third of skeletal cancers form chondrosarcoma

Effect of a program of short bouts of exercise on bone health in adolescents involved in different sports: the PRO-BONE study protocol.

PubMed

Vlachopoulos, Dimitris; Barker, Alan R; Williams, Craig A; Knapp, Karen M; Metcalf, Brad S; Gracia-Marco, Luis

2015-04-11

Osteoporosis is a skeletal disease associated with high morbidity, mortality and increased economic costs. Early prevention during adolescence appears to be one of the most beneficial practices. Exercise is an effective approach for developing bone mass during puberty, but some sports may have a positive or negative impact on bone mass accrual. Plyometric jump training has been suggested as a type of exercise that can augment bone, but its effects on adolescent bone mass have not been rigorously assessed. The aims of the PRO-BONE study are to: 1) longitudinally assess bone health and its metabolism in adolescents engaged in osteogenic (football), non-osteogenic (cycling and swimming) sports and in a control group, and 2) examine the effect of a 9 month plyometric jump training programme on bone related outcomes in the sport groups. This study will recruit 105 males aged 12-14 years who have participated in sport specific training for at least 3 hours per week during the last 3 years in the following sports groups: football (n = 30), cycling (n = 30) and swimming (n = 30). An age-matched control group (n = 15) that does not engage in these sports more than 3 hours per week will also be recruited. Participants will be measured on 5 occasions: 1) at baseline; 2) after 12 months of sport specific training where each sport group will be randomly allocated into two sub-groups: intervention group (sport + plyometric jump training) and sport group (sport only); 3) exactly after the 9 months of intervention; 4) 6 months following the intervention; 5) 12 months following the intervention. Body composition (dual energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance), bone stiffness index (ultrasounds), physical activity (accelerometers), diet (24 h recall questionnaire), pubertal maturation (Tanner stage), physical fitness (cardiorespiratory and muscular), bone turnover markers and vitamin D will be measured at each visit. The PRO-BONE study is designed to investigate the impact of osteogenic and non-osteogenic sports on bone development in adolescent males during puberty, and how a plyometric jump training programme is associated with body composition parameters.

A study of stress-free living bone and its application to space flight

NASA Technical Reports Server (NTRS)

Leblanc, A.; Spira, M.

1983-01-01

Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

Targeted delivery of mesenchymal stem cells to the bone.

PubMed

Yao, Wei; Lane, Nancy E

2015-01-01

Osteoporosis is a disease of excess skeletal fragility that results from estrogen loss and aging. Age related bone loss has been attributed to both elevated bone resorption and insufficient bone formation. We developed a hybrid compound, LLP2A-Ale in which LLP2A has high affinity for the α4β1 integrin on mesenchymal stem cells (MSCs) and alendronate has high affinity for bone. When LLP2A-Ale was injected into mice, the compound directed MSCs to both trabecular and cortical bone surfaces and increased bone mass and bone strength. Additional studies are underway to further characterize this hybrid compound, LLP2A-Ale, and how it can be utilized for the treatment of bone loss resulting from hormone deficiency, aging, and inflammation and to augment bone fracture healing. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

P38 MAPK / beta-catenin canonical wnt signaling mediated bone formation effects of blueberries

USDA-ARS?s Scientific Manuscript database

Appropriate nutrition is one of the critical factors that influences bone development. We studied the effects of dietary blueberry supplementation on bone growth in weanling rats. Weanling male and female rats were fed AIN-93G semi-purified diets supplemented with 10% whole blueberry powder for 14 a...

Interventional radiology in bone metastases.

PubMed

Chiras, J; Shotar, E; Cormier, E; Clarençon, F

2017-11-01

Interventional radiology plays a significant role in the treatment of bone metastases by various techniques, percutaneous or endovascular. Vertebroplasty is the most well-studied technique for stabilisation of spine metastases as it induces satisfactory stabilisation of the vertebra and offers clear improvement of the quality of life. Due to the success of this technique cementoplasty of other bones, mainly pelvic girdle, has been largely developed. The development of reinforced cementoplasty allows treatment of pre-fractural osteolysis of some long bones. The heat due to the polymerisation of the cement induces carcinolytic effect but this effect is not as important as that which results from radiofrequency destruction. This last technique appears currently as the most important development to definitively destroy bone metastases and is progressively replacing percutaneous alcoholic destruction of such lesions. Angiographic techniques, such as endovascular embolisation, can also be very useful to reduce the risk of surgical treatment of hyper vascular metastases. Chemoembolisation is currently developed to associate pain relief induced by Endovascular embolisation and the carcinolytic effect obtained by local endovascular chemotherapy. All these techniques should develop largely during the next years. © 2017 John Wiley & Sons Ltd.

3D printed porous ceramic scaffolds for bone tissue engineering: a review.

PubMed

Wen, Yu; Xun, Sun; Haoye, Meng; Baichuan, Sun; Peng, Chen; Xuejian, Liu; Kaihong, Zhang; Xuan, Yang; Jiang, Peng; Shibi, Lu

2017-08-22

This study summarizes the recent research status and development of three-dimensional (3D)-printed porous ceramic scaffolds in bone tissue engineering. Recent literature on 3D-printed porous ceramic scaffolds was reviewed. Compared with traditional processing and manufacturing technologies, 3D-printed porous ceramic scaffolds have obvious advantages, such as enhancement of the controllability of the structure or improvement of the production efficiency. More sophisticated scaffolds were fabricated by 3D printing technology. 3D printed bioceramics have broad application prospects in bone tissue engineering. Through understanding the advantages and limitations of different 3D-printing approaches, new classes of bone graft substitutes can be developed.

Mesenchymal Stem Cells for Osteochondral Tissue Engineering

PubMed Central

Ng, Johnathan; Bernhard, Jonathan; Vunjak-Novakovic, Gordana

2017-01-01

Summary Mesenchymal stem cells (MSC) are of major interest to regenerative medicine, because of the ease of harvesting from a variety of sources (including bone marrow and fat aspirates) and ability to form a range of mesenchymal tissues, in vitro and in vivo. We focus here on the use of MSCs for engineering of cartilage, bone, and complex osteochondral tissue constructs, using protocols that replicate some aspects of the natural mesodermal development. For engineering of human bone, we discuss some of the current advances, and highlight the use of perfusion bioreactors for supporting anatomically exact human bone grafts. For engineering of human cartilage, we discuss limitations of current approaches, and highlight engineering of stratified, mechanically functional human cartilage interfaced with bone by mesenchymal condensation of MSCs. Taken together, the current advances enable engineering physiologically relevant bone, cartilage and osteochondral composites, and physiologically relevant studies of osteochondral development and disease. PMID:27236665

Engineering a humanized bone organ model in mice to study bone metastases.

PubMed

Martine, Laure C; Holzapfel, Boris M; McGovern, Jacqui A; Wagner, Ferdinand; Quent, Verena M; Hesami, Parisa; Wunner, Felix M; Vaquette, Cedryck; De-Juan-Pardo, Elena M; Brown, Toby D; Nowlan, Bianca; Wu, Dan Jing; Hutmacher, Cosmo Orlando; Moi, Davide; Oussenko, Tatiana; Piccinini, Elia; Zandstra, Peter W; Mazzieri, Roberta; Lévesque, Jean-Pierre; Dalton, Paul D; Taubenberger, Anna V; Hutmacher, Dietmar W

2017-04-01

Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months. Additive biomanufactured scaffolds seeded and cultured with human bone-forming cells are implanted ectopically in combination with osteogenic factors into mice to generate a physiological bone 'organ', which is partially humanized. The model comprises human bone cells and secreted extracellular matrix (ECM); however, other components of the engineered tissue, such as the vasculature, are of murine origin. The model can be further humanized through the engraftment of human hematopoietic stem cells (HSCs) that can lead to human hematopoiesis within the murine host. The humanized organ bone model has been well characterized and validated and allows dissection of some of the mechanisms of the bone metastatic processes in prostate and breast cancer.

Expression of CD44v6 as matrix-associated ectodomain in the bone development.

PubMed

Nakajima, Kosei; Taniguchi, Kazumi; Mutoh, Ken-ichiro

2010-08-01

This study describes the expression of CD44v6 in the bone development and is the first study of its kind to the authors' best knowledge. The CD44 family is a family of transmembrane glycoproteins that acts as cell adhesion molecules binding cells to other cells as well as cells to the extracellular matrix. It has been suggested that the CD44v6, a family member of CD44, is closely related to the osteosarcoma metastasis. In general, when cancer cells metastasize, they revert to their immature forms. In the present study, therefore, we have investigated CD44v6 and the standard form of CD44 (CD44st) in two types of immature forms of bone tissues: developmentally immature stages from fetuses to adults as well as experimentally immature stages using fracture models. CD44st expression was identified in osteoblasts, osteocytes, and in the peripheral portion of the bone matrix from the fetal to young ages of rats. Many more intense reactions for CD44v6 were observed in the bone matrix than CD44st in fetal stages. In experimental fracture models, positive immunoreactions to CD44st were clearly observed in the osteoblasts and osteocytes. CD44v6-positive immunoreactivity, however, was not detected in either osteoblasts or the bone matrix. In conclusion, CD44v6 is expressed in the embryonic stages and may be involved in the bone matrix formation as a matrix-associated ectodomain during normal ontogenetic development but not involved in the process of fracture healing.

Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes

NASA Technical Reports Server (NTRS)

Smith, S. M.; Wastney, M. E.; Morukov, B. V.; Larina, I. M.; Nyquist, L. E.; Abrams, S. A.; Taran, E. N.; Shih, C. Y.; Nillen, J. L.; Davis-Street, J. E.;

Bone remodelling of a proximal femur with the thrust plate prosthesis: an in vitro case.

PubMed

Taylor, W R; Ploeg, H; Hertig, D; Warner, M D; Clift, S E

2004-06-01

The key to the development of a successful implant is an understanding of the effect of bone remodelling on its long-term fixation. In this study, clinically observed patterns of bone remodelling have been compared with computer-based predictions for one particular design of prosthesis, the Thrust Plate Prosthesis (Centerpulse Orthopedics, Winterthur, Switzerland). Three-dimensional finite-element models were created using geometrical and bone density data obtained from CT scanning. Results from the bone remodelling simulation indicated that varying the relative rate of bone deposition/resorption and the interfacial conditions between the bone and the implant could produce the trend towards the two clinically observed patterns of remodelling.

Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

PubMed Central

Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

2009-01-01

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

Aging and the 4 kHz Air-bone Gap

PubMed Central

Nondahl, David M.; Tweed, Ted S.; Cruickshanks, Karen J.; Wiley, Terry L.; Dalton, Dayna S.

2011-01-01

Purpose To assess age- and gender-related patterns in the prevalence and 10-year incidence of 4 kHz air-bone gaps, and associated factors. Method Data were obtained as part of the longitudinal, population-based Epidemiology of Hearing Loss Study. An air-bone gap at 4 kHz was defined as an air-conduction threshold ≥15 dB higher than the bone-conduction threshold in the right ear. Results Among 3,553 participants aged 48 to 92 years at baseline (1993-1995), 3.4% had a 4 kHz air-bone gap in the right ear. The prevalence increased with age. Among the 120 participants with an air-bone gap, 60.0% did not have a flat tympanogram or an air-bone gap at .5 kHz. Ten years later we assessed 2093 participants who did not have a 4 kHz air-bone gap at baseline; 9.2% had developed a 4 kHz air-bone gap in the right ear. The incidence increased with age. Among the 192 participants who had developed an air-bone gap, 60.9% did not have a flat tympanogram or air-bone gaps at other frequencies. Conclusions These results suggest that a finding of a 4 kHz air-bone gap may reflect a combination of aging and other factors and not necessarily exclusively abnormal middle ear function. PMID:22232408

A 6-DOF parallel bone-grinding robot for cervical disc replacement surgery.

PubMed

Tian, Heqiang; Wang, Chenchen; Dang, Xiaoqing; Sun, Lining

2017-12-01

Artificial cervical disc replacement surgery has become an effective and main treatment method for cervical disease, which has become a more common and serious problem for people with sedentary work. To improve cervical disc replacement surgery significantly, a 6-DOF parallel bone-grinding robot is developed for cervical bone-grinding by image navigation and surgical plan. The bone-grinding robot including mechanical design and low level control is designed. The bone-grinding robot navigation is realized by optical positioning with spatial registration coordinate system defined. And a parametric robot bone-grinding plan and high level control have been developed for plane grinding for cervical top endplate and tail endplate grinding by a cylindrical grinding drill and spherical grinding for two articular surfaces of bones by a ball grinding drill. Finally, the surgical flow for a robot-assisted cervical disc replacement surgery procedure is present. The final experiments results verified the key technologies and performance of the robot-assisted surgery system concept excellently, which points out a promising clinical application with higher operability. Finally, study innovations, study limitations, and future works of this present study are discussed, and conclusions of this paper are also summarized further. This bone-grinding robot is still in the initial stage, and there are many problems to be solved from a clinical point of view. Moreover, the technique is promising and can give a good support for surgeons in future clinical work.

Facial bone fragmentation in blind cavefish arises through two unusual ossification processes.

PubMed

Powers, Amanda K; Kaplan, Shane A; Boggs, Tyler E; Gross, Joshua B

2018-05-03

The precise mechanisms underlying cranial bone development, evolution and patterning remain incompletely characterised. This poses a challenge to understanding the etiologies of craniofacial malformations evolving in nature. Capitalising on natural variation, "evolutionary model systems" provide unique opportunities to identify underlying causes of aberrant phenotypes as a complement to studies in traditional systems. Mexican blind cavefish are a prime evolutionary model for cranial disorders since they frequently exhibit extreme alterations to the skull and lateral asymmetries. These aberrations occur in stark contrast to the normal cranial architectures of closely related surface-dwelling fish, providing a powerful comparative paradigm for understanding cranial bone formation. Using a longitudinal and in vivo analytical approach, we discovered two unusual ossification processes in cavefish that underlie the development of 'fragmented' and asymmetric cranial bones. The first mechanism involves the sporadic appearance of independent bony elements that fail to fuse together later in development. The second mechanism involves the "carving" of channels in the mature bone, a novel form of post-ossification remodeling. In the extreme cave environment, these novel mechanisms may have evolved to augment sensory input, and may indirectly result in a trade-off between sensory expansion and cranial bone development.

Investigation into mechanical properties of bone and its main constituents

NASA Astrophysics Data System (ADS)

Evdokimenko, Ekaterina

Bone is a hierarchically structured natural composite material, consisting of organic phase (type-I collagen), inorganic phase (hydroxyapatite), and water. Studies of the two main bone constituents, utilizing controlled demineralization and deproteinization, can shed light on mineral-collagen interaction which makes bone such a unique biological material. This knowledge is necessary for computational analysis of bone structure to identify preferential sites in the collagen matrix and mineral network that degrade more easily. The main goal of this work is to develop a comprehensive picture of mechanical properties of bone and its main constituents. Following the Introduction, Chapter 2 presents an investigation of microstructure and compressive mechanical properties of bovine femur cortical bone carried out on completely demineralized, completely deproteinized, and untreated bone samples in three anatomical directions. Anisotropic nature of bone was clearly identified in all cases. Extra levels of porosity along with microstructural differences for the three directions were found to be the main sources of the anisotropy. In Chapter 3, a new theoretical model of cortical and trabecular bone as composite materials with hierarchical structure spanning from nanometer (collagen-mineral) level to millimeter (bone) level was developed. Compression testing was performed on untreated, demineralized, and deproteinized cortical and trabecular bovine femur bone samples to verify the model. The experimental data were compared with theoretical predictions; excellent agreement was found between the theory and experiments for all bone phases. Optical microscopy, scanning electron microscopy, and micro-computed tomography techniques were applied to characterize the structure of the samples at multiple length scales and provide further inputs for the modeling. Chapter 4 presents a comparative study of mechanical properties, microstructure, and porosity of mature and young bovine femur cortical bone. It was found that the amount of porosity decreases, while the microhardness increases with maturation. Osteoporotic degradation of trabecular bone elasticity, described in Chapter 5, was modeled using a cellular mechanics approach. Evolution equations for elastic modulus of bone in terms of those of mineral and protein trabeculae and in terms of demineralized and deproteinized bones were formulated and verified by the analysis of compressive properties of bovine femur trabecular bone.

Effect of maternal obesity on fetal bone development in the rat

USDA-ARS?s Scientific Manuscript database

Epidemiological studies show that quality of nutrition during intrauterine and postnatal early life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

Epigenetic control of fetal bone development through HoxA10 in the rat

USDA-ARS?s Scientific Manuscript database

Epidemiological studies show that quality of nutrition during intrauterine and early postnatal life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

The Morphogenesis of Cranial Sutures in Zebrafish

PubMed Central

Topczewska, Jolanta M.; Shoela, Ramy A.; Tomaszewski, Joanna P.; Mirmira, Rupa B.; Gosain, Arun K.

2016-01-01

Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone. Parietal and frontal bones are formed by intramembranous ossification within a layer of mesenchyme positioned between the dermal mesenchyme and meninges surrounding the brain. The supraoccipital bone has an endochondral origin. Cranial bones are separated by connective tissue with a distinctive architecture of osteogenic cells and collagen fibrils. Here we show RNA in situ hybridization for col1a1a, col2a1a, col10a1, bglap/osteocalcin, fgfr1a, fgfr1b, fgfr2, fgfr3, foxq1, twist2, twist3, runx2a, runx2b, sp7/osterix, and spp1/ osteopontin, indicating that the expression of genes involved in suture development in mammals is preserved in zebrafish. We also present methods for examining the cranium and its sutures, which permit the study of the mechanisms involved in suture patency as well as their pathological obliteration. The model we develop has implications for the study of human disorders, including craniosynostosis, which affects 1 in 2,500 live births. PMID:27829009

Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies.

PubMed

Reichert, Johannes C; Epari, Devakara R; Wullschleger, Martin E; Saifzadeh, Siamak; Steck, Roland; Lienau, Jasmin; Sommerville, Scott; Dickinson, Ian C; Schütz, Michael A; Duda, Georg N; Hutmacher, Dietmar W

2010-02-01

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties; however, they are limited in access and availability and associated with donor-site morbidity, hemorrhage, risk of infection, insufficient transplant integration, graft devitalization, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. The field of tissue engineering has emerged as an important approach to bone regeneration. However, bench-to-bedside translations are still infrequent as the process toward approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. The subsequent gap between research and clinical translation, hence, commercialization, is referred to as the "Valley of Death" and describes a large number of projects and/or ventures that are ceased due to a lack of funding during the transition from product/technology development to regulatory approval and subsequently commercialization. One of the greatest difficulties in bridging the Valley of Death is to develop good manufacturing processes and scalable designs and to apply these in preclinical studies. In this article, we describe part of the rationale and road map of how our multidisciplinary research team has approached the first steps to translate orthopedic bone engineering from bench to bedside by establishing a preclinical ovine critical-sized tibial segmental bone defect model, and we discuss our preliminary data relating to this decisive step.

Early development and osteoporosis and bone health.

PubMed

Dennison, E M; Cooper, C; Cole, Z A

2010-06-01

Osteoporosis is a skeletal disorder characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) and hypothalamo-pituitary-adrenal (HPA) axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have shown that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Childhood growth rates have been directly linked to the risk of hip fracture many decades later, and now evidence is emerging from experimental animal studies that support these observational data. Recent studies have also highlighted epigenetic phenomena as potential mechanisms underlying the findings from epidemiological studies.

Diet-induced obesity, gut microbiota and bone, including alveolar bone loss.

PubMed

Eaimworawuthikul, Sathima; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-06-01

Obesity is a major risk factor for several pathologies, including jaw bone resorption. The underlying mechanisms involved in pathological conditions resulting from obesity include chronic systemic inflammation and the development of insulin resistance. Although numerous studies have indicated the importance of the role of gut microbiota in the pathogenesis of inflammation and insulin resistance in obesity, only a few studies have established a relationship between obesity, gut microbiota and status of the jaw bone. This review aims to summarize current findings relating to these issues, focusing on the role of obesity and gut microbiota on jaw bone health, including possible mechanisms which can explain this link. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism

PubMed Central

Shih, Yu-Ru; Kang, Heemin; Rao, Vikram; Chiu, Yu-Jui; Kwon, Seong Keun; Varghese, Shyni

2017-01-01

Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor–host cell dynamics, tumor tropism, and hematopoietic cell transplantation. PMID:28484009

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism.

PubMed

Shih, Yu-Ru; Kang, Heemin; Rao, Vikram; Chiu, Yu-Jui; Kwon, Seong Keun; Varghese, Shyni

2017-05-23

Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor-host cell dynamics, tumor tropism, and hematopoietic cell transplantation.

Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass☆,☆☆

PubMed Central

Gennero, Isabelle; Laurencin-Dalicieux, Sara; Conte-Auriol, Françoise; Briand-Mésange, Fabienne; Laurencin, Danielle; Rue, Jackie; Beton, Nicolas; Malet, Nicole; Mus, Marianne; Tokumura, Akira; Bourin, Philippe; Vico, Laurence; Brunel, Gérard; Oreffo, Richard O. C.; Chun, Jerold; Salles, Jean Pierre

2013-01-01

Lysophosphatidic acid (LPA) is a lipid mediator that acts in paracrine systems via interaction with a subset of G protein-coupled receptors (GPCRs). LPA promotes cell growth and differentiation, and has been shown to be implicated in a variety of developmental and pathophysiological processes. At least 6 LPA GPCRs have been identified to date: LPA1–LPA6. Several studies have suggested that local production of LPA by tissues and cells contributes to paracrine regulation, and a complex interplay between LPA and its receptors, LPA1 and LPA4, is believed to be involved in the regulation of bone cell activity. In particular, LPA1may activate both osteoblasts and osteoclasts. However, its role has not as yet been examined with regard to the overall status of bone in vivo. We attempted to clarify this role by defining the bone phenotype of LPA1(−/−) mice. These mice demonstrated significant bone defects and low bone mass, indicating that LPA1 plays an important role in osteogenesis. The LPA1(−/−) mice also presented growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrated osteoporosis in the trabecular and cortical bone of LPA1(−/−) mice. Finally, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. These results suggest that LPA1 strongly influences bone development both qualitatively and quantitatively and that, in vivo, its absence results in decreased osteogenesis with no clear modification of osteoclasis. They open perspectives for a better understanding of the role of the LPA/LPA1 paracrine pathway in bone pathophysiology. PMID:21569876

Engineering tubular bone using mesenchymal stem cell sheets and coral particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, Wenxin; Ma, Dongyang; Yan, Xingrong

Highlights: • We developed a novel engineering strategy to solve the limitations of bone grafts. • We fabricated tubular constructs using cell sheets and coral particles. • The composite constructs showed high radiological density and compressive strength. • These characteristics were similar to those of native bone. -- Abstract: The development of bone tissue engineering has provided new solutions for bone defects. However, the cell-scaffold-based approaches currently in use have several limitations, including low cell seeding rates and poor bone formation capacity. In the present study, we developed a novel strategy to engineer bone grafts using mesenchymal stem cell sheetsmore » and coral particles. Rabbit bone marrow mesenchymal stem cells were continuously cultured to form a cell sheet with osteogenic potential and coral particles were integrated into the sheet. The composite sheet was then wrapped around a cylindrical mandrel to fabricate a tubular construct. The resultant tubular construct was cultured in a spinner-flask bioreactor and subsequently implanted into a subcutaneous pocket in a nude mouse for assessment of its histological characteristics, radiological density and mechanical property. A similar construct assembled from a cell sheet alone acted as a control. In vitro observations demonstrated that the composite construct maintained its tubular shape, and exhibited higher radiological density, compressive strength and greater extracellular matrix deposition than did the control construct. In vivo experiments further revealed that new bone formed ectopically on the composite constructs, so that the 8-week explants of the composite sheets displayed radiological density similar to that of native bone. These results indicate that the strategy of using a combination of a cell sheet and coral particles has great potential for bone tissue engineering and repairing bone defects.« less

A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

PubMed

Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

2016-11-01

The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue response near the implant surface in a bone marrow microenvironment, and it also shows great potential in making transgenic animal resource applicable to biomaterial studies, so that the design of novel biomaterials could be better guided.

Animal Models of Bone Metastasis

PubMed Central

Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

2015-01-01

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

[Development, physiology, and cell activity of bone].

PubMed

de Baat, P; Heijboer, M P; de Baat, C

2005-07-01

Bones are of crucial importance for the human body, providing skeletal support, serving as a home for the formation of haematopoietic cells, and reservoiring calcium and phosphate. Long bones develop by endochondral ossification. Flat bones develop by intramembranous ossification. Bone tissue contains hydroxyapatite and various extracellular proteins, producing bone matrix. Two biological mechanisms, determining the strength of bone, are modelling and remodelling. Modelling can change bone shape and size through bone formation by osteoblasts at some sites and through bone destruction by osteoclasts at other sites. Remodelling is bone turnover, also performed by osteoclasts and osteoblasts. The processes of modelling and remodelling are induced by mechanical loads, predominantly muscle loads. Osteoblasts develop from mesenchymal stem cells. Many stimulating factors are known to activate the differentiation. Mature osteoblasts synthesize bone matrix and may further differentiate into osteocytes. Osteocytes maintain structural bone integrity and allow bone to adapt to any mechanical and chemical stimulus. Osteoclasts derive from haematopoietic stem cells. A number of transcription and growth factors have been identified essential for osteoclast differentiation and function. Finally, there is a complex interaction between osteoblasts and osteoclasts. Bone destruction starts by attachment of osteoclasts to the bone surface. Following this, osteoclasts undergo specific morphological changes. The process of bone destruction starts by acid dissolution of hydroxyapatite. After that osteoclasts start to destruct the organic matrix.

Three-dimensional visualization and characterization of bone structure using reconstructed in-vitro μCT images: A pilot study for bone microarchitecture analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Latief, Fourier Dzar Eljabbar, E-mail: fourier@fi.itb.ac.id; Dewi, Dyah Ekashanti Octorina; Shari, Mohd Aliff Bin Mohd

Micro Computed Tomography (μCT) has been largely used to perform micrometer scale imaging of specimens, bone biopsies and small animals for the study of porous or cavity-containing objects. One of its favored applications is for assessing structural properties of bone. In this research, we perform a pilot study to visualize and characterize bone structure of a chicken bone thigh, as well as to delineate its cortical and trabecular bone regions. We utilize an In-Vitro μCT scanner Skyscan 1173 to acquire a three dimensional image data of a chicken bone thigh. The thigh was scanned using X-ray voltage of 45 kVmore » and current of 150 μA. The reconstructed images have spatial resolution of 142.50 μm/pixel. Using image processing and analysis e.i segmentation by thresholding the gray values (which represent the pseudo density) and binarizing the images, we were able to visualize each part of the bone, i.e., the cortical and trabecular regions. Total volume of the bone is 4663.63 mm{sup 3}, and the surface area of the bone is 7913.42 mm{sup 2}. The volume of the cortical is approximately 1988.62 mm{sup 3} which is nearly 42.64% of the total bone volume. This pilot study has confirmed that the μCT is capable of quantifying 3D bone structural properties and defining its regions separately. For further development, these results can be improved for understanding the pathophysiology of bone abnormality, testing the efficacy of pharmaceutical intervention, or estimating bone biomechanical properties.« less

A comparison of skeletal maturity and growth.

PubMed

Molinari, Luciano; Gasser, Theo; Largo, Remo

2013-07-01

Somatic and bone development have each been studied in detail, but rarely in conjunction. The aim of this study was to determine what somatic and bone development have in common and how they differ. A second aim was to check for a pubertal spurt in bone age (BA) and to quantify it in a similar way as has been done for height. The Preece-Baines model is used to fit longitudinal data for BA. The data analysed are from the 1st Zurich Longitudinal Growth Study comprising 120 boys and 112 girls with almost complete data from birth to adulthood. Variability of somatic milestones was reduced in terms of BA and there was an aftergrowth after reaching adult RUS score 1000. A strong increase in the RUS score was seen at a late stage of the pubertal spurt (PS). Somatic milestones correlated with the RUS score attained at these ages and more so at an early stage of the PS. A PS for BA was clearly identified with a location at 14.2 years for boys and 12.2 years for girls. Age of peak bone development correlated highly with age of peak velocity of somatic variables. BA can be successfully modelled as a semi-quantitative entity. Bone development shows marked associations with somatic development, despite the fact that the latter reflects changes in size, while the former is essentially a maturity index and reflects changes in biochemical composition of tissues.

An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells.

PubMed

Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

2016-11-22

One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes.

An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells

PubMed Central

Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

2016-01-01

One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes. PMID:27765913

Osteoporosis in premenopausal women.

PubMed

Langdahl, Bente L

2017-07-01

The scope of this review was to review the newest developments in the context of the existing knowledge on premenopausal bone fragility. Fragility fractures are common in postmenopausal women and men and diagnostic criteria for osteoporosis have been agreed and multiple pharmacological treatments have been developed over the last 25 years. In premenopausal women, fragility fractures and very low bone mass are uncommon and osteoporosis in premenopausal women has therefore attracted much less interest. Recent studies have highlighted that lifestyle and dietary habits affect premenopausal bone mass. Bone mass may be improved by sufficient intake of calcium and vitamin D together with increased physical activity in premenopausal women with idiopathic osteoporosis. If pharmacological treatment is needed, teriparatide has been demonstrated to efficiently increase bone mass; however, no fracture studies and no comparative studies against antiresorptive therapies have been conducted. Pregnancy affects bone turnover and mass significantly, but pregnancy-associated osteoporosis is a rare and heterogeneous condition. The diagnosis of osteoporosis should only be considered in premenopausal women with existing fragility fractures, diseases or treatments known to cause bone loss or fractures. Secondary causes of osteoporosis should be corrected or treated if possible. The women should be recommended sufficient intake of calcium and vitamin and physical activity. In women with recurrent fractures or secondary causes that cannot be eliminated, for example glucocorticoid or cancer treatment, pharmacological intervention with bisphosphonates or teriparatide (not in the case of cancer) may be considered.

Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna.

PubMed

Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi

2015-06-01

Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons.

[New therapies for children affected by bone diseases].

PubMed

Ballhausen, Diana; Dépraz, Nuria Garcia; Kern, Ilse; Unger, Sheila; Bonafé, Luisa

2012-02-22

Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

Pediatric inflammatory bowel disease and bone health.

PubMed

Mascarenhas, Maria R; Thayu, Meena

2010-08-01

Childhood and adolescence are important periods for bone development. Any disease that affects bone health has the potential to affect the bones not only in the short term but also later in life. Bone health abnormalities in patients with inflammatory bowel disease are being increasingly recognized. Screening the at-risk patient is important so that appropriate treatments can be instituted. Treatment options are limited to vitamin D and calcium supplementation, control of underlying disease activity, and appropriate physical activity. The role of bisphosphonates in these patients needs to be better studied, and treatment with bisphosphonates may be considered for some patients in consultation with a bone health expert.

Denosumab for the management of bone disease in patients with solid tumors.

PubMed

Body, Jean-Jacques

2012-03-01

Many patients with advanced cancer develop bone metastases, which reduces their quality of life. Bone metastases are associated with an increased risk of skeletal-related events, which can lead to increased morbidity and mortality. In patients with bone metastases, tumor cells disrupt the normal process of bone remodeling, leading to increased bone destruction. Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL), a key regulatory factor in bone remodeling. By binding to RANKL, denosumab disrupts the cycle of bone destruction. In clinical studies in patients with prostate or breast cancer and bone metastases, denosumab was superior to the current standard of care, zoledronic acid, for delaying skeletal-related events, while in patients with other solid tumors or multiple myeloma, denosumab was noninferior to zoledronic acid. This article examines the pharmacokinetics, efficacy, and safety and tolerability of denosumab for the management of bone events in patients with cancer.

The gut microbiota regulates bone mass in mice

PubMed Central

Sjögren, Klara; Engdahl, Cecilia; Henning, Petra; Lerner, Ulf H; Tremaroli, Valentina; Lagerquist, Marie K; Bäckhed, Fredrik; Ohlsson, Claes

2012-01-01

The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4+ T cells and CD11b+/GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis. © 2012 American Society for Bone and Mineral Research. PMID:22407806

Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss

PubMed Central

Jeney, Viktória

2017-01-01

Diseases/conditions with diverse etiology, such as hemoglobinopathies, hereditary hemochromatosis and menopause, could lead to chronic iron accumulation. This condition is frequently associated with a bone phenotype; characterized by low bone mass, osteoporosis/osteopenia, altered microarchitecture and biomechanics, and increased incidence of fractures. Osteoporotic bone phenotype constitutes a major complication in patients with iron overload. The purpose of this review is to summarize what we have learnt about iron overload-associated bone loss from clinical studies and animal models. Bone is a metabolically active tissue that undergoes continuous remodeling with the involvement of osteoclasts that resorb mineralized bone, and osteoblasts that form new bone. Growing evidence suggests that both increased bone resorption and decreased bone formation are involved in the pathological bone-loss in iron overload conditions. We will discuss the cellular and molecular mechanisms that are involved in this detrimental process. Fuller understanding of this complex mechanism may lead to the development of improved therapeutics meant to interrupt the pathologic effects of excess iron on bone. PMID:28270766

Percutaneous osteoplasty with a bone marrow nail for fractures of long bones: experimental study.

PubMed

Nakata, Kouhei; Kawai, Nobuyuki; Sato, Morio; Cao, Guang; Sahara, Shinya; Tanihata, Hirohiko; Takasaka, Isao; Minamiguchi, Hiroyuki; Nakai, Tomoki

2010-09-01

To develop percutaneous osteoplasty with the use of a bone marrow nail for fixation of long-bone fractures, and to evaluate its feasibility and safety in vivo and in vitro. Six long bones in three healthy swine were used in the in vivo study. Acrylic cement was injected through an 11-gauge bone biopsy needle and a catheter into a covered metallic stent placed within the long bone, creating a bone marrow nail. In the in vitro study, we determined the bending, tug, and compression strengths of the acrylic cement nails 9 cm long and 8 mm in diameter (N = 10). The bending strength of the artificially fractured bones (N = 6) restored with the bone marrow nail and cement augmentation was then compared with that of normal long bones (N = 6). Percutaneous osteoplasty with a bone marrow nail was successfully achieved within 1 hour for all swine. After osteoplasty, all swine regained the ability to run until they were euthanized. Blood tests and pathologic findings showed no adverse effects. The mean bending, tug, and compression strengths of the nail were 91.4 N/mm(2) (range, 75.0-114.1 N/mm(2)), 20.9 N/mm(2) (range, 6.6-30.4 N/mm(2)), and 103.0 N/mm(2) (range, 96.3-110.0 N/mm(2)), respectively. The bending strength ratio of artificially fractured bones restored with bone marrow nail and cement augmentation to normal long bone was 0.32. Percutaneous osteoplasty with use of a bone marrow nail and cement augmentation appears to have potential in treating fractures of non-weight-bearing long bones. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

The response of bone to unloading

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Halloran, B. P.

1999-01-01

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with the expectation that such understanding will lead to effective treatment for disuse osteoporosis.

Development and characterization of a lung-protective method of bone marrow transplantation in the mouse.

PubMed

Janssen, William J; Muldrow, Alaina; Kearns, Mark T; Barthel, Lea; Henson, Peter M

2010-05-31

Allogeneic bone marrow transplantation is a common method used to study the contribution of myeloid and lymphoid cell populations in murine models of disease. The method requires lethal doses of radiation to ablate the bone marrow. Unintended consequences of radiation include organ injury and inflammatory cell activation. The goal of our study was to determine the degree to which bone marrow transplantation alters lungs and to develop a system to protect the lungs during radiation. C57BL/6 mice were subjected to total body irradiation with 900cGy and then transplanted with bone marrow from green fluorescent protein (GFP) expressing mice. Resultant chimeras exhibited a significant decline in alveolar macrophage numbers within 72h, modest influx of neutrophils in the lungs at 14days, and repopulation of the lungs by alveolar macrophages of bone marrow origin by 28days. Neutrophil influx and alveolar macrophage turnover were prevented when 1cm thick lead shields were used to protect the lungs during radiation, such that 8weeks after transplantation less than 30% of alveolar macrophages were of donor origin. Lung-shielded mice achieved a high level of bone marrow engraftment with greater than 95% of circulating leukocytes expressing GFP. In addition, their response to intratracheal lipopolysaccharide was similar to non-transplanted mice. We describe a model whereby lead shields protect resident cell populations in the lungs from radiation during bone marrow transplantation but permit full bone marrow engraftment. This system may be applicable to other organ systems in which protection from radiation during bone marrow transplantation is desired.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of themore » craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.« less

What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy?

PubMed

Blaslov, Kristina; Katalinic, Lea; Kes, Petar; Spasovski, Goce; Smalcelj, Ruzica; Basic-Jukic, Nikolina

2014-05-01

Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal transplant recipients or comparing sirolimus versus everolimus impact on bone, so only general conclusions could be drawn. Hence, the use of mTORi might be useful in patients with PRO due to their possible potential to inhibit osteoclast activity which might lead to a decreased rate of bone resorption. In addition, it should be also emphasized that they might inhibit osteoblast activity which may lead to a decreased bone formation and adynamic bone disease. Further studies are urgently needed to solve these important clinical dilemmas.

Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques.

PubMed

Birmingham, E; Grogan, J A; Niebur, G L; McNamara, L M; McHugh, P E

2013-04-01

Bone marrow found within the porous structure of trabecular bone provides a specialized environment for numerous cell types, including mesenchymal stem cells (MSCs). Studies have sought to characterize the mechanical environment imposed on MSCs, however, a particular challenge is that marrow displays the characteristics of a fluid, while surrounded by bone that is subject to deformation, and previous experimental and computational studies have been unable to fully capture the resulting complex mechanical environment. The objective of this study was to develop a fluid structure interaction (FSI) model of trabecular bone and marrow to predict the mechanical environment of MSCs in vivo and to examine how this environment changes during osteoporosis. An idealized repeating unit was used to compare FSI techniques to a computational fluid dynamics only approach. These techniques were used to determine the effect of lower bone mass and different marrow viscosities, representative of osteoporosis, on the shear stress generated within bone marrow. Results report that shear stresses generated within bone marrow under physiological loading conditions are within the range known to stimulate a mechanobiological response in MSCs in vitro. Additionally, lower bone mass leads to an increase in the shear stress generated within the marrow, while a decrease in bone marrow viscosity reduces this generated shear stress.

The influence of anthropometry and body composition on children's bone health: the childhood health, activity and motor performance school (the CHAMPS) study, Denmark.

PubMed

Heidemann, Malene; Holst, René; Schou, Anders J; Klakk, Heidi; Husby, Steffen; Wedderkopp, Niels; Mølgaard, Christian

2015-02-01

Overweight, physical inactivity and sedentary behaviour have become increasing problems during the past decade. Increased sedentary behaviour may change the body composition (BC) by increasing the fat mass relative to the lean mass (LM). These changes may influence bone health to describe how anthropometry and BC predict the development of the bone accruement. The longitudinal study is a part of The CHAMPS study-DK. Children were DXA scanned at baseline and at 2-year follow-up. BC (LM, BF %) and BMC, BMD and BA were measured. The relationship between bone traits, anthropometry and BC was analysed by multilevel regression analyses. Of the invited children, 742/800 (93%) accepted to participate. Of these, 682/742 (92%) participated at follow-up. Mean (range) of age at baseline was 9.5 years (7.7-12.1). Height, BMI, LM and BF % predicted bone mineral accrual and bone size positively and independently. Height and BMI are both positive predictors of bone accruement. LM is a more precise predictor of bone traits than BF % in both genders. The effects of height and BMI and LM on bone accruement are nearly identical in the two genders, while changes in BF % have different but positive effects on bone accretion in both boys and girls.

Osteological Development of the Larvae and Juvenile of Bullhead torrent catfish, Liobagrus obesus

PubMed Central

Seo, Won-Il; Park, Jae-Min; Lee, Sung-Hun; Yoon, Seong Min; Hwang, Seon-Yeong; Han, Kyeong-Ho

2018-01-01

ABSTRACT This study was conducted to investigate the skeletal development of bullhead torrent catfish, Liobagrus obesus larvae and to utilize them as basic data for the taxonomic study of Liobagrus larvae. Skeletal development was observed by being divided into cranium, visceral skeleton, shoulder girdle bone, pelvic girdle bone and vertebra. On the first day after hatching, the pre-larvae had an average total length of 7.92 mm, and a line-shaped parasphenoid ossified in the cranium. In the jaw bone, the dentary supporting the lower jaw and the maxillary supporting the upper jaw were ossified. In the anterior abdominal vertebrae of the vertebra, seven centrums began to ossify and five neural spines ossified simultaneously. On the 3 day after hatching, pre-larvae had an average total length of 8.95 mm, and the prefrontal ossified in cranium. The number of abdominal vertebrae was increased to 14, and three parapophysis developed from the front side. On the 24th day after hatching, post-larvae had an average total length of 15.2 mm and the epural bone ossified in coccyx. The parhypural bone was ossified, and ossification of coccyx and pelvic girdle bone was completed. On the 30th day after hatching, the average total length of the juvenile was 17.8 mm, and the ossification of cranium and visceral skeleton was all completed while the preorbital and three suborbitals were ossified in the orbital region of the cranium. PMID:29707680

Prediction of low bone mass using a combinational approach of cortical and trabecular bone measures from dental panoramic radiographs.

PubMed

Kathirvelu, D; Anburajan, M

2014-09-01

The aim of this study is to extract cortical and trabecular features of the mandible and to develop a novel combinational model of mandibular cortical thickness, trabecular bone area and age in order to predict low bone mineral density or osteoporosis from a dental panoramic radiograph. The study involved 64 south Indian women (age = 52.5 ± 12.7 years) categorised into two groups (normal and low bone mineral density) based on total femur bone mineral density. The dental panoramic radiographs were obtained by a digital scanner, and measurement of total bone mineral density at the right femur was performed by a dual-energy X-ray absorptiometry scanner. The mandibular cortical thickness and panoramic mandibular index were measured bilaterally, and the mean values were considered. The region of interest of 128 × 128 pixels around the mental foramen region was manually cropped and subjected to pre-processing, normalisation and average threshold-based segmentation to determine trabecular bone area. Multiple linear regression analyses of cortical and trabecular measures along with age were performed to develop a combinational model to classify subjects as normal and low bone mineral density. The proposed approach demonstrated strong correlation (r = 0.76; p < 0.01) against the total bone mineral density and resulted in accuracy, sensitivity and positive predictive values of 0.84, 0.92 and 0.85, respectively; the receiver operating characteristic outcomes disclosed that the area under the curve was 0.89.Our results suggest that the proposed combinational model could be useful to diagnose subjects with low bone mineral density. © IMechE 2014.

Calcium Kinetics During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Wastney, Meryl E.; OBrien, Kimberly O.; Lane, Helen W.

1999-01-01

Bone loss is one of the most detrimental effects of space flight, threatening to limit the duration of human space missions. The ability to understand and counteract this loss will be critical for crew health and safety during and after extended-duration missions. The hypotheses to be tested in this project are that space flight alters calcium homeostasis and bone mineral metabolism, and that calcium homeostasis and bone mineral metabolism will return to baseline within days to weeks of return to Earth. These hypotheses will be evidenced by elevated rates of bone mineral resorption and decreased bone mineral deposition, decreased absorption of dietary calcium, altered calcitropic endocrine profiles, elevated excretion of calcium in urine and feces, and elevated excretion of markers of bone resorption. The second hypothesis will be evidenced by return of indices of calcium homeostasis and bone metabolism to preflight levels within days to weeks of return to Earth. Studies will be conducted on International Space Station astronauts before, during, and after extended-duration flights. Measurements of calcium kinetics, bone mass, and endocrine/biochemical markers of bone and calcium homeostasis will be conducted. Kinetic studies utilizing dual isotope tracer kinetic studies and mathematical modeling techniques will allow for determination of bone calcium deposition, bone calcium resorption, dietary calcium absorption and calcium excretion (both urinary and endogenous fecal excretion). These studies will build upon preliminary work conducted on the Russian Mir space station. The results from this project will be critical for clarifying how microgravity affects bone and calcium homeostasis, and will provide an important control point for assessment of countermeasure efficacy. These results are expected to aid in developing countermeasures for bone loss, both for space crews and for individuals on Earth who have metabolic bone diseases.

Conditional disruption of the prolyl hydroxylase domain-containing protein 2 (Phd2) gene defines its key role in skeletal development.

PubMed

Cheng, Shaohong; Xing, Weirong; Pourteymoor, Sheila; Mohan, Subburaman

2014-10-01

We have previously shown that the increase in osterix (Osx) expression during osteoblast maturation is dependent on the activity of the prolyl hydroxylase domain-containing protein 2 (Phd2), a key regulator of protein levels of the hypoxia-inducible factor family proteins in many tissues. In this study, we generated conditional Phd2 knockout mice (cKO) in osteoblast lineage cells by crossing floxed Phd2 mice with a Col1α2-iCre line to investigate the function of Phd2 in vivo. The cKO mice developed short stature and premature death at 12 to 14 weeks of age. Bone mineral content, bone area, and bone mineral density were decreased in femurs and tibias, but not vertebrae of the cKO mice compared to WT mice. The total volume (TV), bone volume (BV), and bone volume fraction (BV/TV) in the femoral trabecular bones of cKO mice were significantly decreased. Cross-sectional area of the femoral mid-diaphysis was also reduced in the cKO mice. The reduced bone size and trabecular bone volume in the cKO mice were a result of impaired bone formation but not bone resorption as revealed by dynamic histomorphometric analyses. Bone marrow stromal cells derived from cKO mice formed fewer and smaller nodules when cultured with mineralization medium. Quantitative RT-PCR and immunohistochemistry detected reduced expression of Osx, osteocalcin, and bone sialoprotein in cKO bone cells. These data indicate that Phd2 plays an important role in regulating bone formation in part by modulating expression of Osx and bone formation marker genes. © 2014 American Society for Bone and Mineral Research.

Breed-specific incidence rates of canine primary bone tumors — A population based survey of dogs in Norway

PubMed Central

Anfinsen, Kristin P.; Grotmol, Tom; Bruland, Oyvind S.; Jonasdottir, Thora J.

2011-01-01

This is one of few published population-based studies describing breed specific rates of canine primary bone tumors. Incidence rates related to dog breeds could help clarify the impact of etiological factors such as birth weight, growth rate, and adult body weight/height on development of these tumors. The study population consisted of dogs within 4 large/giant breeds; Irish wolfhound (IW), Leonberger (LB), Newfoundland (NF), and Labrador retriever (LR), born between January 1st 1989 and December 31st 1998. Questionnaires distributed to owners of randomly selected dogs — fulfilling the criteria of breed, year of birth, and registration in the Norwegian Kennel Club — constituted the basis for this retrospective, population-based survey. Of the 3748 questionnaires received by owners, 1915 were completed, giving a response rate of 51%. Forty-three dogs had been diagnosed with primary bone tumors, based upon clinical examination and x-rays. The breeds IW and LB, with 126 and 72 cases per 10 000 dog years at risk (DYAR), respectively, had significantly higher incidence rates of primary bone tumors than NF and LR (P < 0.0001). Incidence rates for the latter were 11 and 2 cases per 10 000 DYAR, respectively. Pursuing a search for risk factors other than body size/weight is supported by the significantly different risks of developing primary bone tumors between similarly statured dogs, like NF and LB, observed in this study. Defining these breed-specific incidence rates enables subsequent case control studies, ultimately aiming to identify specific etiological factors for developing primary bone tumors. PMID:22210997

Lions as Bone Accumulators? Paleontological and Ecological Implications of a Modern Bone Assemblage from Olduvai Gorge.

PubMed

Arriaza, Mari Carmen; Domínguez-Rodrigo, Manuel; Yravedra, José; Baquedano, Enrique

2016-01-01

Analytic models have been developed to reconstruct early hominin behaviour, especially their subsistence patterns, revealed mainly through taphonomic analyses of archaeofaunal assemblages. Taphonomic research is used to discern which agents (carnivores, humans or both) generate the bone assemblages recovered at archaeological sites. Taphonomic frameworks developed during the last decades show that the only large-sized carnivores in African biomes able to create bone assemblages are leopards and hyenas. A carnivore-made bone assemblage located in the short-grassland ecological unit of the Serengeti (within Olduvai Gorge) was studied. Taphonomic analyses of this assemblage including skeletal part representation, bone density, breakage patterns and anatomical distribution of tooth marks, along with an ecological approach to the prey selection made by large carnivores of the Serengeti, were carried out. The results show that this bone assemblage may be the first lion-accumulated assemblage documented, although other carnivores (namely spotted hyenas) may have also intervened through postdepositional ravaging. This first faunal assemblage potentially created by lions constitutes a new framework for neotaphonomic studies. Since lions may accumulate carcasses under exceptional circumstances, such as those documented at the site reported here, this finding may have important consequences for interpretations of early archaeological and paleontological sites, which provide key information about human evolution.

Lions as Bone Accumulators? Paleontological and Ecological Implications of a Modern Bone Assemblage from Olduvai Gorge

PubMed Central

Arriaza, Mari Carmen; Domínguez-Rodrigo, Manuel; Yravedra, José; Baquedano, Enrique

2016-01-01

Analytic models have been developed to reconstruct early hominin behaviour, especially their subsistence patterns, revealed mainly through taphonomic analyses of archaeofaunal assemblages. Taphonomic research is used to discern which agents (carnivores, humans or both) generate the bone assemblages recovered at archaeological sites. Taphonomic frameworks developed during the last decades show that the only large-sized carnivores in African biomes able to create bone assemblages are leopards and hyenas. A carnivore-made bone assemblage located in the short-grassland ecological unit of the Serengeti (within Olduvai Gorge) was studied. Taphonomic analyses of this assemblage including skeletal part representation, bone density, breakage patterns and anatomical distribution of tooth marks, along with an ecological approach to the prey selection made by large carnivores of the Serengeti, were carried out. The results show that this bone assemblage may be the first lion-accumulated assemblage documented, although other carnivores (namely spotted hyenas) may have also intervened through postdepositional ravaging. This first faunal assemblage potentially created by lions constitutes a new framework for neotaphonomic studies. Since lions may accumulate carcasses under exceptional circumstances, such as those documented at the site reported here, this finding may have important consequences for interpretations of early archaeological and paleontological sites, which provide key information about human evolution. PMID:27144649

In vivo immunogenicity of bovine bone removed by a novel decellularization protocol based on supercritical carbon dioxide.

PubMed

You, Ling; Weikang, Xu; Lifeng, Yang; Changyan, Liang; Yongliang, Lin; Xiaohui, Wei; Bin, Xu

2018-05-04

Trauma or infections associated critical bone defects lead to a huge economic burden in the healthcare system worldwide. Recent advances in tissue engineering have led to potential new strategies for the repair, replacement, and regeneration of bone defects, especially in biomaterials and decellularization protocols from xenogenic tissues. However, the complexity in bone structure and mechanical environment limits the synthesis of artificial bone with biomaterials. Thus, the purpose of our study is to develop a natural bone scaffold with great immunocompatibility. We combined decellularization techniques base on SC-CO 2 to decellularize bovine bone. In order to study the immune response of mice to materials, the histology, spleen index, immune cells contents and in vitro proliferative performance, cytokine and immunoglobulin light chain expression of mice were characterized. Compared with the fresh bone group, the immune responses of decellularized group were significantly reduced. In conclusion, decellularization via this method can achieve a decellularized scaffold with great immunocompatibility. Our findings suggest the potential of using decellularized BB as a scaffold for bone bioengineering.

Thermal Model to Investigate the Temperature in Bone Grinding for Skull Base Neurosurgery

PubMed Central

Zhang, Lihui; Tai, Bruce L.; Wang, Guangjun; Zhang, Kuibang; Sullivan, Stephen; Shih, Albert J.

2013-01-01

This study develops a thermal model utilizing the inverse heat transfer method (IHTM) to investigate the bone grinding temperature created by a spherical diamond tool used for skull base neurosurgery. Bone grinding is a critical procedure in the expanded endonasal approach to remove the cranial bone and access to the skull base tumor via nasal corridor. The heat is generated during grinding and could damage the nerve or coagulate the blood in the carotid artery adjacent to the bone. The finite element analysis is adopted to investigate the grinding-induced bone temperature rise. The heat source distribution is defined by the thermal model, and the temperature distribution is solved using the IHTM with experimental inputs. Grinding experiments were conducted on a bovine cortical bone with embedded thermocouples. Results show significant temperature rise in bone grinding. Using 50°C as the threshold, the thermal injury can propagate about 3 mm in the traverse direction, and 3 mm below the ground surface under the dry grinding condition. The presented methodology demonstrated the capability of being a thermal analysis tool for bone grinding study. PMID:23683875

Effects of Imbalanced Muscle Loading on Hip Joint Development and Maturation

PubMed Central

Ford, Caleb A.; Nowlan, Niamh C.; Thomopoulos, Stavros; Killian, Megan L.

2017-01-01

The mechanical loading environment influences the development and maturation of joints. In this study, the influence of imbalanced muscular loading on joint development was studied using localized chemical denervation of hip stabilizing muscle groups in neonatal mice. It was hypothesized that imbalanced muscle loading, targeting either gluteal muscles or quadriceps muscles, would lead to bilateral hip joint asymmetry, as measured by acetabular coverage, femoral head volume and bone morphometry, and femoral-acetabular shape. The contralateral hip joints as well as age-matched, uninjected mice were used as controls. Altered bone development was analyzed using micro-computed tomography, histology, and image registration techniques at postnatal days (P) 28, 56, and 120. This study found that unilateral muscle unloading led to reduced acetabular coverage of the femoral head, lower total volume, lower bone volume ratio, and lower mineral density, at all three time points. Histologically, the femoral head was smaller in unloaded hips, with thinner triradiate cartilage at P28 and thinner cortical bone at P120 compared to contralateral hips. Morphological shape changes were evident in unloaded hips at P56. Unloaded hips had lower trabecular thickness and increased trabecular spacing of the femoral head compared to contralateral hips. The present study suggests that decreased muscle loading of the hip leads to altered bone and joint shape and growth during postnatal maturation. Statement of Clinical Significance: Adaptations from altered muscle loading during postnatal growth investigated in this study have implications on developmental hip disorders that result from asymmetric loading, such as patients with limb-length inequality or dysplasia. PMID:27391299

Mineral distributions at the developing tendon enthesis.

PubMed

Schwartz, Andrea G; Pasteris, Jill D; Genin, Guy M; Daulton, Tyrone L; Thomopoulos, Stavros

2012-01-01

Tendon attaches to bone across a functionally graded interface, "the enthesis". A gradient of mineral content is believed to play an important role for dissipation of stress concentrations at mature fibrocartilaginous interfaces. Surgical repair of injured tendon to bone often fails, suggesting that the enthesis does not regenerate in a healing setting. Understanding the development and the micro/nano-meter structure of this unique interface may provide novel insights for the improvement of repair strategies. This study monitored the development of transitional tissue at the murine supraspinatus tendon enthesis, which begins postnatally and is completed by postnatal day 28. The micrometer-scale distribution of mineral across the developing enthesis was studied by X-ray micro-computed tomography and Raman microprobe spectroscopy. Analyzed regions were identified and further studied by histomorphometry. The nanometer-scale distribution of mineral and collagen fibrils at the developing interface was studied using transmission electron microscopy (TEM). A zone (∼20 µm) exhibiting a gradient in mineral relative to collagen was detected at the leading edge of the hard-soft tissue interface as early as postnatal day 7. Nanocharacterization by TEM suggested that this mineral gradient arose from intrinsic surface roughness on the scale of tens of nanometers at the mineralized front. Microcomputed tomography measurements indicated increases in bone mineral density with time. Raman spectroscopy measurements revealed that the mineral-to-collagen ratio on the mineralized side of the interface was constant throughout postnatal development. An increase in the carbonate concentration of the apatite mineral phase over time suggested possible matrix remodeling during postnatal development. Comparison of Raman-based observations of localized mineral content with histomorphological features indicated that development of the graded mineralized interface is linked to endochondral bone formation near the tendon insertion. These conserved and time-varying aspects of interface composition may have important implications for the growth and mechanical stability of the tendon-to-bone attachment throughout development.

Biomechanical Studies on Patterns of Cranial Bone Fracture Using the Immature Porcine Model.

PubMed

Haut, Roger C; Wei, Feng

2017-02-01

This review was prepared for the American Society of Mechanical Engineers Lissner Medal. It specifically discusses research performed in the Orthopaedic Biomechanics Laboratories on pediatric cranial bone mechanics and patterns of fracture in collaboration with the Forensic Anthropology Laboratory at Michigan State University. Cranial fractures are often an important element seen by forensic anthropologists during the investigation of pediatric trauma cases litigated in courts. While forensic anthropologists and forensic biomechanists are often called on to testify in these cases, there is little basic science developed in support of their testimony. The following is a review of studies conducted in the above laboratories and supported by the National Institute of Justice to begin an understanding of the mechanics and patterns of pediatric cranial bone fracture. With the lack of human pediatric specimens, the studies utilize an immature porcine model. Because much case evidence involves cranial bone fracture, the studies described below focus on determining input loading based on the resultant bone fracture pattern. The studies involve impact to the parietal bone, the most often fractured cranial bone, and begin with experiments on entrapped heads, progressing to those involving free-falling heads. The studies involve head drops onto different types and shapes of interfaces with variations of impact energy. The studies show linear fractures initiating from sutural boundaries, away from the impact site, for flat surface impacts, in contrast to depressed fractures for more focal impacts. The results have been incorporated into a "Fracture Printing Interface (FPI)," using machine learning and pattern recognition algorithms. The interface has been used to help interpret mechanisms of injury in pediatric death cases collected from medical examiner offices. The ultimate aim of this program of study is to develop a "Human Fracture Printing Interface" that can be used by forensic investigators in determining mechanisms of pediatric cranial bone fracture.

Development of a Drilling Simulator for Dental Implant Surgery.

PubMed

Kinoshita, Hideaki; Nagahata, Masahiro; Takano, Naoki; Takemoto, Shinji; Matsunaga, Satoru; Abe, Shinichi; Yoshinari, Masao; Kawada, Eiji

2016-01-01

The aim of this study was to develop and evaluate a dental implant surgery simulator that allows learners to experience the drilling forces necessary to perform an osteotomy in the posterior mandibular bone. The simulator contains a force-sensing device that receives input and counteracts this force, which is felt as resistance by the user. The device consists of an actuator, a load cell, and a control unit. A mandibular bone model was fabricated in which the predicted forces necessary to drill the cortical and trabecular bone were determined via micro CT image-based 3D finite element analysis. The simulator was evaluated by five dentists from the Department of Implantology at Tokyo Dental College. The ability of the evaluators to distinguish the drilling resistance through different regions of the mandibular bone was investigated. Of the five dentists, four sensed the change in resistance when the drill perforated the upper cortical bone. All five dentists were able to detect when the drill made contact with lingual cortical bone and when the lingual bone was perforated. This project successfully developed a dental implant surgery simulator that allows users to experience the forces necessary to drill through types of bone encountered during osteotomy. Furthermore, the researchers were able to build a device by which excessive drilling simulates a situation in which the lingual cortical bone is perforated--a situation that could lead to negative repercussions in a clinical setting. The simulator was found to be useful to train users to recognize the differences in resistance when drilling through the mandibular bone.

Structural characterization and mechanical performance of calcium phosphate scaffolds and natural bones: a comparative study.

PubMed

Fuentes, Elena; Sáenz de Viteri, Virginia; Igartua, Amaya; Martinetti, Roberta; Dolcini, Laura; Barandika, Gotzone

2010-01-01

The knowledge of the mechanical response of bones and their substitutes is pertinent to numerous medical problems. Understanding the effects of mechanical influence on the body is the first step toward developing innovative treatment and rehabilitation concepts for orthopedic disorders. This was a comparative study of 5 synthetic scaffolds based on porous calcium phosphates and natural bones, with regard to their microstructural, chemical, and mechanical characterizations. The structural and chemical characterizations of the scaffolds were examined by means of X-ray diffraction, scanning electron microscopy, and X-ray spectroscopy analysis. The mechanical characterization of bones and bone graft biomaterials was carried out through compression tests using samples with noncomplex geometry. Analysis of the chemical composition, surface features, porosity, and compressive strength indicates that hydroxyapatite-based materials and trabecular bone have similar properties.

BMP-2/PLGA delayed-release microspheres composite graft, selection of bone particulate diameters, and prevention of aseptic inflammation for bone tissue engineering.

PubMed

Ji, Ye; Xu, Gong Ping; Zhang, Zhi Peng; Xia, Jing Jun; Yan, Jing Long; Pan, Shang Ha

2010-03-01

Autogenous bone grafts are widely used in the repair of bone defects. Growth factors such as bone morphogenetic protein 2 (BMP-2) can induce bone regeneration and enhance bone growth. The combination of an autogenous bone graft and BMP-2 may provide a better osteogenic effect than either treatment alone, but BMP-2 is easily inactivated in body fluid. The objective of this study was to develop a technique that can better preserve the in vivo activity of BMP-2 incorporated in bone grafts. In this study, we first prepared BMP-2/poly(lactic-co-glycolic acid) (PLGA) delayed-release microspheres, and then combined collagen, the delayed-release microspheres, and rat autologous bone particulates to form four groups of composite grafts with different combinations: collagen in group A; collagen combined with bone particulates in group B; collagen combined with BMP-2/PLGA delayed-release microspheres in group C; and collagen combined with both bone particulates and BMP-2/PLGA delayed-release microspheres in group D. The four groups of composite grafts were implanted into the gluteus maximus pockets in rats. The ectopic osteogenesis and ALP level in group D (experimental group) were compared with those in groups A, B, and C (control groups) to study whether it had higher osteogenic capability. Results showed that the composite graft design increased the utility of BMP-2 and reduced the required dose of BMP-2 and volume of autologous bone. The selection of bone particulate diameter had an impact on the osteogenetic potential of bone grafts. Collagen prevented the occurrence of aseptic inflammation and improved the osteoinductivity of BMP-2. These results showed that this composite graft design is effective and feasible for use in bone repair.

Type I Collagen and Strontium-Containing Mesoporous Glass Particles as Hybrid Material for 3D Printing of Bone-Like Materials.

PubMed

Montalbano, Giorgia; Fiorilli, Sonia; Caneschi, Andrea; Vitale-Brovarone, Chiara

2018-04-28

Bone tissue engineering offers an alternative promising solution to treat a large number of bone injuries with special focus on pathological conditions, such as osteoporosis. In this scenario, the bone tissue regeneration may be promoted using bioactive and biomimetic materials able to direct cell response, while the desired scaffold architecture can be tailored by means of 3D printing technologies. In this context, our study aimed to develop a hybrid bioactive material suitable for 3D printing of scaffolds mimicking the natural composition and structure of healthy bone. Type I collagen and strontium-containing mesoporous bioactive glasses were combined to obtain suspensions able to perform a sol-gel transition under physiological conditions. Field emission scanning electron microscopy (FESEM) analyses confirmed the formation of fibrous nanostructures homogeneously embedding inorganic particles, whereas bioactivity studies demonstrated the large calcium phosphate deposition. The high-water content promoted the strontium ion release from the embedded glass particles, potentially enhancing the osteogenic behaviour of the composite. Furthermore, the suspension printability was assessed by means of rheological studies and preliminary extrusion tests, showing shear thinning and fast material recovery upon deposition. In conclusion, the reported results suggest that promising hybrid systems suitable for 3D printing of bioactive scaffolds for bone tissue engineering have been developed.

Men's health-seeking behaviours regarding bone health after a fragility fracture: a secondary analysis of qualitative data.

PubMed

Sale, J E M; Ashe, M C; Beaton, D; Bogoch, E; Frankel, L

2016-10-01

In our qualitative study, men with fragility fractures described their spouses as playing an integral role in their health behaviours. Men also described taking risks, preferring not to dwell on the meaning of the fracture and/or their bone health. Communication strategies specific to men about bone health should be developed. We examined men's experiences and behaviours regarding bone health after a fragility fracture. We conducted a secondary analysis of five qualitative studies. In each primary study, male and female participants were interviewed for 1-2 h and asked to describe recommendations they had received for bone health and what they were doing about those recommendations. Maintaining the phenomenological approach of the primary studies, the transcripts of all male participants were re-analyzed to highlight experiences and behaviours particular to men. Twenty-two men (50-88 years old) were identified. Sixteen lived with a wife, male partner, or family member and the remaining participants lived alone. Participants had sustained hip fractures (n = 7), wrist fractures (n = 5), vertebral fractures (n = 2) and fractures at other locations (n = 8). Fourteen were taking antiresorptive medication at the time of the interview. In general, men with a wife/female partner described these women as playing an integral role in their health behaviours, such as removing tripping hazards and organizing their medication regimen. While participants described giving up activities due to their bone health, they also described taking risks such as drinking too much alcohol and climbing ladders or deliberately refusing to adhere to bone health recommendations. Finally, men did not dwell on the meaning of the fracture and/or their bone health. Behaviours consistent with those shown in other studies on men were described by our sample. We recommend that future research address these findings in more detail so that communication strategies specific to men about bone health be developed.

Development and Assessment of a 3D-Printed Scaffold with rhBMP-2 for an Implant Surgical Guide Stent and Bone Graft Material: A Pilot Animal Study.

PubMed

Bae, Ji Cheol; Lee, Jin-Ju; Shim, Jin-Hyung; Park, Keun-Ho; Lee, Jeong-Seok; Bae, Eun-Bin; Choi, Jae-Won; Huh, Jung-Bo

2017-12-16

In this study, a new concept of a 3D-printed scaffold was introduced for the accurate placement of an implant and the application of a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded bone graft. This preliminary study was conducted using two adult beagles to evaluate the 3D-printed polycaprolactone (PCL)/ β -tricalcium phosphate ( β -TCP)/bone decellularized extracellular matrix (bdECM) scaffold conjugated with rhBMP-2 for the simultaneous use as an implant surgical guide stent and bone graft material that promotes new bone growth. Teeth were extracted from the mandible of the beagle model and scanned by computed tomography (CT) to fabricate a customized scaffold that would fit the bone defect. After positioning the implant guide scaffold, the implant was placed and rhBMP-2 was injected into the scaffold of the experimental group. The two beagles were sacrificed after three months. The specimen block was obtained and scanned by micro-CT. Histological analysis showed that the control and experimental groups had similar new bone volume (NBV, %) but the experimental group with BMP exhibited a significantly higher bone-to-implant contact ratio (BIC, %). Within the limitations of this preliminary study, a 3D-printed scaffold conjugated with rhBMP-2 can be used simultaneously as an implant surgical guide and a bone graft in a large bone defect site. Further large-scale studies will be needed to confirm these results.

Atmospheric pressure as a force that fills developing bones with marrow and air.

PubMed

Kurbel, Sven; Radić, Radivoje; Kristek, Branka; Ivezić, Zdravko; Selthofer, Robert; Kotromanović, Zeljko

2004-01-01

Many theories try to explain the existence and function of paranasal sinuses. This paper is an attempt to correlate process of paranasal sinus development in human with bone pneumatization processes in animals. It is here proposed that this mechanism starts in utero and continues after birth. During endochondral development, a solid hyaline cartilage model transforms into long bones. Central chondrocytes hypertrophy and their lacunae become confluent. Dissolving of the cartilage intercellular matrix forms a primitive marrow cavity. It is soon invaded by the periostal bud. Once circulation is established in the developing bone, the dissolved hyaline matrix can be slowly washed away from the bone cavity. Circulation in the bone cavity can develop slight subatmospheric pressures, similar to negative interstitial pressures in subcutaneous tissues. The amniotic fluid conducts atmospheric pressure to the fetal body. The pressure is trying to fill enlarging bone cavities through the existing vascular openings, or to create new openings. Bone walls of developing paranasal bones are to weak to resist the pressure gradient on their walls. New openings form on the weakest spots allowing airway mucosa to form initial paranasal sinuses. The enlarging cavities of long bones that are remote from the body surface and airway also develop a slightly subatmospheric pressure that fills them with cellular elements. These elements enter bone through the feeding vessels and form bone marrow. During after birth skeletal growth, bone remodeling shapes paranasal sinuses in a process of slow evolution that do not require measurable pressure gradients. When two sinuses come in vicinity, their growth rate declines, since the remaining thin and fragile bone lamella between them does not retract anymore.

Role of sediment size and biostratinomy on the development of biofilms in recent avian vertebrate remains

NASA Astrophysics Data System (ADS)

Peterson, Joseph E.; Lenczewski, Melissa E.; Clawson, Steven R.; Warnock, Jonathan P.

2017-04-01

Microscopic soft tissues have been identified in fossil vertebrate remains collected from various lithologies. However, the diagenetic mechanisms to preserve such tissues have remained elusive. While previous studies have described infiltration of biofilms in Haversian and Volkmann’s canals, biostratinomic alteration (e.g., trampling), and iron derived from hemoglobin as playing roles in the preservation processes, the influence of sediment texture has not previously been investigated. This study uses a Kolmogorov Smirnov Goodness-of-Fit test to explore the influence of biostratinomic variability and burial media against the infiltration of biofilms in bone samples. Controlled columns of sediment with bone samples were used to simulate burial and subsequent groundwater flow. Sediments used in this study include clay-, silt-, and sand-sized particles modeled after various fluvial facies commonly associated with fossil vertebrates. Extant limb bone samples obtained from Gallus gallus domesticus (Domestic Chicken) buried in clay-rich sediment exhibit heavy biofilm infiltration, while bones buried in sands and silts exhibit moderate levels. Crushed bones exhibit significantly lower biofilm infiltration than whole bone samples. Strong interactions between biostratinomic alteration and sediment size are also identified with respect to biofilm development. Sediments modeling crevasse splay deposits exhibit considerable variability; whole-bone crevasse splay samples exhibit higher frequencies of high-level biofilm infiltration, and crushed-bone samples in modeled crevasse splay deposits display relatively high frequencies of low-level biofilm infiltration. These results suggest that sediment size, depositional setting, and biostratinomic condition play key roles in biofilm infiltration in vertebrate remains, and may influence soft tissue preservation in fossil vertebrates.

[THE IMPORTANCE OF "MILK BONES" TO "WISDOM BONES" - COW MILK AND BONE HEALTH - LESSONS FROM MILK ALLERGY PATIENTS].

PubMed

Nachshon, Liat; Katz, Yitzhak

2016-03-01

The necessity of milk consumption in the western diet is a subject of intense controversy. One of the main benefits of milk is that it is the main source of dietary calcium. Calcium is a major bone mineral, mandatory for bone health. Its supply is derived exclusively from external dietary sources. During the growth period, an increased calcium supply is needed for the process of bone mass accumulation. An optimal bone mass achieved by the end of the growth period may be protective later in life against the bone mass loss that commonly occurs. This in turn, can be preventative against the occurrence of osteoporosis and the development of spontaneous bone fractures. Over the past several decades, an increased incidence of osteoporosis has been documented in western countries, leading to high rates of morbidity and mortality in the middle-aged and geriatric population. Many studies have investigated the dietary calcium requirements for different ages, to achieve and maintain proper bone health. Based on their results, guidelines concerning calcium intake in every stage of life have been published by national and international organizations. In the western diet, it is difficult to achieve the recommended calcium intake without milk consumption. Moreover, calcium bioavailability for intestinal absorption is high. Several studies have recently raised doubts concerning the amounts of calcium intake in the western diet and its effectiveness in preventing osteoporosis. The main disadvantage of these studies is their being based on the patient's past memory recall of milk consumption. Patients with IgE-mediated cow's milk protein allergy are a unique population. Their lifetime negligible milk consumption is undisputed. A recent study investigated for the first time, the bone density of young adults with milk allergy at the end of their growth period. Their severe reduction in bone mineral density and dietary calcium intake defines them as a high risk group for the development of early osteoporosis. Another finding of this study was that normal bone density was found in milk allergic patients who started to consume milk after a successful desensitization program. Interestingly, these patients had consumed milk for a period of only 12-36 months and had only partially achieved the recommended dietary intake for calcium. It appears that dietary milk is essential for optimal peak bone mass. The required amounts of calcium and the preferred form for consumption, however, requires further investigation.

Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile.

PubMed

Rosen, J; Negro-Vilar, A

2002-03-01

A novel approach to the treatment of osteoporosis in men, and possibly women, is the development of selective androgen receptor modulators (SARMs) that can stimulate formation of new bone with substantially diminished proliferative activity in the prostate, as well as reduced virilizing activity in women. Over the last several years, we have developed a program to discover and develop novel, non-steroidal, orally-active selective androgen receptor modulators (SARMs) that provide improved therapeutic benefits and reduce risk and side effects. In recent studies, we have used a skeletally mature orchiectomized (ORX) male rat as an animal model of male hypogonadism for assessing the efficacy of LGD2226, a nonsteroidal, non-aromatizable, and non-5alpha-reducible SARM. We assessed the activity of LGD2226 on bone turnover, bone mass and bone strength, and also evaluated the effects exerted on classic androgen-dependent targets, such as prostate, seminal vesicles and muscle. A substantial loss of bone density was observed in ORX animals, and this loss was prevented by SARMs, as well as standard androgens. Biochemical markers of bone turnover revealed an early increase of bone resorption in androgen-deficient rats that was repressed in ORX animals treated with the oral SARM, LGD2226, during a 4-month treatment period. Differences in architectural properties and bone strength were detected by histomorphometric and mechanical analyses, demonstrating beneficial effects of LGD2226 on bone quality in androgen-deficient rats. Histomorphometric analysis of cortical bone revealed distinct anabolic activity of LGD2226 in periosteal bone. LGD2226 was able to prevent bone loss and maintain bone quality in ORX rats by stimulating bone formation, while also inhibiting bone turnover. LGD2226 also exerted anabolic activity on the levator ani muscle. Taken together, these results suggest that orally-active, non-steroidal SARMs may be useful therapeutics for both muscle and bone in elderly hypogonadal men through their anabolic activities. Since SARMs both prevent bone loss, and also stimulate formation of new bone, they may have significant advantages relative to currently used anti-resorptive therapies. Coupled with their activity in muscle and their ability to maintain or restore libido, they offer new therapeutic approaches for male and female hormone replacement.

THE EFFECT OF THE GROWTH HORMONE FROM THE ANTERIOR LOBE OF THE PITUITARY ON BONE UNDER CONDITIONS OF IRRADIATION (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanova, E.A.

1963-05-21

Young rats 3 to 4 days old were given an x-ray dose of 1000 r on the left hind leg. A daily dose of 200 gamma of growth hormone obtained from the pituitary of a bull was administered, until the animals were killed on the 36th, 41st, and 44th days after the irradiation. The length of the tibia in the left and right legs was determined by x rays. In the irradiated animals, the ratio of the length of the left tibia to the right tibia was about 0.50, and the introduction of growth hormone into the rat had onlymore » a slight effect on tibial growth. The bones were then fixed in a Zenkerformalin fluid, and cytological studies were carried out. These studies show that irradiation of the extremity of a four-day rat with an x-ray dose of 2000 r resulted in deep disturbances in the cartilage bone with subsequent arrest in the development of the bone. The introduction of growth hormone ameliorated the changes in bone structure, but did not result in normal bone development. (TTT)« less

Osteoporosis and bone fractures in alcoholic liver disease: a meta-analysis.

PubMed

Bang, Chang Seok; Shin, In Soo; Lee, Sung Wha; Kim, Jin Bong; Baik, Gwang Ho; Suk, Ki Tae; Yoon, Jai Hoon; Kim, Yeon Soo; Kim, Dong Joon

2015-04-07

To evaluate the association between alcoholic liver disease (ALD) and bone fractures or osteoporosis. Non-randomized studies were identified from databases (PubMed, EMBASE, and the Cochrane Library). The search was conducted using Boolean operators and keywords, which included "alcoholic liver diseases", "osteoporosis", or "bone fractures". The prevalence of any fractures or osteoporosis, and bone mineral density (BMD) were extracted and analyzed using risk ratios and standardized mean difference (SMD). A random effects model was applied. In total, 15 studies were identified and analyzed. Overall, ALD demonstrated a RR of 1.944 (95%CI: 1.354-2.791) for the development of bone fractures. However, ALD showed a RR of 0.849 (95%CI: 0.523-1.380) for the development of osteoporosis. BMD was not significantly different between the ALD and control groups, although there was a trend toward lower BMD in patients with ALD (SMD in femur-BMD: -0.172, 95%CI: -0.453-0.110; SMD in spine-BMD: -0.169, 95%CI: -0.476-0.138). Sensitivity analyses showed consistent results. Current publications indicate significant associations between bone fractures and ALD, independent of BMD or the presence of osteoporosis.

Osteoporosis and bone fractures in alcoholic liver disease: A meta-analysis

PubMed Central

Bang, Chang Seok; Shin, In Soo; Lee, Sung Wha; Kim, Jin Bong; Baik, Gwang Ho; Suk, Ki Tae; Yoon, Jai Hoon; Kim, Yeon Soo; Kim, Dong Joon

2015-01-01

AIM: To evaluate the association between alcoholic liver disease (ALD) and bone fractures or osteoporosis. METHODS: Non-randomized studies were identified from databases (PubMed, EMBASE, and the Cochrane Library). The search was conducted using Boolean operators and keywords, which included “alcoholic liver diseases”, “osteoporosis”, or “bone fractures”. The prevalence of any fractures or osteoporosis, and bone mineral density (BMD) were extracted and analyzed using risk ratios and standardized mean difference (SMD). A random effects model was applied. RESULTS: In total, 15 studies were identified and analyzed. Overall, ALD demonstrated a RR of 1.944 (95%CI: 1.354-2.791) for the development of bone fractures. However, ALD showed a RR of 0.849 (95%CI: 0.523-1.380) for the development of osteoporosis. BMD was not significantly different between the ALD and control groups, although there was a trend toward lower BMD in patients with ALD (SMD in femur-BMD: -0.172, 95%CI: -0.453-0.110; SMD in spine-BMD: -0.169, 95%CI: -0.476-0.138). Sensitivity analyses showed consistent results. CONCLUSION: Current publications indicate significant associations between bone fractures and ALD, independent of BMD or the presence of osteoporosis. PMID:25852292

A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone

PubMed Central

Thibaudeau, Laure; Taubenberger, Anna V.; Holzapfel, Boris M.; Quent, Verena M.; Fuehrmann, Tobias; Hesami, Parisa; Brown, Toby D.; Dalton, Paul D.; Power, Carl A.; Hollier, Brett G.; Hutmacher, Dietmar W.

2014-01-01

ABSTRACT The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact ‘organ’ bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo. PMID:24713276

Novel Development of Phosphate Treated Porous Hydroxyapatite.

PubMed

Doi, Kazuya; Abe, Yasuhiko; Kobatake, Reiko; Okazaki, Yohei; Oki, Yoshifumi; Naito, Yoshihito; Prananingrum, Widyasri; Tsuga, Kazuhiro

2017-12-08

Phosphoric acid-etching treatment to the hydroxyapatite (HA) surface can modify the solubility calcium structure. The aim of the present study was to develop phosphate treated porous HA, and the characteristic structures and stimulation abilities of bone formation were evaluated to determine its suitability as a new type of bone graft material. Although the phosphoric acid-etching treatment did not alter the three-dimensional structure, a micrometer-scale rough surface topography was created on the porous HA surface. Compared to porous HA, the porosity of phosphate treated porous HA was slightly higher and the mechanical strength was lower. Two weeks after placement of the cylindrical porous or phosphate treated porous HA in a rabbit femur, newly formed bone was detected in both groups. At the central portion of the bone defect area, substantial bone formation was detected in the phosphate treated porous HA group, with a significantly higher bone formation ratio than detected in the porous HA group. These results indicate that phosphate treated porous HA has a superior surface topography and bone formation abilities in vivo owing to the capacity for both osteoconduction and stimulation abilities of bone formation conferred by phosphoric acid etching.

Novel Development of Phosphate Treated Porous Hydroxyapatite

PubMed Central

Doi, Kazuya; Abe, Yasuhiko; Kobatake, Reiko; Okazaki, Yohei; Oki, Yoshifumi; Naito, Yoshihito; Prananingrum, Widyasri; Tsuga, Kazuhiro

2017-01-01

Phosphoric acid-etching treatment to the hydroxyapatite (HA) surface can modify the solubility calcium structure. The aim of the present study was to develop phosphate treated porous HA, and the characteristic structures and stimulation abilities of bone formation were evaluated to determine its suitability as a new type of bone graft material. Although the phosphoric acid-etching treatment did not alter the three-dimensional structure, a micrometer-scale rough surface topography was created on the porous HA surface. Compared to porous HA, the porosity of phosphate treated porous HA was slightly higher and the mechanical strength was lower. Two weeks after placement of the cylindrical porous or phosphate treated porous HA in a rabbit femur, newly formed bone was detected in both groups. At the central portion of the bone defect area, substantial bone formation was detected in the phosphate treated porous HA group, with a significantly higher bone formation ratio than detected in the porous HA group. These results indicate that phosphate treated porous HA has a superior surface topography and bone formation abilities in vivo owing to the capacity for both osteoconduction and stimulation abilities of bone formation conferred by phosphoric acid etching. PMID:29292788

Aneurysmal bone cyst: a hereditary disease?

PubMed

Leithner, Andreas; Machacek, Felix; Haas, Oskar A; Lang, Susanna; Ritschl, Peter; Radl, Roman; Windhager, Reinhard

2004-05-01

Recent genetic and immunohistochemical studies propose that the primary aneurysmal bone cyst is a tumour and not a reactive tumour-simulating lesion. Based on a familial case of aneurysmal bone cyst the authors contacted 135 patients with this disease. Sixty-eight females and 67 males (median age 14 years; range 2-73 years) were asked if other family members had bone lesions. One hundred and seven patients (79%) denied having other family members with lesions, 23 patients (17%) did not answer, and five patients (4%) gave evidence of other bone lesions in the family. These data indicate that a predisposing genetic defect could be part of a multifactorial pathogenesis in the development of some aneurysmal bone cysts.

Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models

PubMed Central

Su, Nan; Jin, Min; Chen, Lin

2014-01-01

Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-in/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis. PMID:26273516

[Experimental-morphologic study of bone tissue reaction to carbon-containing material implantation with initiated X-ray contrast property].

PubMed

Grigorian, A S; Nabiev, F Kh; Golovin, R V

2005-01-01

In experimental study on 15 rabbits (chinchilla) influence of titanium plates implanted lapped on adjacent tissues in the region of the lower jaw body (comparison group) and carbon material with added boron in the concentrations of 8 and 15% (the study group) was studied. Results of the experimental-morphological investigation show that carbon-based materials with boron addition (with its content 8 and 15%) did not impede adaptive rebuilding of bone tissues and in particular bone structure regeneration in the process of reactive rebuilding of the "maternal" bone. Moreover, as the result of reactive processes developing in osseous tissues after implantation of the tested materials their successful integration in surrounding tissue structures was detected.

Incidence and variation of interpretably bone (os incae) in northeastern Thailand.

PubMed

Thanapaisal, Chaiwit; Duangthongpon, Pichayen; Kitkuandee, Amnat; Chaiciwamongkol, Kowit; Morthong, Vilaiwan

2013-09-01

The squamous segment of occipital bone consists of cartilaginous and membranous origin. The cartilaginous part develops to supra-occipital bone. The membranous part has three primary ossification centers on each side. The first pair ossification center lies above the cartilaginous part between the superior nuchal line and the highest nuchal line and fuse with the cartilaginous part to form a supra-occipital segment of occipital bone. The second and third pairs have two nuclei each forming lateral and medial plates. All of these ossification centers fuse to form squamous segments of occipital bone. The fusion failure between ossification centers of second and third pair nuclei with each other or supra-occipital segment causes separated bone(s) called interparietal bone(s) or os incae. The interparietal bone should be differentiated from Wormian (intrasutural) bone. The incidence from various studies ranges from 0.37% to 9.50% of the population. To study the incidence and variation of interparietal bone in Northeastern Thailand as compared with other studies. A total of 400 Thai native skulls (276 male and 124 female) from the collection of Anatomical Museum of the Faculty of Medicine Khon Kaen University aged from 16 to 93 years old were examined by naked eye and photographed. Wormian bone was excluded by shape and site. The statistical method used was percentage of relative frequency. The incidence of interparietal bone in Northeastern Thailand is 7.25% (29 from 400). Males have a two times higher incidence rate than females, (8.33% versus 4.84%). Eleven patterns of interparietal bone were found. Fusion failure of a third pair ossification center is more common than second pair Knowledge of interparietal bone is useful for neurosurgeons and radiologists to avoid missed diagnosis of skull fracture. Presented interparietal bone may cause difficulty in surgery of occipital and parietal bone. Forensic scientist can use interparietal bone for personal identification.

Proposed equations and reference values for calculating bone health in children and adolescent based on age and sex

PubMed Central

Gómez-Campos, Rossana; Andruske, Cynthia Lee; de Arruda, Miguel; Urra Albornoz, Camilo; Cossio-Bolaños, Marco

2017-01-01

Background The Dual Energy X-Ray Absorptiometry (DXA) is the gold standard for measuring BMD and bone mineral content (BMC). In general, DXA is ideal for pediatric use. However, the development of specific standards for particular geographic regions limits its use and application for certain socio-cultural contexts. Additionally, the anthropometry may be a low cost and easy to use alternative method in epidemiological contexts. The goal of our study was to develop regression equations for predicting bone health of children and adolescents based on anthropometric indicators to propose reference values based on age and sex. Methods 3020 students (1567 males and 1453 females) ranging in ages 4.0 to 18.9 were studied from the Maule Region (Chile). Anthropometric variables evaluated included: weight, standing height, sitting height, forearm length, and femur diameter. A total body scan (without the head) was conducted by means of the Dual Energy X-Ray Absorptiometry. Bone mineral density (BMD) and the bone mineral content (BMC) were also determined. Calcium consumption was controlled for by recording the intake of the three last days prior to the evaluation. Body Mass Index (BMI) was calculated, and somatic maturation was determined by using the years of peak growth rate (APHV). Results Four regression models were generated to calculate bone health: for males BMD = (R2 = 0.79) and BMC = (R2 = 0.84) and for the females BMD = (R2 = 0.76) and BMC = (R2 = 0.83). Percentiles were developed by using the LMS method (p3, p5, p15, p25, p50, p75, p85, p95 and p97). Conclusions Regression equations and reference curves were developed to assess the bone health of Chilean children and adolescents. These instruments help identify children with potential underlying problems in bone mineralization during the growth stage and biological maturation. PMID:28759569

Proposed equations and reference values for calculating bone health in children and adolescent based on age and sex.

PubMed

Gómez-Campos, Rossana; Andruske, Cynthia Lee; Arruda, Miguel de; Urra Albornoz, Camilo; Cossio-Bolaños, Marco

2017-01-01

The Dual Energy X-Ray Absorptiometry (DXA) is the gold standard for measuring BMD and bone mineral content (BMC). In general, DXA is ideal for pediatric use. However, the development of specific standards for particular geographic regions limits its use and application for certain socio-cultural contexts. Additionally, the anthropometry may be a low cost and easy to use alternative method in epidemiological contexts. The goal of our study was to develop regression equations for predicting bone health of children and adolescents based on anthropometric indicators to propose reference values based on age and sex. 3020 students (1567 males and 1453 females) ranging in ages 4.0 to 18.9 were studied from the Maule Region (Chile). Anthropometric variables evaluated included: weight, standing height, sitting height, forearm length, and femur diameter. A total body scan (without the head) was conducted by means of the Dual Energy X-Ray Absorptiometry. Bone mineral density (BMD) and the bone mineral content (BMC) were also determined. Calcium consumption was controlled for by recording the intake of the three last days prior to the evaluation. Body Mass Index (BMI) was calculated, and somatic maturation was determined by using the years of peak growth rate (APHV). Four regression models were generated to calculate bone health: for males BMD = (R2 = 0.79) and BMC = (R2 = 0.84) and for the females BMD = (R2 = 0.76) and BMC = (R2 = 0.83). Percentiles were developed by using the LMS method (p3, p5, p15, p25, p50, p75, p85, p95 and p97). Regression equations and reference curves were developed to assess the bone health of Chilean children and adolescents. These instruments help identify children with potential underlying problems in bone mineralization during the growth stage and biological maturation.

Biological Assessment of a Calcium Silicate Incorporated Hydroxyapatite-Gelatin Nanocomposite: A Comparison to Decellularized Bone Matrix

PubMed Central

Lee, Dong Joon; Padilla, Ricardo; Zhang, He; Hu, Wei-Shou; Ko, Ching-Chang

2014-01-01

Our laboratory utilized biomimicry to develop a synthetic bone scaffold based on hydroxyapatite-gelatin-calcium silicate (HGCS). Here, we evaluated the potential of HGCS scaffold in bone formation in vivo using the rat calvarial critical-sized defect (CSD). Twelve Sprague-Dawley rats were randomized to four groups: control (defect only), decellularized bone matrix (DECBM), and HGCS with and without multipotent adult progenitor cells (MAPCs). DECBM was prepared by removing all the cells using SDS and NH4OH. After 12 weeks, the CSD specimens were harvested to evaluate radiographical, histological, and histomorphometrical outcomes. The in vitro osteogenic effects of the materials were studied by focal adhesion, MTS, and alizarin red. Micro-CT analysis indicated that the DECBM and the HGCS scaffold groups developed greater radiopaque areas than the other groups. Bone regeneration, assessed using histological analysis and fluorochrome labeling, was the highest in the HGCS scaffold seeded with MAPCs. The DECBM group showed limited osteoinductivity, causing a gap between the implant and host tissue. The group grafted with HGCS+MAPCs resulting in twice as much new bone formation seems to indicate a role for effective bone regeneration. In conclusion, the novel HGCS scaffold could improve bone regeneration and is a promising carrier for stem cell-mediated bone regeneration. PMID:25054149

A Computational Model for Simulating Spaceflight Induced Bone Remodeling

NASA Technical Reports Server (NTRS)

Pennline, James A.; Mulugeta, Lealem

2014-01-01

An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model.

Facial growth and development in unilateral cleft lip and palate: comparison between secondary alveolar bone grafting and primary periosteoplasty.

PubMed

Cagáňová, Veronika; Borský, Jiří; Smahel, Zbyněk; Velemínská, Jana

2014-01-01

To describe the effect of secondary alveolar bone grafting in patients with unilateral cleft lip and palate by comparison with a sample of patients who have undergone primary periosteoplasty. Cephalometric analysis of lateral x-ray films in a retrospective semilongitudinal study. Lateral x-ray films of 18 secondary alveolar bone grafting patients and 48 primary periosteoplasty patients at 10 years of age and again at 15 years of age. The treatment of secondary alveolar bone grafting patients included lip repair according to Tennison, palatoplasty including retropositioning, pharyngeal flap surgery, and secondary alveolar bone grafting. The lips of primary periosteoplasty patient were repaired using the methods of Tennison and Veau, followed by primary periosteoplasty, palatoplasty including retropositioning, and pharyngeal flap surgery. Lateral radiographs were assessed using classical morphometry. There were few significant differences at 10 years of age between the secondary alveolar bone grafting and primary periosteoplasty patients. At 15 years of age, there were several significant differences. Compared with primary periosteoplasty patients, subsequent development in patients who had undergone secondary alveolar bone grafting was characterized by a significantly better position of the upper and lower dentoalveolar components in relation to the facial plane, a higher increase in the global convexity of the soft profile, a significantly better maxillary inclination, and a more favorable development of vertical intermaxillary relationships. Craniofacial development in secondary alveolar bone grafting patients was better than that in primary periosteoplasty patients due to the more marked facial convexity, the increased prominence of the nose, and better vertical intermaxillary relationships.

Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments

PubMed Central

Pneumaticos, Spyros G; Triantafyllopoulos, Georgios K; Basdra, Efthimia K; Papavassiliou, Athanasios G

2010-01-01

Abstract Several conditions in clinical orthopaedic practice can lead to the development of a diaphyseal segmental bone defect, which cannot heal without intervention. Segmental bone defects have been traditionally treated with bone grafting and/or distraction osteogenesis, methods that have many advantages, but also major drawbacks, such as limited availability, risk of disease transmission and prolonged treatment. In order to overcome such limitations, biological treatments have been developed based on specific pathways of bone physiology and healing. Bone tissue engineering is a dynamic field of research, combining osteogenic cells, osteoinductive factors, such as bone morphogenetic proteins, and scaffolds with osteoconductive and osteoinductive attributes, to produce constructs that could be used as bone graft substitutes for the treatment of segmental bone defects. Scaffolds are usually made of ceramic or polymeric biomaterials, or combinations of both in composite materials. The purpose of the present review is to discuss in detail the molecular and cellular basis for the development of bone tissue engineering constructs. PMID:20345845

Longitudinal relationships between whole body and central adiposity on weight-bearing bone geometry, density, and bone strength: a pQCT study in young girls

PubMed Central

Farr, Joshua N.; Laudermilk, Monica J.; Lee, Vinson R.; Blew, Robert M.; Stump, Craig; Houtkooper, Linda; Lohman, Timothy G.; Going, Scott B.

2015-01-01

Summary Longitudinal relationships between adiposity (total body and central) and bone development were assessed in young girls. Total body and android fat masses were positively associated with bone strength and density parameters of the femur and tibia. These results suggest adiposity may have site-specific stimulating effects on the developing bone. Introduction Childhood obesity may impair bone development, but the relationships between adiposity and bone remain unclear. Failure to account for fat pattern may explain the conflicting results. Purpose Longitudinal associations of total body fat mass (TBFM) and android fat mass (AFM) with 2-year changes in weight-bearing bone parameters were examined in 260 girls aged 8–13 years at baseline. Peripheral quantitative computed tomography was used to measure bone strength index (BSI, square milligrams per quartic millimeter), strength–strain index (SSI, cubic millimeters), and volumetric bone mineral density (vBMD, milligrams per cubic centimeter) at distal metaphyseal and diaphyseal regions of the femur and tibia. TBFM and AFM were assessed by dual-energy x-ray absorptiometry. Results Baseline TBFM and AFM were positively associated with the change in femur BSI (r =0.20, r =0.17, respectively) and femur trabecular vBMD (r =0.19, r =0.19, respectively). Similarly, positive associations were found between TBFM and change in tibia BSI and SSI (r =0.16, r =0.15, respectively), and femur total and trabecular vBMD (r =0.12, r =0.14, respectively). Analysis of covariance showed that girls in the middle thirds of AFM had significantly lower femur trabecular vBMD and significantly higher tibia cortical vBMD than girls in the highest thirds of AFM. All results were significant at p <0.05. Conclusions Whereas baseline levels of TBFM and AFM are positive predictors of bone strength and density at the femur and tibia, higher levels of AFM above a certain level may impair cortical vBMD growth at weight-bearing sites. Future studies in obese children will be needed to test this possibility. NIH/NICHD #HD-050775. PMID:24113839

Bone health in Down syndrome.

PubMed

García-Hoyos, Marta; Riancho, José Antonio; Valero, Carmen

2017-07-21

Patients with Down syndrome have a number of risk factors that theoretically could predispose them to osteoporosis, such as early aging, development disorders, reduced physical activity, limited sun exposure, frequent comorbidities and use of drug therapies which could affect bone metabolism. In addition, the bone mass of these people may be affected by their anthropometric and body composition peculiarities. In general terms, studies in adults with Down syndrome reported that these people have lower areal bone mineral density (g/cm 2 ) than the general population. However, most of them have not taken the smaller bone size of people with Down syndrome into account. In fact, when body mineral density is adjusted by bone size and we obtain volumetric body mineral density (g/cm 3 ), the difference between both populations disappears. On the other hand, although people with Down syndrome have risk factor of hypovitaminosis D, the results of studies regarding 25(OH)D in this population are not clear. Likewise, the studies about biochemical bone markers or the prevalence of fractures are not conclusive. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Bone Repair and Military Readiness

DTIC Science & Technology

2013-10-19

prototype in animal models. By addressing the shortcomings of current PMMA bone cement, the development of the novel silorane bone cement will result in a...heat generation. We have developed a silorane based resin superior to polymethyl methacrylate ( PMMA ) with many improved properties such as significantly...treatment of patients. By addressing the shortcomings of current PMMA bone cement, the development of the novel silorane bone cement will result in a

Label-free Raman spectroscopy provides early determination and precise localization of breast cancer-colonized bone alterations.

PubMed

Zhang, Chi; Winnard, Paul T; Dasari, Sidarth; Kominsky, Scott L; Doucet, Michele; Jayaraman, Swaathi; Raman, Venu; Barman, Ishan

2018-01-21

Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones - significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer.

Multidisciplinary characterization of the long-bone cortex growth patterns through sheep's ontogeny.

PubMed

Cambra-Moo, Oscar; Nacarino-Meneses, Carmen; Díaz-Güemes, Idoia; Enciso, Silvia; García Gil, Orosia; Llorente Rodríguez, Laura; Rodríguez Barbero, Miguel Ángel; de Aza, Antonio H; González Martín, Armando

2015-07-01

Bone researches have studied extant and extinct taxa extensively trying to disclose a complete view of the complex structural and chemical transformations that model and remodel the macro and microstructure of bone during growth. However, to approach bone growth variations is not an easy task, and many aspects related with histological transformations during ontogeny remain unresolved. In the present study, we conduct a holistic approach using different techniques (polarized microscopy, Raman spectroscopy and X-ray diffraction) to examine the histomorphological and histochemical variations in the cortical bone of sheep specimens from intrauterine to adult stages, using environmentally controlled specimens from the same species. Our results suggest that during sheep bone development, the most important morphological (shape and size) and chemical transformations in the cortical bone occur during the first weeks of life; synchronized but dissimilar variations are established in the forelimb and hind limb cortical bone; and the patterns of bone tissue maturation in both extremities are differentiated in the adult stage. All of these results indicate that standardized histological models are useful not only for evaluating many aspects of normal bone growth but also to understand other important influences on the bones, such as pathologies that remain unknown. Copyright © 2015 Elsevier Inc. All rights reserved.

Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration.

PubMed

Freeman, Fiona E; McNamara, Laoise M

2017-04-01

Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for bone tissue graft.

Bone-Protective Effects of Dried Plum in Postmenopausal Women: Efficacy and Possible Mechanisms

PubMed Central

Arjmandi, Bahram H.; Johnson, Sarah A.; Pourafshar, Shirin; Navaei, Negin; George, Kelli S.; Hooshmand, Shirin; Chai, Sheau C.; Akhavan, Neda S.

2017-01-01

Osteoporosis is an age-related chronic disease characterized by a loss of bone mass and quality, and is associated with an increased risk of fragility fractures. Postmenopausal women are at the greatest risk of developing osteoporosis due to the cessation in ovarian hormone production, which causes accelerated bone loss. As the demographic shifts to a more aged population, a growing number of postmenopausal women will be afflicted with osteoporosis. Certain lifestyle factors, including nutrition and exercise, are known to reduce the risk of developing osteoporosis and therefore play an important role in bone health. In terms of nutrition, accumulating evidence suggests that dried plum (Prunus domestica L.) is potentially an efficacious intervention for preventing and reversing bone mass and structural loss in an ovariectomized rat model of osteoporosis, as well as in osteopenic postmenopausal women. Here, we provide evidence supporting the efficacy of dried plum in preventing and reversing bone loss associated with ovarian hormone deficiency in rodent models and in humans. We end with the results of a recent follow-up study demonstrating that postmenopausal women who previously consumed 100 g dried plum per day during our one-year clinical trial conducted five years earlier retained bone mineral density to a greater extent than those receiving a comparative control. Additionally, we highlight the possible mechanisms of action by which bioactive compounds in dried plum exert bone-protective effects. Overall, the findings of our studies and others strongly suggest that dried plum in its whole form is a promising and efficacious functional food therapy for preventing bone loss in postmenopausal women, with the potential for long-lasting bone-protective effects. PMID:28505102

The role of extracellular matrix components in pin bone attachments during storage-a comparison between farmed Atlantic salmon (Salmo salar) and cod (Gadus morhua L.).

PubMed

Rønning, Sissel B; Østbye, Tone-Kari; Krasnov, Aleksei; Vuong, Tram T; Veiseth-Kent, Eva; Kolset, Svein O; Pedersen, Mona E

2017-04-01

Pin bones represent a major problem for processing and quality of fish products. Development of methods of removal requires better knowledge of the pin bones' attachment to the muscle and structures involved in the breakdown during loosening. In this study, pin bones from cod and salmon were dissected from fish fillets after slaughter or storage on ice for 5 days, and thereafter analysed with molecular methods, which revealed major differences between these species before and after storage. The connective tissue (CT) attaches the pin bone to the muscle in cod, while the pin bones in salmon are embedded in adipose tissue. Collagens, elastin, lectin-binding proteins and glycosaminoglycans (GAGs) are all components of the attachment site, and this differ between salmon and cod, resulting in a CT in cod that is more resistant to enzymatic degradation compared to the CT in salmon. Structural differences are reflected in the composition of transcriptome. Microarray analysis comparing the attachment sites of the pin bones with a reference muscle sample showed limited differences in salmon. In cod, on the other hand, the variances were substantial, and the gene expression profiles suggested difference in myofibre structure, metabolism and cell processes between the pin bone attachment site and the reference muscle. Degradation of the connective tissue occurs closest to the pin bones and not in the neighbouring tissue, which was shown using light microscopy. This study shows that the attachment of the pin bones in cod and salmon is different; therefore, the development of methods for removal should be tailored to each individual species.

Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.

PubMed

Hambli, Ridha

2014-01-01

Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone adaptation. The proposed FEM model gives insight into how bone cells adapt their architecture to the mechanical and biological environment.

Prebiotic and Probiotic Regulation of Bone Health: Role of the Intestine and its Microbiome

PubMed Central

McCabe, Laura; Britton, Robert A.; Parameswaran, Narayanan

2015-01-01

Recent advances in our understanding of how the intestinal microbiome contributes to health and disease have generated great interest in developing strategies for modulating the abundance of microbes and/or their activity to improve overall human health and prevent pathologies such as osteoporosis. Bone is an organ that the gut has long been known to regulate through absorption of calcium, the key bone mineral. However, it is clear that modulation of the gut and its microbiome can affect bone density and strength in a variety of animal models (zebra fish, rodents, chicken) and humans. This is demonstrated in studies ablating the microbiome through antibiotic treatment or using germ-free mouse conditions as well as in studies modulating the microbiome activity and composition through prebiotic and/or probiotic treatment. This review will discuss recent developments in this new and exciting area. PMID:26419466

Differential proteomic analysis of a human breast tumor and its matched bone metastasis identifies cell membrane and extracellular proteins associated with bone metastasis.

PubMed

Dumont, Bruno; Castronovo, Vincent; Peulen, Olivier; Blétard, Noëlla; Clézardin, Philippe; Delvenne, Philippe; De Pauw, Edwin A; Turtoi, Andrei; Bellahcène, Akeila

2012-04-06

The classical fate of metastasizing breast cancer cells is to seed and form secondary colonies in bones. The molecules closely associated with these processes are predominantly present at the cell surface and in the extracellular space, establishing the first contacts with the target tissue. In this study, we had the rare opportunity to analyze a bone metastatic lesion and its corresponding breast primary tumor obtained simultaneously from the same patient. Using mass spectrometry, we undertook a proteomic study on cell surface and extracellular protein-enriched material. We provide a repertoire of significantly modulated proteins, some with yet unknown roles in the bone metastatic process as well as proteins notably involved in cancer cell invasiveness and in bone metabolism. The comparison of these clinical data with those previously obtained using a human osteotropic breast cancer cell line highlighted an overlapping group of proteins. Certain differentially expressed proteins are validated in the present study using immunohistochemistry on a retrospective collection of breast tumors and matched bone metastases. Our exclusive set of selected proteins supports the setup of further investigations on both clinical samples and experimental bone metastasis models that will help to reveal the finely coordinated expression of proteins that favor the development of metastases in the bone microenvironment.

Disturbances of bone growth and development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ledesma-Medina, J.; Newman, B.; Oh, K.S.

1988-03-01

''What is growth anyway. Can one talk about positive growth in childhood, neutral growth in maturity, and negative growth in old age. Our goal is to help promote normal positive growth in infants and children. To achieve this, we must be cognizant of the morphologic changes of both normal and abnormal bone formation as they are reflected in the radiographic image of the skeleton. The knowledge of the various causes and the pathophysiologic mechanisms of the disturbances of bone growth and development allows us to recognize the early radiographic manifestations. Endocrine and metabolic disorders affect the whole skeleton, but themore » early changes are best seen in the distal ends of the femurs, where growth rate is most rapid. In skeletal infections and in some vascular injuries two-or three-phase bone scintigraphy supercedes radiography early in the course of the disease. MRI has proved to be very helpful in the early detection of avascular bone necrosis, osteomyelitis, and tumor. Some benign bone tumors and many bone dysplasias have distinct and diagnostic radiographic findings that may preclude further studies. In constitutional diseases of bone, including chromosomal aberrations, skeletal surveys of the patient and all family members together with biochemical and cytogenetic studies are essential for both diagnosis and genetic counseling. Our role is to perform the least invasive and most informative diagnostic imaging modalities that corroborate the biochemical and histologic findings to establish the definitive diagnosis. Unrecognized, misdiagnosed, or improperly treated disturbance of bone growth can result in permanent deformity usually associated with disability. 116 references.« less

Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.

PubMed

Hogan, Mary Beth; Piktel, Debra; Hubbs, Ann F; McPherson, Leslie E; Landreth, Kenneth S

2008-12-01

Patient factors that cause long-term airway remodeling are largely unidentified. This suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. To investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. The C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure.

Study of Osteoclast Adhesion to Cortical Bone Surfaces: A Correlative Microscopy Approach for Concomitant Imaging of Cellular Dynamics and Surface Modifications

PubMed Central

2015-01-01

Bone remodeling relies on the coordinated functioning of osteoblasts, bone-forming cells, and osteoclasts, bone-resorbing cells. The effects of specific chemical and physical bone features on the osteoclast adhesive apparatus, the sealing zone ring, and their relation to resorption functionality are still not well-understood. We designed and implemented a correlative imaging method that enables monitoring of the same area of bone surface by time-lapse light microscopy, electron microscopy, and atomic force microscopy before, during, and after exposure to osteoclasts. We show that sealing zone rings preferentially develop around surface protrusions, with lateral dimensions of several micrometers, and ∼1 μm height. Direct overlay of sealing zone rings onto resorption pits on the bone surface shows that the rings adapt to pit morphology. The correlative procedure presented here is noninvasive and performed under ambient conditions, without the need for sample labeling. It can potentially be applied to study various aspects of cell-matrix interactions. PMID:26682493

Histological analysis of the alterations on cortical bone channels network after radiotherapy: A rabbit study.

PubMed

Rabelo, Gustavo Davi; Beletti, Marcelo Emílio; Dechichi, Paula

2010-10-01

The aim of this study was to evaluate the effects of radiotherapy in cortical bone channels network. Fourteen rabbits were divided in two groups and test group received single dose of 15 Gy cobalt-60 radiation in tibia, bilaterally. The animals were sacrificed and a segment of tibia was removed and histologically processed. Histological images were taken and had their bone channels segmented and called regions of interest (ROI). Images were analyzed through developed algorithms using the SCILAB mathematical environment, getting percentage of bone matrix, ROI areas, ROI perimeters, their standard deviations and Lacunarity. The osteocytes and empty lacunae were also counted. Data were evaluated using Kolmogorov-Smirnov, Mann Whitney, and Student's t test (P < 0.05). Significant differences in bone matrix percentage, area and perimeters of the channels, their respective standard deviations and lacunarity were found between groups. In conclusion, the radiotherapy causes reduction of bone matrix and modifies the morphology of bone channels network. © 2010 Wiley-Liss, Inc.

Tissue Reaction to a Novel Bone Substitute Material Fabricated With Biodegradable Polymer-Calcium Phosphate Nanoparticle Composite.

PubMed

Shimizu, Hideo; Jinno, Yohei; Ayukawa, Yasunori; Atsuta, Ikiru; Arahira, Takaaki; Todo, Mitsugu; Koyano, Kiyoshi

2016-10-01

The aim of this study was to evaluate the effectiveness of a novel bone substitute material fabricated using a biodegradable polymer-calcium phosphate nanoparticle composite. Porous structured poly-L-lactic acid (PLLA) and hydroxyapatite (HA) nanoparticle composite, which was fabricated using solid-liquid phase separation and freeze-drying methods, was grafted into bone defects created in rat calvarium or tibia. Rats were killed 4 weeks after surgery, and histological analyses were performed to evaluate new bone formation. Scanning electron microscopic observation showed the interconnecting pores within the material and the pore diameter was approximately 100 to 300 μm. HA nanoparticles were observed to be embedded into the PLLA beams. In the calvarial implantation model, abundant blood vessels and fibroblastic cells were observed penetrating into pores, and in the tibia model, newly formed bone was present around and within the composite. The PLLA-HA nanoparticle composite bone substitute developed in this study showed biocompatibility, elasticity, and operability and thus has potential as a novel bone substitute.

Bone Histology in Dysalotosaurus lettowvorbecki (Ornithischia: Iguanodontia) – Variation, Growth, and Implications

PubMed Central

Hübner, Tom R.

2012-01-01

Background Dysalotosaurus lettowvorbecki is a small ornithopod dinosaur known from thousands of bones and several ontogenetic stages. It was found in a single locality within the Tendaguru Formation of southeastern Tanzania, possibly representing a single herd. Dysalotosaurus provides an excellent case study for examining variation in bone microstructure and life history and helps to unravel the still mysterious growth pattern of small ornithopods. Methodology/Principal Findings Five different skeletal elements were sampled, revealing microstructural variation between individuals, skeletal elements, cross sectional units, and ontogenetic stages. The bone wall consists of fibrolamellar bone with strong variability in vascularization and development of growth cycles. Larger bones with a high degree of utilization have high relative growth rates and seldom annuli/LAGs, whereas small and less intensively used bones have lower growth rates and a higher number of these resting lines. Due to the scarcity of annuli/LAGs, the reconstruction of the life history of Dysalotosaurus was carried out using regularly developed and alternating slow and fast growing zones. Dysalotosaurus was a precocial dinosaur, which experienced sexual maturity at ten years, had an indeterminate growth pattern, and maximum growth rates comparable to a large kangaroo. Conclusions/Significance The variation in the bone histology of Dysalotosaurus demonstrates the influence of size, utilization, and shape of bones on relative growth rates. Annuli/LAGs are not the only type of annual growth cycles that can be used to reconstruct the life history of fossil vertebrates, but the degree of development of these lines may be of importance for the reconstruction of paleobehavior. The regular development of annuli/LAGs in subadults and adults of large ornithopods therefore reflects higher seasonal stress due to higher food demands, migration, and altricial breeding behavior. Small ornithopods often lack regularly developed annuli/LAGs due to lower food demands, no need for migration, and precocial behavior. PMID:22238683

Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

PubMed Central

Cottrell, Jessica A.; Vales, Francis M.; Schachter, Deborah; Wadsworth, Scott; Gundlapalli, Rama; Kapadia, Rasesh; O'Connor, J. Patrick

2010-01-01

The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts. PMID:20625499

[Osteoporosis treatment in patients with hyperthyroidism].

PubMed

Saito, Jun; Nishikawa, Tetsuo

2009-05-01

Childhood thyroid hormone (T3) is essential for the normal development of endochondral and intramembranous bone and plays an important role in the linear growth and maintenance of bone mass. In adult, T3 stimulates osteoclastic bone resorption mediated primarily by TR alpha and local conversion by deiodinase D2 may play a role in local activation. TSH seems to be an inhibitor of bone resorption and formation. In thyrotoxicosis patients with Graves' disease, there is increased bone remodelling, characterized by an imbalance between bone resorption and formation, which results in a decrease of bone mineral density (BMD) and an increased risk for osteoporotic fracture. Antithyroid treatment is able to reduce dramatically the bone resorption and to normalize BMD reduction. But previous hyperthyroidism is independently associated with an increased risk for fracture. Although further studies relating to the mechanism for possible impaired bone strength in these patients will be needed, bisphosphonates may be beneficial treatment for prevention of bone fractures in patients with severe risk for fractures, such as post-menopausal women.

In vitro characterization of MG-63 osteoblast-like cells cultured on organic-inorganic lyophilized gelatin sponges for early bone healing.

PubMed

Rodriguez, Isaac A; Saxena, Gunjan; Hixon, Katherine R; Sell, Scott A; Bowlin, Gary L

2016-08-01

The development of three-dimensional porous scaffolds with enhanced osteogenic and angiogenic potential would be beneficial for inducing early-stage bone regeneration. Previous studies have demonstrated the advantages of mineralized and nonmineralized acellular 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linked gelatin sponges enhanced with preparations rich in growth factors, hydroxyapatite, and chitin whiskers. In this study, those same scaffolds were mineralized and dynamically seeded with MG-63 cells. Cell proliferation, protein/cytokine secretion, and compressive mechanical properties of scaffolds were evaluated. It was found that mineralization and the addition of growth factors increased cell proliferation compared to gelatin controls. Cells on all scaffolds responded in an appropriate bone regenerative fashion as shown through osteocalcin secretion and little to no secretion of bone resorbing markers. However, compressive mechanical properties of cellularized scaffolds were not significantly different from acellular scaffolds. The combined results of increased cellular attachment, infiltration, and bone regenerative protein/cytokine secretion on scaffolds support the need for the addition of a bone-like mineral surface. Cellularized scaffolds containing growth factors reported similar advantages and mechanical values in the range of native tissues present in the early stages of bone healing. These results suggest that the developed composite sponges exhibited cellular responses and mechanical properties appropriate for promoting early bone healing in various applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2011-2019, 2016. © 2016 Wiley Periodicals, Inc.

Mechanical signaling in the development of postmenopausal osteoporosis

NASA Technical Reports Server (NTRS)

Turner, R. T.

1999-01-01

Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

[Fetal programming and the etiology of osteoporosis].

PubMed

Pieńkowski, Wojciech; Wolski, Hubert; Drews, Krzysztof; Seremak-Mrozikiewicz, Agnieszka

2015-08-01

Osteoporosis is a multifactorial skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. Peak bone mass is an important predictor of later risk of osteoporosis. Epidemiological studies revealed that the risk of osteoporosis might be modified by exposure to environmental factors during intrauterine life and early postnatal period. This review summarizes the influence of fetal programming on the development of osteoporosis based on the epidemiological studies and potential mechanisms of epigenetic regulation of gene expression.

Muscle volume is related to trabecular and cortical bone architecture in typically developing children.

PubMed

Bajaj, Deepti; Allerton, Brianne M; Kirby, Joshua T; Miller, Freeman; Rowe, David A; Pohlig, Ryan T; Modlesky, Christopher M

2015-12-01

Muscle is strongly related to cortical bone architecture in children; however, the relationship between muscle volume and trabecular bone architecture is poorly studied. The aim of this study was to determine if muscle volume is related to trabecular bone architecture in children and if the relationship is different than the relationship between muscle volume and cortical bone architecture. Forty typically developing children (20 boys and 20 girls; 6 to 12y) were included in the study. Measures of trabecular bone architecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the distal femur, cortical bone architecture [cortical volume, total volume, section modulus (Z) and polar moment of inertia (J)] in the midfemur, muscle volume in the midthigh and femur length were assessed using magnetic resonance imaging. Total physical activity and moderate-to-vigorous physical activity were assessed using an accelerometer-based activity monitor worn around the waist for four days. Calcium intake was assessed using diet records. Relationships among the measures were tested using multiple linear regression analysis. Muscle volume was moderately-to-strongly related to measures of trabecular bone architecture [appBV/TV (r=0.81), appTb.N (r=0.53), appTb.Th (r=0.67), appTb.Sp (r=-0.71); all p<0.001] but more strongly related to measures of cortical bone architecture [cortical volume (r=0.96), total volume (r=0.94), Z (r=0.94) and J (r=0.92; all p<0.001)]. Similar relationships were observed between femur length and measures of trabecular (p<0.01) and cortical (p<0.001) bone architecture. Sex, physical activity and calcium intake were not related to any measure of bone architecture (p>0.05). Because muscle volume and femur length were strongly related (r=0.91, p<0.001), muscle volume was scaled for femur length (muscle volume/femur length(2.77)). When muscle volume/femur length(2.77) was included in a regression model with femur length, sex, physical activity and calcium intake, muscle volume/femur length(2.77) was a significant predictor of appBV/TV, appTb.Th and appTb.Sp (partial r=0.44 to 0.49, p<0.05) and all measures of cortical bone architecture (partial r=0.47 to 0.54; p<0.01). The findings suggest that muscle volume in the midthigh is related to trabecular bone architecture in the distal femur of typically developing children. The relationship is weaker than the relationship between muscle volume in the midthigh and cortical bone architecture in the midfemur, but the discrepancy is driven, in large part, by the greater dependence of cortical bone architecture measures on femur length. Copyright © 2015. Published by Elsevier Inc.

Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization.

PubMed

Holm, Erik; Aubin, Jane E; Hunter, Graeme K; Beier, Frank; Goldberg, Harvey A

2015-02-01

Bone sialoprotein (BSP) is an anionic phosphoprotein in the extracellular matrix of mineralized tissues, and a promoter of biomineralization and osteoblast development. Previous studies on the Bsp-deficient mouse (Bsp(-/-)) have demonstrated a significant bone and periodontal tissue phenotype in adulthood. However, the role of BSP during early long bone development is not known. To address this, early endochondral ossification in the Bsp(-/-) mouse was studied. Embryonic day 15.5 (E15.5) wild-type (WT) tibiae showed early stages of ossification that were absent in Bsp(-/-) mice. At E16.5, mineralization had commenced in the Bsp(-/-) mice, but staining for mineral was less intense and more dispersed compared with that in WT controls. Tibiae from Bsp(-/-) mice also demonstrated decreased mineralization and shortened length at postnatal day 0.5 (P0.5) compared to WT bones. There was no detectable difference in the number of tartrate-resistant acid phosphatase-positive foci at P0.5, although the P0.5 Bsp(-/-) tibiae had decreased Vegfα expression compared with WT tissue. Due to the shortened tibiae the growth plates were examined and determined to be of normal overall length. However, the length of the resting zone was increased in P0.5 Bsp(-/-) tibiae whereas that of the proliferative zone was decreased, with no change in the hypertrophic zone length of Bsp(-/-) mice. A reduction in cells positive for Ki-67, an S-phase cell-cycle marker, was noted in the proliferative zone. Decreased numbers of TUNEL-positive hypertrophic chondrocytes were also apparent in the Bsp(-/-) tibial growth plates, suggesting decreased apoptosis. Expression of the osteogenic markers Alp1, Col1a1, Sp7, Runx2, and Bglap was reduced in the endochondral bone of the neonatal Bsp(-/-) compared to WT tibiae. These results suggest that BSP is an important and multifaceted protein that regulates both chondrocyte proliferation and apoptosis as well as transition from cartilage to bone during development of endochondral bone. Copyright © 2014 Elsevier Inc. All rights reserved.

Osthole inhibits bone metastasis of breast cancer

PubMed Central

Guo, Baofeng; Ye, Yiyi; Han, Xianghui; Qin, Yuenong; Liu, Sheng

2017-01-01

Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potential mechanism of this inhibition. In the murine model of breast cancer osseous metastasis, mice that received osthole developed significantly less bone metastases and displayed decreased tumor burden when compared with mice in the control group. Osthole inhibited breast cancer cell growth, migration, and invasion, and induced apoptosis of breast cancer cells. Additionally, it also regulated OPG/RANKL signals in the interactions between bone cells (osteoblasts and osteoclasts) and cancer cells. Besides, it also inhibited TGF-β/Smads signaling in breast cancer metastasis to bone in MDA-231BO cells. The results of this study suggest that osthole has real potential as a therapeutic candidate in the treatment of breast cancer patients with bone metastases. PMID:28938572

Indentation experiments and simulation of ovine bone using a viscoelastic-plastic damage model

PubMed Central

Zhao, Yang; Wu, Ziheng; Turner, Simon; MacLeay, Jennifer; Niebur, Glen L.; Ovaert, Timothy C.

2015-01-01

Indentation methods have been widely used to study bone at the micro- and nanoscales. It has been shown that bone exhibits viscoelastic behavior with permanent deformation during indentation. At the same time, damage due to microcracks is induced due to the stresses beneath the indenter tip. In this work, a simplified viscoelastic-plastic damage model was developed to more closely simulate indentation creep data, and the effect of the model parameters on the indentation curve was investigated. Experimentally, baseline and 2-year postovariectomized (OVX-2) ovine (sheep) bone samples were prepared and indented. The damage model was then applied via finite element analysis to simulate the bone indentation data. The mechanical properties of yielding, viscosity, and damage parameter were obtained from the simulations. The results suggest that damage develops more quickly for OVX-2 samples under the same indentation load conditions as the baseline data. PMID:26136623

Central Nervous System Fibrosis Is Associated with Fibrocyte-Like Infiltrates

PubMed Central

Aldrich, Amy; Kielian, Tammy

2011-01-01

Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow–derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrow–derived cells were capable of acquiring fibrotic characteristics during brain abscess development. Immunofluorescence staining revealed partial overlap between green fluorescent protein, α-smooth muscle actin, and procollagen, suggesting that a population of cells forming the brain abscess capsule originate from a bone marrow precursor. In addition, the influx of fibrocyte-like cells into brain abscesses immediately preceded the onset of fibrotic encapsulation. Fibrotic wall formation was also associated with increased numbers of alternatively activated M2 microglia and macrophages. To our knowledge, this is the first study demonstrating that bone marrow–derived infiltrates are capable of expressing fibrotic molecules during CNS inflammation. PMID:22015460

Automated cortical bone segmentation for multirow-detector CT imaging with validation and application to human studies

PubMed Central

Li, Cheng; Jin, Dakai; Chen, Cheng; Letuchy, Elena M.; Janz, Kathleen F.; Burns, Trudy L.; Torner, James C; Levy, Steven M.; Saha, Punam K

2015-01-01

Purpose: Cortical bone supports and protects human skeletal functions and plays an important role in determining bone strength and fracture risk. Cortical bone segmentation at a peripheral site using multirow-detector CT (MD-CT) imaging is useful for in vivo assessment of bone strength and fracture risk. Major challenges for the task emerge from limited spatial resolution, low signal-to-noise ratio, presence of cortical pores, and structural complexity over the transition between trabecular and cortical bones. An automated algorithm for cortical bone segmentation at the distal tibia from in vivo MD-CT imaging is presented and its performance and application are examined. Methods: The algorithm is completed in two major steps—(1) bone filling, alignment, and region-of-interest computation and (2) segmentation of cortical bone. After the first step, the following sequence of tasks is performed to accomplish cortical bone segmentation—(1) detection of marrow space and possible pores, (2) computation of cortical bone thickness, detection of recession points, and confirmation and filling of true pores, and (3) detection of endosteal boundary and delineation of cortical bone. Effective generalizations of several digital topologic and geometric techniques are introduced and a fully automated algorithm is presented for cortical bone segmentation. Results: An accuracy of 95.1% in terms of volume of agreement with manual outlining of cortical bone was observed in human MD-CT scans, while an accuracy of 88.5% was achieved when compared with manual outlining on postregistered high resolution micro-CT imaging. An intraclass correlation coefficient of 0.98 was obtained in cadaveric repeat scans. A pilot study was conducted to describe gender differences in cortical bone properties. This study involved 51 female and 46 male participants (age: 19–20 yr) from the Iowa Bone Development Study. Results from this pilot study suggest that, on average after adjustment for height and weight differences, males have thicker cortex (mean difference 0.33 mm and effect size 0.92 at the anterior region) with lower bone mineral density (mean difference −28.73 mg/cm3 and effect size 1.35 at the posterior region) as compared to females. Conclusions: The algorithm presented is suitable for fully automated segmentation of cortical bone in MD-CT imaging of the distal tibia with high accuracy and reproducibility. Analysis of data from a pilot study demonstrated that the cortical bone indices allow quantification of gender differences in cortical bone from MD-CT imaging. Application to larger population groups, including those with compromised bone, is needed. PMID:26233184

Bioglass incorporation improves mechanical properties and enhances cell-mediated mineralization on electrochemically aligned collagen threads.

PubMed

Nijsure, Madhura P; Pastakia, Meet; Spano, Joseph; Fenn, Michael B; Kishore, Vipuil

2017-09-01

Bone tissue engineering mandates the development of a functional scaffold that mimics the physicochemical properties of native bone. Bioglass 45S5 (BG) is a highly bioactive material known to augment bone formation and restoration. Hybrid scaffolds fabricated using collagen type I and BG resemble the organic and inorganic composition of the bone extracellular matrix and hence have been extensively investigated for bone tissue engineering applications. However, collagen-BG scaffolds developed thus far do not recapitulate the aligned structure of collagen found in native bone. In this study, an electrochemical fabrication method was employed to synthesize BG-incorporated electrochemically aligned collagen (BG-ELAC) threads that are compositionally similar to native bone. Further, aligned collagen fibrils within BG-ELAC threads mimic the anisotropic arrangement of collagen fibrils in native bone. The effect of BG incorporation on the mechanical properties and cell-mediated mineralization on ELAC threads was investigated. The results indicated that BG can be successfully incorporated within ELAC threads, without disturbing collagen fibril alignment. Further, BG incorporation significantly increased the ultimate tensile stress (UTS) and modulus of ELAC threads (p < 0.05). SBF conditioning showed extensive mineralization on BG-ELAC threads that increased over time demonstrating the bone bioactivity of BG-ELAC threads. Additionally, BG incorporation into ELAC threads resulted in increased cell proliferation (p < 0.05) and deposition of a highly dense and continuous mineralized matrix. In conclusion, incorporation of BG into ELAC threads is a viable strategy for the development of an osteoconductive material for bone tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2429-2440, 2017. © 2017 Wiley Periodicals, Inc.

Absence of bone sialoprotein (BSP) impairs cortical defect repair in mouse long bone.

PubMed

Malaval, Luc; Monfoulet, Laurent; Fabre, Thierry; Pothuaud, Laurent; Bareille, Reine; Miraux, Sylvain; Thiaudiere, Eric; Raffard, Gerard; Franconi, Jean-Michel; Lafage-Proust, Marie-Hélène; Aubin, Jane E; Vico, Laurence; Amédée, Joëlle

2009-11-01

Matrix proteins of the SIBLING family interact with bone cells and with bone mineral and are thus in a key position to regulate bone development, remodeling and repair. Within this family, bone sialoprotein (BSP) is highly expressed by osteoblasts, hypertrophic chondrocytes and osteoclasts. We recently reported that mice lacking BSP (BSP-/-) have very low trabecular bone turnover. In the present study, we set up an experimental model of bone repair by drilling a 1 mm diameter hole in the cortical bone of femurs in both BSP-/- and +/+ mice. A non-invasive MRI imaging and bone quantification procedure was designed to follow bone regeneration, and these data were extended by microCT imaging and histomorphometry on undecalcified sections for analysis at cellular level. These combined approaches revealed that the repair process as reflected in defect-refilling in the cortical area was significantly delayed in BSP-/- mice compared to +/+ mice. Concomitantly, histomorphometry showed that formation, mineralization and remodeling of repair (primary) bone in the medulla were delayed in BSP-/- mice, with lower osteoid and osteoclast surfaces at day 15. In conclusion, the absence of BSP delays bone repair at least in part by impairing both new bone formation and osteoclast activity.

NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

PubMed Central

Yao, Zhenqiang; Li, Yanyun; Yin, Xiaoxiang; Dong, Yufeng; Xing, Lianping; Boyce, Brendan F.

2013-01-01

RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through non-canonical signaling, but they involved a complex knockout mouse model and the molecular mechanisms involved were not investigated. Here, we report that RelB−/− mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB−/− bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runx2. In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB−/− bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. PMID:24115294

The associations of exposure to combined hormonal contraceptive use on bone mineral content and areal bone mineral density accrual from adolescence to young adulthood: A longitudinal study.

PubMed

Jackowski, Stefan A; Baxter-Jones, Adam D G; McLardy, Ashlee J; Pierson, Roger A; Rodgers, Carol D

2016-12-01

The association of long term combined hormone based contraceptives (CHC) use on bone mineral content (BMC) and areal bone mineral density (aBMD) development remains controversial, as it appears that the relationship may be age-dependent. The purpose of this study was to investigate the long-term associations of CHC exposure on the accrual of bone parameters from adolescence into young-adulthood. 110 women (67 exposed to CHC) were drawn from the Pediatric Bone Mineral Accrual Study (PBMAS). Serial measures of total body (TB), lumbar spine (LS) and femoral neck (FN) BMC and aBMD were assessed by DXA (a total of 950 scans) and aligned by biological age (BA, years from peak height velocity [PHV]). Multilevel random effects models were constructed to assess the time dependent associations between annual CHC exposure and the development of bone parameters. After BA, height, lean tissue mass, fat mass, calcium and vitamin D intake, and physical activity were controlled, it was observed that those individuals exposed to CHC 6-years post PHV developed significantly less (-0.00986 ± 0.00422 g/cm 2 ) TB aBMD than their non CHC exposed peers. Additionally, there were significant BA by CHC exposure interactions, where CHC exposure 6-years or more post PHV resulted in developing less TB BMC (-4.94 ± 2.41 g), LS BMC (-0.29 ± 0.11 g) and LS aBMD (-0.00307 ± 0.00109 g/cm 2 ). One year after the attainment of PHV, CHC users were predicted to have 1.2% more TB BMC, 3.8% more LS BMC and 1.7% more LS aBMD than non-users. At 9-years post PHV the predicted differences showed that CHC users had 0.9% less TB BMC and 2.7% less LS BMC and 1.6% less LS BMD than those not exposed to CHC. CHC may not hinder the development of BMC or aBMD during adolescence; however, exposure 6-years or more after PHV may be detrimental.

Use of cervical vertebral dimensions for assessment of children growth.

PubMed

Caldas, Maria de Paula; Ambrosano, Gláucia Maria Bovi; Haiter-Neto, Francisco

2007-04-01

The purpose of this study was to investigate whether skeletal maturation using cephalometric radiographs could be used in a Brazilian population. The study population was selected from the files of the Oral Radiological Clinic of the Dental School of Piracicaba, Brazil and consisted of 128 girls and 110 boys (7.0 to 15.9 years old) who had cephalometric and hand-wrist radiographs taken on the same day. Cervical vertebral bone age was evaluated using the method described by Mito and colleagues in 2002. Bone age was assessed by the Tanner-Whitehouse (TW3) method and was used as a gold standard to determine the reliability of cervical vertebral bone age. An analysis of variance and Tukey's post-hoc test were used to compare cervical vertebral bone age, bone age and chronological age at 5% significance level. The analysis of the Brazilian female children data showed that there was a statistically significant difference (p<0.05) between cervical vertebral bone age and chronological age and between bone age and chronological age. However no statistically significant difference (p>0.05) was found between cervical vertebral bone age and bone age. Differently, the analysis of the male children data revealed a statistically significant difference (p<0.05) between cervical vertebral bone age and bone age and between cervical vertebral bone age and chronological age (p<0.05). The findings of the present study suggest that the method for objectively evaluating skeletal maturation on cephalometric radiographs by determination of vertebral bone age can be applied to Brazilian females only. The development of a new method to objectively evaluate cervical vertebral bone age in males is needed.

Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis

PubMed Central

Su, Nan; Sun, Qidi; Li, Can; Lu, Xiumin; Qi, Huabing; Chen, Siyu; Yang, Jing; Du, Xiaolan; Zhao, Ling; He, Qifen; Jin, Min; Shen, Yue; Chen, Di; Chen, Lin

2010-01-01

Achondroplasia (ACH) is a short-limbed dwarfism resulting from gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). Previous studies have shown that ACH patients have impaired chondrogenesis, but the effects of FGFR3 on bone formation and bone remodeling at adult stages of ACH have not been fully investigated. Using micro-computed tomography and histomorphometric analyses, we found that 2-month-old Fgfr3G369C/+ mice (mouse model mimicking human ACH) showed decreased bone mass due to reduced trabecular bone volume and bone mineral density, defect in bone mineralization and increased osteoclast numbers and activity. Compared with primary cultures of bone marrow stromal cells (BMSCs) from wild-type mice, Fgfr3G369C/+ cultures showed decreased cell proliferation, increased osteogenic differentiation including up-regulation of alkaline phosphatase activity and expressions of osteoblast marker genes, and reduced bone matrix mineralization. Furthermore, our studies also suggest that decreased cell proliferation and enhanced osteogenic differentiation observed in Fgfr3G369C/+ BMSCs are caused by up-regulation of p38 phosphorylation and that enhanced Erk1/2 activity is responsible for the impaired bone matrix mineralization. In addition, in vitro osteoclast formation and bone resorption assays demonstrated that osteoclast numbers and bone resorption area were increased in cultured bone marrow cells derived from Fgfr3G369C/+ mice. These findings demonstrate that gain-of-function mutation in FGFR3 leads to decreased bone mass by regulating both osteoblast and osteoclast activities. Our studies provide new insight into the mechanism underlying the development of ACH. PMID:20053668

Serial Scanning and Registration of High Resolution Quantitative Computed Tomography Volume Scans for the Determination of Local Bone Density Changes

NASA Technical Reports Server (NTRS)

Whalen, Robert T.; Napel, Sandy; Yan, Chye H.

1996-01-01

Progress in development of the methods required to study bone remodeling as a function of time is reported. The following topics are presented: 'A New Methodology for Registration Accuracy Evaluation', 'Registration of Serial Skeletal Images for Accurately Measuring Changes in Bone Density', and 'Precise and Accurate Gold Standard for Multimodality and Serial Registration Method Evaluations.'

Mechanistic, Mathematical Model to Predict the Dynamics of Tissue Genesis in Bone Defects via Mechanical Feedback and Mediation of Biochemical Factors

PubMed Central

Moore, Shannon R.; Saidel, Gerald M.; Knothe, Ulf; Knothe Tate, Melissa L.

2014-01-01

The link between mechanics and biology in the generation and the adaptation of bone has been well studied in context of skeletal development and fracture healing. Yet, the prediction of tissue genesis within - and the spatiotemporal healing of - postnatal defects, necessitates a quantitative evaluation of mechano-biological interactions using experimental and clinical parameters. To address this current gap in knowledge, this study aims to develop a mechanistic mathematical model of tissue genesis using bone morphogenetic protein (BMP) to represent of a class of factors that may coordinate bone healing. Specifically, we developed a mechanistic, mathematical model to predict the dynamics of tissue genesis by periosteal progenitor cells within a long bone defect surrounded by periosteum and stabilized via an intramedullary nail. The emergent material properties and mechanical environment associated with nascent tissue genesis influence the strain stimulus sensed by progenitor cells within the periosteum. Using a mechanical finite element model, periosteal surface strains are predicted as a function of emergent, nascent tissue properties. Strains are then input to a mechanistic mathematical model, where mechanical regulation of BMP-2 production mediates rates of cellular proliferation, differentiation and tissue production, to predict healing outcomes. A parametric approach enables the spatial and temporal prediction of endochondral tissue regeneration, assessed as areas of cartilage and mineralized bone, as functions of radial distance from the periosteum and time. Comparing model results to histological outcomes from two previous studies of periosteum-mediated bone regeneration in a common ovine model, it was shown that mechanistic models incorporating mechanical feedback successfully predict patterns (spatial) and trends (temporal) of bone tissue regeneration. The novel model framework presented here integrates a mechanistic feedback system based on the mechanosensitivity of periosteal progenitor cells, which allows for modeling and prediction of tissue regeneration on multiple length and time scales. Through combination of computational, physical and engineering science approaches, the model platform provides a means to test new hypotheses in silico and to elucidate conditions conducive to endogenous tissue genesis. Next generation models will serve to unravel intrinsic differences in bone genesis by endochondral and intramembranous mechanisms. PMID:24967742

An Essential Physiological Role for MCT8 in Bone in Male Mice

PubMed Central

Leitch, Victoria D.; Di Cosmo, Caterina; Liao, Xiao-Hui; O’Boy, Sam; Galliford, Thomas M.; Evans, Holly; Croucher, Peter I.; Boyde, Alan; Dumitrescu, Alexandra; Weiss, Roy E.; Refetoff, Samuel; Williams, Graham R.

2017-01-01

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance. PMID:28637283

Microfibrous β-TCP/collagen scaffolds mimic woven bone in structure and composition.

PubMed

Zhang, Shen; Zhang, Xin; Cai, Qing; Wang, Bo; Deng, Xuliang; Yang, Xiaoping

2010-12-01

Woven bone, as the initial form of bone tissue, is always found in developing and repairing bone. It is thought of as a temporary scaffold for the deposition of osteogenic cells and the laying down of lamellar bone. Thus, we hypothesize that a matrix which resembles the architecture and components of woven bone can provide an osteoblastic microenvironment for bone cell growth and new bone formation. In this study, woven-bone-like beta-tricalcium phosphate (β-TCP)/collagen scaffolds were fabricated by sol-gel electrospinning and impregnating methods. Optimization studies on sol-gel synthesis and electrospinning process were conducted respectively to prepare pure β-TCP fibers with dimensions close to mineralized collagen fibrils in woven bone. The collagen-coating layer prepared by impregnation had an adhesive role that held the β-TCP fibers together, and resulted in rapid degradation and matrix mineralization in in vitro tests. MG63 osteoblast-like cells seeded on the resultant scaffolds showed three-dimensional (3D) morphologies, and merged into multicellular layers after 7 days culture. Cytotoxicity test further revealed that extracts from the resultant scaffolds could promote the proliferation of MG63 cells. Therefore, the woven-bone-like matrix that we constructed favored the attachment and proliferation of MG63 cells in three dimensions. It has great potential ability to shorten the time of formation of new bone.

Quantitative MRI and spectroscopy of bone marrow

PubMed Central

Ruschke, Stefan; Dieckmeyer, Michael; Diefenbach, Maximilian; Franz, Daniela; Gersing, Alexandra S.; Krug, Roland; Baum, Thomas

2017-01-01

Bone marrow is one of the largest organs in the human body, enclosing adipocytes, hematopoietic stem cells, which are responsible for blood cell production, and mesenchymal stem cells, which are responsible for the production of adipocytes and bone cells. Magnetic resonance imaging (MRI) is the ideal imaging modality to monitor bone marrow changes in healthy and pathological states, thanks to its inherent rich soft‐tissue contrast. Quantitative bone marrow MRI and magnetic resonance spectroscopy (MRS) techniques have been also developed in order to quantify changes in bone marrow water–fat composition, cellularity and perfusion in different pathologies, and to assist in understanding the role of bone marrow in the pathophysiology of systemic diseases (e.g. osteoporosis). The present review summarizes a large selection of studies published until March 2017 in proton‐based quantitative MRI and MRS of bone marrow. Some basic knowledge about bone marrow anatomy and physiology is first reviewed. The most important technical aspects of quantitative MR methods measuring bone marrow water–fat composition, fatty acid composition, perfusion, and diffusion are then described. Finally, previous MR studies are reviewed on the application of quantitative MR techniques in both healthy aging and diseased bone marrow affected by osteoporosis, fractures, metabolic diseases, multiple myeloma, and bone metastases. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:332–353. PMID:28570033

Effects of imbalanced muscle loading on hip joint development and maturation.

PubMed

Ford, Caleb A; Nowlan, Niamh C; Thomopoulos, Stavros; Killian, Megan L

2017-05-01

The mechanical loading environment influences the development and maturation of joints. In this study, the influence of imbalanced muscular loading on joint development was studied using localized chemical denervation of hip stabilizing muscle groups in neonatal mice. It was hypothesized that imbalanced muscle loading, targeting either gluteal muscles or quadriceps muscles, would lead to bilateral hip joint asymmetry, as measured by acetabular coverage, femoral head volume and bone morphometry, and femoral-acetabular shape. The contralateral hip joints as well as age-matched, uninjected mice were used as controls. Altered bone development was analyzed using micro-computed tomography, histology, and image registration techniques at postnatal days (P) 28, 56, and 120. This study found that unilateral muscle unloading led to reduced acetabular coverage of the femoral head, lower total volume, lower bone volume ratio, and lower mineral density, at all three time points. Histologically, the femoral head was smaller in unloaded hips, with thinner triradiate cartilage at P28 and thinner cortical bone at P120 compared to contralateral hips. Morphological shape changes were evident in unloaded hips at P56. Unloaded hips had lower trabecular thickness and increased trabecular spacing of the femoral head compared to contralateral hips. The present study suggests that decreased muscle loading of the hip leads to altered bone and joint shape and growth during postnatal maturation. Statement of Clinical Significance: Adaptations from altered muscle loading during postnatal growth investigated in this study have implications on developmental hip disorders that result from asymmetric loading, such as patients with limb-length inequality or dysplasia. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1128-1136, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Microcomputed tomographic and histomorphometric analyses of novel titanium mesh membranes for guided bone regeneration: a study in rat calvarial defects.

PubMed

Rakhmatia, Yunia Dwi; Ayukawa, Yasunori; Furuhashi, Akihiro; Koyano, Kiyoshi

2014-01-01

The objective of this study was to evaluate the optimal thickness and porosity of novel titanium mesh membranes to enhance bone augmentation, prevent soft tissue ingrowth, and prevent membrane exposure. Six types of novel titanium meshes with different thicknesses and pore sizes, along with three commercially available membranes, were used to cover surgically created calvarial defects in 6-week-old Sprague-Dawley rats. The animals were killed after 4 or 8 weeks. Microcomputed tomographic analyses were performed to analyze the three-dimensional bone volume and bone mineral density. Soft tissue ingrowth was also evaluated histologically and histomorphometrically. The novel titanium membranes used in this study were as effective at augmenting bone in the rat calvarial defect model as the commercially available membranes. The greatest bone volume was observed on 100-μm-thick membranes with larger pores, although these membranes promoted growth of bone with lower mineral density. Soft tissue ingrowth when 100-μm membranes were used was increased at 4 weeks but decreased again by 8 weeks to a level not statistically significantly different from other membranes. Membrane thickness affects the total amount of new bone formation, and membrane porosity is an essential factor for guided bone regeneration, especially during the initial healing period, although the final bone volume obtained is essentially the same. Newly developed titanium mesh membranes of 100 μm in thickness and with large pores appear to be optimal for guided bone regeneration.

Image processing, geometric modeling and data management for development of a virtual bone surgery system.

PubMed

Niu, Qiang; Chi, Xiaoyi; Leu, Ming C; Ochoa, Jorge

2008-01-01

This paper describes image processing, geometric modeling and data management techniques for the development of a virtual bone surgery system. Image segmentation is used to divide CT scan data into different segments representing various regions of the bone. A region-growing algorithm is used to extract cortical bone and trabecular bone structures systematically and efficiently. Volume modeling is then used to represent the bone geometry based on the CT scan data. Material removal simulation is achieved by continuously performing Boolean subtraction of the surgical tool model from the bone model. A quadtree-based adaptive subdivision technique is developed to handle the large set of data in order to achieve the real-time simulation and visualization required for virtual bone surgery. A Marching Cubes algorithm is used to generate polygonal faces from the volumetric data. Rendering of the generated polygons is performed with the publicly available VTK (Visualization Tool Kit) software. Implementation of the developed techniques consists of developing a virtual bone-drilling software program, which allows the user to manipulate a virtual drill to make holes with the use of a PHANToM device on a bone model derived from real CT scan data.

New mechanisms and targets in the treatment of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2007-01-01

Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with other pathways in determining bone formation, is likely to lead to new therapeutic developments. The recent discovery through mouse genetics that PTHrP (PTH-related protein) is a crucial bone-derived paracrine regulator of remodelling offers new and interesting therapeutic targets.

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

PubMed Central

Takeda, Tsuyoshi; Sato, Yoshihiro

2006-01-01

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest. PMID:16642543

Study of tissue engineered bone nodules by Fourier transform infrared spectroscopy.

PubMed

Aydin, Halil Murat; Hu, Bin; Suso, Josep Sulé; El Haj, Alicia; Yang, Ying

2011-02-21

The key criteria for assessing the success of bone tissue engineering are the quality and quantity of the produced minerals within the cultured constructs. The accumulation of calcium ions and inorganic phosphates in culture medium serves as nucleating agents for the formation of hydroxyapatite, which is the main inorganic component of bone. Bone nodule formation is one of the hallmarks of mineralization in such cell cultures. In this study, we developed a new two-step procedure to accelerate bone formation in which mouse bone cell aggregates were produced first on various chemically treated non-adhesive substrates. After this step, the bone cells' growth and mineralization were followed in conventional culture plates. The number and size of cell aggregates were studied with light microscopy. The minerals' formation in the form of nodules produced by the cell aggregates and the bone crystal quality were studied with Fourier Transform Infrared (FTIR) spectroscopy. The FTIR spectra of the ash specimens (mineral phase only) from thermal gravimetric analysis (TGA) provided valuable information of the quality of the minerals. The υ(4) PO(4) region (550-650 cm(-1)), which reveals apatitic and non-apatitic HPO(4) or PO(4) environments, and phosphate region (910-1180 cm(-1)) were examined for the minerals produced in the form of nodules. The peak position and intensity of the spectra demonstrate that the quality of the bone produced by cell aggregates, especially from the bigger ones, which were formed on Plunoric treated substrates, exhibit a composition more similar to that of native bone. This work establishes a new protocol for high quality bone formation and characterization, with the potential to be applied to bone tissue engineering.

The nanometre-scale physiology of bone: steric modelling and scanning transmission electron microscopy of collagen–mineral structure

PubMed Central

Alexander, Benjamin; Daulton, Tyrone L.; Genin, Guy M.; Lipner, Justin; Pasteris, Jill D.; Wopenka, Brigitte; Thomopoulos, Stavros

2012-01-01

The nanometre-scale structure of collagen and bioapatite within bone establishes bone's physical properties, including strength and toughness. However, the nanostructural organization within bone is not well known and is debated. Widely accepted models hypothesize that apatite mineral (‘bioapatite’) is present predominantly inside collagen fibrils: in ‘gap channels’ between abutting collagen molecules, and in ‘intermolecular spaces’ between adjacent collagen molecules. However, recent studies report evidence of substantial extrafibrillar bioapatite, challenging this hypothesis. We studied the nanostructure of bioapatite and collagen in mouse bones by scanning transmission electron microscopy (STEM) using electron energy loss spectroscopy and high-angle annular dark-field imaging. Additionally, we developed a steric model to estimate the packing density of bioapatite within gap channels. Our steric model and STEM results constrain the fraction of total bioapatite in bone that is distributed within fibrils at less than or equal to 0.42 inside gap channels and less than or equal to 0.28 inside intermolecular overlap regions. Therefore, a significant fraction of bone's bioapatite (greater than or equal to 0.3) must be external to the fibrils. Furthermore, we observe extrafibrillar bioapatite between non-mineralized collagen fibrils, suggesting that initial bioapatite nucleation and growth are not confined to the gap channels as hypothesized in some models. These results have important implications for the mechanics of partially mineralized and developing tissues. PMID:22345156

Effects of lead and cadmium exposure from electronic waste on child physical growth.

PubMed

Yang, Hui; Huo, Xia; Yekeen, Taofeek Akangbe; Zheng, Qiujian; Zheng, Minghao; Xu, Xijin

2013-07-01

Many studies indicate that lead (Pb) and cadmium (Cd) exposure may alter bone development through both direct and indirect mechanisms, increasing the risk of osteoporosis later in life. The aim of this study was to investigate the association between Pb and Cd exposure, physical growth, and bone and calcium metabolism in children of an electronic waste (e-waste) processing area. We recruited 246 children (3-8 years) in a kindergarten located in Guiyu, China. Blood lead levels (BLLs) and blood cadmium levels (BCLs) of recruited children were measured as biomarkers for exposure. Serum calcium, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline were used as biomarkers for bone and calcium metabolism. Physical indexes such as height, weight, and head and chest circumference were also measured. The mean values of BLLs and BCLs obtained were 7.30 μg/dL and 0.69 μg/L, respectively. The average of BCLs increased with age. In multiple linear regression analysis, BLLs were negatively correlated with both height and weight, and positively correlated with bone resorption biomarkers. Neither bone nor calcium metabolic biomarkers showed significant correlation with cadmium. Childhood lead exposure affected both physical development and increased bone resorption of children in Guiyu. Primitive e-waste recycling may threaten the health of children with elevated BLL which may eventually cause adult osteoporosis.

Knee joint transplantation combined with surgical angiogenesis in rabbits – a new experimental model

PubMed Central

Kremer, Thomas; Giusti, Guilherme; Friedrich, Patricia F.; Willems, Wouter; Bishop, Allen T.; Giessler, Goetz A.

2012-01-01

Summary Purpose We have previously described a means to maintain bone allotransplant viability, without long-term immune modulation, replacing allogenic bone vasculature with autogenous vessels. A rabbit model for whole knee joint transplantation was developed and tested using the same methodology, initially as an autotransplant. Materials/Methods Eight New Zealand White rabbit knee joints were elevated on a popliteal vessel pedicle to evaluate limb viability in a non-survival study. Ten additional joints were elevated and replaced orthotopically in a fashion identical to allotransplantation, obviating only microsurgical repairs and immunosuppression. A superficial inferior epigastric facial (SIEF) flap and a saphenous arteriovenous (AV) bundle were introduced into the femur and tibia respectively, generating a neoangiogenic bone circulation. In allogenic transplantation, this step maintains viability after cessation of immunosuppression. Sixteen weeks later, x-rays, microangiography, histology, histomorphometry and biomechanical analysis were performed. Results Limb viability was preserved in the initial 8 animals. Both soft tissue and bone healing occurred in 10 orthotopic transplants. Surgical angiogenesis from the SIEF flap and AV bundle was always present. Bone and joint viability was maintained, with demonstrable new bone formation. Bone strength was less than the opposite side. Arthrosis and joint contractures were frequent. Conclusion We have developed a rabbit knee joint model and evaluation methods suitable for subsequent studies of whole joint allotransplantation. PMID:22113889

Lead arthritis and lead poisoning following bullet wounds: a clinicopathologic, ultrastructural, and microanalytic study of two cases.

PubMed

Slavin, R E; Swedo, J; Cartwright, J; Viegas, S; Custer, E M

1988-02-01

Bullet wounds causing lead synovitis in the wrist and knee are reported in two patients, one of whom also developed clinical plumbism. Very high lead levels in the synovial fluid are believed to be responsible for toxicity changes that occurred in the synovium and bone. Ultrastructurally, these alterations included the formation of nuclear lead inclusions, dilation, and degranulation of the rough endoplasmic reticulum and deposition of crystalline precipitates in the matrix of the mitochondria in macrophages, osteoclasts, and synoviocytes, as well as the development of cytoplasmic lead inclusions in osteoclasts. Energy-dispersive x-ray elemental analysis (EDXEA) indicated that the nuclear inclusions contained only lead, whereas precipitates within the mitochondria and elsewhere in the cytoplasm were composed of complexes containing lead, calcium, and phosphorus. Similarly constituted extracellular complexes were incorporated into newly formed trabecular bone laid down as a physiologic response to the bullet lodged within the wrist bones. This bone subsequently exhibited defects in bone resorption, which were characterized by depressed osteoclastic function and a unique lesion termed incomplete osteocytic osteolysis. The genesis of this latter lesion is uncertain. The sequestration of the partially degraded bone fragments containing lead complexes into the marrow and eventually into the joint spaces and synovium permitted the recycling of bone lead, and this may have played an important role in inducing clinical plumbism in one of the patients in this study.

Face and content validation of a novel three-dimensional printed temporal bone for surgical skills development.

PubMed

Da Cruz, M J; Francis, H W

2015-07-01

To assess the face and content validity of a novel synthetic, three-dimensional printed temporal bone for surgical skills development and training. A synthetic temporal bone was printed using composite materials and three-dimensional printing technology. Surgical trainees were asked to complete three structured temporal bone dissection exercises. Attitudes and impressions were then assessed using a semi-structured questionnaire. Previous cadaver and real operating experiences were used as a reference. Trainees' experiences of the synthetic temporal bone were analysed in terms of four domains: anatomical realism, usefulness as a training tool, task-based usefulness and overall reactions. Responses across all domains indicated a high degree of acceptance, suggesting that the three-dimensional printed temporal bone was a useful tool in skills development. A sophisticated three-dimensional printed temporal bone that demonstrates face and content validity was developed. The efficiency in cost savings coupled with low associated biohazards make it likely that the printed temporal bone will be incorporated into traditional temporal bone skills development programmes in the near future.

Thermal model to investigate the temperature in bone grinding for skull base neurosurgery.

PubMed

Zhang, Lihui; Tai, Bruce L; Wang, Guangjun; Zhang, Kuibang; Sullivan, Stephen; Shih, Albert J

2013-10-01

This study develops a thermal model utilizing the inverse heat transfer method (IHTM) to investigate the bone grinding temperature created by a spherical diamond tool used for skull base neurosurgery. Bone grinding is a critical procedure in the expanded endonasal approach to remove the cranial bone and access to the skull base tumor via nasal corridor. The heat is generated during grinding and could damage the nerve or coagulate the blood in the carotid artery adjacent to the bone. The finite element analysis is adopted to investigate the grinding-induced bone temperature rise. The heat source distribution is defined by the thermal model, and the temperature distribution is solved using the IHTM with experimental inputs. Grinding experiments were conducted on a bovine cortical bone with embedded thermocouples. Results show significant temperature rise in bone grinding. Using 50°C as the threshold, the thermal injury can propagate about 3mm in the traverse direction, and 3mm below the ground surface under the dry grinding condition. The presented methodology demonstrated the capability of being a thermal analysis tool for bone grinding study. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Osteoporosis affects both post-yield microdamage accumulation and plasticity degradation in vertebra of ovariectomized rats

NASA Astrophysics Data System (ADS)

Li, Siwei; Niu, Guodong; Dong, Neil X.; Wang, Xiaodu; Liu, Zhongjun; Song, Chunli; Leng, Huijie

2017-04-01

Estrogen withdrawal in postmenopausal women increases bone loss and bone fragility in the vertebra. Bone loss with osteoporosis not only reduces bone mineral density (BMD), but actually alters bone quality, which can be comprehensively represented by bone post-yield behaviors. This study aimed to provide some information as to how osteoporosis induced by estrogen depletion could influence the evolution of post-yield microdamage accumulation and plastic deformation in vertebral bodies. This study also tried to reveal the part of the mechanisms of how estrogen deficiency-induced osteoporosis would increase the bone fracture risk. A rat bilateral ovariectomy (OVX) model was used to induce osteoporosis. Progressive cyclic compression loading was developed for vertebra testing to elucidate the post-yield behaviors. BMD, bone volume fraction, stiffness degradation, and plastic deformation evolution were compared among rats raised for 5 weeks (ovx5w and sham5w groups) and 35 weeks (ovx35w and sham35w groups) after sham surgery and OVX. The results showed that a higher bone loss in vertebral bodies corresponded to lower stiffness and higher plastic deformation. Thus, osteoporosis could increase the vertebral fracture risk probably through microdamage accumulation and plastic deforming degradation.

Denosumab for bone diseases: translating bone biology into targeted therapy.

PubMed

Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

2011-12-01

Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

European network using fish as osteoporosis research models (ENFORM)

NASA Astrophysics Data System (ADS)

Goerlich, R.; Renn, J.; Alestrom, P.; Nouizadeh-Lillabadi, R.; Schartl, M.; Winkler, C.; Muller, M.; Midtyng, P. J.; Eberius, M.; Slenzka, K.

2005-08-01

Osteoporosis, characterised by loss of bone density, is one of the most important bone diseases of humans worldwide. It causes problems in post-menopausal women, in astronauts during long-term spaceflights and in industrial animal production. Bone alterations leading to osteoporosis are well-documented at the cellular level, but the underlying molecular events are still poorly understood and most of our knowledge is derived from in vitro studies using cell culture systems. Recent findings indicate a remarkable conservation of the key regulators of bone development and homeostasis between mammals and fish. Medaka (Oryzias latipes) and zebrafish (Danio rerio) offer experimental advantages that can be exploited for bone research.

A computer-assisted microscopic analysis of bone tissue developed inside a polyactive polymer implanted into an equine articular surface.

PubMed

Albert, Réka; Vásárhelyi, Gábor; Bodó, Gábor; Kenyeres, Annamária; Wolf, Ervin; Papp, Tamás; Terdik, Tünde; Módis, László; Felszeghy, Szabolcs

2012-09-01

One of the most promising applications for the restoration of small or moderately sized focal articular lesions is mosaicplasty (MP). Although recurrent hemarthrosis is a rare complication after MP, recently, various strategies have been designed to find an effective filling material to prevent postoperative bleeding from the donor site. The porous biodegradable polymer Polyactive (PA; a polyethylene glycol terephthalate - polybutylene terephthalate copolymer) represents a promising solution in this respect. A histological evaluation of the longterm PA-filled donor sites obtained from 10 experimental horses was performed. In this study, attention was primarily focused on the bone tissue developed in the plug. A computer-assisted image analysis and quantitative polarized light microscopic measurements of decalcified, longitudinally sectioned, dimethylmethylene blue (DMMB)- and picrosirius red (PS) stained sections revealed that the coverage area of the bone trabecules in the PA-filled donor tunnels was substantially (25%) enlarged compared to the neighboring cancellous bone. For this quantification, identical ROIs (regions of interest) were used and compared. The birefringence retardation values were also measured with a polarized light microscope using monochromatic light. Identical retardation values could be recorded from the bone trabeculae developed in the PA and in the neighboring bone, which indicates that the collagen orientation pattern does not differ significantly among these bone trabecules. Based on our new data, we speculate that PA promotes bone formation, and some of the currently identified degradation products of PA may enhance osteo-conduction and osteoinduction inside the donor canal.

A procedure for preparing undecalcified and unembedded bone sections for light microscopy.

PubMed

Mancini, M; Spoliti, M; Botti, F; Ragazzoni, E; Cocchia, D

1997-07-01

We have developed a procedure for light microscopic investigation of undecalcified and unembedded bone sections. Biopsy samples of human metatarsus and femur and rat femur were fixed in aldehydes and sectioned with a cutting machine equipped with a diamond saw blade. Free sections 100-150 microns thick, stained with toluidine blue and von Kossa, did not show artifacts following the cutting, and the spatial relations of mineralized and nonmineralized components remained intact. Compact and trabecular bone, bone marrow and all cell types appeared well preserved and easily recognizable. Our procedure provides a simple and rapid method for preparing bone sections which undergo no chemical treatment other than fixation. This method is a useful alternative to standard histological protocols for studying bone specimens.

Use of radiation to discourage ectopic bone. A nine-year study in surgery about the hip

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coventry, M.B.; Scanlon, P.W.

1981-02-01

Patients who had total hip arthroplasty were categorized according to the risk of development of ectopic bone. Radiation therapy was administered after operation to those considered to be at high risk of formation of ectopic bone. The dosage used was 2000 rads given in ten fractions (875 rets). Forty-eight hips in forty-two patients were treated from 1970 to 1977. Massive formation of ectopic bone did not occur in any hip when the radiation was given relatively early after operation. Thus, we believe that radiation aids in the prevention of formation of ectopic bone. Radiation was found to be of doubtfulmore » value, however, hence the ectopic bone was visible on radiography.« less

Development of the turtle plastron, the order-defining skeletal structure.

PubMed

Rice, Ritva; Kallonen, Aki; Cebra-Thomas, Judith; Gilbert, Scott F

2016-05-10

The dorsal and ventral aspects of the turtle shell, the carapace and the plastron, are developmentally different entities. The carapace contains axial endochondral skeletal elements and exoskeletal dermal bones. The exoskeletal plastron is found in all extant and extinct species of crown turtles found to date and is synaptomorphic of the order Testudines. However, paleontological reconstructed transition forms lack a fully developed carapace and show a progression of bony elements ancestral to the plastron. To understand the evolutionary development of the plastron, it is essential to know how it has formed. Here we studied the molecular development and patterning of plastron bones in a cryptodire turtle Trachemys scripta We show that plastron development begins at developmental stage 15 when osteochondrogenic mesenchyme forms condensates for each plastron bone at the lateral edges of the ventral mesenchyme. These condensations commit to an osteogenic identity and suppress chondrogenesis. Their development overlaps with that of sternal cartilage development in chicks and mice. Thus, we suggest that in turtles, the sternal morphogenesis is prevented in the ventral mesenchyme by the concomitant induction of osteogenesis and the suppression of chondrogenesis. The osteogenic subroutines later direct the growth and patterning of plastron bones in an autonomous manner. The initiation of plastron bone development coincides with that of carapacial ridge formation, suggesting that the development of dorsal and ventral shells are coordinated from the start and that adopting an osteogenesis-inducing and chondrogenesis-suppressing cell fate in the ventral mesenchyme has permitted turtles to develop their order-specific ventral morphology.

Expression of the growth factor pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta in the serum, cartilage and subchondral bone of patients with osteoarthritis.

PubMed

Kaspiris, Angelos; Mikelis, Constantinos; Heroult, Melanie; Khaldi, Lubna; Grivas, Theodoros B; Kouvaras, Ioannis; Dangas, Spyridon; Vasiliadis, Elias; Lioté, Frédéric; Courty, José; Papadimitriou, Evangelia

2013-07-01

Pleiotrophin is a heparin-binding growth factor expressed in embryonic but not mature cartilage, suggesting a role in cartilage development. Elucidation of the molecular changes observed during the remodelling process in osteoarthritis is of paramount importance. This study aimed to investigate serum pleiotrophin levels and expression of pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta in the cartilage and subchondral bone of osteoarthritis patients. Serum samples derived from 16 osteoarthritis patients and 18 healthy donors. Pleiotrophin and receptor protein tyrosine phosphatase beta/zeta in the cartilage and subchondral bone were studied in 29 patients who had undergone total knee or hip replacement for primary osteoarthritis and in 10 control patients without macroscopic osteoarthritis changes. Serum pleiotrophin levels and expression of pleiotrophin in chondrocytes and subchondral bone osteocytes significantly increased in osteoarthritis patients graded Ahlback II to III. Receptor protein tyrosine phosphatase beta/zeta was mainly detected in the subchondral bone osteocytes of patients with moderate osteoarthritis and as disease severity increased, in the osteocytes and bone lining cells of the distant trabeculae. These data render pleiotrophin and receptor protein tyrosine phosphatase beta/zeta promising candidates for further studies towards developing targeted therapeutic schemes for osteoarthritis. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.

PubMed

Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

2016-07-08

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. Copyright © 2016 Elsevier Inc. All rights reserved.

Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

NASA Astrophysics Data System (ADS)

Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

2015-04-01

Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4 °C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4 °C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts' heath and NASA's missions.

Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

PubMed Central

Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

2015-01-01

Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4°C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4°C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts’ heath and NASA’s mission. PMID:25821722

Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Wastney, Meryl E.; O'Brien, Kimberly O.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Davis-Street, Janis E.; Oganov, Victor; Shackelford, Linda C.

2005-01-01

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01). CONCLUSIONS: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.

The development of hyaline-cell cartilage in the head of the black molly, Poecilia sphenops. Evidence for secondary cartilage in a teleost.

PubMed Central

Benjamin, M

1989-01-01

The development of hyaline-cell cartilage attached to membrane (dentary, maxilla, nasal, lacrimal and cleithrum) and cartilage (basioccipital) bones has been studied in the viviparous black molly, Poecilia sphenops. Intramembranous ossification commences before the first appearance of hyaline cells. As hyaline-cell cartilage is densely cellular and as that attached to the dentary, maxilla and cleithrum develops from the periosteum of these membrane bones, it must be regarded as secondary cartilage according to current concepts. It is also argued that the hyaline-cell cartilage attached to the perichondral bone of the basioccipital (a cartilage bone), could also be viewed as secondary. The status of the cartilage on the nasal and lacrimal bones is less clear, for it develops, at least in part, from mucochondroid (mucous connective) tissue. This is the first definitive report of secondary cartilage in any lower vertebrate. The tissue is therefore not restricted to birds and mammals as hitherto believed, and a multipotential periosteum must have arisen early in vertebrate evolution. Images Fig. 1 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:2481666

Gold-coated carbon nanotube electrode arrays: Immunosensors for impedimetric detection of bone biomarkers.

PubMed

Ramanathan, Madhumati; Patil, Mitali; Epur, Rigved; Yun, Yeoheung; Shanov, Vasselin; Schulz, Mark; Heineman, William R; Datta, Moni K; Kumta, Prashant N

2016-03-15

C-terminal telopeptide (cTx), a fragment generated during collagen degradation, is a key biomarker of bone resorption during the bone remodeling process. The presence of varying levels of cTx in the bloodstream can hence be indicative of abnormal bone metabolism. This study focuses on the development of an immunosensor utilizing carbon nanotube (CNT) electrodes coated with gold nanoparticles for the detection of cTx, which could ultimately lead to the development of an inexpensive and rapid point-of-care (POC) tool for bone metabolism detection and prognostics. Electrochemical impedance spectroscopy (EIS) was implemented to monitor and detect the antigen-antibody binding events occurring on the surface of the gold-deposited CNT electrode. Type I cTx was used as the model protein to test the developed sensor. The sensor was accordingly characterized at various stages of development for evaluation of the optimal sensor performance. The biosensor could detect cTx levels as low as 0.05 ng/mL. The feasibility of the sensor for point-of-care (POC) applications was further demonstrated by determining the single frequency showing maximum changes in impedance, which was determined to be 18.75 Hz. Copyright © 2015 Elsevier B.V. All rights reserved.

A Boon for Bone Research

NASA Technical Reports Server (NTRS)

1996-01-01

NASA studies for astronaut health in long-term space missions led to the development of the Mechanical Response Tissue Analyzer (MRTA), a research tool for astronaut disuse, osteoporosis and related bone disorders among the general population. Ames Research Center and Stanford University generated a workable device and with Gait Scan, Inc., refined and commercialized it. The MRTA is a portable dsinstrument that measures the bending stiffness of bones using electrically-induced vibration and detects and analyzes the frequencies of the resonating bone. Unlike some other methods, the MRTA uses no radiation and is fast, simple and relatively inexpensive.

Cortical bone drilling: An experimental and numerical study.

PubMed

Alam, Khurshid; Bahadur, Issam M; Ahmed, Naseer

2014-12-16

Bone drilling is a common surgical procedure in orthopedics, dental and neurosurgeries. In conventional bone drilling process, the surgeon exerts a considerable amount of pressure to penetrate the drill into the bone tissue. Controlled penetration of drill in the bone is necessary for safe and efficient drilling. Development of a validated Finite Element (FE) model of cortical bone drilling. Drilling experiments were conducted on bovine cortical bone. The FE model of the bone drilling was based on mechanical properties obtained from literature data and additionally conducted microindentation tests on the cortical bone. The magnitude of stress in bone was found to decrease exponentially away from the lips of the drill in simulations. Feed rate was found to be the main influential factor affecting the force and torque in the numerical simulations and experiments. The drilling thrust force and torque were found to be unaffected by the drilling speed in numerical simulations. Simulated forces and torques were compared with experimental results for similar drilling conditions and were found in good agreement.CONCLUSIONS: FE schemes may be successfully applied to model complex kinematics of bone drilling process.

Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma

PubMed Central

Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W.; Novane, Nora; Shah, Jatin J.; Davis, Richard E.; Hou, Jian; Gagel, Robert F.; Yang, Jing

2016-01-01

Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP upregulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP upregulated the methylation of IRF8, thereby enhanced expression of NFATc1, leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2DDR. Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K/Akt signaling, and increased DNMT3A expression, resulting in hypermethylation of RUNX2, osterix, and IRF8. This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. As TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. PMID:27559096

Ewing's sarcoma of bone tumor cells produces MCSF that stimulates monocyte proliferation in a novel mouse model of Ewing's sarcoma of bone.

PubMed

Margulies, B S; DeBoyace, S D; Damron, T A; Allen, M J

2015-10-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Ewing's Sarcoma of Bone Tumor Cells Produce MCSF that Stimulates Monocyte Proliferation in a Novel Mouse Model of Ewing's Sarcoma of Bone

PubMed Central

Margulies, BS; DeBoyace, SD; Damron, TA; Allen, MJ

2015-01-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy. PMID:26051470

Topography of Acoustical Properties of Long Bones: From Biomechanical Studies to Bone Health Assessment

PubMed Central

Tatarinov, Alexey; Sarvazyan, Armen

2010-01-01

The article presents a retrospective view on the assessment of long bones condition using topographical patterns of the acoustic properties. The application of ultrasonic point-contact transducers with exponential waveguides on a short acoustic base for detailed measurements in human long bones by the surface transmission was initiated during the 1980s in Latvia. The guided wave velocity was mapped on the surface of the long bones and the topographical patterns reflected the biomechanical peculiarities. Axial velocity profiles obtained in vivo by measurements along the medial surface of tibia varied due to aging, hypokinesia, and physical training. The method has been advanced at Artann Laboratories (West Trenton, NJ) by the introduction of multifrequency data acquisition and axial scanning. The model studies carried out on synthetic phantoms and in bone specimens confirmed the potential to evaluate separately changes of the bone material properties and of the cortical thickness by multifrequency acoustic measurements at the 0.1 to 1 MHz band. The bone ultrasonic scanner (BUSS) is an axial mode ultrasonometer developed to depict the acoustic profile of bone that will detect the onset of bone atrophy as a spatial process. Clinical trials demonstrated a high sensitivity of BUSS to osteoporosis and the capability to assess early stage of osteopenia. PMID:18599416

DMP-1-mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH.

PubMed

Liu, Zhongbo; Kennedy, Oran D; Cardoso, Luis; Basta-Pljakic, Jelena; Partridge, Nicola C; Schaffler, Mitchell B; Rosen, Clifford J; Yakar, Shoshana

2016-02-01

Bone minerals are acquired during growth and are key determinants of adult skeletal health. During puberty, the serum levels of growth hormone (GH) and its downstream effector IGF-1 increase and play critical roles in bone acquisition. The goal of the current study was to determine how bone cells integrate signals from the GH/IGF-1 to enhance skeletal mineralization and strength during pubertal growth. Osteocytes, the most abundant bone cells, were shown to orchestrate bone modeling during growth. We used dentin matrix protein (Dmp)-1-mediated Ghr knockout (DMP-GHRKO) mice to address the role of the GH/IGF axis in osteocytes. We found that DMP-GHRKO did not affect linear growth but compromised overall bone accrual. DMP-GHRKO mice exhibited reduced serum inorganic phosphate and parathyroid hormone (PTH) levels and decreased bone formation indices and were associated with an impaired response to intermittent PTH treatment. Using an osteocyte-like cell line along with in vivo studies, we found that PTH sensitized the response of bone to GH by increasing Janus kinase-2 and IGF-1R protein levels. We concluded that endogenously secreted PTH and GHR signaling in bone are necessary to establish radial bone growth and optimize mineral acquisition during growth. © FASEB.

Multiscale imaging of bone microdamage

PubMed Central

Poundarik, Atharva A.; Vashishth, Deepak

2015-01-01

Bone is a structural and hierarchical composite that exhibits remarkable ability to sustain complex mechanical loading and resist fracture. Bone quality encompasses various attributes of bone matrix from the quality of its material components (type-I collagen, mineral and non-collagenous matrix proteins) and cancellous microarchitecture, to the nature and extent of bone microdamage. Microdamage, produced during loading, manifests in multiple forms across the scales of hierarchy in bone and functions to dissipate energy and avert fracture. Microdamage formation is a key determinant of bone quality, and through a range of biological and physical mechanisms, accumulates with age and disease. Accumulated microdamage in bone decreases bone strength and increases bone’s propensity to fracture. Thus, a thorough assessment of microdamage, across the hierarchical levels of bone, is crucial to better understand bone quality and bone fracture. This review article details multiple imaging modalities that have been used to study and characterize microdamage; from bulk staining techniques originally developed by Harold Frost to assess linear microcracks, to atomic force microscopy, a modality that revealed mechanistic insights into the formation diffuse damage at the ultrastructural level in bone. New automated techniques using imaging modalities such as microcomputed tomography are also presented for a comprehensive overview. PMID:25664772

Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats

PubMed Central

King, Tristan J.; Shandala, Tetyana; Lee, Alice M.; Foster, Bruce K.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.

2015-01-01

Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage. PMID:26258775

Chondroblastoma of the patella with aneurysmal bone cyst.

PubMed

Tan, Honglue; Yan, Mengning; Yue, Bing; Zeng, Yiming; Wang, You

2014-01-01

Chondroblastoma of the patella is rare. Aneurysmal bone cysts, which develop from a prior lesion such as a chondroblastoma, are seldom seen in the patella. The authors report a case of a 36-year-old man who presented with 2 years of right knee pain without calor, erythema, pain on palpation, or abnormal range of motion. Radiological studies suggested aneurysmal bone cyst. The lesion was excised with curettage and the residual cavity filled with autogenous bone graft. Histopathology revealed chondroblastoma associated with a secondary aneurysmal bone cyst. In the follow-up period, the patient demonstrated normal joint activities with no pain. Normal configuration of the patella and bone union were shown on plain radiographs. The authors present a review of the literature of all cases of patellar chondroblastoma with aneurysmal bone cyst. This case is the 14th report of aneurysmal bone cyst arising in a chondroblastoma of the patella. According to the literature, computed tomography and magnetic resonance imaging are useful in the study of these lesions. The pathologic diagnosis is based on the presence of chondroblastoma and aneurysmal bone cyst. Treatment of this lesion includes patellectomy, curettage alone, and curettage with bone grafting. Despite the risk of recurrence of this lesion in the patella, the authors first recommend curettage followed by filling the cavity with bone graft. To protect the anterior tension of the patella intraoperatively, the bone window should be made at the medial edge of the patella to perform the curettage and bone grafting.

Early changes in the distal intertarsal joint of Dutch Warmblood foals and the influence of exercise on bone density in the third tarsal bone.

PubMed

Barneveld, A; van Weeren, P R

1999-11-01

It was hypothesised that imposition of different exercise levels at a young age would lead to differences in bone density in the third tarsal bone and to difference in the prevalence of pathological lesions that might contribute to the development of bone spavin later in life. Furthermore, based on earlier literature, it was hypothesised that such lesions could be classified as a manifestation of osteochondrosis. Changes in bone density in the third tarsal bone and early pathological changes in the articular cartilage of the distal intertarsal joint were studied in the offspring of sires with radiographic evidence of osteochondrosis in either stifle or hock. Twenty-four foals were studied at age 5 months after having been subjected to different exercise programmes (box-rest, box-rest with sprint training, pasture exercise) from age one week. Nineteen other foals that originally belonged to the same exercise groups were studied at age 11 months, after they had been weaned, housed together and subjected to an identical low level exercise regimen for an additional 6 months. Bone density was quantified using a microscopic technique. Histomorphological analysis was performed semiquantitatively and using high detail radiography techniques. At age 5 months, mean +/- s.d. bone density in the compact bone of the third tarsal bone was significantly lower in the box-rested foals (37 +/- 4%) than in both the trained and pastured foals (48 +/- 7% and 52 +/- 11%, respectively). After 6 months of identical exercise the previously box-rested foals showed an increase in bone density (53 +/- 12%) which became similar to the value found in the formerly pastured foals (52 +/- 8%). Major pathological lesions (chondrocyte necrosis, fragmentation and chondrone formation) of the articular cartilage of the third and central tarsal bones were already present at age 5 months, but were significantly more numerous at 11 months. There was no relation between the number of cartilage lesions and the osteochondrosis status of the foals. Only 2 lesions in 11-month-old foals had histological characteristics compatible with osteochondrosis, all other lesions were degenerative in nature. It is concluded that bone density of the compact bone of the subchondral bone plate in the third tarsal bone reacts strongly to variations in exercise at a very young age. Low bone density, caused by lack of exercise, can be compensated for when exercise is later increased. Pathological changes in the distal intertarsal joint are common at 5 months and increase to 11 months. These lesions are degenerative in nature and seem not to be related to osteochondrosis. Although the clinical relevance of these abnormalities is uncertain, they may be relevant for the development of osteoarthritic processes in this region later in life.

Intracranial volume, cranial thickness, and hyperostosis frontalis interna in the elderly.

PubMed

May, Hila; Mali, Yael; Dar, Gali; Abbas, Janan; Hershkovitz, Israel; Peled, Nathan

2012-01-01

According to the "brain reserve hypothesis," a larger premorbid brain protects against the development of dementia. The aim of this study was to reveal a possible pathophysiology of brain degenerative diseases by studying intracranial bone lesions that act to reduce intracranial volume (ICV), such as hyperostosis frontalis interna (HFI). Three hundred and eighty postmenopausal females (aged 60+) who had undergone a head computerized tomography scan (Brilliance 64, Philips Healthcare, Cleveland, OH) at the Carmel Medical Center, Haifa, Israel, before the study were included. The subjects were divided into four groups according to their degree of HFI. Six measurements of the skull and brain were taken. As HFI becomes more severe, the cranial bone thickness and cranial bone volume increase. This process is accompanied by a decrease in ICV. In none of the HFI groups studied there was a significant association between ICV and cranial bone thickness. The inter-relationships between the various thickness parameters are not disturbed by the degree of HFI. HFI is accompanied by an increase in thickness of all calvarial bones and reduced ICV. In addition, the thickening process initiated by HFI is synchronized among the calvarial bones. Presence of HFI suggests a decrease in brain volume and has a major clinical significance as it may indicate the beginning of degenerative processes of the brain. In addition, as females age, their skulls tend to develop more robust characteristics. Copyright © 2012 Wiley Periodicals, Inc.

Effect of Hydroxyapatite on Bone Integration in a Rabbit Tibial Defect Model

PubMed Central

Sohn, Sung-Keun; Kim, Kyung-Taek; Kim, Chul-Hong; Ahn, Hee-Bae; Rho, Mee-Sook; Jeong, Min-Ho; Sun, Sang-Kyu

2010-01-01

Background The aim of the present study was to prepare hydroxyapatite (HA) and then characterize its effect on bone integration in a rabbit tibial defect model. The bone formation with different designs of HA was compared and the bony integration of several graft materials was investigated qualitatively by radiologic and histologic study. Methods Ten rabbits were included in this study; two holes were drilled bilaterally across the near cortex and the four holes in each rabbit were divided into four treatment groups (HAP, hydroxyapatite powder; HAC, hydroxyapatite cylinder; HA/TCP, hydroxyapatite/tri-calcium phosphate cylinder, and titanium cylinder). The volume of bone ingrowth and the change of bone mineral density were statistically calculated by computed tomography five times for each treatment group at 0, 2, 4, 6, and 8 weeks after grafting. Histologic analysis was performed at 8 weeks after grafting. Results The HAP group showed the most pronounced effect on the bone ingrowth surface area, which seen at 4, 6, and 8 weeks after graft (p < 0.05). On comparing the change of bone mineral density the bone ingrowth surface area among the 4 groups, there were no statistically significant differences among the groups found for any period (p > 0.05). On histological examination, the HAP group revealed well-recovered cortical bone, but the bone was irregularly thickened and haphazardly admixed with powder. The HAC group showed similar histological features to those of the HA/TCP group; the cortical surface of the newly developed bone was smooth and the bone matrix on the surface of the cylinder was regularly arranged. Conclusions We concluded that both the hydroxyapatite powder and cylinder models investigated in our study may be suitable as a bone substitute in the rabbit tibial defect model, but their characteristic properties are quite different. In contrast to hydroxyapatite powder, which showed better results for the bone ingrowth surface, the hydroxyapatite cylinder showed better results for the sustained morphology. PMID:20514266

Infant milk feeding influences adult bone health: a prospective study from birth to 32 years.

PubMed

Pirilä, Satu; Taskinen, Mervi; Viljakainen, Heli; Kajosaari, Merja; Turanlahti, Maila; Saarinen-Pihkala, Ulla M; Mäkitie, Outi

2011-04-27

Peak bone mass, attained by early adulthood, is influenced by genetic and life-style factors. Early infant feeding and duration of breastfeeding in particular, associate with several health-related parameters in childhood. The aim of this study was to examine whether the effects of early infant feeding extend to peak bone mass and other bone health characteristics at adult age. A cohort of 158 adults (76 males) born in Helsinki, Finland, 1975, prospectively followed up from birth, underwent physical examination and bone densitometry to study bone area, bone mineral content (BMC), and bone mineral density (BMD) at 32 years of age. Life-style factors relevant for bone health were recorded. For data analysis the cohort was divided into three equal-size groups according to the total duration of breastfeeding (BF): Short (≤3 months), Intermediate and Prolonged (≥7 months) BF groups. In males short BF is associated with higher bone area, BMC, and BMD compared to longer BF. Males in the Short BF group had on average 4.7% higher whole body BMD than males in the Prolonged BF group. In multivariate analysis, after controlling for multiple confounding factors, the influence of BF duration on adult bone characteristics persisted in males. Differences between the three feeding groups were observed in lumbar spine bone area and BMC, and whole body BMD (MANCOVA; p = 0.025, p = 0.013, and p = 0.048, respectively), favoring the Short BF group. In women no differences were observed. In men, early infant milk feeding may have a significant impact on adult bone health. A potential explanation is that the calcium and phosphate contents were strikingly higher in formula milk and commercial cow milk/cow milk dilutions as opposed to human milk. Our novel finding merits further studies to determine means to ensure optimal bone mass development in infants with prolonged breastfeeding.

Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.

PubMed

Pereira, Aline D'Avila; Ribeiro, Danielle Cavalcante; de Santana, Fernanda Carvalho; de Sousa Dos Santos, Aline; Mancini-Filho, Jorge; do Nascimento-Saba, Celly Cristina Alves; Velarde, Luis Guillermo Coca; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

2016-08-01

Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups.

Zebrafish sp7 mutants show tooth cycling independent of attachment, eruption and poor differentiation of teeth.

PubMed

Kague, E; Witten, P E; Soenens, M; Campos, C L; Lubiana, T; Fisher, S; Hammond, C; Brown, K Robson; Passos-Bueno, M R; Huysseune, A

2018-03-15

The capacity to fully replace teeth continuously makes zebrafish an attractive model to explore regeneration and tooth development. The requirement of attachment bone for the appearance of replacement teeth has been hypothesized but not yet investigated. The transcription factor sp7 (osterix) is known in mammals to play an important role during odontoblast differentiation and root formation. Here we study tooth replacement in the absence of attachment bone using sp7 zebrafish mutants. We analysed the pattern of tooth replacement at different stages of development and demonstrated that in zebrafish lacking sp7, attachment bone is never present, independent of the stage of tooth development or fish age, yet replacement is not interrupted. Without bone of attachment we observed abnormal orientation of teeth, and abnormal connection of pulp cavities of predecessor and replacement teeth. Mutants lacking sp7 show arrested dentinogenesis, with non-polarization of odontoblasts and only a thin layer of dentin deposited. Osteoclast activity was observed in sp7 mutants; due to the lack of bone of attachment, remodelling was diminished but nevertheless present along the pharyngeal bone. We conclude that tooth replacement is ongoing in the sp7 mutant despite poor differentiation and defective attachment. Without bone of attachment tooth orientation and pulp organization are compromised. Copyright © 2018 Elsevier Inc. All rights reserved.

Semaphorin 3A

PubMed Central

Xu, Ren

2014-01-01

Semaphorin 3A (Sema3A) is a protein identified originally as a diffusible axonal chemorepellent. Sema3A has multifunctional roles in embryonic development, immune regulation, vascularization, and oncogenesis. Bone remodeling consists of two phases: the removal of mineralized bone by osteoclasts and the formation of new bone by osteoblasts, and plays an essential role in skeletal diseases such as osteoporosis. Recent studies have shown that Sema3A is implicated in the regulation of osteoblastgenesis and osteoclastgenesis. Moreover, low bone mass in mice with specific knockout of Sema3A in the neurons indicates that Sema3A regulates bone remodeling indirectly. This review highlights recent advances on our understanding of the role of sema3A as a new player in the regulation of bone remodeling and proposes the potential of sema3A in the diagnosis and therapy of bone diseases. PMID:24589620

Determination of the ruminant origin of bone particles using fluorescence in situ hybridization (FISH)

PubMed Central

Lecrenier, M. C.; Ledoux, Q.; Berben, G.; Fumière, O.; Saegerman, C.; Baeten, V.; Veys, P.

2014-01-01

Molecular biology techniques such as PCR constitute powerful tools for the determination of the taxonomic origin of bones. DNA degradation and contamination by exogenous DNA, however, jeopardise bone identification. Despite the vast array of techniques used to decontaminate bone fragments, the isolation and determination of bone DNA content are still problematic. Within the framework of the eradication of transmissible spongiform encephalopathies (including BSE, commonly known as “mad cow disease”), a fluorescence in situ hybridization (FISH) protocol was developed. Results from the described study showed that this method can be applied directly to bones without a demineralisation step and that it allows the identification of bovine and ruminant bones even after severe processing. The results also showed that the method is independent of exogenous contamination and that it is therefore entirely appropriate for this application. PMID:25034259

Determination of the ruminant origin of bone particles using fluorescence in situ hybridization (FISH).

PubMed

Lecrenier, M C; Ledoux, Q; Berben, G; Fumière, O; Saegerman, C; Baeten, V; Veys, P

2014-07-17

Molecular biology techniques such as PCR constitute powerful tools for the determination of the taxonomic origin of bones. DNA degradation and contamination by exogenous DNA, however, jeopardise bone identification. Despite the vast array of techniques used to decontaminate bone fragments, the isolation and determination of bone DNA content are still problematic. Within the framework of the eradication of transmissible spongiform encephalopathies (including BSE, commonly known as "mad cow disease"), a fluorescence in situ hybridization (FISH) protocol was developed. Results from the described study showed that this method can be applied directly to bones without a demineralisation step and that it allows the identification of bovine and ruminant bones even after severe processing. The results also showed that the method is independent of exogenous contamination and that it is therefore entirely appropriate for this application.

A novel approach for studying the temporal modulation of embryonic skeletal development using organotypic bone cultures and microcomputed tomography.

PubMed

Kanczler, Janos M; Smith, Emma L; Roberts, Carol A; Oreffo, Richard O C

2012-10-01

Understanding the structural development of embryonic bone in a three dimensional framework is fundamental to developing new strategies for the recapitulation of bone tissue in latter life. We present an innovative combined approach of an organotypic embryonic femur culture model, microcomputed tomography (μCT) and immunohistochemistry to examine the development and modulation of the three dimensional structures of the developing embryonic femur. Isolated embryonic chick femurs were organotypic (air/liquid interface) cultured for 10 days in either basal, chondrogenic, or osteogenic supplemented culture conditions. The growth development and modulating effects of basal, chondrogenic, or osteogenic culture media of the embryonic chick femurs was investigated using μCT, immunohistochemistry, and histology. The growth and development of noncultured embryonic chick femur stages E10, E11, E12, E13, E15, and E17 were very closely correlated with increased morphometric indices of bone formation as determined by μCT. After 10 days in the organotpyic culture set up, the early aged femurs (E10 and E11) demonstrated a dramatic response to the chondrogenic or osteogenic culture conditions compared to the basal cultured femurs as determined by a change in μCT morphometric indices and modified expression of chondrogenic and osteogenic markers. Although the later aged femurs (E12 and E13) increased in size and structure after 10 days organotpypic culture, the effects of the osteogenic and chondrogenic organotypic cultures on these femurs were not significantly altered compared to basal conditions. We have demonstrated that the embryonic chick femur organotpyic culture model combined with the μCT and immunohistochemical analysis can provide an integral methodology for investigating the modulation of bone development in an ex vivo culture setting. Hence, these interdisciplinary techniques of μCT and whole organ bone cultures will enable us to delineate some of the temporal, structural developmental paradigms and modulation of bone tissue formation to underpin innovative skeletal regenerative technology for clinical therapeutic strategies in musculoskeletal trauma and diseases.

Strontium attenuates rhBMP-2-induced osteogenic differentiation via formation of Sr-rhBMP-2 complex and suppression of Smad-dependent signaling pathway.

PubMed

Zhang, Wenjing; Tian, Yu; He, Hongyan; Chen, Rui; Ma, Yifan; Guo, Han; Yuan, Yuan; Liu, Changsheng

2016-03-01

Strontium (Sr(2+)) has pronounced effects on stimulating bone formation and inhibiting bone resorption in bone regeneration. In this current study, the effect and the underlying mechanism involved of Sr(2+) on the biological activity of bone morphogenetic protein-2 (BMP-2) were studied in detail with pluripotent skeletal muscle myogenic progenitor C2C12 model cell line. The results indicated that Sr(2+) could bind recombinant human BMP-2 (rhBMP-2) rapidly, even in the presence of Ca(2+) and Mg(2+), and inhibited rhBMP-2-induced osteogenic differentiation in vitro and osteogenetic efficiency in vivo. Further studies demonstrated that Sr(2+) treatment undermined the binding capacity of rhBMP-2 with its receptor BMPRIA and thus attenuated Smad 1/5/8 phosphorylation without affecting their dephosphorylation in C2C12 cells. Furthermore, circular dichroism spectroscopy, fluorescence spectroscopy and X-ray photoelectron spectroscopy all revealed that the inhibitory effect of Sr(2+) on the rhBMP-2 osteogenic activity was associated with the formation of Sr-rhBMP-2 complex and ensuing enhancement of β-sheet structure. Our work suggests the activity of rhBMP-2 to induce osteogenic differentiation was decreased by directly interaction with free Sr ions in solution, which should provide guide and assist for development of BMP-2-based materials for bone regeneration. Due to easy denaturation and ensuing the reduced activity of rhBMP-2, preserving/enhancing the capacity of rhBMP-2 to induce osteogenic differentiation is of critical importance in developing the protein-based therapy. Cations as effective elements influence the conformation and thereby the bioactivity of protein. Strontium (Sr(2+)), stimulating bone formation and inhibiting bone resorption, has been incorporated into biomaterials/scaffold to improve the bioactivity for bone-regeneration applications. However, Sr(2+)-induced changes in the conformation and bioactivity of BMP-2 have never been investigated. In this study, the formation of Sr-rhBMP-2 complex inhibited the osteogenic differentiation in vitro and osteogenetic efficiency in vivo through the inhibition of BMP/Smad signaling pathway, providing guidance for development of Sr-containing BMP-2-based bone scaffold/matrice and other Sr-dopped protein therapy. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An interesting case of peripheral vascular disease, vascular reperfusion, and subsequent development of pain due to Paget's disease of bone.

PubMed

Kwun, Sunna; Tucci, Joseph R

2013-01-01

To present a case of Paget's disease of bone that was unmasked after vascular reperfusion. In this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget's disease and peripheral vascular disease. A 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget's disease of bone, which was subsequently confirmed by imaging. This patient's development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget's disease of bone.

Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis.

PubMed

Ferreira, Diêgo Dos Santos; Faria, Samilla Dornelas; Lopes, Sávia Caldeira de Araújo; Teixeira, Cláudia Salviano; Malachias, Angelo; Magalhães-Paniago, Rogério; de Souza Filho, José Dias; Oliveira, Bruno Luis de Jesus Pinto; Guimarães, Alexander Ramos; Caravan, Peter; Ferreira, Lucas Antônio Miranda; Alves, Ricardo José; Oliveira, Mônica Cristina

2016-01-01

Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges. To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases. Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals. Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart. These results suggest that bone-targeted pH-sensitive liposomes containing DOX can be an interesting strategy for selectively delivering this drug into bone-tumor sites, increasing its activity, and reducing DOX-related toxicity.

Bisphosphonates for prevention of postmenopausal osteoporosis.

PubMed

Ravn, Pernille

2002-02-01

Our studies showed that 5 mg alendronate per day was the lowest, most effective dose that persistently prevented bone loss in recently postmenopausal women with normal bone mass. The effect on bone mass and biochemical markers was found comparable to that of commonly recommended regimens of postmenopausal HRT, and 5 mg alendronate per day is suggested as a new option for prevention of postmenopausal osteoporosis. HRT must, however, still be considered the first choice for this indication because of additional beneficial effects on other organ systems. The effect of alendronate was unaffected by bone or fat mass status, but increased with increasing postmenopausal age. The implications were that alendronate stabilized bone mass to a comparable extent in women at particular risk of osteoporosis because of thin body habitus or low bone mass and in healthy postmenopausal women with normal bone mass. Calcium supplementation was insufficient to prevent bone loss and did not add an effect on bone metabolism when combined with alendronate treatment in recently postmenopausal women. The gastrointestinal risk and adverse event profile of 5 mg alendronate per day was comparable to that of placebo, and this dose of alendronate appeared safe for long-term use. Bone loss resumed at a normal postmenopausal rate promptly after withdrawal of alendronate in early postmenopausal women consistent with a substantial underlying natural bone loss during early menopause. Oral ibandronate increased bone mass at all skeletal regions in elderly postmenopausal women with low bone mass, and 2.5 mg ibandronate per day was the lowest dose with this effect. The results are indicative of ibandronate as an option for secondary prevention of postmenopausal osteoporosis, but longer-term phase III trials should be performed before ibandronate can be recommended for this indication. The study showed that 2.5 mg ibandronate per day was efficient for prevention of bone loss and increment in bone mass in a population of women at particular risk of osteoporosis because of low bone mass. There were no differences between 2.5 mg ibandronate per day and placebo in terms of side effects, including complaints from the gastrointestinal tract, and ibandronate appeared safe for longer-term use in this dosing. Bone loss resumed at a normal postmenopausal rate when treatment was withdrawn. The response in bone mass and biochemical markers indicated that 2.5 mg ibandronate per day is equivalent to 10 mg alendronate per day in postmenopausal women. Our studies of two recently developed biochemical markers, urine CTX and serum total OC, showed that bone turnover was lowest in the premenopausal period, where these biochemical markers furthermore revealed a negative association with bone mass. It indicated that increased bone turnover contributes to a small premenopausal bone loss and resulting lowered bone mass. In consistence, a small premenopausal bone loss was observed in some regions of the hip. The biochemical markers increased at the time of menopause, consistent with initiation of the postmenopausal bone loss, and became gradually more negatively associated with bone mass as time past the menopause increased. The biochemical markers were furthermore higher in postmenopausal women with low bone mass, consistent with the characterization of postmenopausal osteoporosis as a condition with increased bone turnover. Our results consistently indicated a central role of increased bone turnover for development of low bone mass and osteoporosis. It is, however, also important to stress that the associations between biochemical markers and bone mass were too weak to allow for a valid individual estimation of bone mass based on biochemical markers. In contrast, the biochemical markers were shown as valid tools for monitoring and prediction of treatment effect of bisphosphonates. CTX, NTX, and total OC revealed the best performance characteristics in this respect. Six months after start of treatment, the level of suppression of these biochemical markers of bone resorption and formation accurately reflected the size of the 1-2 year response in bone mass in groups of women treated with bisphosphonate. This was a clear advance over bone densitometry, which has a precision error in the area of the anticipated yearly bone mass response during bisphosphonate therapy. The relationship was consistent during treatment with alendronate or ibandronate and in younger or elderly postmenopausal women. In individual patients, cut-off values of an about 40% decrease in urine CTX or NTX and an about 20% decrease in total OC validly predicted long-term prevention of bone loss. The sensitivity of prediction was high, but the specificity low. This implicated that the biochemical markers could be used as an exact method to detect "responders" to therapy, whereas "non-responders" to bisphosphonate treatment should be detected with bone densitometry in patients who do not reveal a decrease below the cut-off value in the biochemical marker during treatment. However, before such approach can be generally recommended the cut-off values of the biochemical markers should be validated in future clinical trials of bisphosphonate. Postmenopausal osteoporosis develops slowly over many years and mainly becomes a significant individual and socio-economic health problem 1-3 decades after the menopause. Prevention of postmenopausal osteoporosis by bisphosphonates is therefore likely to imply a treatment regimen of at least a decade, as presently recommended for HRT (Consensus Development Statement 1997). However, future cost-effectiveness studies should reveal when bisphosphonate treatment should ideally be initiated. Our studies showed that the bisphosphonates were effective over the range from general recommendation (recently postmenopausal women with normal bone mass) to a reservation for women at particular risk of osteoporosis (elderly women, thin women, or women with osteopenia). Presently available biochemical markers could be used for groupwise and individual monitoring and prediction of treatment response. Most presently available biochemical markers, however, have the drawback of a low specificity. Recent studies of CTX measured in serum are promising, and indicate that this new biochemical marker might have overcome these drawbacks due to a pronounced response to treatment and a low long-term biological variation (Christgau et al. 1998b, Rosen et al. 1998, and 2000).

[MRI diagnostics of bone marrow oedema and its significance for the forensic medical evaluation of the injuries to bones and articulations].

PubMed

Fetisov, V A; Kulinkovich, K Yu

The objective of the present study was the analysis of the publications in the literature dealing with radiological methods employed for the diagnostics of injuries to and diseases of the bones and articulations as well as the role of bone marrow oedema in the development of these conditions in the specific context of the problems facing forensic medical expertise. The main results of the domestic and foreign authors concerning MRI-based investigations into the nature of injuries and other pathological changes in bones and articulations during different periods after their development are discussed with the major emphasis placed on diagnostics of bone marrow oedema. Magnetic resonance visualization of this diagnostic feature and the related manifestations of the above conditions in many cases provides an indisputable evidence of the damage whereas the discovery of its distribution to and localization in the bone structures makes it possible to elucidate the sources of this condition, such as a blow, torsional stress, stretching, etc., and its underlying mechanisms. The character and the mode of distribution of the signal from a bone marrow oedema under various conditions of visualization allow to carry out differential diagnostics of the damage prescription period of up to 1.5 months.

Development of a novel method for surgical implant design optimization through noninvasive assessment of local bone properties.

PubMed

Schiuma, D; Brianza, S; Tami, A E

2011-03-01

A method was developed to improve the design of locking implants by finding the optimal paths for the anchoring elements, based on a high resolution pQCT assessment of local bone mineral density (BMD) distribution and bone micro-architecture (BMA). The method consists of three steps: (1) partial fixation of the implant to the bone and creation of a reference system, (2) implant removal and pQCT scan of the bone, and (3) determination of BMD and BMA of all implant-anchoring locations along the actual and alternative directions. Using a PHILOS plate, the method uncertainty was tested on an artificial humerus bone model. A cadaveric humerus was used to quantify how the uncertainty of the method affects the assessment of bone parameters. BMD and BMA were determined along four possible alternative screw paths as possible criteria for implant optimization. The method is biased by a 0.87 ± 0.12 mm systematic uncertainty and by a 0.44 ± 0.09 mm random uncertainty in locating the virtual screw position. This study shows that this method can be used to find alternative directions for the anchoring elements, which may possess better bone properties. This modification will thus produce an optimized implant design. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

Irradiation conditions for fiber laser bonding of HAp-glass ceramics with bovine cortical bone.

PubMed

Tadano, Shigeru; Yamada, Satoshi; Kanaoka, Masaru

2014-01-01

Orthopedic implants are widely used to repair bones and to replace articulating joint surfaces. It is important to develop an instantaneous technique for the direct bonding of bone and implant materials. The aim of this study was to develop a technique for the laser bonding of bone with an implant material like ceramics. Ceramic specimens (10 mm diameter and 1 mm thickness) were sintered with hydroxyapatite and MgO-Al2O3-SiO2 glass powders mixed in 40:60 wt% proportions. A small hole was bored at the center of a ceramic specimen. The ceramic specimen was positioned onto a bovine bone specimen and a 5 mm diameter area of the ceramic specimen was irradiated using a fiber laser beam (1070-1080 nm wavelength). As a result, the bone and the ceramic specimens bonded strongly under the irradiation conditions of a 400 W laser power and a 1.0 s exposure time. The maximum shear strength was 5.3 ± 2.3 N. A bonding substance that penetrated deeply into the bone specimen was generated around the hole in the ceramic specimen. On using the fiber laser, the ceramic specimen instantaneously bonded to the bone specimen. Further, the irradiation conditions required for the bonding were investigated.

Cranial base morphology and temporal bone pneumatization in Asian Homo erectus.

PubMed

Balzeau, Antoine; Grimaud-Hervé, Dominique

2006-10-01

The external morphological features of the temporal bone are used frequently to determine taxonomic affinities of fossils of the genus Homo. Temporal bone pneumatization has been widely studied in great apes and in early hominids. However, this feature is rarely examined in the later hominids, particularly in Asian Homo erectus. We provide a comparative morphological and quantitative analysis of Asian Homo erectus from the sites of Ngandong, Sambungmacan, and Zhoukoudian, and of Neandertals and anatomically modern Homo sapiens in order to discuss causes and modalities of temporal bone pneumatization during hominid evolution. The evolution of temporal bone pneumatization in the genus Homo is more complex than previously described. Indeed, the Zhoukoudian fossils have a unique pattern of temporal bone pneumatization, whereas Ngandong and Sambungmacan fossils, as well as the Neandertals, more closely resemble the modern human pattern. Moreover, these Chinese fossils are characterized by a wide midvault and a relatively narrow occipital bone. Our results support the point of view that cell development does not play an active role in determining cranial base morphology. Instead, pneumatization is related to available space and to temporal bone morphology, and its development is related to correlated morphology and the relative disposition of the bones and cerebral lobes. Because variation in pneumatization is extensive within the same species, the phyletic implications of pneumatization are limited in the taxa considered here.

Gut microbiota-bone axis.

PubMed

Villa, Christopher R; Ward, Wendy E; Comelli, Elena M

2017-05-24

The gut microbiota (GM) is an important regulator of body homeostasis, including intestinal and extra-intestinal effects. This review focuses on the GM-bone axis, which we define as the effect of the gut-associated microbial community or the molecules they synthesize, on bone health. While research in this field is limited, findings from preclinical studies support that gut microbes positively impact bone mineral density and strength parameters. Moreover, administration of beneficial bacteria (probiotics) in preclinical models has demonstrated higher bone mineralization and greater bone strength. The preferential bacterial genus that has shown these beneficial effects in bone is Lactobacillus and thus lactobacilli are among the best candidates for future clinical intervention trials. However, their effectiveness is dependent on stage of development, as early life constitutes an important time for impacting bone health, perhaps via modulation of the GM. In addition, sex-specific difference also impacts the efficacy of the probiotics. Although auspicious, many questions regarding the GM-bone axis require consideration of potential mechanisms; sex-specific efficacy; effective dose of probiotics; and timing and duration of treatment.

NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis

PubMed Central

Goettsch, Claudia; Babelova, Andrea; Trummer, Olivia; Erben, Reinhold G.; Rauner, Martina; Rammelt, Stefan; Weissmann, Norbert; Weinberger, Valeska; Benkhoff, Sebastian; Kampschulte, Marian; Obermayer-Pietsch, Barbara; Hofbauer, Lorenz C.; Brandes, Ralf P.; Schröder, Katrin

2013-01-01

ROS are implicated in bone diseases. NADPH oxidase 4 (NOX4), a constitutively active enzymatic source of ROS, may contribute to the development of such disorders. Therefore, we studied the role of NOX4 in bone homeostasis. Nox4–/– mice displayed higher bone density and reduced numbers and markers of osteoclasts. Ex vivo, differentiation of monocytes into osteoclasts with RANKL and M-CSF induced Nox4 expression. Loss of NOX4 activity attenuated osteoclastogenesis, which was accompanied by impaired activation of RANKL-induced NFATc1 and c-JUN. In an in vivo model of murine ovariectomy–induced osteoporosis, pharmacological inhibition or acute genetic knockdown of Nox4 mitigated loss of trabecular bone. Human bone obtained from patients with increased osteoclast activity exhibited increased NOX4 expression. Moreover, a SNP of NOX4 was associated with elevated circulating markers of bone turnover and reduced bone density in women. Thus, NOX4 is involved in bone loss and represents a potential therapeutic target for the treatment of osteoporosis. PMID:24216508

Biomechanical analysis on fracture risk associated with bone deformity

NASA Astrophysics Data System (ADS)

Kamal, Nur Amalina Nadiah Mustafa; Som, Mohd Hanafi Mat; Basaruddin, Khairul Salleh; Daud, Ruslizam

2017-09-01

Osteogenesis Imperfecta (OI) is a disease related to bone deformity and is also known as `brittle bone' disease. Currently, medical personnel predict the bone fracture solely based on their experience. In this study, the prediction for risk of fracture was carried out by using finite element analysis on the simulated OI bone of femur. The main objective of this research was to analyze the fracture risk of OI-affected bone with respect to various loadings. A total of 12 models of OI bone were developed by applying four load cases and the angle of deformation for each of the models was calculated. The models were differentiated into four groups, namely standard, light, mild and severe. The results show that only a small amount of load is required to increase the fracture risk of the bone when the model is tested with hopping conditions. The analysis also shows that the torsional load gives a small effect to the increase of the fracture risk of the bone.

Bmp7 and Lef1 are the downstream effectors of androgen signaling in androgen-induced sex characteristics development in medaka.

PubMed

Ogino, Yukiko; Hirakawa, Ikumi; Inohaya, Keiji; Sumiya, Eri; Miyagawa, Shinichi; Denslow, Nancy; Yamada, Gen; Tatarazako, Norihisa; Iguchi, Taisen

2014-02-01

Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgen-dependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.

Tendon-to-bone attachment: from development to maturity.

PubMed

Zelzer, Elazar; Blitz, Einat; Killian, Megan L; Thomopoulos, Stavros

2014-03-01

The attachment between tendon and bone occurs across a complex transitional tissue that minimizes stress concentrations and allows for load transfer between muscles and skeleton. This unique tissue cannot be reconstructed following injury, leading to high incidence of recurrent failure and stressing the need for new clinical approaches. This review describes the current understanding of the development and function of the attachment site between tendon and bone. The embryonic attachment unit, namely, the tip of the tendon and the bone eminence into which it is inserted, was recently shown to develop modularly from a unique population of Sox9- and Scx-positive cells, which are distinct from tendon fibroblasts and chondrocytes. The fate and differentiation of these cells is regulated by transforming growth factor beta and bone morphogenetic protein signaling, respectively. Muscle loads are then necessary for the tissue to mature and mineralize. Mineralization of the attachment unit, which occurs postnatally at most sites, is largely controlled by an Indian hedgehog/parathyroid hormone-related protein feedback loop. A number of fundamental questions regarding the development of this remarkable attachment system require further study. These relate to the signaling mechanism that facilitates the formation of an interface with a gradient of cellular and extracellular phenotypes, as well as to the interactions between tendon and bone at the point of attachment. Copyright © 2014 Wiley Periodicals, Inc.

Age dependent regulation of bone-mass and renal function by the MEPE ASARM-motif

PubMed Central

Zelenchuk, Lesya V; Hedge, Anne-Marie; Rowe, Peter S N

2015-01-01

Context Mice with null mutations in Matrix Extracellular Phosphoglycoprotein (MEPE) have increased bone mass, increased trabecular density and abnormal cancellous bone (MN-mice). These defects worsen with age and MEPE over expression induces opposite effects. Also, Genome Wide Association studies show MEPE plays a major role in bone mass. We hypothesized the conserved C-terminal MEPE ASARM-motif is chiefly responsible for regulating bone mass and trabecular structure. Design To test our theory we over expressed C-terminal ASARM-peptide in MN-mice using the Col1α1 promoter (MNAt-mice). We then compared the bone and renal phenotypes of the MNAt-mouse with the MN-mouse and the X-linked hypophosphatemic rickets mouse (HYP). The HYP mouse over expresses ASARM-peptides and is defective for the PHEX gene. Results The MN-mouse developed increased bone mass, bone strength and trabecular abnormalities that worsened markedly with age. Defects in bone formation were chiefly responsible with suppressed sclerostin and increased active β-catenin. Increased uric acid levels also suggested abnormalities in purine-metabolism and a reduced fractional excretion of uric acid signaled additional renal transport changes. The MN mouse developed a worsening hyperphosphatemia and reduced FGF23 with age. An increase in the fractional excretion of phosphate (FEP) despite the hyperphosphatemia confirms an imbalance in kidney-intestinal phosphate regulation. Also, the MN mice showed an increased creatinine clearance suggesting hyperfiltration. A reversal of the MN bone-renal phenotype changes occurred with the MNAt mice including the apparent hyperfiltration. The MNAt mice also developed localized hypomineralization, hypophosphatemia and increased FGF23. Conclusions The C-terminal ASARM-motif plays a major role in regulating bone–mass and cancellous structure as mice age. In healthy mice, the processing and release of free ASARM-peptide is chiefly responsible for preserving normal bone and renal function. Free ASARM-peptide also effects renal mineral phosphate handling by influencing FGF23 expression. These findings have implications for understanding age-dependent osteoporosis, unraveling drug-targets and developing treatments. PMID:26051469

Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

PubMed Central

Ros-Tárraga, Patricia; Mazón, Patricia; Rodríguez, Miguel A.; Meseguer-Olmo, Luis; De Aza, Piedad N.

2016-01-01

This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ) rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared). The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially) and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung) as a result of degradation products being released. PMID:28773906

A multiscale framework based on the physiome markup languages for exploring the initiation of osteoarthritis at the bone-cartilage interface.

PubMed

Shim, Vickie B; Hunter, Peter J; Pivonka, Peter; Fernandez, Justin W

2011-12-01

The initiation of osteoarthritis (OA) has been linked to the onset and progression of pathologic mechanisms at the cartilage-bone interface. Most importantly, this degenerative disease involves cross-talk between the cartilage and subchondral bone environments, so an informative model should contain the complete complex. In order to evaluate this process, we have developed a multiscale model using the open-source ontologies developed for the Physiome Project with cartilage and bone descriptions at the cellular, micro, and macro levels. In this way, we can effectively model the influence of whole body loadings at the macro level and the influence of bone organization and architecture at the micro level, and have cell level processes that determine bone and cartilage remodeling. Cell information is then passed up the spatial scales to modify micro architecture and provide a macro spatial characterization of cartilage inflammation. We evaluate the framework by linking a common knee injury (anterior cruciate ligament deficiency) to proinflammatory mediators as a possible pathway to initiate OA. This framework provides a "virtual bone-cartilage" tool for evaluating hypotheses, treatment effects, and disease onset to inform and strengthen clinical studies.

Label-free Raman spectroscopy provides early determination and precise localization of breast cancer-colonized bone alterations† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02905e

PubMed Central

Zhang, Chi; Winnard Jr, Paul T.; Dasari, Sidarth; Kominsky, Scott L.; Doucet, Michele; Jayaraman, Swaathi

2017-01-01

Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones – significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer. PMID:29629144

SU-E-J-250: A Methodology for Active Bone Marrow Protection for Cervical Cancer Intensity-Modulated Radiotherapy Using 18F-FLT PET/CT Image

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Yin, Y

Purpose: The purpose of this study was to compare a radiation therapy treatment planning that would spare active bone marrow and whole pelvic bone marrow using 18F FLT PET/CT image. Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using 18F FLT/CT scans. Plans were generated for two cervical cancer patients, where pelvicactive bone marrow region was incorporated as avoidance regions based on the range: SUV>2., another region was whole pelvic bone marrow. Dose objectives were set to reduce the volume of active bone marrow and whole bone marraw. The volumes of received 10 (V10) andmore » 20 (V20) Gy for active bone marrow were evaluated. Results: Active bone marrow regions identified by 18F FLT with an SUV>2 represented an average of 48.0% of the total osseous pelvis for the two cases studied. Improved dose volume histograms for identified bone marrow SUV volumes and decreases in V10(average 18%), and V20(average 14%) were achieved without clinically significant changes to PTV or OAR doses. Conclusion: Incorporation of 18F FLT/CT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in cervical cancer.« less

Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms.

PubMed

Li, Zhi Gang; Mathew, Paul; Yang, Jun; Starbuck, Michael W; Zurita, Amado J; Liu, Jie; Sikes, Charles; Multani, Asha S; Efstathiou, Eleni; Lopez, Adriana; Wang, Jing; Fanning, Tina V; Prieto, Victor G; Kundra, Vikas; Vazquez, Elba S; Troncoso, Patricia; Raymond, Austin K; Logothetis, Christopher J; Lin, Sue-Hwa; Maity, Sankar; Navone, Nora M

2008-08-01

In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor-negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer-induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells.

Androgen receptor–negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms

PubMed Central

Li, Zhi Gang; Mathew, Paul; Yang, Jun; Starbuck, Michael W.; Zurita, Amado J.; Liu, Jie; Sikes, Charles; Multani, Asha S.; Efstathiou, Eleni; Lopez, Adriana; Wang, Jing; Fanning, Tina V.; Prieto, Victor G.; Kundra, Vikas; Vazquez, Elba S.; Troncoso, Patricia; Raymond, Austin K.; Logothetis, Christopher J.; Lin, Sue-Hwa; Maity, Sankar; Navone, Nora M.

2008-01-01

In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor–negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer–induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor–null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells. PMID:18618013

Aberrant Bone Density in Aging Mice Lacking the Adenosine Transporter ENT1

PubMed Central

Hinton, David J.; McGee-Lawrence, Meghan E.; Lee, Moonnoh R.; Kwong, Hoi K.; Westendorf, Jennifer J.; Choi, Doo-Sup

2014-01-01

Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1) is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months) compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density. PMID:24586402

Evaluation of the 3D spatial distribution of the Calcium/Phosphorus ratio in bone using computed-tomography dual-energy analysis.

PubMed

Hadjipanteli, A; Kourkoumelis, N; Fromme, P; Huang, J; Speller, R D

2016-01-01

The Calcium/Phosphorus (Ca/P) ratio was shown to vary between healthy bones and bones with osteoporotic symptoms. The relation of the Ca/P ratio to bone quality remains under investigation. To study this relation and determine if the ratio can be used to predict bone fractures, a non-invasive 3D imaging technique is required. The first aim of this study was to test the effectiveness of a computed-tomography dual-energy analysis (CT-DEA) technique developed to assess the Ca/P ratio in bone apatite (collagen-free bone) in identifying differences between healthy and inflammation-mediated osteoporotic (IMO) bones. The second aim was to extend the above technique for its application to a more complex structure, intact bone, that could potentially lead to clinical use. For the first aim, healthy and IMO rabbit cortical bone apatite samples were assessed. For the second aim, some changes were made to the technique, which was applied to healthy and IMO intact bone samples. Statistically significant differences between healthy and IMO bone apatite were found for the bulk Ca/P ratio, low Ca/P ratio proportion and interconnected low Ca/P ratio proportion. For the intact bone samples, the bulk Ca/P ratio was found to be significantly different between healthy and IMO. Results show that the CT-DEA technique can be used to identify differences in the Ca/P ratio between healthy and osteoporotic, in both bone apatite and intact bone. With quantitative imaging becoming an increasingly important advancement in medical imaging, CT-DEA for bone decomposition could potentially have several applications. Copyright © 2015. Published by Elsevier Ltd.

Replacing zoledronic acid with denosumab is a risk factor for developing osteonecrosis of the jaw.

PubMed

Higuchi, Tomoko; Soga, Yoshihiko; Muro, Misato; Kajizono, Makoto; Kitamura, Yoshihisa; Sendo, Toshiaki; Sasaki, Akira

2018-06-01

Intravenous zoledronic acid (ZA) is often replaced with subcutaneous denosumab in patients with bone metastatic cancer. Despite their different pharmacologic mechanisms of action, both denosumab and ZA are effective in bone metastasis but cause osteonecrosis of the jaw (ONJ) as a side effect. ZA persists in the body almost indefinitely, whereas denosumab does not persist for long periods. This study evaluated the risks of developing ONJ when replacing ZA with denosumab. In total, 161 Japanese patients administered ZA for bone metastatic cancer were enrolled in this single-center, retrospective, observational study. The risk of developing ONJ was evaluated by logistic regression analysis using the following factors: age, gender, cancer type, angiogenesis inhibitors, steroids, and replacement of ZA with denosumab. Seventeen patients (10.6%) developed ONJ. Multiple regression analysis indicated a significant difference in rate of ONJ associated with replacement of ZA with denosumab (odds ratio = 3.81; 95% confidence interval 1.04-13.97; P = .043). Replacing ZA with denosumab is a risk factor for the development of ONJ. Both binding of bisphosphonate to bone and receptor activator of nuclear factor-κ B ligand inhibition could additively increase the risk of ONJ. We bring the replacement of ZA with denosumab to the attention of clinical oncologists. Copyright © 2018 Elsevier Inc. All rights reserved.

Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.

PubMed

Jung, Ronald E; Kokovic, Vladimir; Jurisic, Milan; Yaman, Duygu; Subramani, Karthikeyan; Weber, Franz E

2011-08-01

The aim of the present study was to compare a newly developed biodegradable polylactide/polyglycolide/N-methyl-2-pyrrolidone (PLGA/NMP) membrane with a standard resorbable collagen membrane (RCM) in combination with and without the use of a bone substitute material (deproteinized bovine bone mineral [DBBM]) looking at the proposed tenting effect and bone regeneration. In five adult German sheepdogs, the mandibular premolars P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects on each site. A total of 20 dental implants were inserted and allocated to four different treatment modalities within each dog: PLGA/NMP membrane only (Test 1), PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with DBBM (positive control). A histomorphometric analysis was performed 12 weeks after implantation. For statistical analysis, a Friedman test and subsequently a Wilcoxon signed ranks test were applied. In four out of five PLGA/NMP membrane-treated defects, the membranes had broken into pieces without the support of DBBM. This led to a worse outcome than in the RCM group. In combination with DBBM, both membranes revealed similar amounts of area of bone regeneration and bone-to-implant contact without significant differences. On the level of the third implant thread, the PLGA/NMP membrane induced more horizontal bone formation beyond the graft than the RCM. The newly developed PLGA/NMP membrane performs equally well as the RCM when applied in combination with DBBM. Without bone substitute material, the PLGA/NMP membrane performed worse than the RCM in challenging defects, and therefore, a combination with a bone substitute material is recommended. © 2010 John Wiley & Sons A/S.

Development of a protocol to quantify local bone adaptation over space and time: Quantification of reproducibility.

PubMed

Lu, Yongtao; Boudiffa, Maya; Dall'Ara, Enrico; Bellantuono, Ilaria; Viceconti, Marco

2016-07-05

In vivo micro-computed tomography (µCT) scanning of small rodents is a powerful method for longitudinal monitoring of bone adaptation. However, the life-time bone growth in small rodents makes it a challenge to quantify local bone adaptation. Therefore, the aim of this study was to develop a protocol, which can take into account large bone growth, to quantify local bone adaptations over space and time. The entire right tibiae of eight 14-week-old C57BL/6J female mice were consecutively scanned four times in an in vivo µCT scanner using a nominal isotropic image voxel size of 10.4µm. The repeated scan image datasets were aligned to the corresponding baseline (first) scan image dataset using rigid registration. 80% of tibia length (starting from the endpoint of the proximal growth plate) was selected as the volume of interest and partitioned into 40 regions along the tibial long axis (10 divisions) and in the cross-section (4 sectors). The bone mineral content (BMC) was used to quantify bone adaptation and was calculated in each region. All local BMCs have precision errors (PE%CV) of less than 3.5% (24 out of 40 regions have PE%CV of less than 2%), least significant changes (LSCs) of less than 3.8%, and 38 out of 40 regions have intraclass correlation coefficients (ICCs) of over 0.8. The proposed protocol allows to quantify local bone adaptations over an entire tibia in longitudinal studies, with a high reproducibility, an essential requirement to reduce the number of animals to achieve the necessary statistical power. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Using Non-linear Homogenization to Improve the Performance of Macroscopic Damage Models of Trabecular Bone.

PubMed

Levrero-Florencio, Francesc; Pankaj, Pankaj

2018-01-01

Realistic macro-level finite element simulations of the mechanical behavior of trabecular bone, a cellular anisotropic material, require a suitable constitutive model; a model that incorporates the mechanical response of bone for complex loading scenarios and includes post-elastic phenomena, such as plasticity (permanent deformations) and damage (permanent stiffness reduction), which bone is likely to experience. Some such models have been developed by conducting homogenization-based multiscale finite element simulations on bone micro-structure. While homogenization has been fairly successful in the elastic regime and, to some extent, in modeling the macroscopic plastic response, it has remained a challenge with respect to modeling damage. This study uses a homogenization scheme to upscale the damage behavior from the tissue level (microscale) to the organ level (macroscale) and assesses the suitability of different damage constitutive laws. Ten cubic specimens were each subjected to 21 strain-controlled load cases for a small range of macroscopic post-elastic strains. Isotropic and anisotropic criteria were considered, density and fabric relationships were used in the formulation of the damage law, and a combined isotropic/anisotropic law with tension/compression asymmetry was formulated, based on the homogenized results, as a possible alternative to the currently used single scalar damage criterion. This computational study enhances the current knowledge on the macroscopic damage behavior of trabecular bone. By developing relationships of damage progression with bone's micro-architectural indices (density and fabric) the study also provides an aid for the creation of more precise macroscale continuum models, which are likely to improve clinical predictions.

Osteoporosis and its association with non-gonadal hormones involved in hypertension, adiposity and hyperglycaemia.

PubMed

Poudyal, Hemant; Brown, Lindsay

2013-12-01

Osteoporosis is a high-prevalence disease, particularly in developed countries, and results in high costs both to the individual and to society through associated fragility fractures. There is an urgent need for identification of novel drug targets and development of new anti-osteoporotic agents. Between 30 and 80% of osteoporotic fractures cannot be prevented despite current treatments achieving relative fracture risk reduction of up to 20%, 50%, and 70% for non-vertebral, hip and spine fractures, respectively. Traditionally, the decline in gonadal hormones has been studied as the sole hormonal determinant for the loss of bone mineral density in osteoporosis. However, recent studies have identified receptors for numerous non-gonadal hormones such as PTH, angiotensin II, leptin, adiponectin, insulin and insulin-like growth factor-1 on the osteoblast lineage cells that directly regulate bone turnover. These hormones are also involved in the pathogenesis of metabolic syndrome risk factors, particularly hypertension, type-II diabetes and obesity. By activating their respective receptors on osteoblastic lineage cells, these hormones appear to act through a common mechanism by down-regulating receptors for activation of nuclear factor kappa B ligand (RANKL) and up-regulating osteoprotegerin (OPG) with inverse responses for adiponectin. Receptors for amylin, gastric inhibitory polypeptide and ghrelin and have also been identified on the osteoblast lineage cells although the roles of these receptors in bone turnover are controversial or poorly studied. Moreover, bone turnover may be independently regulated by modulation of osteoclast-osteoblast function and bone marrow adiposity. Leptin appears to be the only hormone that is a known regulator of both bone mineralisation and bone adiposity.

Carbon nanotubes play an important role in the spatial arrangement of calcium deposits in hydrogels for bone regeneration.

PubMed

Cancian, Giulia; Tozzi, Gianluca; Hussain, Amirul Ashraf Bin; De Mori, Arianna; Roldo, Marta

2016-08-01

Age related bone diseases such as osteoporosis are considered among the main causes of reduced bone mechanical stability and bone fractures. In order to restore both biological and mechanical function of diseased/fractured bones, novel bioactive scaffolds that mimic the bone structure are constantly under development in tissue engineering applications. Among the possible candidates, chitosan-based thermosensitive hydrogel scaffolds represent ideal systems due to their biocompatibility, biodegradability, enhanced antibacterial properties, promotion of osteoblast formation and ease of injection, which makes them suitable for less invasive surgical procedures. As a main drawback, these chitosan systems present poor mechanical performance that could not support load-bearing applications. In order to produce more mechanically-competent biomaterials, the combined addition of hydroxyapatite and carbon nanotubes (CNTs) is proposed in this study. Specifically, the aim of this work is to develop thermosensitive chitosan hydrogels containing stabilised single-walled and multi-walled CNTs, where their effect on the mechanical/physiochemical properties, calcium deposition patterns and ability to provide a platform for the controlled release of protein drugs was investigated. It was found that the addition of CNTs had a significant effect on the sol-gel transition time and significantly increased the resistance to compression for the hydrogels. Moreover, in vitro calcification studies revealed that CNTs played a major role in the spatial arrangements of newly formed calcium deposits in the composite materials studied, suggesting that they may have a role in the way the repair of fragile and/or fractured bones occurs in vivo.

Weibull analysis of fracture test data on bovine cortical bone: influence of orientation.

PubMed

Khandaker, Morshed; Ekwaro-Osire, Stephen

2013-01-01

The fracture toughness, K IC, of a cortical bone has been experimentally determined by several researchers. The variation of K IC values occurs from the variation of specimen orientation, shape, and size during the experiment. The fracture toughness of a cortical bone is governed by the severest flaw and, hence, may be analyzed using Weibull statistics. To the best of the authors' knowledge, however, no studies of this aspect have been published. The motivation of the study is the evaluation of Weibull parameters at the circumferential-longitudinal (CL) and longitudinal-circumferential (LC) directions. We hypothesized that Weibull parameters vary depending on the bone microstructure. In the present work, a two-parameter Weibull statistical model was applied to calculate the plane-strain fracture toughness of bovine femoral cortical bone obtained using specimens extracted from CL and LC directions of the bone. It was found that the Weibull modulus of fracture toughness was larger for CL specimens compared to LC specimens, but the opposite trend was seen for the characteristic fracture toughness. The reason for these trends is the microstructural and extrinsic toughening mechanism differences between CL and LC directions bone. The Weibull parameters found in this study can be applied to develop a damage-mechanics model for bone.

Effects of Trypsinization and Mineralization on Intrasynovial Tendon Allograft Healing to Bone

PubMed Central

Qu, Jin; van Alphen, Nick A.; Thoreson, Andrew R.; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C.; Schmid, Thomas M.; Zhao, Chunfeng

2014-01-01

The purpose of the current study was to develop a novel technology to enhance tendon-to-bone interface healing by trypsinizing and mineralizing (TM) an intrasynovial tendon allograft in a rabbit bone tunnel model. Eight rabbit flexor digitorum profundus (FDP) tendons were used to optimize the trypsinization process. An additional 24 FDP tendons were stratified into control and TM groups; in each group, 4 tendons were used for in vitro evaluation of TM and 8 were transplanted into proximal tibial bone tunnels in rabbits. The samples were evaluated histologically and with mechanical testing at postoperative week 8. Maximum failure strength and linear stiffness were not significantly different between the control and TM tendons. A thin fibrous band of scar tissue formed at the graft-to-bone interface in the control group. However, only the TM group showed obvious new bone formation inside the tendon graft and a visible fibrocartilage layer at the bone tunnel entrance. This study is the first to explore effects of TM on the intrasynovial allograft healing to a bone tunnel. TM showed beneficial effects on chondrogenesis, osteogenesis, and integration of the intrasynovial tendon graft, but mechanical strength was the same as the control tendons in this short-term in vivo study. PMID:25611186

The Function of Naringin in Inducing Secretion of Osteoprotegerin and Inhibiting Formation of Osteoclasts

PubMed Central

Xu, Tong; Wang, Lu; Tao, You; Ji, Yan; Deng, Feng; Wu, Xiao-Hong

2016-01-01

Osteoporosis has become one of the most prevalent and costly diseases in the world. It is a metabolic disease characterized by reduction in bone mass due to an imbalance between bone formation and resorption. Osteoporosis causes fractures, prolongs bone healing, and impedes osseointegration of dental implants. Its pathological features include osteopenia, degradation of bone tissue microstructure, and increase of bone fragility. In traditional Chinese medicine, the herb Rhizoma Drynariae has been commonly used to treat osteoporosis and bone nonunion. However, the precise underlying mechanism is as yet unclear. Osteoprotegerin is a cytokine receptor shown to play an important role in osteoblast differentiation and bone formation. Hence, activators and ligands of osteoprotegerin are promising drug targets and have been the focus of studies on the development of therapeutics against osteoporosis. In the current study, we found that naringin could synergistically enhance the action of 1α,25-dihydroxyvitamin D3 in promoting the secretion of osteoprotegerin by osteoblasts in vitro. In addition, naringin can also influence the generation of osteoclasts and subsequently bone loss during organ culture. In conclusion, this study provides evidence that natural compounds such as naringin have the potential to be used as alternative medicines for the prevention and treatment of osteolysis. PMID:26884798

Future human bone research in space

NASA Technical Reports Server (NTRS)

LeBlanc, A.; Shackelford, L.; Schneider, V.

1998-01-01

Skylab crewmembers demonstrated negative calcium (Ca) balance reaching about -300 mg/day by flight day 84. Limited bone density (BMD) measurements documented that bone was not lost equally from all parts of the skeleton. Subsequent BMD studies during long duration Russian flights documented the regional extent of bone loss. These studies demonstrated mean losses in the spine, femur neck, trochanter, and pelvis of about 1%-1.6% with large differences between individuals as well as between bone sites in a given individual. Limited available data indicate postflight bone recovery occurred in some individuals, but may require several years for complete restoration. Long duration bedrest studies showed a similar pattern of bone loss and calcium balance (-180 mg/day) as spaceflight. During long duration bedrest, resorption markers were elevated, formation markers were unchanged, 1,25 vitamin D (VitD) and calcium absorption were decreased, and serum ionized Ca was increased. Although this information is a good beginning, additional spaceflight research is needed to assess architectural and subregional bone changes, elucidate mechanisms, and develop efficient as well as effective countermeasures. Space research poses a number of unique problems not encountered in ground-based laboratory research. Therefore, researchers contemplating human spaceflight research need to consider a number of unique problems related to spaceflight in their experimental design.

The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

NASA Astrophysics Data System (ADS)

Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard Oc

2016-08-01

Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

Decrease in local volumetric bone mineral density (vBMD) in osteoarthritic joints is associated with the increase in cartilage damage: a pQCT study

NASA Astrophysics Data System (ADS)

Tamaddon, Maryam; Chen, Shen Mao; Vanaclocha, Leyre; Hart, Alister; El-Husseiny, Moataz; Henckel, Johann; Liu, Chaozong

2017-11-01

Osteoarthritis (OA) is the most common type of arthritis and a major cause of disability in the adult population. It affects both cartilage and subchondral bone in the joints. There has been some progress in understanding the changes in subchondral bone with progression of osteoarthritis. However, local changes in subchondral bone such as microstructure or volumetric bone mineral density in connection with the defect in cartilage are relatively unexplored. To develop an effective treatment for progression of OA, it is important to understand how the physical environment provided by the subchondral bone affects the overlying cartilage. In this study we examined the volumetric bone mineral density (vBMD) distribution in the osteoarthritic joint tissues obtained from total hip replacement surgeries due to osteoarthritis, using peripheral quantitative CT (pQCT). It was found that there is a significant decrease in volumetric bone mineral density, which co-localises with the damage in the overlying cartilage. This was not limited to the subchondral bone immediately adjacent to the cartilage defect but continued in the layers below. Bone resorption and cyst formation in the OA tissues were also detected. We observed that the bone surrounding subchondral bone cysts exhibited much higher volumetric bone mineral density than that of the surrounding bones. PQCT was able to detect significant changes in vBMD between OA and non-OA samples, as well as between areas of different cartilage degeneration, which points to its potential as a technique for detection of early OA.

Bone mineral content measurement in small infants by single-photon absorptiometry: current methodologic issues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steichen, J.J.; Asch, P.A.; Tsang, R.C.

1988-07-01

Single-photon absorptiometry (SPA), developed in 1963 and adapted for infants by Steichen et al. in 1976, is an important tool to quantitate bone mineralization in infants. Studies of infants in which SPA was used include studies of fetal bone mineralization and postnatal bone mineralization in very low birth weight infants. The SPA technique has also been used as a research tool to investigate longitudinal bone mineralization and to study the effect of nutrition and disease processes such as rickets or osteopenia of prematurity. At present, it has little direct clinical application for diagnosing bone disease in single patients. The bonesmore » most often used to measure bone mineral content (BMC) are the radius, the ulna, and, less often, the humerus. The radius appears to be preferred as a suitable bone to measure BMC in infants. It is easily accessible; anatomic reference points are easily palpated and have a constant relationship to the radial mid-shaft site; soft tissue does not affect either palpation of anatomic reference points or BMC quantitation in vivo. The peripheral location of the radius minimizes body radiation exposure. Trabecular and cortical bone can be measured separately. Extensive background studies exist on radial BMC in small infants. Most important, the radius has a relatively long zone of constant BMC. Finally, SPA for BMC in the radius has a high degree of precision and accuracy. 61 references.« less

Acute development of cortical porosity and endosteal naïve bone formation from the daily but not weekly short-term administration of PTH in rabbit

PubMed Central

Yamane, Hiroshi; Takakura, Aya; Shimadzu, Yukari; Kodama, Toshiyuki; Lee, Ji-Won; Isogai, Yukihiro; Ishizuya, Toshinori; Takao-Kawabata, Ryoko

2017-01-01

Teriparatide [human parathyroid hormone (1–34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity. The present study developed 4 teriparatide regimens [20 μg/kg/day (D20), 40 μg/kg/day (D40), 140 μg/kg/week (W140) and 280 μg/kg/week (W280)] in the rabbit as a model animal with a well-developed Haversian system and osteons. The total weekly doses were equivalent in the low-dose groups (D20 and W140) and in the high-dose groups (D40 and W280). After the short-term (1 month) administration of TPDT, micro-CT, histomorphometry and three-dimensional second harmonic generation (3D-SHG) imaging to visualize the bone collagen demonstrated that daily regimens but not weekly regimens were associated with the significant development of cortical porosity and endosteal naïve bone formation by marrow fibrosis. We concomitantly monitored the pharmacokinetics of the plasma teriparatide levels as well as the temporal changes in markers of bone formation and resorption. The analyses in the present study suggested that the daily repeated administration of teriparatide causes more deleterious changes in the cortical microarchitecture than the less frequent administration of higher doses. The findings of the present study may have some implications for use of teriparatide in clinical treatment. PMID:28394900

Bone mineral density in developing children with osteogenesis imperfecta

PubMed Central

Sakkers, Ralph J B; Pruijs, Hans E H; Joosse, Pieter; Castelein, René M

2013-01-01

Background and purpose — Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue caused by a defect in collagen type I synthesis. For bone, this includes fragility, low bone mass, and progressive skeletal deformities, which can result in various degrees of short stature. The purpose of this study was to investigate development of bone mineral density in children with OI. Patients and methods — Development of lumbar bone mineral density was studied retrospectively in a cohort of 74 children with OI. Mean age was 16.3 years (SD 4.3). In 52 children, repeated measurements were available. Mean age at the start of measurement was 8.8 years (SD 4.1), and mean follow-up was 9 years (SD 2.7). A longitudinal data analysis was performed. In the total cohort (74 children), a cross-sectional analysis was performed with the latest-measured BMD. Age at the latest BMD measurement was almost equal for girls and boys: 17.4 and 17.7 years respectively. Result — Mean annual increase in BMD in the 52 children was 0.038 g/cm2/year (SD 0.024). Annual increase in BMD was statistically significantly higher in girls, in both the unadjusted and adjusted analysis. In cross-sectional analysis, in the whole cohort the latest-measured lumbar BMD was significantly higher in girls, in the children with OI of type I, in walkers, and in those who were older, in both unadjusted and adjusted analysis. Interpretation — During 9 years of follow-up, there appeared to be an increase in bone mineral density, which was most pronounced in girls. One possible explanation might be a later growth spurt and older age at peak bone mass in boys. PMID:23992144

Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging

PubMed Central

Batey, Michael A.; Almeida, Gilberto S.; Wilson, Ian; Dildey, Petra; Sharma, Abhishek; Blair, Helen; Hide, I. Geoff; Heidenreich, Olaf; Vormoor, Josef; Maxwell, Ross J.; Bacon, Chris M.

2014-01-01

Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2−/−/γc−/− mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which resemble the human disease. We have shown the utility of small animal bioimaging for tracking disease progression, making this model a useful assay for preclinical drug testing. PMID:24409320

Biodistribution of strontium and barium in the developing and mature skeleton of rats.

PubMed

Panahifar, Arash; Chapman, L Dean; Weber, Lynn; Samadi, Nazanin; Cooper, David M L

2018-06-19

Bone acts as a reservoir for many trace elements. Understanding the extent and pattern of elemental accumulation in the skeleton is important from diagnostic, therapeutic, and toxicological perspectives. Some elements are simply adsorbed to bone surfaces by electric force and are buried under bone mineral, while others can replace calcium atoms in the hydroxyapatite structure. In this article, we investigated the extent and pattern of skeletal uptake of barium and strontium in two different age groups, growing, and skeletally mature, in healthy rats. Animals were dosed orally for 4 weeks with either strontium chloride or barium chloride or combined. The distribution of trace elements was imaged in 3D using synchrotron K-edge subtraction micro-CT at 13.5 µm resolution and 2D electron probe microanalysis (EPMA). Bulk concentration of the elements in serum and bone (tibiae) was also measured by mass spectrometry to study the extent of uptake. Toxicological evaluation did not show any cardiotoxicity or nephrotoxicity. Both elements were primarily deposited in the areas of active bone turnover such as growth plates and trabecular bone. Barium and strontium concentration in the bones of juvenile rats was 2.3 times higher, while serum levels were 1.4 and 1.5 times lower than adults. In all treatment and age groups, strontium was preferred to barium even though equal molar concentrations were dosed. This study displayed spatial co-localization of barium and strontium in bone for the first time. Barium and strontium can be used as surrogates for calcium to study the pathological changes in animal models of bone disease and to study the effects of pharmaceutical compounds on bone micro-architecture and bone remodeling in high spatial sensitivity and precision.

Development of countermeasures for medical problems encountered in space flight.

PubMed

Nicogossian, A E; Rummel, J D; Leveton, L; Teeter, R

1992-01-01

By the turn of this century, long-duration space missions, either in low Earth orbit or for got early planetary missions, will become commonplace. From the physiological standpoint, exposure to the weightless environment results in changes in body function, some of which are adaptive in nature and some of which can be life threatening. Important issues such as environmental health, radiation protection, physical deconditioning, and bone and muscle loss are of concern to life scientists and mission designers. Physical conditioning techniques such as exercise are not sufficient to protect future space travellers. A review of past experience with piloted missions has shown that gradual breakdown in bone and muscle tissue, together with fluid losses, despite a vigorous exercise regimen can ultimately lead to increased evidence of renal stones, musculoskeletal injuries, and bone fractures. Biological effects of radiation can, over long periods of time increase the risk of cancer development. Today, a vigorous program of study on the means to provide a complex exercise regimen to the antigravity muscles and skeleton is under study. Additional evaluation of artificial gravity as a mechanism to counteract bone and muscle deconditioning and cardiovascular asthenia is under study. New radiation methods are being developed. This paper will deal with the results of these studies.

Development of countermeasures for medical problems encountered in space flight

NASA Astrophysics Data System (ADS)

Nicogossian, Arnauld E.; Rummel, John D.; Leveton, Lauren; Teeter, Ron

1992-08-01

By the turn of this century, long-duration space missions, either in low Earth orbit or for got early planetary missions, will become commonplace. From the physiological standpoint, exposure to the weightless environment results in changes in body function, some of which are adaptive in nature and some of which can be life threatening. Important issues such as environmental health, radiation protection, physical deconditioning, and bone and muscle loss are of concern to life scientists and mission designers. Physical conditioning techniques such as exercise are not sufficient to protect future space travellers. A review of past experience with piloted missions has shown that gradual breakdown in bone and muscle tissue, together with fluid losses, despite a vigorous exercise regimen can ultimately lead to increased evidence of renal stones, musculoskeletal injuries, and bone fractures. Biological effects of radiation can, over long periods of time increase the risk of cancer development. Today, a vigorous program of study on the means to provide a complex exercise regimen to the antigravity muscles and skeleton is under study. Additional evaluation of artificial gravity as a mechanism to counteract bone and muscle deconditioning and cardiovascular asthenia is under study. New radiation methods are being developed. This paper will deal with the results of these studies.

Bone metastasis from ovarian cancer. Clinical analysis of 26 cases.

PubMed

Zhang, Min; Sun, Jimei

2013-12-01

To study the clinical characteristics of bone metastasis from ovarian cancer, and facilitate physicians to develop treatment strategies. This retrospective study was carried out in the Provincial Hospital Affiliated to Shandong University, Shandong, China. Twenty-six cases of bone metastasis from ovarian cancer treated between January 2002 and May 2008 were reviewed, and the clinical data were collected. In the current study, the incidence of bone metastasis is 0.82%. Twelve cases of bone metastasis occurred in the cervical vertebra, 10 in the lumbar vertebra, 8 in the pelvis, 7 in the thoracic vertebra, 5 in the limbs, one in the ribs, and 2 in the sternum. Lung metastasis occurred concomitantly in 9 cases, liver metastasis in 5 cases, brain metastasis in 4 cases, splenic metastasis in 3 cases, adrenal metastasis in 2 cases, and lymphatic metastasis in 12 cases. Twenty-three cases (88.5%) of bone metastasis were detected in stage III-IV, and 3 (11.5%) in stage II (p=0.000). The survival time in cases treated using comprehensive therapy was longer than those using radiotherapy or chemotherapy alone (p=0.047). Bone metastasis from ovarian cancer is rare, however, the increasing pathological stage of ovarian cancer may add to the risk of bone metastasis, especially in the cases with lung or lymphatic metastasis. The pelvis and vertebral bone are the most common location of bone metastasis, and comprehensive treatment may improve the survival time of patients.

Effect of bone conduction transducer placement on distortion product otoacoustic emissions

NASA Astrophysics Data System (ADS)

Hazelbaker, Julie L.

The purpose of this study was to develop a technique to determine the magnitude of bone conducted sound in the cochlea when stimuli are delivered from three different locations on the head. Distortion product otoacoustic emissions (DPOAE) at 1000 and 2000 Hz were used as tools to determine cochlear response to stimuli introduced via air conduction and bone conduction in three subjects. The bone conduction transducer was moved to three head locations (ipsilateral mastoid, contralateral mastoid and forehead). The intensity of the emissions elicited was compared. The differences in DPOAE magnitude created by varying the location of the bone conduction transducer were compared with behavioral threshold differences with the same transducers at the same locations. It was assumed that results of behavioral measures would provide a prediction of the relationship between air and bone conducted DPOAE. However, in the current study, this was not the case. Behavioral bone conduction threshold data did not predict differences in DPOAE at different bone conduction transducer locations. This was a somewhat surprising result and should be considered further in future studies examining the properties of DPOAE elicited by bone conduction. Additionally, a wide band noise masker was introduced to the non-test ear when bone conducted stimuli were introduced to make DPOAE and behavioral test conditions as similar as possible. No great suppression effects were noted across subjects for either frequency. This was likely due to the shape and intensity of the contralateral masked used.

The skeletal consequences of thyrotoxicosis.

PubMed

Nicholls, Jonathan J; Brassill, Mary Jane; Williams, Graham R; Bassett, J H Duncan

2012-06-01

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.

Surface and interface investigation of aluminosilicate biomaterial by the “in vivo” experiments

NASA Astrophysics Data System (ADS)

Oudadesse, H.; Derrien, A. C.; Martin, S.; Chaair, H.; Cathelineau, G.

2008-11-01

Porous mixtures of aluminosilicate/calcium phosphate have been studied for biomaterials applications. Aluminosilicates formed with an inorganic polymeric constitution present amorphous zeolites because of their 3D network structure and present the ability to link to bone matrix. Amorphous geopolymers of the potassium-poly(sialate)-nanopolymer type were synthesised at low temperature and studied for their use as potential biomaterials. They were mixed with 13% weight of calcium phosphate like biphasic hydroxyapatite and β-tricalcium phosphate. In this study, " in vivo" experiments were monitored to evaluate the biocompatibility, the surface and the interface behaviour of these composites when used as bone implants. Moreover, it has been demonstrated using histological and physicochemical studies that the developed materials exhibited a remarkable bone bonding when implanted in a rabbit's thighbone for a period of 1 month. The easy synthesis conditions (low temperature) of this composite and the fast intimate links with bone constitute an improvement of synthetic bone graft biomaterial.

Uniaxial and Multiaxial Fatigue Life Prediction of the Trabecular Bone Based on Physiological Loading: A Comparative Study.

PubMed

Fatihhi, S J; Harun, M N; Abdul Kadir, Mohammed Rafiq; Abdullah, Jaafar; Kamarul, T; Öchsner, Andreas; Syahrom, Ardiyansyah

2015-10-01

Fatigue assessment of the trabecular bone has been developed to give a better understanding of bone properties. While most fatigue studies are relying on uniaxial compressive load as the method of assessment, in various cases details are missing, or the uniaxial results are not very realistic. In this paper, the effect of three different load histories from physiological loading applied on the trabecular bone were studied in order to predict the first failure surface and the fatigue lifetime. The fatigue behaviour of the trabecular bone under uniaxial load was compared to that of multiaxial load using a finite element simulation. The plastic strain was found localized at the trabecular structure under multiaxial load. On average, applying multiaxial loads reduced more than five times the fatigue life of the trabecular bone. The results provide evidence that multiaxial loading is dominated in the low cycle fatigue in contrast to the uniaxial one. Both bone volume fraction and structural model index were best predictors of failure (p < 0.05) in fatigue for both types of loading, whilst uniaxial loading has indicated better values in most cases.

Relationships among diet, physical activity, and dual plane dual-energy X-ray absorptiometry bone outcomes in pre-pubertalgirls.

PubMed

Ren, Jie; Brann, Lynn S; Bruening, Kay S; Scerpella, Tamara A; Dowthwaite, Jodi N

2017-12-01

In pre-pubertal girls, nutrient intakes and non-aquatic organized activity were evaluated as factors in vertebral body bone mass, structure, and strength. Activity, vitamin B 12 , and dietary fiber predicted bone outcomes most consistently. Exercise and vitamin B 12 appear beneficial, whereas high fiber intake appears to be adverse for vertebral body development. Childhood development sets the baseline for adult fracture risk. Most studies evaluate development using postero-anterior (PA) dual-energy X-ray absorptiometry (DXA) areal bone mineral density, bone mineral content, and bone mineral apparent density. In a prior analysis, we demonstrated that PA DXA reflects posterior element properties, rather than vertebral body fracture sites, such that loading is associated with subtle differences in vertebral body geometry, not 3D density. The current analysis is restricted to pre-pubertal girls, for a focused exploration of key nutrient intakes and physical activity as factors in dual plane indices of vertebral body geometry, density, and strength. This cross-sectional analysis used paired PA and supine lateral (LAT) lumbar spine DXA scans to assess "3D" vertebral body bone mineral apparent density (PALATBMAD), "3D" index of structural strength in axial compression (PALATIBS), and fracture risk index (PALATFRI). Diet data were collected using the Youth/Adolescent Questionnaire (YAQ, 1995); organized physical activity was recorded via calendar-based form. Pearson correlations and backward stepwise multiple linear regression analyzed associations among key nutrients, physical activity, and bone outcomes. After accounting for activity and key covariates, fiber, unsupplemented vitamin B 12 , zinc, carbohydrate, vitamin C, unsupplemented magnesium, and unsupplemented calcium intake explained significant variance for one or more bone outcomes (p < 0.05). After adjustment for influential key nutrients and covariates, activity exposure was associated with postero-anterior (PA) areal bone mineral density, PA bone mineral content, PA width, lateral (LAT) BMC, "3D" bone cross-sectional area (coronal plane), "3D" PALATIBS, and PALATFRI benefits (p < 0.05). Physical activity, fiber intake, and unsupplemented B 12 intake appear to influence vertebral body bone mass, density, geometry, and strength in well-nourished pre-pubertal girls; high fiber intakes may adversely affect childhood vertebral body growth.

Nanocellulose-collagen-apatite composite associated with osteogenic growth peptide for bone regeneration.

PubMed

Saska, Sybele; Teixeira, Lucas Novaes; de Castro Raucci, Larissa Moreira Spinola; Scarel-Caminaga, Raquel Mantuaneli; Franchi, Leonardo Pereira; Dos Santos, Raquel Alves; Santagneli, Silvia Helena; Capela, Marisa Veiga; de Oliveira, Paulo Tambasco; Takahashi, Catarina Satie; Gaspar, Ana Maria Minarelli; Messaddeq, Younès; Ribeiro, Sidney José Lima; Marchetto, Reinaldo

2017-10-01

Despite advances in the field of biomaterials for bone repair/regeneration, some challenges for developing an ideal bone substitute need to be overcome. Herein, this study synthesized and evaluated in vitro a nanocomposite based on bacterial cellulose (BC), collagen (COL), apatite (Ap) and osteogenic growth peptide (OGP) or its C-terminal pentapeptide [OGP(10-14)] for bone regeneration purposes. The BC-COL nanocomposites were successfully obtained by carbodiimide-mediated coupling as demonstrated by spectroscopy analysis. SEM, FTIR and 31 P NMR analyses revealed that in situ synthesis to apatite was an effective route for obtaining of bone-like apatite. The OGP-containing (BC-COL)-Ap stimulated the early development of the osteoblastic phenotype. Additionally, the association among collagen, apatite, and OGP peptides enhanced cell growth compared with OGP-containing BC-Ap. Furthermore, none of the nanocomposites showed cytotoxic, genotoxic or mutagenic effects. These promising results suggest that the (BC-COL)-Ap associated with OGP peptides might be considered a potential candidate for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

An update on the Application of Nanotechnology in Bone Tissue Engineering.

PubMed

Griffin, M F; Kalaskar, D M; Seifalian, A; Butler, P E

2016-01-01

Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Future studies to improve the application of nanomaterials for bone tissue engineering are needed.

Roles of Chondrocytes in Endochondral Bone Formation and Fracture Repair

PubMed Central

Hinton, R.J.; Jing, Y.; Jing, J.; Feng, J.Q.

2016-01-01

The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes. In this review, the authors will briefly discuss the history of this idea and describe recent studies that clearly demonstrate that the direct transformation of chondrocytes into bone cells is common in both long bone and mandibular condyle development and during bone fracture repair. The authors will also provide new evidence of a distinct difference in ossification orientation in the condylar ramus (1 ossification center) versus long bone ossification formation (2 ossification centers). Based on our recent findings and those of other laboratories, we propose a new model that contrasts the mode of bone formation in much of the mandibular ramus (chondrocyte-derived) with intramembranous bone formation of the mandibular body (non-chondrocyte-derived). PMID:27664203

Bone Tissue Engineering Under Xenogeneic-Free Conditions in a Large Animal Model as a Basis for Early Clinical Applicability.

PubMed

Weigand, Annika; Beier, Justus P; Schmid, Rafael; Knorr, Tobias; Kilian, David; Götzl, Rebekka; Gerber, Thomas; Horch, Raymund E; Boos, Anja M

2017-03-01

For decades, researchers have been developing a range of promising strategies in bone tissue engineering with the aim of producing a significant clinical benefit over existing therapies. However, a major problem concerns the traditional use of xenogeneic substances for the expansion of cells, which complicates direct clinical transfer. The study's aim was to establish a totally autologous sheep model as a basis for further preclinical studies and future clinical application. Ovine mesenchymal stromal cells (MSC) were cultivated in different concentrations (0%, 2%, 5%, 10%, and 25%) of either autologous serum (AS) or fetal calf serum (FCS). With an increase of serum concentration, enhanced metabolic activity and proliferation could be observed. There were minor differences between MSC cultivated in AS or FCS, comparing gene and protein expression of osteogenic and stem cell markers, morphology, and osteogenic differentiation. MSC implanted subcutaneously in the sheep model, together with a nanostructured bone substitute, either in stable block or moldable putty form, induced similar vascularization and remodeling of the bone substitute irrespective of cultivation of MSC in AS or FCS and osteogenic differentiation. The bone substitute in block form together with MSC proved particularly advantageous in the induction of ectopic bone formation compared to the cell-free control and putty form. It could be demonstrated that AS is suitable for replacement of FCS for cultivation of ovine MSC for bone tissue engineering purposes. Substantial progress has been made in the development of a strictly xenogeneic-free preclinical animal model to bring future clinical application of bone tissue engineering strategies within reach.

Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development

PubMed Central

Witkowska, Agata; Alibhai, Aziza; Hughes, Chloe; Price, Jennifer; Klisch, Karl; Sturrock, Craig J.

2014-01-01

The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8–12 months and life expectancy is ∼5–6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0–1 month, 1–3 months, 3–6 months, 6 months–1 year and 1–4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most guinea pigs have reached full weight. This study is the first to show the high abundance (100% in this study) of the supratrochlear foramen within the guinea pig humerus and the complete absence of a supracondylar foramen, which is different to many other species and may also affect potential fracture points and frequencies. Understanding bone morphology and growth is essential in not only understanding the requirements of the healthy guinea pig, but also necessary in order to investigate disease states. PMID:25289194

Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development.

PubMed

Witkowska, Agata; Alibhai, Aziza; Hughes, Chloe; Price, Jennifer; Klisch, Karl; Sturrock, Craig J; Rutland, Catrin S

2014-01-01

The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8-12 months and life expectancy is ∼5-6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0-1 month, 1-3 months, 3-6 months, 6 months-1 year and 1-4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most guinea pigs have reached full weight. This study is the first to show the high abundance (100% in this study) of the supratrochlear foramen within the guinea pig humerus and the complete absence of a supracondylar foramen, which is different to many other species and may also affect potential fracture points and frequencies. Understanding bone morphology and growth is essential in not only understanding the requirements of the healthy guinea pig, but also necessary in order to investigate disease states.

Mice lacking bone sialoprotein (BSP) lose bone after ovariectomy and display skeletal site-specific response to intermittent PTH treatment.

PubMed

Wade-Gueye, Ndéye Marième; Boudiffa, Maya; Laroche, Norbert; Vanden-Bossche, Arnaud; Fournier, Carole; Aubin, Jane E; Vico, Laurence; Lafage-Proust, Marie-Hélène; Malaval, Luc

2010-11-01

Bone sialoprotein (BSP) belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, whose members play multiple and distinct roles in the development, turnover, and mineralization of bone and dentin. The functions of BSP in bone remodeling are not yet well established. We previously showed that BSP knockout (BSP(-/-)) mice exhibit a higher trabecular bone volume, concomitant with lower bone remodeling, than wild-type (BSP(+/+)) mice. To determine whether bone turnover can be stimulated in the absence of BSP, we subjected BSP(+/+) and BSP(-/-) mice to catabolic [ovariectomy (OVX)] or anabolic (intermittent PTH administration) hormonal challenges. BSP(-/-) mice progressively develop hypocalcemia and high serum PTH between 2 and 4 months of age. Fifteen and 30 d after OVX, microtomography analysis showed a significant decrease of trabecular bone volume in tibiae of both genotypes. Histomorphometric parameters of bone formation and resorption were significantly increased by OVX. PTH treatment resulted in an increase of trabecular thickness and both bone formation and resorption parameters at all skeletal sites in both genotypes and a decrease of trabecular bone volume in tibiae of BSP(+/+) but not BSP(-/-) mice. PTH increased cortical thickness and bone area in BSP(+/+) but not BSP(-/-) mice and stimulated the bone formation rate specifically in the endosteum of BSP(+/+) mice and the periosteum of BSP(-/-) mice. PTH enhanced the expression of RANKL, MEPE, and DMP1 in both genotypes but increased OPG and OPN expression only in BSP(-/-) mice. In conclusion, despite the low basal turnover, both catabolic and anabolic challenges increase bone formation and resorption in BSP(-/-) mice, suggesting that compensatory pathways are operative in the skeleton of BSP-deficient mice. Although up-regulation of one or several other SIBLINGs is a possible mechanism, further studies are needed to analyze the interplay and cross-regulation involved in compensating for the absence of BSP.

External ear canal exostosis and otitis media in temporal bones of prehistoric and historic chilean populations. A paleopathological and paleoepidemiological study.

PubMed

Castro, Mario; Goycoolea, Marcos; Silva-Pinto, Verónica

2017-04-01

External ear canal exostosis is more prevalent in northern coastal groups than in the highlands, suggesting that ocean activities facilitate the appearance of exostosis. However, southern coastal groups exposed to colder ocean water have a lesser incidence of exostosis, possibly due to less duration of exposure. There was a high incidence of otitis media in all groups of native population in Chile. One coastal group had a higher incidence, presumably due to racial factors. This is a paleopathological and paleoepidemiological study in temporal bones which assesses external ear canal exostosis and otitis media in prehistoric and historic native populations in Chile. A total of 460 temporal bones were evaluated for exostosis (ex) and 542 temporal bones were evaluated for otitis media (om). The study involved four groups: (1) Prehistoric Coastal (400-1000 AD) populations in Northern Chile (Pisagua-Tiwanaku) (22 temporal bones ex; 28 om); (2) Prehistoric Highland (400-1000 AD) populations in Northern Chile (292 temporal bones ex; 334 om); (3) Pisagua-Regional Developments (coastal) in Northern Chile (1000-1450 AD) (66 temporal bones ex; 82 om); and (4) Historic (1500-1800 AD) coastal populations in Southern Chile (80 temporal bones ex: 18 Chonos, 62 Fuegians. 98 om: 22 Chonos, 76 Fuegians). Skulls were evaluated visually and with an operating microscope. In addition, the otitis media group was evaluated with Temporal bone radiology - -lateral XRays-Schuller view - to assess pneumatization as evidence of previous middle ear disease. Prehistoric northern coastal groups had an incidence of exostosis of 15.91%, the northern highlands group 1.37%, and the southern coastal group 1.25%. There were changes suggestive of otitis media in: Pisagua/Tiwanaku 53.57%; Pisagua/Regional Developments 70.73%; Northern Highlands population 47.90%; Chonos 63.64%; and Fuegian tribes 64.47%.

A predictive bone drilling force model for haptic rendering with experimental validation using fresh cadaveric bone.

PubMed

Lin, Yanping; Chen, Huajiang; Yu, Dedong; Zhang, Ying; Yuan, Wen

2017-01-01

Bone drilling simulators with virtual and haptic feedback provide a safe, cost-effective and repeatable alternative to traditional surgical training methods. To develop such a simulator, accurate haptic rendering based on a force model is required to feedback bone drilling forces based on user input. Current predictive bone drilling force models based on bovine bones with various drilling conditions and parameters are not representative of the bone drilling process in bone surgery. The objective of this study was to provide a bone drilling force model for haptic rendering based on calibration and validation experiments in fresh cadaveric bones with different bone densities. Using a commonly used drill bit geometry (2 mm diameter), feed rates (20-60 mm/min) and spindle speeds (4000-6000 rpm) in orthognathic surgeries, the bone drilling forces of specimens from two groups were measured and the calibration coefficients of the specific normal and frictional pressures were determined. The comparison of the predicted forces and the measured forces from validation experiments with a large range of feed rates and spindle speeds demonstrates that the proposed bone drilling forces can predict the trends and average forces well. The presented bone drilling force model can be used for haptic rendering in surgical simulators.

Effects of Physical Activity and Muscle Quality on Bone Development in Girls

PubMed Central

Farr, Joshua N.; Laddu, Deepika R.; Blew, Robert M.; Lee, Vinson R.; Going, Scott B.

2013-01-01

Poor muscle quality and sedentary behavior are risk factors for metabolic dysfunction in children and adolescents. However, because longitudinal data are scarce, relatively little is known about how changes in muscle quality and physical activity influence bone development. Purpose In a 2-year longitudinal study, we examined the effects of physical activity and changes in muscle quality on bone parameters in young girls. Methods The sample included 248 healthy girls aged 9–12 years at baseline. Peripheral quantitative computed tomography was used to measure calf and thigh muscle density, an indicator of skeletal muscle fat content or muscle quality, as well as bone parameters at diaphyseal and metaphyseal sites of the femur and tibia. Physical activity was assessed using a validated questionnaire specific for youth. Results After controlling for covariates in multiple regression models, increased calf muscle density was independently associated with greater gains in cortical (β = 0.13, P < 0.01) and trabecular (β = 0.25, P < 0.001) volumetric bone mineral density (vBMD) and the bone strength index (BSI; β = 0.25, P < 0.001) of the tibia. Importantly, these relationships were generalized, as similar changes were present at the femur. Associations between physical activity and changes in bone parameters were weaker than those observed for muscle density. Nevertheless, physical activity was significantly (all P < 0.05) associated with greater gains in trabecular vBMD and the BSI of the distal femur. Conclusions These findings suggest that poor muscle quality may put girls at risk for suboptimal bone development. Physical activity is associated with more optimal gains in weight-bearing bone density and strength in girls, but to a lesser extent than changes in muscle quality. PMID:23698240

Heavy metals accumulation affects bone microarchitecture in osteoporotic patients.

PubMed

Scimeca, Manuel; Feola, Maurizio; Romano, Lorenzo; Rao, Cecilia; Gasbarra, Elena; Bonanno, Elena; Brandi, Maria Luisa; Tarantino, Umberto

2017-04-01

Bone metabolism is affected by mechanical, genetic, and environmental factors and plays a major role in osteoporosis. Nevertheless, the influence of environmental pollution on the occurrence of osteoporosis is still unclear and controversial. In this context, heavy metals are the most important pollutants capable to affect bone mass. The aim of this study was to investigate whether heavy metals accumulation in bone tissues could be related to the altered bone metabolism and architecture of osteoporotic patients. To this end, we analyzed 25 bone head biopsies osteoporotic patients and 25 bone head biopsies of osteoarthritic patients. Moreover we enrolled 15 patients underwent hip arthroplasty for high-energy hip fracture or osteonecrosis of the femoral head as a control group. Bone head biopsies were studied by BioQuant-osteo software, scanning electron microscopy and Energy Dispersive X-ray microanalysis. We found a prevalence of lead, cadmium and chromium accumulation in osteoporotic patients. Noteworthy, high levels of sclerostin, detected by immunohistochemistry, correlate with the accumulation of heavy metal found in the bone of osteoporotic patients, suggesting a molecular link between heavy metal accumulation and bone metabolism impairment. In conclusion, the presence of heavy metals into bone shed new light on the comprehension of the pathogenesis of osteoporosis since these elements could play a non redundant role in the development of osteoporosis at cellular/molecular and epigenetic level. Nevertheless, in vivo and in vitro studies need to better elucidate the molecular mechanism in which heavy metals can participate to osteoporosis. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1333-1342, 2017. © 2016 Wiley Periodicals, Inc.

Peri-implant and systemic effects of high-/low-affinity bisphosphonate-hydroxyapatite composite coatings in a rabbit model with peri-implant high bone turnover

PubMed Central

2012-01-01

Background Hydroxyapatite (HA) coatings composed with bisphosphonates (BPs) which have high mineral-binding affinities have been confirmed to successfully enhance implant stability. However, few previous studies focused on HA coatings composed with low-affinity BPs or on systemic effects of locally released BPs. Methods In this long-term study, we developed two kinds of BP-HA composite coatings using either high-affinity BP (alendronate, ALN) or low-affinity BP (risedronate, RIS). Thirty-six rabbits were divided into three groups according to different coating applications (group I: HA, group II: ALN-HA, and group III: RIS-HA). Implants were inserted into the proximal region of the medullary cavity of the left tibiay. At insertion, 2 × 108 wear particles were injected around implants to induce a peri-implant high bone turnover environment. Both local (left tibias) and systemic (right tibias and lumbar vertebrae) inhibitory effect on bone resorption were compared, including bone-implant integration, bone architecture, bone mineral density (BMD), implant stability, and serum levels of bone turnover markers. Results The results indicated that ALN-HA composite coating, which could induce higher bone-implant contact (BIC) ratio, bone mass augmentation, BMD, and implant stability in the peri-implant region, was more potent on peri-implant bone, while RIS-HA composite coating, which had significant systemic effect, was more potent on non-peri-implant bone, especially lumbar vertebrae. Conclusions It is instructive and meaningful to further clinical studies that we could choose different BP-HA composite coatings according to the patient’s condition. PMID:22686414

Subchondral bone histology and grading in osteoarthritis

PubMed Central

Aho, Olli-Matti; Finnilä, Mikko; Thevenot, Jerome; Saarakkala, Simo; Lehenkari, Petri

2017-01-01

Objective Osteoarthritis (OA) has often regarded as a disease of articular cartilage only. New evidence has shifted the paradigm towards a system biology approach, where also the surrounding tissue, especially bone is studied more vigorously. However, the histological features of subchondral bone are only poorly characterized in current histological grading scales of OA. The aim of this study is to specifically characterize histological changes occurring in subchondral bone at different stages of OA and propose a simple grading system for them. Design 20 patients undergoing total knee replacement surgery were randomly selected for the study and series of osteochondral samples were harvested from the tibial plateaus for histological analysis. Cartilage degeneration was assessed using the standardized OARSI grading system, while a novel four-stage grading system was developed to illustrate the changes in subchondral bone. Subchondral bone histology was further quantitatively analyzed by measuring the thickness of uncalcified and calcified cartilage as well as subchondral bone plate. Furthermore, internal structure of calcified cartilage-bone interface was characterized utilizing local binary patterns (LBP) based method. Results The histological appearance of subchondral bone changed drastically in correlation with the OARSI grading of cartilage degeneration. As the cartilage layer thickness decreases the subchondral plate thickness and disorientation, as measured with LBP, increases. Calcified cartilage thickness was highest in samples with moderate OA. Conclusion The proposed grading system for subchondral bone has significant relationship with the corresponding OARSI grading for cartilage. Our results suggest that subchondral bone remodeling is a fundamental factor already in early stages of cartilage degeneration. PMID:28319157

Mechanical torque measurement for in vivo quantification of bone strength in the proximal femur.

PubMed

Mueller, Marc Andreas; Hengg, Clemens; Hirschmann, Michael; Schmid, Denise; Sprecher, Christoph; Audigé, Laurent; Suhm, Norbert

2012-10-01

Bone strength determines fracture risk and fixation strength of osteosynthesis implants. In vivo, bone strength is currently measured indirectly by quantifying bone mineral density (BMD) which is however only one determinant of the bone's biomechanical competence besides the bone's macro- and micro-architecture and tissue related parameters. We have developed a measurement principle (DensiProbe™ Hip) for direct, mechanical quantification of bone strength within the proximal femur upon hip fracture fixation. Previous cadaver tests indicated a close correlation between DensiProbe™ Hip measurements, 3D micro-CT analysis and biomechanical indicators of bone strength. The goal of this study was to correlate DensiProbe™ Hip measurements with areal bone mineral density (BMD). Forty-three hip fracture patients were included in this study. Intraoperatively, DensiProbe™ Hip was inserted to the subsequent hip screw tip position within the femoral head. Peak torque to breakaway of local cancellous bone was registered. Thirty-seven patients underwent areal BMD measurements of the contralateral proximal femur. Failure of fixation was assessed radio graphically 6 and 12 weeks postoperatively. Peak torque and femoral neck BMD showed significant correlations (R=0.60, P=0.0001). In regression analysis, areal BMD explained 46% of femoral neck BMD variance in a quadratic relationship. Throughout the 12-week follow-up period, no failure of fixation was observed. DensiProbe™ Hip may capture variations of bone strength beyond areal BMD which are currently difficult to measure in vivo. A multicenter study will clarify if peak torque predicts fixation failure. Copyright © 2012 Elsevier Ltd. All rights reserved.

Drilling of bone: A comprehensive review

PubMed Central

Pandey, Rupesh Kumar; Panda, S.S.

2013-01-01

Background Bone fracture treatment usually involves restoring of the fractured parts to their initial position and immobilizing them until the healing takes place. Drilling of bone is common to produce hole for screw insertion to fix the fractured parts for immobilization. Orthopaedic drilling during surgical process causes increase in the bone temperature and forces which can cause osteonecrosis reducing the stability and strength of the fixation. Methods A comprehensive review of all the relevant investigations carried on bone drilling is conducted. The experimental method used, results obtained and the conclusions made by the various researchers are described and compared. Result Review suggests that the further improvement in the area of bone drilling is possible. The systematic review identified several consequential factors (drilling parameters and drill specifications) affecting bone drilling on which there no general agreement among investigators or are not adequately evaluated. These factors are highlighted and use of more advanced methods of drilling is accentuated. The use of more precise experimental set up which resembles the actual situation and the development of automated bone drilling system to minimize human error is addressed. Conclusion In this review, an attempt has been made to systematically organize the research investigations conducted on bone drilling. Methods of treatment of bone fracture, studies on the determination of the threshold for thermal osteonecrosis, studies on the parameters influencing bone drilling and methods of the temperature measurement used are reviewed and the future work for the further improvement of bone drilling process is highlighted. PMID:26403771

Improvement of adynamic bone disease after renal transplantation.

PubMed

Abdallah, K A; Jorgetti, V; Pereira, R C; Reis, L M dos; Pereira, L M; Corrêa, P H S; Borelli, A; Ianhez, L E; Moysés, R M A; David-Neto, E

2006-01-01

Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

Function of Matrix IGF-1 in Coupling Bone Resorption and Formation

PubMed Central

Crane, Janet L.; Cao, Xu

2013-01-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space and time dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of MSCs and HSCs and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis. PMID:24068256

Function of matrix IGF-1 in coupling bone resorption and formation.

PubMed

Crane, Janet L; Cao, Xu

2014-02-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

Advances in bionanomaterials for bone tissue engineering.

PubMed

Scott, Timothy G; Blackburn, Gary; Ashley, Michael; Bayer, Ilker S; Ghosh, Anindya; Biris, Alexandru S; Biswas, Abhijit

2013-01-01

Bone is a specialized form of connective tissue that forms the skeleton of the body and is built at the nano and microscale levels as a multi-component composite material consisting of a hard inorganic phase (minerals) in an elastic, dense organic network. Mimicking bone structure and its properties present an important frontier in the fields of nanotechnology, materials science and bone tissue engineering, given the complex morphology of this tissue. There has been a growing interest in developing artificial bone-mimetic nanomaterials with controllable mineral content, nanostructure, chemistry for bone, cartilage tissue engineering and substitutes. This review describes recent advances in bionanomaterials for bone tissue engineering including developments in soft tissue engineering. The significance and basic process of bone tissue engineering along with different bionanomaterial bone scaffolds made of nanocomposites and nanostructured biopolymers/bioceramics and the prerequisite biomechanical functions are described. It also covers latest developments in soft-tissue reconstruction and replacement. Finally, perspectives on the future direction in nanotechnology-enabled bone tissue engineering are presented.

Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

PubMed

Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

2006-06-01

Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts.

Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

PubMed

Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

2015-05-01

Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

Rabbit Calvarial Defect Model for Customized 3D-Printed Bone Grafts.

PubMed

Lee, Kang-Gon; Lee, Kang-Sik; Kang, Yu-Jeoung; Hwang, Jong-Hyun; Lee, Se-Hwan; Park, Sang-Hyug; Park, Yongdoo; Cho, Young-Sam; Lee, Bu-Kyu

2018-05-01

Bone graft materials are commonly used to regenerate various bone defects, but their application is often limited because of the complex defect shape in various clinical conditions. Hence, customized bone grafts using three-dimensional (3D) printing techniques have been developed. However, conventional simple bone defect models are limited for evaluating the benefits and manufacturing accuracy of 3D-printed customized bone grafts. Thus, the aim of the present study was to develop a complex-shaped bone defect model. We designed an 8-shaped bony defect that consists of two simple circles attached to the rabbit calvarium. To determine the critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter trephine burs were tested, and the 7-mm-diameter bur could successfully create a CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone formation was 28.65% ± 8.63% at 16 weeks following creation of the defect. To confirm its efficacy for clinical use, the 8-shaped defect was created on a rabbit calvarium and 3D computed tomography (CT) was performed. A stereolithography file was produced using the CT data, and a 3D-printed polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were able to modify the tolerances of the bone graft and calvarial defect to fabricate a more precise bone graft. Customized characteristics of the bone graft were then used to improve the accuracy of the bone graft. In addition, we confirmed the fitting ability of the 3D-printed graft during implantation of the graft. Our 8-shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a useful CSD model for evaluating 3D-printed graft materials.

It May Seem Inflammatory, but Some T Cells Are Innately Healing to the Bone.

PubMed

Kalyan, Shirin

2016-11-01

Among the most significant developments to have taken place in osteology over the last few decades is an evolution from treating and viewing bone disorders primarily through an endocrine lens to instead seeing them as metabolic disorders that interface at the molecular and cellular level with the immune system. Osteoimmunology was officially born in response to accumulating evidence that the immune system is integrally involved in bone remodeling, but much of the early work focused on the role of conventional αβ T cells in driving bone loss. There is, however, emerging data indicating that innate lymphocytes, in particular γδ T cells, may in fact be important for bone regeneration. We first observed that bisphosphonate-associated osteonecrosis of the jaw (ONJ), a rare but serious adverse drug effect characterized by nonhealing necrotic bone tissue of the mandible or maxilla, was linked to a deficiency in a subset of γδ T cells found in human peripheral blood. Patients who developed ONJ while on bisphosphonate therapy not only lacked the main subset of circulating γδ T cells, but they also all had underlying conditions that compromised their immune integrity. A number of recent studies have unraveled the role of γδ T cells (and lymphocytes sharing their characteristics) in bone regeneration-particularly for fracture healing. These findings seem to contradict the prevailing view of such "inflammatory" T cells as being bone degenerative rather than restorative. This viewpoint melds together the emerging evidence of these so-called inflammatory T cells in bone remodeling and healing-showing that they are not in fact "all bad to the bone." © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

High Resolution Peripheral Quantitative Computed Tomography for Assessment of Bone Quality

NASA Astrophysics Data System (ADS)

Kazakia, Galateia

2014-03-01

The study of bone quality is motivated by the high morbidity, mortality, and societal cost of skeletal fractures. Over 10 million people are diagnosed with osteoporosis in the US alone, suffering 1.5 million osteoporotic fractures and costing the health care system over 17 billion annually. Accurate assessment of fracture risk is necessary to ensure that pharmacological and other interventions are appropriately administered. Currently, areal bone mineral density (aBMD) based on 2D dual-energy X-ray absorptiometry (DXA) is used to determine osteoporotic status and predict fracture risk. Though aBMD is a significant predictor of fracture risk, it does not completely explain bone strength or fracture incidence. The major limitation of aBMD is the lack of 3D information, which is necessary to distinguish between cortical and trabecular bone and to quantify bone geometry and microarchitecture. High resolution peripheral quantitative computed tomography (HR-pQCT) enables in vivo assessment of volumetric BMD within specific bone compartments as well as quantification of geometric and microarchitectural measures of bone quality. HR-pQCT studies have documented that trabecular bone microstructure alterations are associated with fracture risk independent of aBMD.... Cortical bone microstructure - specifically porosity - is a major determinant of strength, stiffness, and fracture toughness of cortical tissue and may further explain the aBMD-independent effect of age on bone fragility and fracture risk. The application of finite element analysis (FEA) to HR-pQCT data permits estimation of patient-specific bone strength, shown to be associated with fracture incidence independent of aBMD. This talk will describe the HR-pQCT scanner, established metrics of bone quality derived from HR-pQCT data, and novel analyses of bone quality currently in development. Cross-sectional and longitudinal HR-pQCT studies investigating the impact of aging, disease, injury, gender, race, and therapeutics on bone quality will be discussed.

Histological evolution of the regenerate during bone transport: an experimental study in sheep.

PubMed

López-Pliego, Esperanza Macarena; Giráldez-Sánchez, Miguel Ángel; Mora-Macías, Juan; Reina-Romo, Esther; Domínguez, Jaime

2016-09-01

Bone transport (BT) for segmentary bone defects is a well-known technique as it enables correction with new bone formation, which is similar to the previous bone. Despite the high number of experimental studies of distraction osteogenesis in bone lengthening, the types of ossification and histological changes that occur in the regenerate of the bone transport process remain controversial. The aim of this study is to provide the complete evolution of tissues and the types of ossification in the regenerate during the different phases of bone formation after BT until the end of the remodelling period. A histological study was performed using ten adult sheep that were submitted to BT. The types of ossification as well as the evolution of different tissues in the regenerate were determined using histomorphometry and inmunohistochemical studies. The evolution of trabeculae thickness, osteoblast and osteoclast densities, relationship between collagen types and changes in vascularization were also studied. Ossification was primarily intramembranous, with some focus of endochondral ossification in isolated animals. The cell counts showed a progression of cellular activity from the periphery to the centre, presenting the same progression as the growth of bone trabeculae, whose trabeculae thickness was quadrupled at the end of remodelling. Inmunohistochemical studies confirmed the prevalence of type I collagen and the ratio of the Type I/Type II collagen ratio was found to be 2.48. The percentages of the vascularized areas were proximally higher than distally in all animals, but distal zone obtained higher rates than the central region. Bone transport regenerate exhibits a centripetal ossification model and a mixed pattern with predominance of intramembranous over endochondral ossification. The data obtained resemble partially to those found in models of bone lengthening applied to large animals. This study provides a detailed structural characterization of the newly formed tissue, which may help to explain the development of the regenerate of bone transport in humans. It will also serve for future mechanobiological models that may aid research on the effect of loading or distractor stiffness in clinical results. © 2016 Elsevier Ltd. All rights reserved.

Lattice strains and load partitioning in bovine trabecular bone.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akhtar, R.; Daymond, M. R.; Almer, J. D.

2012-02-01

Microdamage and failure mechanisms have been well characterized in bovine trabecular bone. However, little is known about how elastic strains develop in the apatite crystals of the trabecular struts and their relationship with different deformation mechanisms. In this study, wide-angle high-energy synchrotron X-ray diffraction has been used to determine bulk elastic strains under in situ compression. Dehydrated bone is compared to hydrated bone in terms of their response to load. During compression, load is initially borne by trabeculae aligned parallel to loading direction with non-parallel trabeculae deforming by bending. Ineffective load partitioning is noted in dehydrated bone whereas hydrated bonemore » behaves like a plastically yielding foam« less

Benzene-induced myelotoxicity: application of flow cytofluorometry for the evaluation of early proliferative change in bone marrow.

PubMed Central

Irons, R D

1981-01-01

A detailed description of flow cytofluorometric DNA cell cycle analysis is presented. A number of studies by the author and other investigators are reviewed in which a method is developed for the analysis of cell cycle phase in bone marrow of experimental animals. Bone marrow cell cycle analysis is a sensitive indicator of changes in bone marrow proliferative activity occurring early in chemically-induced myelotoxicity. Cell cycle analysis, used together with other hematologic methods, has revealed benzene-induced toxicity in proliferating bone marrow cells to be cycle specific, appearing to affect a population in late S phase which then accumulate in G2/M. PMID:7016521

Nanobiotechnology and bone regeneration: a mini-review.

PubMed

Gusić, Nadomir; Ivković, Alan; VaFaye, John; Vukasović, Andreja; Ivković, Jana; Hudetz, Damir; Janković, Saša

2014-09-01

The purpose of this paper is to review current developments in bone tissue engineering, with special focus on the promising role of nanobiotechnology. This unique fusion between nanotechnology and biotechnology offers unprecedented possibilities in studying and modulating biological processes on a molecular and atomic scale. First we discuss the multiscale hierarchical structure of bone and its implication on the design of new scaffolds and delivery systems. Then we briefly present different types of nanostructured scaffolds, and finally we conclude with nanoparticle delivery systems and their potential use in promoting bone regeneration. This review is not meant to be exhaustive and comprehensive, but aims to highlight concepts and key advances in the field of nanobiotechnology and bone regeneration.

Development of electrospun bone-mimetic matrices for bone regenerative applications

NASA Astrophysics Data System (ADS)

Phipps, Matthew Christopher

Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein show that BMMs supported great-er adhesion, proliferation, and integrin activation of mesenchymal stem cells (MSCs), the multipotent bone-progenitor cells within bone marrow and the periosteum, in comparison to electrospun PCL alone. These cellular responses, which are essential early steps in the process of bone regeneration, highlight the benefits of presenting cells with natural bone molecules. Subsequently, evaluation of new bone formation in a rat cortical tibia defect showed that BMMs are highly osteoconductive. However, these studies also revealed the inability of endogenous cells to migrate within electrospun matrices due to the inherently small pore sizes. To address this limitation, which will negatively impact the rate of scaf-fold-to-bone turnover and inhibit vascularization, sacrificial fibers were added to the ma-trix. The removal of these fibers after fabrication resulted in BMMs with larger pores, leading to increased infiltration of MSCs and endogenous bone cells. Lastly, we evaluat-ed the potential of our matrices to stimulate the recruitment of MSCs, a vital step in bone healing, through the sustained delivery of platelet derived growth factor-BB (PDGF-BB). BMMs were found to adsorb and subsequently release greater quantities of PDGF-BB, compared to PCL scaffolds, over an 8-week interval. The released PDGF-BB retained its bioactivity, stimulating MSC chemotaxis in two separate assays. Collectively, these re-sults suggest that electrospun matrices incorporating the bone matrix molecules collagen I and HA, with sacrificial fibers, provide a favorable scaffold for MSC survival and infil-tration as well as the ability to sequester PDGF-BB from solution, leading to sustained local delivery and MSC chemotaxis.

A Path Analysis to Identify the Psychosocial Factors Influencing Physical Activity and Bone Health in Middle-School Girls

PubMed Central

Sharma, Shreela V.; Hoelscher, Deanna M.; Kelder, Steven H.; Diamond, Pamela M.; Day, R. Sue; Hergenroeder, Albert C.

2011-01-01

Background The purpose of this study was to identify pathways used by psychosocial factors to influence physical activity and bone health in middle-school girls. Methods Baseline data from the Incorporating More Physical Activity and Calcium in Teens (IMPACT) study collected in 2001 to 2003 were used. IMPACT was a 1 1/2 years nutrition and physical activity intervention study designed to improve bone density in 717 middle-school girls in Texas. Structural Equations Modeling was used to examine the interrelationships and identify the direct and indirect pathways used by various psychosocial and environmental factors to influence physical activity and bone health. Results Results show that physical activity self-efficacy and social support (friend, family engagement, and encouragement in physical activity) had a significant direct and indirect influence on physical activity with participation in sports teams as the mediator. Participation in sports teams had a direct effect on both physical activity (β= 0.20, P < .05) and bone health and (β=0.13, P < .05). Conclusion The current study identified several direct and indirect pathways that psychosocial factors use to influence physical activity and bone health among adolescent girls. These findings are critical for the development of effective interventions for promoting bone health in this population. PMID:19953837

A path analysis to identify the psychosocial factors influencing physical activity and bone health in middle-school girls.

PubMed

Sharma, Shreela V; Hoelscher, Deanna M; Kelder, Steven H; Diamond, Pamela M; Day, R Sue; Hergenroeder, Albert C

2009-09-01

The purpose of this study was to identify pathways used by psychosocial factors to influence physical activity and bone health in middle-school girls. Baseline data from the Incorporating More Physical Activity and Calcium in Teens (IMPACT) study collected in 2001 to 2003 were used. IMPACT was a 1 1/2 years nutrition and physical activity intervention study designed to improve bone density in 717 middle-school girls in Texas. Structural Equations Modeling was used to examine the interrelationships and identify the direct and indirect pathways used by various psychosocial and environmental factors to influence physical activity and bone health. Results show that physical activity self-efficacy and social support (friend, family engagement, and encouragement in physical activity) had a significant direct and indirect influence on physical activity with participation in sports teams as the mediator. Participation in sports teams had a direct effect on both physical activity (beta = 0.20, P < .05) and bone health and (beta = 0.13, P < .05). The current study identified several direct and indirect pathways that psychosocial factors use to influence physical activity and bone health among adolescent girls. These findings are critical for the development of effective interventions for promoting bone health in this population.

Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women.

PubMed

Bilek, Laura D; Waltman, Nancy L; Lappe, Joan M; Kupzyk, Kevin A; Mack, Lynn R; Cullen, Diane M; Berg, Kris; Langel, Meghan; Meisinger, Melissa; Portelli-Trinidad, Ashlee; Lang, Molly

2016-08-30

In the United States, over 34 million American post-menopausal women have low bone mass (osteopenia) which increases their risk of osteoporosis and fractures. Calcium, vitamin D and exercise are recommended for prevention of osteoporosis, and bisphosphonates (BPs) are prescribed in women with osteoporosis. BPs may also be prescribed for women with low bone mass, but are more controversial due to the potential for adverse effects with long-term use. A bone loading exercise program (high-impact weight bearing and resistance training) promotes bone strength by preserving bone mineral density (BMD), improving bone structure, and by promoting bone formation at sites of mechanical stress. The sample for this study will be 309 women with low bone mass who are within 5 years post-menopause. Subjects are stratified by exercise history (≥2 high intensity exercise sessions per week; < 2 sessions per week) and randomized to a control or one of two treatment groups: 1) calcium + vitamin D (CaD) alone (Control); 2) a BP plus CaD (Risedronate); or 3) a bone loading exercise program plus CaD (Exercise). After 12 months of treatment, changes in bone structure, BMD, and bone turnover will be compared in the 3 groups. Primary outcomes for the study are bone structure measures (Bone Strength Index [BSI] at the tibia and Hip Structural Analysis [HSA] scores). Secondary outcomes are BMD at the hip and spine and serum biomarkers of bone formation (alkaline phosphase, AlkphaseB) and resorption (Serum N-terminal telopeptide, NTx). Our central hypothesis is that improvements in bone strength will be greater in subjects randomized to the Exercise group compared to subjects in either Control or Risedronate groups. Our research aims to decrease the risk of osteoporotic fractures by improving bone strength in women with low bone mass (pre-osteoporotic) during their first 5 years' post-menopause, a time of rapid and significant bone loss. Results of this study could be used in developing a clinical management pathway for women with low bone mass at their peak period of bone loss that would involve lifestyle modifications such as exercises prior to medications such as BPs. Clinicaltrials.gov NCT02186600 . Initial registration: 7/7/2014.

Microtomographic imaging in the process of bone modeling and simulation

NASA Astrophysics Data System (ADS)

Mueller, Ralph

1999-09-01

Micro-computed tomography ((mu) CT) is an emerging technique to nondestructively image and quantify trabecular bone in three dimensions. Where the early implementations of (mu) CT focused more on technical aspects of the systems and required equipment not normally available to the general public, a more recent development emphasized practical aspects of micro- tomographic imaging. That system is based on a compact fan- beam type of tomograph, also referred to as desktop (mu) CT. Desk-top (mu) CT has been used extensively for the investigation of osteoporosis related health problems gaining new insight into the organization of trabecular bone and the influence of osteoporotic bone loss on bone architecture and the competence of bone. Osteoporosis is a condition characterized by excessive bone loss and deterioration in bone architecture. The reduced quality of bone increases the risk of fracture. Current imaging technologies do not allow accurate in vivo measurements of bone structure over several decades or the investigation of the local remodeling stimuli at the tissue level. Therefore, computer simulations and new experimental modeling procedures are necessary for determining the long-term effects of age, menopause, and osteoporosis on bone. Microstructural bone models allow us to study not only the effects of osteoporosis on the skeleton but also to assess and monitor the effectiveness of new treatment regimens. The basis for such approaches are realistic models of bone and a sound understanding of the underlying biological and mechanical processes in bone physiology. In this article, strategies for new approaches to bone modeling and simulation in the study and treatment of osteoporosis and age-related bone loss are presented. The focus is on the bioengineering and imaging aspects of osteoporosis research. With the introduction of desk-top (mu) CT, a new generation of imaging instruments has entered the arena allowing easy and relatively inexpensive access to the three-dimensional microstructure of bone, thereby giving bone researchers a powerful tool for the exploration of age-related bone loss and osteoporosis.

Hydrogel Delivery of Mesenchymal Stem Cell–Expressing Bone Morphogenetic Protein-2 Enhances Bone Defect Repair

PubMed Central

Hsiao, Hui-Yi; Yang, Shu-Rui; Brey, Eric M.; Chu, I-Ming

2016-01-01

Background: The application of bone tissue engineering for repairing bone defects has gradually shown some satisfactory progress. One of the concerns raising scientific attention is the poor supply of growth factors. A number of growth factor delivery approaches have been developed for promoting bone formation. However, there is no systematic comparison of those approaches on efficiency of neobone formation. In this study, the approaches using periosteum, direct supply of growth factors, or gene transfection of growth factors were evaluated to determine the osteogenic capacity on the repair of bone defect. Methods: In total, 42 male 21-week-old Sprague-Dawley rats weighing 250 to 400 g were used as the bone defect model to evaluate the bone repair efficiency. Various tissue engineered constructs of poly(ethylene glycol)-poly(l-lactic acid) (PEG-PLLA) copolymer hydrogel with periosteum, with external supply of bone morphogenetic protein-2 (BMP2), or with BMP2-transfected bone marrow–derived mesenchymal stem cells (BMMSCs) were filled in a 7-mm bone defect region. Animals were euthanized at 3 months, and the hydrogel constructs were harvested. The evaluation with histological staining and radiography analysis were performed for the volume of new bone formation. Results: The PEG-PLLA scaffold with BMMSCs promotes bone regeneration with the addition of periosteum. The group with BMP2-transfected BMMSCs demonstrated the largest volume of new bone among all the testing groups. Conclusions: Altogether, the results of this study provide the evidence that the combination of PEG-PLLA hydrogels with BMMSCs and sustained delivery of BMP2 resulted in the maximal bone regeneration. PMID:27622106

Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy

PubMed Central

Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

2011-01-01

Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy. PMID:21765896

Stem Cell Mobilizers: Novel Therapeutics for Acute Kidney Injury.

PubMed

Xu, Yue; Zeng, Song; Zhang, Qiang; Zhang, Zijian; Hu, Xiaopeng

2017-01-01

In the past decade, rapid developments in stem cell studies have occurred. Researchers have confirmed the plasticity of bone marrow stem cells and the repair and regeneration effects of bone marrow hematopoietic stem cells on solid organs. These findings have suggested the possibility of using bone marrow stem cell mobilizers to repair and regenerate injured organs. Recent studies on the effects of granulocyte colony-stimulating factor (G-CSF) and Plerixafor (AMD3100) on mouse acute kidney injury models have confirmed that the use of bone marrow stem cell mobilizers may be an effective therapeutic measure. This paper summarizes studies describing the effects of G-CSF and AMD3100 on various acute kidney injury models over the past 10 years. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Novel microinjector for carrying bone substitutes for bone regeneration in periodontal diseases.

PubMed

Tsai, Hsiao-Cheng; Li, Yi-Chen; Young, Tai-Horng; Chen, Min-Huey

2016-01-01

Traditionally, guide bone regeneration (GBR) was a widely used method for repairing bone lost from periodontal disease. There were some disadvantages associated with the GBR method, such as the need for a stable barrier membrane and a new creative cavity during the surgical process. To address these disadvantages, the purpose of this study was to evaluate a novel microinjector developed for dental applications. The microinjector was designed to carry bone graft substitutes to restore bone defects for bone regeneration in periodontal diseases. The device would be used to replace the GBR method. In this study, the injected force and ejected volume of substitutes (including air, water, and ethanol) were defined by Hooke's law (n = 3). The optimal particle size of bone graft substitutes was determined by measuring the recycle ratio of bone graft substitutes from the microinjector (n = 3). Furthermore, a novel agarose gel model was used to evaluate the feasibility of the microinjector. The current study found that the injected force was less than 0.4 N for obtaining the ejected volume of approximately 2 mL, and when the particle size of tricalcium phosphate (TCP) was smaller than 0.5 mm, 80% TCP could be ejected from the microinjector. Furthermore, by using an agarose model to simulate the periodontal soft tissue, it was also found that bone graft substitutes could be easily injected into the gel. The results confirmed the feasibility of this novel microinjector for dental applications to carry bone graft substitutes for the restoration of bone defects of periodontal disease. Copyright © 2015. Published by Elsevier B.V.

Prediction on fracture risk of femur with Osteogenesis Imperfecta using finite element models: Preliminary study

NASA Astrophysics Data System (ADS)

Wanna, S. B. C.; Basaruddin, K. S.; Mat Som, M. H.; Mohamad Hashim, M. S.; Daud, R.; Majid, M. S. Abdul; Sulaiman, A. R.

2017-10-01

Osteogenesis imperfecta (OI) is a genetic disease which affecting the bone geometry. In a severe case, this disease can cause death to patients. The main issue of this disease is the prediction on bone fracture by the orthopaedic surgeons. The resistance of the bone to withstand the force before the bones fracture often become the main concern. Therefore, the objective of the present preliminary study was to investigate the fracture risk associated with OI bone, particularly in femur, when subjected to the self-weight. Finite element (FEA) was employed to reconstruct the OI bone model and analyse the mechanical stress response of femur before it fractures. Ten deformed models with different severity of OI bones were developed and the force that represents patient self-weight was applied to the reconstructed models in static analysis. Stress and fracture risk were observed and analysed throughout the simulation. None of the deformed model were observed experienced fracture. The fracture risk increased with increased severity of the deformed bone. The results showed that all deformed femur models were able to bear the force without experienced fracture when subjected to only the self-weight.

CO2 laser for the treatment of diabetic foot ulcers with exposed bone. A consecutive series of type 2 diabetic patients.

PubMed

Monami, M; Mirabella, C; Scatena, A; Nreu, B; Zannoni, S; Aleffi, S; Giannoni, L; Mannucci, E

2017-08-01

The treatment of foot ulcers with exposed bone is challenging, because of the risk of infection and of difficulties in the development of granulation tissue. A CO 2 laser beam could be used to produce discontinuities in periosteum, allowing the exposure of blood containing multipotent stem cells, capable of initiating the healing process. The local application of platelet-rich plasma (PRP) has been proposed as a therapeutic tool for accelerating healing in foot ulcers, including those in patients with diabetes. Aim of the present pilot, proof-of-concept study is the assessment of the therapeutic potential of CO 2 laser treatment, either alone or combined with PRP, in the treatment of diabetic foot ulcers with exposed bone. We performed a pilot, uncontrolled 3-month observation study on a consecutive series of 9 type two diabetic patients and foot ulcers with exposed bone. A CO 2 -laser was used for producing nine discontinuities on periosteum for each cm 2 , by directing the focused laser beam on the bone until bleeding. The procedure was repeated up to 6 times, at a distance of 1 week and ulcers assessed weekly until the end of the study (3 months). In the last 5 of the 14 patients, the treatment described above was associated with PRP. Of the nine patients treated, four healed, and one more patient developed granulation tissue covering entirely bone surface. Out of the four patients who did not heal, one underwent minor amputation. Among the five patients treated with a combination of CO 2 laser and PRP, two healed within 3 months, and two more patients developed granulation tissue covering entirely bone surface; the fifth patient did not show any improvement and underwent amputation. The present pilot experience represents a novelty in this field showing a possible use of CO 2 -laser in the treatment of diabetic foot ulcers.

[Ex Vivo Testing of Mechanical Properties of Canine Metacarpal/Metatarsal Bones after Simulated Implant Removal].

PubMed

Srnec, R; Fedorová, P; Pěnčík, J; Vojtová, L; Sedlinská, M; Nečas, A

2016-01-01

PURPOSE OF THE STUDY In a long-term perspective, it is better to remove implants after fracture healing. However, subsequent full or excessive loading of an extremity may result in refracture, and the bone with holes after screw removal may present a site with predilection for this. The aim of the study was to find ways of how to decrease risk factors for refracture in such a case. This involved support to the mechanical properties of a bone during its remodelling until defects following implant removal are repaired, using a material tolerated by bone tissue and easy to apply. It also included an assessment of the mechanical properties of a bone after filling the holes in it with a newly developed biodegradable polymer-composite gel ("bone paste"). The composite also has a prospect of being used to repair bony defects produced by pathological processes. MATERIAL AND METHODS Experiments were carried out on intact weight-bearing small bones in dogs. A total of 27 specimens of metacarpal/metatarsal bones were used for ex vivo testing. They were divided into three groups: K1 (n = 9) control undamaged bones; K2 (n = 9) control bones with iatrogenic damage simulating holes left after cortical screw removal; EXP (n = 9) experimental specimens in which simulated holes in bone were filled with the biodegradable self-hardening composite. The bone specimens were subjected to three-point bending in the caudocranial direction by a force acting parallel to the direction of drilling in their middiaphyses. The value of maximum load achieved (N) and the corresponding value of a vertical displacement (mm) were recorded in each specimen, then compared and statistically evaluated. RESULTS On application of a maximum load (N), all bone specimens broke in the mid-part of their diaphyses. In group K1 the average maximum force of 595.6 ± 79.5 N was needed to break the bone; in group K2 it was 347.6 ± 58.6 N; and in group EXP it was 458.3 ± 102.7 N. The groups with damaged bones, K2 and EXP, were compared and the difference was found to be statistically significant (p ≤ 0.05). CONCLUSIONS The recently developed biodegradable polymer-composite gel is easy and quick to apply to any defect, regardless of its shape, in bone tissue. The ex vivo mechanical tests on canine short bones showed that the composite applied to defects, which simulated holes left after screw removal, provided sufficient mechanical support to the bone architecture. The results of measuring maximum loading forces were statistically significant. However, before the composite could be recommended for use in veterinary or human medical practice, thorough pre-clinical studies will be required. fracture fixation, mechanical testing, bone plate, cortical screw, refracture.

Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy

NASA Technical Reports Server (NTRS)

Headley, J. A.; Theriault, R. L.; LeBlanc, A. D.; Vassilopoulou-Sellin, R.; Hortobagyi, G. N.

1998-01-01

The objective of this cross-sectional study was to determine lumbar spine bone mineral density (BMD) in breast cancer patients previously treated with adjuvant chemotherapy. Sixteen of 27 patients who received adjuvant chemotherapy became permanently amenorrheic as a result of chemotherapy. BMD was measured at the lumbar spine using dual energy X-ray absorptiometry (DEXA). Chemotherapy drugs and dosages along with a history of risk factors for reduced bone density including activity level, tobacco and/or alcohol use, metabolic bone disease, family history, and hormone exposure were identified. Results showed that women who became permanently amenorrheic as a result of chemotherapy had BMD 14% lower than women who maintained menses after chemotherapy. Chemotherapy-treated women who maintained ovarian function had normal BMD. This study suggests that women who have premature menopause as a result of chemotherapy for breast cancer are at increased risk of bone loss and may be at risk for early development of osteoporosis. Women who maintain menses do not appear to be at risk for accelerated trabecular bone loss.

Recent developments in metabolic bone diseases: a gnathic perspective.

PubMed

Raubenheimer, Erich J; Noffke, Claudia E; Hendrik, Hilde D

2014-12-01

Metabolic bone diseases often are asymptomatic and progress sub clinically. Many patients present at a late stage with catastrophic skeletal and extra skeletal complications. In this article, we provide an overview of normal bone remodeling and a synopsis of recent developments in the following conditions: osteoporosis, rickets/osteomalacia, endocrine-induced bone disease, chronic kidney disease-mineral bone disorder and Paget's disease of bone. Our discussion will emphasize the clinical and microscopic manifestations of these diseases in the jaws.

Significance of occipitoaxial angle in subaxial lesion after occipitocervical fusion.

PubMed

Matsunaga, S; Onishi, T; Sakou, T

2001-01-15

The significance of occipitoaxial angle in the development of subaxial subluxation after occipitocervical fusion was determined in a minimum 5-year follow-up study performed retrospectively. To clarify the association between the position of the fixed occipital bone and axis and the development of subaxial subluxation. There have been few reports describing the association between the position of fixation of the occipital bone and axis and subaxial lesion in occipitocervical fusion. Thirty-eight patients with rheumatoid arthritis who underwent occipitocervical fusion for irreducible atlantoaxial dislocation were reviewed. The angle between the McGregor line and the inferior surface of the axis (O-C2) was measured in healthy volunteers and patients who had undergone occipitocervical fusion. The association between any changes in the alignment of the cervical vertebrae and the development of subaxial subluxation during follow-up periods was studied. The number of the patients in whom postoperative kyphosis and swan neck deformity developed was only five, but in four (80%) of them, retroversion of the occipital bone was used to increase the O-C2 angle. In 14 patients, in whom anteversion of the occipital bone against the axis was excessive, 12 (86%) patients experienced subaxial subluxation after surgery. In the patients in whom fixed O-C2 angles were in normal range, only one patient developed such abnormal changes in the middle and lower cervical vertebrae. It is necessary to give attention to the position of the fixed occipital bone and axis during procedures of occipitoaxial fusion for patients with rheumatoid arthritis.

Vertical bone growth following autotransplantation of the developing maxillary third molar to replace a retained mandibular permanent molar: a case report.

PubMed

Plakwicz, Paweł; Czochrowska, Ewa Monika; Milczarek, Anna; Zadurska, Malgorzata

2014-01-01

A retained permanent mandibular first molar caused arrested development and a defect of the alveolar bone in a 16-year-old girl. Extraction of the ankylosed tooth was immediately followed by autotransplantation of the developing maxillary third molar. At the 3-year follow-up examination the interproximal bone level at the autotransplanted molar was equal to that of the neighboring teeth. Cone beam computed tomography showed bone at the labial aspect of the transplant. The eruption of the autotransplanted tooth stimulated vertical alveolar bone development and repaired the bone defect. Additionally, there was closure of the posterior open bite that was initially present at the ankylosed molar site.

Bone scans after total knee arthroplasty in asymptomatic patients. Cemented versus cementless

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hofmann, A.A.; Wyatt, R.W.; Daniels, A.U.

1990-02-01

The natural history of bone scans after total knee arthroplasty (TKA) was studied in 26 patients with 28 cemented TKAs and 29 patients with 31 cementless TKAs. The bone scans were examined at specified postoperative intervals. Radionuclide activity of the femoral, tibial, and patellar regions was measured. Six patients who developed pain postoperatively were excluded. Bone scans immediately postoperative and at three months demonstrated increased uptake, which gradually decreased to baseline levels at ten to 12 months. Radioisotope uptake was comparable in the cemented and cementless groups, but was highly variable in individual patients and in each of the follow-upmore » periods. A single postoperative bone scan cannot differentiate component loosening from early bone remodeling. Sequential bone scans, as a supplement to the clinical examination and conventional radiography, may prove useful in the diagnosis of TKA failure.« less

Aetiology and mechanisms of injury in medial tibial stress syndrome: Current and future developments.

PubMed

Franklyn, Melanie; Oakes, Barry

2015-09-18

Medial tibial stress syndrome (MTSS) is a debilitating overuse injury of the tibia sustained by individuals who perform recurrent impact exercise such as athletes and military recruits. Characterised by diffuse tibial anteromedial or posteromedial surface subcutaneous periostitis, in most cases it is also an injury involving underlying cortical bone microtrauma, although it is not clear if the soft tissue or cortical bone reaction occurs first. Nuclear bone scans and magnetic resonance imaging (MRI) can both be used for the diagnosis of MTSS, but the patient's history and clinical symptoms need to be considered in conjunction with the imaging findings for a correct interpretation of the results, as both imaging modalities have demonstrated positive findings in the absence of injury. However, MRI is rapidly becoming the preferred imaging modality for the diagnosis of bone stress injuries. It can also be used for the early diagnosis of MTSS, as the developing periosteal oedema can be identified. Retrospective studies have demonstrated that MTSS patients have lower bone mineral density (BMD) at the injury site than exercising controls, and preliminary data indicates the BMD is lower in MTSS subjects than tibial stress fracture (TSF) subjects. The values of a number of tibial geometric parameters such as cross-sectional area and section modulus are also lower in MTSS subjects than exercising controls, but not as low as the values in TSF subjects. Thus, the balance between BMD and cortical bone geometry may predict an individual's likelihood of developing MTSS. However, prospective longitudinal studies are needed to determine how these factors alter during the development of the injury and to find the detailed structural cause, which is still unknown. Finite element analysis has recently been used to examine the mechanisms involved in tibial stress injuries and offer a promising future tool to understand the mechanisms involved in MTSS. Contemporary accurate diagnosis of either MTSS or a TSF includes a thorough clinical examination to identify signs of bone stress injury and to exclude other pathologies. This should be followed by an MRI study of the whole tibia. The cause of the injury should be established and addressed in order to facilitate healing and prevent future re-occurrence.

Mineralization behavior and interface properties of BG-PVA/bone composite implants in simulated body fluid.

PubMed

Ma, Yanxuan; Zheng, Yudong; Huang, Xiaoshan; Xi, Tingfei; Lin, Xiaodan; Han, Dongfei; Song, Wenhui

2010-04-01

Due to the non-bioactivity and poor conjunction performance of present cartilage prostheses, the main work here is to develop the bioactive glass-polyvinyl alcohol hydrogel articular cartilage/bone (BG-PVA/bone) composite implants. The essential criterion for a biomaterial to bond with living bone is well-matched mechanical properties as well as biocompatibility and bioactivity. In vitro studies on the formation of a surface layer of carbonate hydroxyl apatite (HCA) and the corresponding variation of the properties of biomaterials are imperative for their clinical application. In this paper, the mineralization behavior and variation of the interface properties of BG-PVA/bone composites were studied in vitro by using simulated body fluid (SBF). The mineralization and HCA layer formed on the interface between the BG-PVA hydrogel and bone in SBF could provide the composites with bioactivity and firmer combination. The compression property, shear strength and interface morphology of BG-PVA/bone composite implants varying with the immersion time in SBF were characterized. Also, the influence laws of the immersion time, content of BG in the composites and aperture of bones to the mineralization behavior and interface properties were investigated. The good mineralization behavior and enhanced conjunction performance of BG-PVA/bone composites demonstrated that this kind of composite implant might be more appropriate cartilage replacements.

Effects of microgravity on bone and calcium homeostasis

NASA Astrophysics Data System (ADS)

Zérath, E.

Mechanical function is known to be of crucial importance for the maintenance of bone tissue. Gravity on one hand and muscular effort on the other hand are required for normal skeletal structure. It has been shown by numerous experimental studies that loss of total-body calcium, and marked skeletal changes occur in people who have flown in space. However, most of the pertinent investigations have been conducted on animal models, including rats and non-human primates, and a reasonably clear picture of bone response to spaceflight has emerged during the past few years. Osteopenia induced by microgravity was found to be associated with reduction in both cortical and trabecular bone formation, alteration in mineralization patterns, and disorganization of collagen, and non-collagenous protein metabolism. Recently, cell-culture techniques have offered a direct approach of altered gravity effects at the osteoblastic-cell level. But the fundamental mechanisms by which bone and calcium are lost during spaceflight are not yet fully known. Infrequenccy and high financial cost of flights have created the necessity to develop on-Earth models designed to mimic weightlessness effects. Antiorthostatic suspension devices are now commonly used to obtain hindlimb unloading in rats, with skeletal effects similar to those observed after spaceflight. Therefore, actual and ``simulated'' spaceflights, with investigations conducted at whole body and cellular levels, are needed to elucidate pathogeny of bone loss in space, to develop effective countermeasures, and to study recovery processes of bone changes after return to Earth.

High serum ALP level is associated with increased risk of denosumab-related hypocalcemia in patients with bone metastases from solid tumors.

PubMed

Kinoshita, Yuka; Arai, Makoto; Ito, Nobuaki; Takashi, Yuichi; Makita, Noriko; Nangaku, Masaomi; Shinoda, Yusuke; Fukumoto, Seiji

2016-05-31

Metastatic bone disease is one of the most common complications of advanced cancers. Pathological fractures, spinal cord compression, and radiotherapy or surgery to the bone are collectively called skeletal-related events (SREs), which cause severe pain, increase hospitalization rates, and impair the quality of life (QOL) of patients with bone metastases. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK pathway is critical in the progression of bone metastases. Previous studies have demonstrated that an anti-RANKL antibody (denosumab) was superior to zoledronic acid in prolonging time to first SRE in patients with bone metastases from prostate and breast cancers. However, severe hypocalcemic events occur more frequently after treatment with denosumab compared with zoledronic acid. In this study, 368 administrations of denosumab in 219 patients with metastatic bone disease from solid tumors were analyzed to clarify the risk factors for developing hypocalcemia. The results showed that grade 2/3 hypocalcemia was observed in 10.4% of the total number of denosumab administrations. Patients with higher baseline serum ALP, higher performance status (PS), or gastric cancer were at higher risk for developing hypocalcemia. The cut-off value for ALP to predict denosumab-related hypocalcemia was 587 U/L with a sensitivity of 0.77 and a specificity of 0.81. Close monitoring of serum calcium, especially after the first treatment with denosumab, is strongly recommended in these patients.

Bone structure studies with holographic interferometric nondestructive testing and x-ray methods

NASA Astrophysics Data System (ADS)

Silvennoinen, Raimo; Nygren, Kaarlo; Rouvinen, Juha; Petrova, Valentina V.

1994-02-01

Changes in the biomechanics and in the molecular texture and structure of isolated radioulnar bones of subadult European moose (Alces alces L.) collected in various environmentally polluted areas of Finland were investigated by means of holographic interferometric non- destructive testing (HNDT), radiological, morphometrical, and x-ray diffraction methods. By means of small caudal-cranial bending forces, the surface movements of the lower end (distal epiphysis) of the radial bone were recorded with the HNDT method. To study bone molecular texture and structure changes under external compressing forces, the samples for x-ray diffraction analysis were taken from the upper end of the ulnar bone (olecranon tip). Results showed that the bones obtained from the Harjavalta area and those of North Karelian moose showing malnutrition and healing femoral fractures produced different HNDT pictures compared with the four normally developed North Karelian moose. In the x-ray diffraction, the Harjavalta samples showed changes in molecular texture and structure compared with the samples from the apparently normal North Karelian animals.

Hypermineralized whale rostrum as the exemplar for bone mineral

PubMed Central

Li, Zhen; Pasteris, Jill D.; Novack, Deborah

2013-01-01

Although bone is a nanocomposite of mineral and collagen, mineral has been the more elusive component to study. A standard for bone mineral clearly is needed. We hypothesized that the most natural, least-processed bone mineral could be retrieved from the most highly mineralized bone. We therefore studied the rostrum of the toothed whale Mesoplodon densirostris, which has the densest recognized bone. Essential to establishment of a standard for bone mineral is documentation that the proposed tissue is bone-like in all properties except for its remarkably high concentration of mineral. Transmitted-light microscopy of unstained sections of rostral material shows normal bone morphology in osteon geometry, lacunae concentration, and vasculature development. Stained sections reveal extremely low density of thin collagen fibers throughout most of the bone, but enrichment in and thicker collagen fibers around vascular holes and in a minority of osteons. FE-SEM shows the rostrum to consist mostly of dense mineral prisms. Most rostral areas have the same chemical-structural features, Raman spectroscopically dominated by strong bands at ~962 Δcm−1 and weak bands at ~2940 Δcm−1. Spectral features indicate that the rostrum is composed mainly of the calcium phosphate mineral apatite and has only about 4 wt.% organic content. The degree of carbonate substitution (~8.5 wt.% carbonate) in the apatite is in the upper range found in most types of bone. We conclude that, despite its enamel-like extraordinarily high degree of mineralization, the rostrum is in all other features bone-like. Its mineral component is the long-sought uncontaminated, unaltered exemplar of bone mineral. PMID:23586370

Development of the turtle plastron, the order-defining skeletal structure

PubMed Central

Rice, Ritva; Kallonen, Aki; Cebra-Thomas, Judith; Gilbert, Scott F.

2016-01-01

The dorsal and ventral aspects of the turtle shell, the carapace and the plastron, are developmentally different entities. The carapace contains axial endochondral skeletal elements and exoskeletal dermal bones. The exoskeletal plastron is found in all extant and extinct species of crown turtles found to date and is synaptomorphic of the order Testudines. However, paleontological reconstructed transition forms lack a fully developed carapace and show a progression of bony elements ancestral to the plastron. To understand the evolutionary development of the plastron, it is essential to know how it has formed. Here we studied the molecular development and patterning of plastron bones in a cryptodire turtle Trachemys scripta. We show that plastron development begins at developmental stage 15 when osteochondrogenic mesenchyme forms condensates for each plastron bone at the lateral edges of the ventral mesenchyme. These condensations commit to an osteogenic identity and suppress chondrogenesis. Their development overlaps with that of sternal cartilage development in chicks and mice. Thus, we suggest that in turtles, the sternal morphogenesis is prevented in the ventral mesenchyme by the concomitant induction of osteogenesis and the suppression of chondrogenesis. The osteogenic subroutines later direct the growth and patterning of plastron bones in an autonomous manner. The initiation of plastron bone development coincides with that of carapacial ridge formation, suggesting that the development of dorsal and ventral shells are coordinated from the start and that adopting an osteogenesis-inducing and chondrogenesis-suppressing cell fate in the ventral mesenchyme has permitted turtles to develop their order-specific ventral morphology. PMID:27114549

Electron Micrographs of Quail Limb Bones formed in microgravity

NASA Technical Reports Server (NTRS)

2003-01-01

Electron micrographs of quail limb bones that formed under the influence of microgravity show decreased mineralization compared to bones formed in normal gravity. The letters B and C indicate bone and cartilage sides of the sample, respectively, with the arrows marking the junction between bone and cartilage cells. The asterisks indicate where mineralization begins. The bone that developed during spaceflight (top) shows less mineral compared to the control sample (bottom); the control sample clearly shows mineral deposits (dark spots) that are absent in the flight sample. Quail eggs are small and develop quickly, making them ideal for space experiments. In late 2001, the Avian Development Facility (ADF) made its first flight and carried eggs used in two investigations, development and function of the irner-ear balance system in normal and altered gravity environments, and skeletal development in embryonic quail.

Current Evidence on the Association of Dietary Patterns and Bone Health: A Scoping Review123

PubMed Central

Movassagh, Elham Z

2017-01-01

Nutrition is an important modifiable factor that affects bone health. Diet is a complex mixture of nutrients and foods that correlate or interact with each other. Dietary pattern approaches take into account contributions from various aspects of diet. Findings from dietary pattern studies could complement those from single-nutrient and food studies on bone health. In this study we aimed to conduct a scoping review of the literature that assessed the impact of dietary patterns (derived with the use of both a priori and data-driven approaches) on bone outcomes, including bone mineral status, bone biomarkers, osteoporosis, and fracture risk. We retrieved 49 human studies up to June 2016 from the PubMed, Embase, and CINAHL databases. Most of these studies used a data-driven method, especially factor analysis, to derive dietary patterns. Several studies examined adherence to a variety of the a priori dietary indexes, including the Mediterranean diet score, the Healthy Eating Index (HEI), and the Alternative Healthy Eating Index (AHEI). The bone mineral density (BMD) diet score was developed to measure adherence to a dietary pattern beneficial to bone mineral density. Findings revealed a beneficial impact of higher adherence to a “healthy” dietary pattern derived using a data-driven method, the Mediterranean diet, HEI, AHEI, Dietary Diversity Score, Diet Quality Index–International, BMD Diet Score, Healthy Diet Indicator, and Korean Diet Score, on bone. In contrast, the “Western” dietary pattern and those featuring some aspects of an unhealthy diet were associated inversely with bone health. In both a priori and data-driven dietary pattern studies, a dietary pattern that emphasized the intake of fruit, vegetables, whole grains, poultry and fish, nuts and legumes, and low-fat dairy products and de-emphasized the intake of soft drinks, fried foods, meat and processed products, sweets and desserts, and refined grains showed a beneficial impact on bone health. Overall, adherence to a healthy dietary pattern consisting of the above-mentioned food groups can improve bone mineral status and decrease osteoporosis and fracture risk. PMID:28096123

Development of an injectable pseudo-bone thermo-gel for application in small bone fractures.

PubMed

Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Kumar, Pradeep; Marimuthu, Thashree; du Toit, Lisa C; Pillay, Viness

2017-03-30

A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures. Copyright © 2017 Elsevier B.V. All rights reserved.

Human mesenchymal stem cells and biomaterials interaction: a promising synergy to improve spine fusion.

PubMed

Barbanti Brodano, G; Mazzoni, E; Tognon, M; Griffoni, C; Manfrini, M

2012-05-01

Spine fusion is the gold standard treatment in degenerative and traumatic spine diseases. The bone regenerative medicine needs (i) in vitro functionally active osteoblasts, and/or (ii) the in vivo induction of the tissue. The bone tissue engineering seems to be a very promising approach for the effectiveness of orthopedic surgical procedures, clinical applications are often hampered by the limited availability of bone allograft or substitutes. New biomaterials have been recently developed for the orthopedic applications. The main characteristics of these scaffolds are the ability to induce the bone tissue formation by generating an appropriate environment for (i) the cell growth and (ii) recruiting precursor bone cells for the proliferation and differentiation. A new prototype of biomaterials known as "bioceramics" may own these features. Bioceramics are bone substitutes mainly composed of calcium and phosphate complex salt derivatives. In this study, the characteristics bioceramics bone substitutes have been tested with human mesenchymal stem cells obtained from the bone marrow of adult orthopedic patients. These cellular models can be employed to characterize in vitro the behavior of different biomaterials, which are used as bone void fillers or three-dimensional scaffolds. Human mesenchymal stem cells in combination with biomaterials seem to be good alternative to the autologous or allogenic bone fusion in spine surgery. The cellular model used in our study is a useful tool for investigating cytocompatibility and biological features of HA-derived scaffolds.

[Bone mineral density, biochemical bone turnover markers and factors associated with bone health in young Korean women].

PubMed

Park, Young Joo; Lee, Sook Ja; Shin, Nah Mee; Shin, Hyunjeong; Kim, Yoo Kyung; Cho, Yunjung; Jeon, Songi; Cho, Inhae

2014-10-01

This study was done to assess the bone mineral density (BMD), biochemical bone turnover markers (BTMs), and factors associated with bone health in young Korean women. Participants were 1,298 women, ages 18-29, recruited in Korea. Measurements were BMD by calcaneus quantitative ultrasound, BTMs for Calcium, Phosphorus, Osteocalcin, and C-telopeptide cross-links (CTX), body composition by physical measurements, nutrients by food frequency questionnaire and psychosocial factors associated with bone health by self-report. The mean BMD (Z-score) was -0.94. 8.7% women had lower BMD (Z-score≤-2) and 14.3% women had higher BMD (Z-score≥0) than women of same age. BTMs were not significantly different between high-BMD (Z-score≥0) and low-BMD (Z-score<0) women. However, Osteocalcin and CTX were higher in women preferring caffeine intake, sedentary lifestyle and alcoholic drinks. Body composition and Calcium intake were significantly higher in high-BMD. Low-BMD women reported significantly higher susceptibility and barriers to exercise in health beliefs, lower bone health self-efficacy and promoting behaviors. Results of this study indicate that bone health of young Korean women is not good. Development of diverse strategies to intervene in factors such as exercise, nutrients, self-efficacy, health beliefs and behaviors, shown to be important, are needed to improve bone health.

Coating with a Modular Bone Morphogenetic Peptide Promotes Healing of a Bone-Implant Gap in an Ovine Model

PubMed Central

Lu, Yan; Lee, Jae Sung; Nemke, Brett; Graf, Ben K.; Royalty, Kevin; Illgen, Richard; Vanderby, Ray; Markel, Mark D.; Murphy, William L.

2012-01-01

Despite the potential for growth factor delivery strategies to promote orthopedic implant healing, there is a need for growth factor delivery methods that are controllable and amenable to clinical translation. We have developed a modular bone growth factor, herein termed “modular bone morphogenetic peptide (mBMP)”, which was designed to efficiently bind to the surface of orthopedic implants and also stimulate new bone formation. The purpose of this study was to coat a hydroxyapatite-titanium implant with mBMP and evaluate bone healing across a bone-implant gap in the sheep femoral condyle. The mBMP molecules efficiently bound to a hydroxyapatite-titanium implant and 64% of the initially bound mBMP molecules were released in a sustained manner over 28 days. The results demonstrated that the mBMP-coated implant group had significantly more mineralized bone filling in the implant-bone gap than the control group in C-arm computed tomography (DynaCT) scanning (25% more), histological (35% more) and microradiographic images (50% more). Push-out stiffness of the mBMP group was nearly 40% greater than that of control group whereas peak force did not show a significant difference. The results of this study demonstrated that mBMP coated on a hydroxyapatite-titanium implant stimulates new bone formation and may be useful to improve implant fixation in total joint arthroplasty applications. PMID:23185610

Bisphosphonate-Based Strategies for Bone Tissue Engineering and Orthopedic Implants

PubMed Central

Cattalini, Juan Pablo; Boccaccini, Aldo R.; Lucangioli, Silvia

2012-01-01

Bisphosphonates (BPs) are a group of well-established drugs that are applied in the development of metabolic bone disorder-related therapies. There is increasing interest also in the application of BPs in the context of bone tissue engineering, which is the topic of this review, in which an extensive overview of published studies on the development and applications of BPs-based strategies for bone regeneration is provided with special focus on the rationale for the use of different BPs in three-dimensional (3D) bone tissue scaffolds. The different alternatives that are investigated to address the delivery and sustained release of these therapeutic drugs in the nearby tissues are comprehensively discussed, and the most significant published approaches on bisphosphonate-conjugated drugs in multifunctional 3D scaffolds as well as the role of BPs within coatings for the improved fixation of orthopedic implants are presented and critically evaluated. Finally, the authors' views regarding the remaining challenges in the fields and directions for future research efforts are highlighted. PMID:22440082

Distinct requirements of wls, wnt9a, wnt5b and gpc4 in regulating chondrocyte maturation and timing of endochondral ossification

PubMed Central

Ling, Irving TC; Rochard, Lucie; Liao, Eric C.

2017-01-01

Formation of the mandible requires progressive morphologic change, proliferation, differentiation and organization of chondrocytes preceding osteogenesis. The Wnt signaling pathway is involved in regulating bone development and maintenance. Chondrocytes that are fated to become bone require Wnt to polarize and orientate appropriately to initiate the endochondral ossification program. Although the canonical Wnt signaling has been well studied in the context of bone development, the effects of non-canonical Wnt signaling in regulating the timing of cartilage maturation and subsequent bone formation in shaping ventral craniofacial structure is not fully understood.. Here we examined the role of the non-canonical Wnt signaling pathway (wls, gpc4, wnt5b and wnt9a) in regulating zebrafish Meckel’s cartilage maturation to the onset of osteogenic differentiation. We found that disruption of wls resulted in a significant loss of craniofacial bone, whereas lack of gpc4, wnt5b and wnt9a resulted in severely delayed endochondral ossification. This study demonstrates the importance of the non-canonical Wnt pathway in regulating coordinated ventral cartilage morphogenesis and ossification. PMID:27908786

An Endochondral Ossification-Based Approach to Bone Repair: Chondrogenically Primed Mesenchymal Stem Cell-Laden Scaffolds Support Greater Repair of Critical-Sized Cranial Defects Than Osteogenically Stimulated Constructs In Vivo.

PubMed

Thompson, Emmet M; Matsiko, Amos; Kelly, Daniel J; Gleeson, John P; O'Brien, Fergal J

2016-03-01

The lack of success associated with the use of bone grafts has motivated the development of tissue engineering approaches for bone defect repair. However, the traditional tissue engineering approach of direct osteogenesis, mimicking the process of intramembranous ossification (IMO), leads to poor vascularization. In this study, we speculate that mimicking an endochondral ossification (ECO) approach may offer a solution by harnessing the potential of hypertrophic chondrocytes to secrete angiogenic signals that support vasculogenesis and enhance bone repair. We hypothesized that stimulation of mesenchymal stem cell (MSC) chondrogenesis and subsequent hypertrophy within collagen-based scaffolds would lead to improved vascularization and bone formation when implanted within a critical-sized bone defect in vivo. To produce ECO-based constructs, two distinct scaffolds, collagen-hyaluronic acid (CHyA) and collagen-hydroxyapatite (CHA), with proven potential for cartilage and bone repair, respectively, were cultured with MSCs initially in the presence of chondrogenic factors and subsequently supplemented with hypertrophic factors. To produce IMO-based constructs, CHA scaffolds were cultured with MSCs in the presence of osteogenic factors. These constructs were subsequently implanted into 7 mm calvarial defects on Fischer male rats for up to 8 weeks in vivo. The results demonstrated that IMO- and ECO-based constructs were capable of supporting enhanced bone repair compared to empty defects. However, it was clear that the scaffolds, which were previously shown to support the greatest cartilage formation in vitro (CHyA), led to the highest new bone formation (p < 0.05) within critical-sized bone defects 8 weeks postimplantation. We speculate this to be associated with the secretion of angiogenic signals as demonstrated by the higher VEGF protein production in the ECO-based constructs before implantation leading to the greater blood vessel ingrowth. This study thus demonstrates the ability of recapitulating a developmental process of bone formation to develop tissue-engineered constructs that manifest appreciable promise for bone defect repair.

What Is Breast in the Bone?

PubMed

Shemanko, Carrie S; Cong, Yingying; Forsyth, Amanda

2016-10-22

The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%-50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural "recycling" of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle.

An interface finite element model can be used to predict healing outcome of bone fractures.

PubMed

Alierta, J A; Pérez, M A; García-Aznar, J M

2014-01-01

After fractures, bone can experience different potential outcomes: successful bone consolidation, non-union and bone failure. Although, there are a lot of factors that influence fracture healing, experimental studies have shown that the interfragmentary movement (IFM) is one of the main regulators for the course of bone healing. In this sense, computational models may help to improve the development of mechanical-based treatments for bone fracture healing. Hence, based on this fact, we propose a combined repair-failure mechanistic computational model to describe bone fracture healing. Despite being a simple model, it is able to correctly estimate the time course evolution of the IFM compared to in vivo measurements under different mechanical conditions. Therefore, this mathematical approach is especially suitable for modeling the healing response of bone to fractures treated with different mechanical fixators, simulating realistic clinical conditions. This model will be a useful tool to identify factors and define targets for patient specific therapeutics interventions. © 2013 Published by Elsevier Ltd.

Oxandrolone treatment of constitutional short stature in boys during adolescence: effect on linear growth, bone age, pubic hair, and testicular development.

PubMed

Marti-Henneberg, C; Niirianen, A K; Rappaport, R

1975-05-01

Seventeen constitutionally short boys were studied throughout puberty. Nine received oxandrolone (0.1 mg/kg/day). Treatment was started before onset of puberty. Eight boys served as control subjects. No significant increase in linear growth or skeletal maturation was observed in the treated group. Likewise the peak height velocity was unchanged. Pubic hair developed similarly in both groups in relation to chronologic and skeletal age. The only significant difference was a diminution in testicular volume index during treatment after bone age of 12 years and until bone age of 14 6/12 years.

Treatment feasibility study of osteoporosis using minimal invasive laser needle system

NASA Astrophysics Data System (ADS)

Kang, Dongyeon; Ko, Chang-Yong; Ryu, Yeon-Hang; Park, Sunwook; Kim, Han-Sung; Jung, Byungjo

2010-02-01

Although the mechanism of laser stimulation effect in bone has not completely understood, laser stimulation is recommended in the treatment of osteoporosis due to positive treatment efficacy. In this study, a minimal invasive laser needle system (MILNS) was developed using a fine hollow needle in order to stimulate directly bone site by guiding an optical fiber. In order to evaluate the MILNS as a treatment method, in-vivo animal experiment study was performed using osteopenic mice. Twelve virginal ICR mice were employed and divided two groups: SHAM-group and LASERgroup. SHARM-group was stimulated by only fine hollow needle and LASER-group by fine hollow needle combined with laser stimulation. All mice were served in-vivo micro-CT images before and after treatment. Three dimensional (3D) structural parameters and vBMD (volume bone mineral density, g/cm3) in the trabecular bone were measured. After 2 weeks of stimulation, the vBMD, BV/TV, Tb.Th and Tb.N in LASER-group were significantly higher than those in SHAM-group (p<0.05). Potentially, this study suggested that the MILNS might prevent the bone loss and maintains the bone mineral density of osteopenic mice.

Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose

PubMed Central

Tomaszewska, Ewa; Muszyński, Siemowit; Blicharski, Tomasz; Pierzynowski, Stefan G

2017-01-01

Synthetic glucocorticoids (GCs) are widely used in the variety of dosages for treatment of premature infants with chronic lung disease, respiratory distress syndrome, allergies, asthma, and other inflammatory and autoimmune conditions. Yet, adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Conversely, 2-oxoglutarate (2-Ox), a precursor of glutamine, glutamate, and collagen amino acids, exerts protective effects on bone development. Our aim was to elucidate the effect of dietary administered 2-Ox on bone loss caused by neonatal treatment with clinically relevant maximal therapeutic dexamethasone (Dex) dose. Long bones of neonatal female piglets receiving Dex, Dex+2-Ox, or untreated were examined through measurements of mechanical properties, density, mineralization, geometry, histomorphometry, and histology. Selected hormones, bone turnover, and growth markers were also analyzed. Neonatal administration of clinically relevant maximal dose of Dex alone led to over 30% decrease in bone mass and the ultimate strength (P < 0.001 for all). The length (13 and 7% for femur and humerus, respectively) and other geometrical parameters (13–45%) decreased compared to the control (P < 0.001 for all). Dex impaired bone growth and caused hormonal imbalance. Dietary 2-Ox prevented Dex influence and vast majority of assessed bone parameters were restored almost to the control level. Piglets receiving 2-Ox had heavier, denser, and stronger bones; higher levels of growth hormone and osteocalcin concentration; and preserved microarchitecture of trabecular bone compared to the Dex group. 2-Ox administered postnatally had a potential to maintain bone structure of animals simultaneously treated with maximal therapeutic doses of Dex, which, in our opinion, may open up a new opportunity in developing combined treatment for children treated with GCs. Impact statement The present study has showed, for the first time, that dietary 2-oxoglutarate (2-Ox) administered postnatally has a potential to improve/maintain bone structure of animals simultaneously treated with maximal therapeutic doses of dexamethasone (Dex). It may open the new direction in searching and developing combined treatment for children treated with glucocorticoids (GCs) since growing group of children is exposed to synthetic GCs and adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Currently proposed combined therapies have numerous side effects. Thus, this study proposed a new direction in combined therapies utilizing dietary supplementation with glutamine derivative. Impairment caused by Dex in presented long bones animal model was prevented by dietary supplementation with 2-Ox and vast majority of assessed bone parameters were restored almost to the control level. These results support previous thesis on the regulatory mechanism of nutrient utilization regulated by glutamine derivatives and enrich the nutritional science. PMID:28178857

Historical background of bone conduction hearing devices and bone conduction hearing aids.

PubMed

Mudry, Albert; Tjellström, Anders

2011-01-01

During the last 20 years, bone-anchored hearing aids (Baha(®)) became a familiar solution in the treatment of some types of hearing loss. The aim of this chapter is to present the different historical steps which have permitted the production of this new bone conduction hearing device. The recognition of bone conduction hearing is old and was known at least in Antiquity. During the Renaissance, Girolamo Cardano demonstrated a method by which sound may be transmitted to the ear by means of a rod or the shaft of a spear held between one's teeth: this was the beginning of teeth stimulators to improve hearing, firstly in connection with a musical instrument and then, in the second part of the 19th century, with the speaker. The development of the carbon microphone at the beginning of the 20th century allowed the construction of the bone conduction vibrator placed on the mastoid area, notably supported by eyeglasses since the 1950s. Confronted by various problems, and notably the loss of part of sound in the soft tissue of the external mastoid, the idea to implant the vibrator into the mastoid bone was developed in Göteborg, and the first Baha was implanted in 1977 by Anders Tjellström. From that date, various improvements allowed the development of the actual Baha. These different steps are presented in this study, supported by original documentation. Copyright © 2011 S. Karger AG, Basel.

Signaling networks in joint development

PubMed Central

Salva, Joanna E.; Merrill, Amy E.

2016-01-01

Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the fluid-filled synovial space between the bones, are found in high-mobility regions and are the most common type of joint. Cartilaginous joints unite adjacent bones through either a hyaline cartilage or fibrocartilage intermediate. Fibrous joints, which include the cranial sutures, form a direct union between bones through fibrous connective tissue. We describe how the distinct morphologic and histogenic characteristics of these joint classes are established during embryonic development. Collectively, these studies reveal that despite the heterogeneity of joint strength and mobility, joint development throughout the skeleton utilizes common signaling networks via long-range morphogen gradients and direct cell-cell contact. This suggests that different joint types represent specialized variants of homologous developmental modules. Identifying the unifying aspects of the signaling networks between joint classes allows a more complete understanding of the signaling code for joint formation, which is critical to improving strategies for joint regeneration and repair. PMID:27859991

Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results From the AZURE (BIG01/04) Trial.

PubMed

Brown, Janet; Rathbone, Emma; Hinsley, Samantha; Gregory, Walter; Gossiel, Fatma; Marshall, Helen; Burkinshaw, Roger; Shulver, Helen; Thandar, Hasina; Bertelli, Gianfilippo; Maccon, Keane; Bowman, Angela; Hanby, Andrew; Bell, Richard; Cameron, David; Coleman, Robert

2018-02-07

Adjuvant therapies can prevent/delay bone metastasis development in breast cancer. We investigated whether serum bone turnover markers in early disease have clinical utility in identifying patients with a high risk of developing bone metastasis. Markers of bone formation (N-terminal propeptide of type-1 collagen [P1NP]) and bone resorption (C-telopeptide of type-1 collagen [CTX], pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen [1-CTP]) were measured in baseline (pretreatment blood samples from 872 patients from a large randomized trial of adjuvant zoledronic acid (AZURE-ISRCTN79831382) in early breast cancer. Cox proportional hazards regression and cumulative incidence functions (adjusted for factors having a statistically significant effect on outcome) were used to investigate prognostic and predictive associations between recurrence events, bone marker levels, and clinical variables. All statistical tests were two-sided. When considered as continuous variables (log transformed), P1NP, CTX, and 1-CTP were each prognostic for future bone recurrence at any time (P = .006, P = .009, P = .008, respectively). Harrell's c-indices were a P1NP of 0.57 (95% confidence interval [CI] = 0.51 to 0.63), CTX of 0.57 (95% CI = 0.51 to 0.62), and 1-CTP of 0.57 (95% CI = 0.52 to 0.63). In categorical analyses based on the normal range, high baseline P1NP (>70 ng/mL) and CTX (>0.299 ng/mL), but not 1-CTP (>4.2 ng/mL), were also prognostic for future bone recurrence (P = .03, P = .03, P = .10, respectively). None of the markers were prognostic for overall distant recurrence; that is, they were bone metastasis specific, and none of the markers were predictive of treatment benefit from zoledronic acid. Serum P1NP, CTX, and 1-CTP are clinically useful, easily measured markers that show good prognostic ability (though low-to-moderate discrimination) for bone-specific recurrence and are worthy of further study. © The Author(s) 2018. Published by Oxford University Press.

Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight.

PubMed

Morey-Holton, E R; Globus, R K

1998-05-01

A model that uses hindlimb unloading of rats was developed to study the consequences of skeletal unloading and reloading as occurs during and following space flight. Studies using the model were initiated two decades ago and further developed at National Aeronautics and Space Administration (NASA)-Ames Research Center. The model mimics some aspects of exposure to microgravity by removing weightbearing loads from the hindquarters and producing a cephalic fluid shift. Unlike space flight, the forelimbs remain loaded in the model, providing a useful internal control to distinguish between the local and systemic effects of hindlimb unloading. Rats that are hindlimb unloaded by tail traction gain weight at the same rate as pairfed controls, and glucocorticoid levels are not different from controls, suggesting that systemic stress is minimal. Unloaded bones display reductions in cancellous osteoblast number, cancellous mineral apposition rate, trabecular bone volume, cortical periosteal mineralization rate, total bone mass, calcium content, and maturation of bone mineral relative to controls. Subsequent studies reveal that these changes also occur in rats exposed to space flight. In hindlimb unloaded rats, bone formation rates and masses of unloaded bones decline relative to controls, while loaded bones do not change despite a transient reduction in serum 1,25-dihydroxyvitamin D (1,25D) concentrations. Studies using the model to evaluate potential countermeasures show that 1,25D, growth hormone, dietary calcium, alendronate, and muscle stimulation modify, but do not completely correct, the suppression of bone growth caused by unloading, whereas continuous infusion of transforming growth factor-beta2 or insulin-like growth factor-1 appears to protect against some of the bone changes caused by unloading. These results emphasize the importance of local as opposed to systemic factors in the skeletal response to unloading, and reveal the pivotal role that osteoblasts play in the response to gravitational loading. The hindlimb unloading model provides a unique opportunity to evaluate in detail the physiological and cellular mechanisms of the skeletal response to weightbearing loads, and has proven to be an effective model for space flight.

Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight

NASA Technical Reports Server (NTRS)

Morey-Holton, E. R.; Globus, R. K.

1998-01-01

A model that uses hindlimb unloading of rats was developed to study the consequences of skeletal unloading and reloading as occurs during and following space flight. Studies using the model were initiated two decades ago and further developed at National Aeronautics and Space Administration (NASA)-Ames Research Center. The model mimics some aspects of exposure to microgravity by removing weightbearing loads from the hindquarters and producing a cephalic fluid shift. Unlike space flight, the forelimbs remain loaded in the model, providing a useful internal control to distinguish between the local and systemic effects of hindlimb unloading. Rats that are hindlimb unloaded by tail traction gain weight at the same rate as pairfed controls, and glucocorticoid levels are not different from controls, suggesting that systemic stress is minimal. Unloaded bones display reductions in cancellous osteoblast number, cancellous mineral apposition rate, trabecular bone volume, cortical periosteal mineralization rate, total bone mass, calcium content, and maturation of bone mineral relative to controls. Subsequent studies reveal that these changes also occur in rats exposed to space flight. In hindlimb unloaded rats, bone formation rates and masses of unloaded bones decline relative to controls, while loaded bones do not change despite a transient reduction in serum 1,25-dihydroxyvitamin D (1,25D) concentrations. Studies using the model to evaluate potential countermeasures show that 1,25D, growth hormone, dietary calcium, alendronate, and muscle stimulation modify, but do not completely correct, the suppression of bone growth caused by unloading, whereas continuous infusion of transforming growth factor-beta2 or insulin-like growth factor-1 appears to protect against some of the bone changes caused by unloading. These results emphasize the importance of local as opposed to systemic factors in the skeletal response to unloading, and reveal the pivotal role that osteoblasts play in the response to gravitational loading. The hindlimb unloading model provides a unique opportunity to evaluate in detail the physiological and cellular mechanisms of the skeletal response to weightbearing loads, and has proven to be an effective model for space flight.

Gene Therapy for Bone Defects in Oral and Maxillofacial Surgery: A Systematic Review and Meta-Analysis of Animal Studies.

PubMed

Fliefel, Riham; Kühnisch, Jan; Ehrenfeld, Michael; Otto, Sven

2017-02-15

Craniofacial bone defects are challenging problems for maxillofacial surgeons over the years. With the development of cell and molecular biology, gene therapy is a breaking new technology with the aim of regenerating tissues by acting as a delivery system for therapeutic genes in the craniofacial region rather than treating genetic disorders. A systematic review was conducted summarizing the articles reporting gene therapy in maxillofacial surgery to answer the question: Was gene therapy successfully applied to regenerate bone in the maxillofacial region? Electronic searching of online databases was performed in addition to hand searching of the references of included articles. No language or time restrictions were enforced. Meta-analysis was done to assess significant bone formation after delivery of gene material in the surgically induced maxillofacial defects. The search identified 2081 articles, of which 57 were included with 1726 animals. Bone morphogenetic proteins were commonly used proteins for gene therapy. Viral vectors were the universally used vectors. Sprague-Dawley rats were the frequently used animal model in experimental studies. The quality of the articles ranged from excellent to average. Meta-analysis results performed on 21 articles showed that defects favored bone formation by gene therapy. Funnel plot showed symmetry with the absence of publication bias. Gene therapy is on the top list of innovative strategies that developed in the last 10 years with the hope of developing a simple chair-side protocol in the near future, combining improvement of gene delivery as well as knowledge of the molecular basis of oral and maxillofacial structures.

In vivo tibial stiffness is maintained by whole bone morphology and cross-sectional geometry in growing female mice

PubMed Central

Main, Russell P.; Lynch, Maureen E.; van der Meulen, Marjolein C.H.

2010-01-01

Whole bone morphology, cortical geometry, and tissue material properties modulate skeletal stresses and strains that in turn influence skeletal physiology and remodeling. Understanding how bone stiffness, the relationship between applied load and tissue strain, is regulated by developmental changes in bone structure and tissue material properties is important in implementing biophysical strategies for promoting healthy bone growth and preventing bone loss. The goal of this study was to relate developmental patterns of in vivo whole bone stiffness to whole bone morphology, cross-sectional geometry, and tissue properties using a mouse axial loading model. We measured in vivo tibial stiffness in three age groups (6wks, 10wks, 16wks old) of female C57Bl/6 mice during cyclic tibial compression. Tibial stiffness was then related to cortical geometry, longitudinal bone curvature, and tissue mineral density using microcomputed tomography (microCT). Tibial stiffness and the stresses induced by axial compression were generally maintained from 6 to 16wks of age. Growth-related increases in cortical cross-sectional geometry and longitudinal bone curvature had counteracting effects on induced bone stresses and, therefore, maintained tibial stiffness similarly with growth. Tissue mineral density increased slightly from 6 to 16wks of age, and although the effects of this increase on tibial stiffness were not directly measured, its role in the modulation of whole bone stiffness was likely minor over the age range examined. Thus, whole bone morphology, as characterized by longitudinal curvature, along with cortical geometry, plays an important role in modulating bone stiffness during development and should be considered when evaluating and designing in vivo loading studies and biophysical skeletal therapies. PMID:20673665

Racial differences in cortical bone and their relationship to biochemical variables in black and white children in the early stages of puberty

PubMed Central

Warden, Stuart J.; Hill, Kathleen M.; Ferira, Ashley J.; Laing, Emma M.; Martin, Berdine R.; Hausman, Dorothy B.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.

2014-01-01

Introduction Racial differences in bone structure likely have roots in childhood as bone size develops predominantly during growth. This study aimed to compare cortical bone health within the tibial diaphysis of black and white children in the early stages of puberty, and explore the contributions of biochemical variables in explaining racial variation in cortical bone properties. Methods A cross-sectional study was performed comparing peripheral quantitative computed tomography-derived cortical bone measures of the tibial diaphysis and biochemical variables in 314 participants (n=155 males; n=164 blacks) in the early stages of puberty. Results Blacks had greater cortical volumetric bone mineral density, mass and size compared to whites (all p<0.01), contributing to blacks having 17.0% greater tibial strength (polar strength-strain index [SSIP]) (p<0.001). Turnover markers indicated blacks had higher bone formation (osteocalcin [OC] and bone specific alkaline phosphatase) and lower bone resorption (N-terminal telopeptide) than whites (all p<0.01). Blacks also had lower 25-hydroxyvitamin D [25(OH)D], and higher 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) (all p<0.05). There were no correlations between tibial bone properties, and 25(OH)D and PTH in whites (all p≥0.10); however, SSIP was negatively and positively correlated with 25(OH)D and PTH in blacks, respectively (all p≤0.02). Variation in bone cross-sectional area and SSIP attributable to race was partially explained by tibial length, 25(OH)D/PTH and OC. Conclusions Divergence in tibial cortical bone properties between blacks and whites is established by the early stages of puberty with the enhanced cortical bone properties in black children possibly being explained by higher PTH and OC. PMID:23093348

Semi-automatic tracking, smoothing and segmentation of hyoid bone motion from videofluoroscopic swallowing study.

PubMed

Kim, Won-Seok; Zeng, Pengcheng; Shi, Jian Qing; Lee, Youngjo; Paik, Nam-Jong

2017-01-01

Motion analysis of the hyoid bone via videofluoroscopic study has been used in clinical research, but the classical manual tracking method is generally labor intensive and time consuming. Although some automatic tracking methods have been developed, masked points could not be tracked and smoothing and segmentation, which are necessary for functional motion analysis prior to registration, were not provided by the previous software. We developed software to track the hyoid bone motion semi-automatically. It works even in the situation where the hyoid bone is masked by the mandible and has been validated in dysphagia patients with stroke. In addition, we added the function of semi-automatic smoothing and segmentation. A total of 30 patients' data were used to develop the software, and data collected from 17 patients were used for validation, of which the trajectories of 8 patients were partly masked. Pearson correlation coefficients between the manual and automatic tracking are high and statistically significant (0.942 to 0.991, P-value<0.0001). Relative errors between automatic tracking and manual tracking in terms of the x-axis, y-axis and 2D range of hyoid bone excursion range from 3.3% to 9.2%. We also developed an automatic method to segment each hyoid bone trajectory into four phases (elevation phase, anterior movement phase, descending phase and returning phase). The semi-automatic hyoid bone tracking from VFSS data by our software is valid compared to the conventional manual tracking method. In addition, the ability of automatic indication to switch the automatic mode to manual mode in extreme cases and calibration without attaching the radiopaque object is convenient and useful for users. Semi-automatic smoothing and segmentation provide further information for functional motion analysis which is beneficial to further statistical analysis such as functional classification and prognostication for dysphagia. Therefore, this software could provide the researchers in the field of dysphagia with a convenient, useful, and all-in-one platform for analyzing the hyoid bone motion. Further development of our method to track the other swallowing related structures or objects such as epiglottis and bolus and to carry out the 2D curve registration may be needed for a more comprehensive functional data analysis for dysphagia with big data.

Identifying Potential Therapeutics for Osteoporosis by Exploiting the Relationship between Mevalonate Pathway and Bone Metabolism.

PubMed

Wan Hasan, Wan Nuraini; Chin, Kok-Yong; Jolly, James Jam; Abd Ghafar, Norzana; Soelaiman, Ima Nirwana

2018-04-23

Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling. This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential. Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans. mevalonate pathway can be exploited to develop effective antiosteoporosis agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Calcium requirements for Asian children and adolescents.

PubMed

Lee, Warren Tak Keung; Jiang, Ji

2008-01-01

Calcium is important for bone health. Over the last 15 years, reference calcium intakes in Western countries have been revised upwards for maximizing bone mass at skeletal maturity and for prevention of osteoporotic fractures. Some of these reference figures have also been adopted for use in Asian countries. However, the scientific data based on for revising reference calcium intakes in the West was largely based on Caucasians. Limited human studies relating to calcium requirements and bone mineralization have been conducted in Asians in Asia. In children and adolescents, a trial has confirmed no effects of calcium supplementation on bone gains in adolescent girls after 7 years. A meta-analysis has also revealed that calcium supplementation has little beneficial effects on bone gain. Given that genetic factors, hormonal status, body size, bone structure, diets, physical activity, vitamin D status and adaptation could modify calcium retention and bone integrity, these factors need to be considered collectively to promote bone health in Asian populations. Furthermore, studies to identify indigenous foods rich in calcium and high in bioavailability are needed to widen sources of dietary calcium. Ethnic differences in calcium retention, hormonal status, bone structure, bone mineral accretion and peak bone mass are evident among Asians, Caucasians and Blacks in USA. Hence, reference calcium intakes for Asians are likely to be unique and different from those of Caucasians. More research has to be conducted in Asian populations in order to develop appropriate reference calcium intakes for the region.

Enhanced osteoblast adhesion on nanostructured selenium compacts for anti-cancer orthopedic applications.

PubMed

Tran, Phong; Webster, Thomas J

2008-01-01

Metallic bone implants possess numerous problems limiting their long-term efficacy, such as poor prolonged osseointegration, stress shielding, and corrosion under in vivo environments. Such problems are compounded for bone cancer patients since numerous patients receive orthopedic implants after cancerous bone resection. Unfortunately, current orthopedic materials were not originally developed to simultaneously increase healthy bone growth (as in traditional orthopedic implant applications) while inhibiting cancerous bone growth. The long-term objective of the present research is to investigate the use of nano-rough selenium to prevent bone cancer from re-occurring while promoting healthy bone growth for this select group of cancer patients. Selenium is a well known anti-cancer chemical. However, what is not known is how healthy bone cells interact with selenium. To determine this, selenium, spherical or semispherical shots, were pressed into cylindrical compacts and these compacts were then etched using 1N NaOH to obtain various surface structures ranging from the micron, submicron to nano scales. Changes in surface chemistry were also analyzed. Through these etching techniques, results of this study showed that biologically inspired surface roughness values were created on selenium compacts to match that of natural bone roughness. Moreover, results showed that healthy bone cell adhesion increased with greater nanometer selenium roughness (more closely matching that of titanium). In this manner, this study suggests that nano-rough selenium should be further tested for orthopedic applications involving bone cancer treatment.

Enhanced osteoblast adhesion on nanostructured selenium compacts for anti-cancer orthopedic applications

PubMed Central

Tran, Phong; Webster, Thomas J

2008-01-01

Metallic bone implants possess numerous problems limiting their long-term efficacy, such as poor prolonged osseointegration, stress shielding, and corrosion under in vivo environments. Such problems are compounded for bone cancer patients since numerous patients receive orthopedic implants after cancerous bone resection. Unfortunately, current orthopedic materials were not originally developed to simultaneously increase healthy bone growth (as in traditional orthopedic implant applications) while inhibiting cancerous bone growth. The long-term objective of the present research is to investigate the use of nano-rough selenium to prevent bone cancer from re-occurring while promoting healthy bone growth for this select group of cancer patients. Selenium is a well known anti-cancer chemical. However, what is not known is how healthy bone cells interact with selenium. To determine this, selenium, spherical or semispherical shots, were pressed into cylindrical compacts and these compacts were then etched using 1N NaOH to obtain various surface structures ranging from the micron, submicron to nano scales. Changes in surface chemistry were also analyzed. Through these etching techniques, results of this study showed that biologically inspired surface roughness values were created on selenium compacts to match that of natural bone roughness. Moreover, results showed that healthy bone cell adhesion increased with greater nanometer selenium roughness (more closely matching that of titanium). In this manner, this study suggests that nano-rough selenium should be further tested for orthopedic applications involving bone cancer treatment. PMID:18990948

Numerical study of effect of elastomeric stress absorbers on stress reduction in bone-dental implant interface.

PubMed

Mehdi, Ghalem; Belarbi, Abderrahmane; Mansouri, Bensmaine; Azari, Zitouni

2015-01-01

This paper focused on optimal stress distribution in the mandibular bone surrounding a dental implant and is devoted to the development of a modified Osteoplant® implant type in order to minimize stress concentration in the bone-implant interface. This study investigated 0.4 mm thick layers of two elastomeric stress barriers incorporated into the dental implant using 3-D finite element analysis. Overall, this proposed implant provoked lower load transfer in bone-implant interface due to the effect of the elastomers as stress absorbers. The stress level in the bone was reduced between 28% and 42% for three load cases: 75 N, 60 N and 27 N in corono-apical, linguo-buccal and disto-mesial direction, respectively. The proposed model provided an acceptable solution for load transfer reduction to the mandible. This investigation also permitted to choose how to incorporate two elastomers into the Osteoplant® implant system.

The fabrication of bioresorbable implants for bone defects replacement using computer tomogram and 3D printing

NASA Astrophysics Data System (ADS)

Kuznetsov, P. G.; Tverdokhlebov, S. I.; Goreninskii, S. I.; Bolbasov, E. N.; Popkov, A. V.; Kulbakin, D. E.; Grigoryev, E. G.; Cherdyntseva, N. V.; Choinzonov, E. L.

2017-09-01

The present work demonstrates the possibility of production of personalized implants from bioresorbable polymers designed for replacement of bone defects. The stages of creating a personalized implant are described, which include the obtaining of 3D model from a computer tomogram, development of the model with respect to shape of bone fitment bore using Autodesk Meshmixer software, and 3D printing process from bioresorbable polymers. The results of bioresorbable polymer scaffolds implantation in pre-clinical tests on laboratory animals are shown. The biological properties of new bioresorbable polymers based on poly(lactic acid) were studied during their subcutaneous, intramuscular, bone and intraosseous implantation in laboratory animals. In all cases, there was a lack of a fibrous capsule formation around the bioresorbable polymer over time. Also, during the performed study, conclusions were made on osteogenesis intensity depending on the initial state of bone tissue.

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases.

PubMed

Callaway, Danielle A; Jiang, Jean X

2015-07-01

Osteoclasts are cells derived from bone marrow macrophages and are important in regulating bone resorption during bone homeostasis. Understanding what drives osteoclast differentiation and activity is important when studying diseases characterized by heightened bone resorption relative to formation, such as osteoporosis. In the last decade, studies have indicated that reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are crucial components that regulate the differentiation process of osteoclasts. However, there are still many unanswered questions that remain. This review will examine the mechanisms by which ROS can be produced in osteoclasts as well as how it may affect osteoclast differentiation and activity through its actions on osteoclastogenesis signaling pathways. In addition, the contribution of ROS to the aging-associated disease of osteoporosis will be addressed and how targeting ROS may lead to the development of novel therapeutic treatment options.

High Density Polyetherurethane Foam as a Fragmentation and Radiographic Surrogate for Cortical Bone

PubMed Central

Beardsley, Christina L; Heiner, Anneliese D; Brandser, Eric A; Marsh, J Lawrence; Brown, Thomas D

2000-01-01

Background Although one of the most important factors in predicting outcome of articular fracture, the comminution of the fracture is only subjectively assessed. To facilitate development of objective, quantitative measures of comminution phenomena, there is need for a bone fragmentation surrogate. Methods Laboratory investigation was undertaken to develop and characterize a novel synthetic material capable of emulating the fragmentation and radiographic behavior of human cortical bone. Result Screening tests performed with a drop tower apparatus identified high-density polyetherurethane foam as having suitable fragmentation properties. The material's impact behavior and its quasi-static mechanical properties are here described. Dispersal of barium sulfate (BaSO4) in the resin achieved radio-density closely resembling that of bone, without detectably altering mechanical behavior. The surrogate material's ultimate strength, elastic modulus, and quasi-static toughness are within an order of magnitude of those of mammalian cortical bone. The spectrum of comminution patterns produced by this material when impacted with varying amounts of energy is very comparable to the spectrum of bone fragment comminution seen clinically. Conclusions A novel high-density polyetherurethane foam, when subjected to impact loading, sustains comminuted fracture in a manner strikingly similar to cortical bone. Moreover, since the material also can be doped with radio-opacifier so as to closely emulate bone's radiographic signature, it opens many new possibilities for CT-based systematic study of comminution phenomena. PMID:10934621

Proteomic analysis of human dental cementum and alveolar bone.

PubMed

Salmon, Cristiane R; Tomazela, Daniela M; Ruiz, Karina Gonzales Silvério; Foster, Brian L; Paes Leme, Adriana Franco; Sallum, Enilson Antonio; Somerman, Martha J; Nociti, Francisco H

2013-10-08

Dental cementum (DC) is a bone-like tissue covering the tooth root and responsible for attaching the tooth to the alveolar bone (AB) via the periodontal ligament (PDL). Studies have unsuccessfully tried to identify factors specific to DC versus AB, in an effort to better understand DC development and regeneration. The present study aimed to use matched human DC and AB samples (n=7) to generate their proteomes for comparative analysis. Bone samples were harvested from tooth extraction sites, whereas DC samples were obtained from the apical root portion of extracted third molars. Samples were denatured, followed by protein extraction reduction, alkylation and digestion for analysis by nanoAcquity HPLC system and LTQ-FT Ultra. Data analysis demonstrated that a total of 318 proteins were identified in AB and DC. In addition to shared proteins between these tissues, 105 and 83 proteins exclusive to AB or DC were identified, respectively. This is the first report analyzing the proteomic composition of human DC matrix and identifying putative unique and enriched proteins in comparison to alveolar bone. These findings may provide novel insights into developmental differences between DC and AB, and identify candidate biomarkers that may lead to more efficient and predictable therapies for periodontal regeneration. Periodontal disease is a highly prevalent disease affecting the world population, which involves breakdown of the tooth supporting tissues, the periodontal ligament, alveolar bone, and dental cementum. The lack of knowledge on specific factors that differentiate alveolar bone and dental cementum limits the development of more efficient and predictable reconstructive therapies. In order to better understand cementum development and potentially identify factors to improve therapeutic outcomes, we took the unique approach of using matched patient samples of dental cementum and alveolar bone to generate and compare a proteome list for each tissue. A potential biomarker for dental cementum was identified, superoxide dismutase 3 (SOD3), which is found in cementum and cementum-associated cells in mouse, pig, and human tissues. These findings may provide novel insights into developmental differences between alveolar bone and dental cementum, and represent the basis for improved and more predictable therapies. © 2013.

TARGETING POLYMER THERAPEUTICS TO BONE

PubMed Central

Low, Stewart; Kopeček, Jindřich

2012-01-01

An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

PubMed

Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

2016-10-27

It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.

The use of water-jetting technology in prostheses revision surgery-first results of parameter studies on bone and bone cement.

PubMed

Honl, M; Rentzsch, R; Müller, G; Brandt, C; Bluhm, A; Hille, E; Louis, H; Morlock, M

2000-01-01

Water-jet cutting techniques have been used in industrial applications for many different materials. Recently these techniques have been developed into a revolutionary cutting tool for soft tissues in visceral surgery. The present study investigates the usage of this cutting technology for the revision surgery of endoprostheses. In the first part of the study, samples of bovine bone and acrylic bone cement (PMMA) were cut using an industrial jet cutting device with pure water. Below 400 bar, only PMMA was cut; above 400 bar, bone was also cut, but only pressures above 800 bar resulted in clinically useful rates of material removal (cut depth 2. 4 mm at 10 mm/min traverse speed). In the second part of the study, the effect of adding biocompatible abrasives to the water in order to reduce the required pressure was investigated, resulting in a significantly higher removal of material. At 600 bar, PMMA was cut 5. 2 mm deep with plain water and 15.2 mm deep with added abrasives. The quality of the cuts was increased by the abrasive. Though there was no clear selectivity between bone and PMMA any more, the rate of material removal at similar pressures was significantly higher for PMMA than for bone (600 bar: 1.6 mm cut depth for bone samples, 15.2 mm for PMMA). The measured cut depths with either method were not influenced by a change of the cutting direction with respect to the main direction of the osteons in the bone. However, a reduction of the jet surface angle (90 degrees to 23 degrees ) resulted for bone in a significantly lower cut depth at 600 bar (plain water: 0.62 mm vs. 0.06 mm; abrasive: 1.61 mm vs. 0.60 mm). The laboratory experiments indicate that abrasive water jets may be suitable for cutting biomaterials like bone and bone cement. Copyright 2000 John Wiley & Sons, Inc.

Kinetic examination of femoral bone modeling in broilers.

PubMed

Prisby, R; Menezes, T; Campbell, J; Benson, T; Samraj, E; Pevzner, I; Wideman, R F

2014-05-01

Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute to subsequent pathology of the femoral head in fast-growing broilers.

Inorganic materials for bone repair or replacement applications.

PubMed

Hertz, Audrey; Bruce, Ian J

2007-12-01

In recent years, excipient systems have been used increasingly in biomedicine in reconstructive and replacement surgery, as bone cements, drug-delivery vehicles and contrast agents. Particularly, interest has been growing in the development and application of controlled pore inorganic ceramic materials for use in bone-replacement and bone-repair roles and, in this context, attention has been focused on calcium-phosphate, bioactive glasses and SiO2- and TiO2-based materials. It has been shown that inorganic materials that most closely mimic bone structure and surface chemistry most closely function best in bone replacement/repair and, in particular, if a substance possesses a macroporous structure (pores and interconnections >100 microm diameter), then cell infiltration, bone growth and vascularization can all be promoted. The surface roughness and micro/mesoporosity of a material have also been observed to significantly influence its ability to promote apatite nucleation and cell attachment significantly. Pores (where present) can also be packed with pharmaceuticals and biomolecules (e.g., bone morphogenetic proteins [BMPs], which can stimulate bone formation). Finally, the most bio-efficient - in terms of collagen formation and apatite nucleation - materials are those that are able to provide soluble mineralizing species (Si, Ca, PO(4)) at their implant sites and/or are doped or have been surface-activated with specific functional groups. This article presents the context and latest advances in the field of bone-repair materials, especially with respect to the development of bioactive glasses and micro/mesoporous and macroporous inorganic scaffolds. It deals with the possible methods of preparing porous pure/doped or functionalized silicas or their composites, the studies that have been undertaken to evaluate their abilities to act as bone repair scaffolds and also presents future directions for work in that context.

3D-Printed Bioactive Ca3SiO5 Bone Cement Scaffolds with Nano Surface Structure for Bone Regeneration.

PubMed

Yang, Chen; Wang, Xiaoya; Ma, Bing; Zhu, Haibo; Huan, Zhiguang; Ma, Nan; Wu, Chengtie; Chang, Jiang

2017-02-22

Silicate bioactive materials have been widely studied for bone regeneration because of their eminent physicochemical properties and outstanding osteogenic bioactivity, and different methods have been developed to prepare porous silicate bioactive ceramics scaffolds for bone-tissue engineering applications. Among all of these methods, the 3D-printing technique is obviously the most efficient way to control the porous structure. However, 3D-printed bioceramic porous scaffolds need high-temperature sintering, which will cause volume shrinkage and reduce the controllability of the pore structure accuracy. Unlike silicate bioceramic, bioactive silicate cements such as tricalcium silicate (Ca 3 SiO 5 and C 3 S) can be self-set in water to obtain high mechanical strength under mild conditions. Another advantage of using C 3 S to prepare 3D scaffolds is the possibility of simultaneous drug loading. Herein, we, for the first time, demonstrated successful preparation of uniform 3D-printed C 3 S bone cement scaffolds with controllable 3D structure at room temperature. The scaffolds were loaded with two model drugs and showed a loading location controllable drug-release profile. In addition, we developed a surface modification process to create controllable nanotopography on the surface of pore wall of the scaffolds, which showed activity to enhance rat bone-marrow stem cells (rBMSCs) attachment, spreading, and ALP activities. The in vivo experiments revealed that the 3D-printed C 3 S bone cement scaffolds with nanoneedle-structured surfaces significantly improved bone regeneration, as compared to pure C 3 S bone cement scaffolds, suggesting that 3D-printed C 3 S bone cement scaffolds with controllable nanotopography surface are bioactive implantable biomaterials for bone repair.

Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation.

PubMed

Sharma, Sunita; Sapkota, Dipak; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Bruland, Ove; Mustafa, Kamal

2016-01-01

Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-є-caprolactone){poly(LLA-co-CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.

A novel composite material specifically developed for ultrasound bone phantoms: cortical, trabecular and skull

NASA Astrophysics Data System (ADS)

Wydra, A.; Maev, R. Gr

2013-11-01

In the various stages of developing diagnostic and therapeutic equipment, the use of phantoms can play a very important role in improving the process, help in implementation, testing and calibrations. Phantoms are especially useful in developing new applications and training new doctors in medical schools. However, devices that use different physical factors, such as MRI, Ultrasound, CT Scan, etc will require the phantom to be made of different physical properties. In this paper we introduce the properties of recently designed new materials for developing phantoms for ultrasonic human body investigation, which in today's market make up more than 30% in the world of phantoms. We developed a novel composite material which allows fabrication of various kinds of ultrasound bone phantoms to mimic most of the acoustical properties of human bones. In contrast to the ex vivo tissues, the proposed material can maintain the physical and acoustical properties unchanged for long periods of time; moreover, these properties can be custom designed and created to suit specific needs. As a result, we introduce three examples of ultrasound phantoms that we manufactured in our laboratory: cortical, trabecular and skull bone phantoms. The paper also presents the results of a comparison study between the acoustical and physical properties of actual human bones (reported in the referenced literatures) and the phantoms manufactured by us.

A novel composite material specifically developed for ultrasound bone phantoms: cortical, trabecular and skull.

PubMed

Wydra, A; Maev, R Gr

2013-11-21

In the various stages of developing diagnostic and therapeutic equipment, the use of phantoms can play a very important role in improving the process, help in implementation, testing and calibrations. Phantoms are especially useful in developing new applications and training new doctors in medical schools. However, devices that use different physical factors, such as MRI, Ultrasound, CT Scan, etc will require the phantom to be made of different physical properties. In this paper we introduce the properties of recently designed new materials for developing phantoms for ultrasonic human body investigation, which in today's market make up more than 30% in the world of phantoms. We developed a novel composite material which allows fabrication of various kinds of ultrasound bone phantoms to mimic most of the acoustical properties of human bones. In contrast to the ex vivo tissues, the proposed material can maintain the physical and acoustical properties unchanged for long periods of time; moreover, these properties can be custom designed and created to suit specific needs. As a result, we introduce three examples of ultrasound phantoms that we manufactured in our laboratory: cortical, trabecular and skull bone phantoms. The paper also presents the results of a comparison study between the acoustical and physical properties of actual human bones (reported in the referenced literatures) and the phantoms manufactured by us.

High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density.

PubMed

Giroux, Sylvie; Elfassihi, Latifa; Clément, Valérie; Bussières, Johanne; Bureau, Alexandre; Cole, David E C; Rousseau, François

2010-11-01

Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable and polygenic trait. Women are more prone than men to develop osteoporosis due to a lower peak bone mass and accelerated bone loss at menopause. Peak bone mass has been convincingly shown to be due to genetic factors with heritability up to 80%. Menopausal bone loss has been shown to have around 38% to 49% heritability depending on the site studied. To have more statistical power to detect small genetic effects we focused on premenopausal women. We studied 23 candidate genes, some involved in calcium and vitamin-D regulation and others because estrogens strongly induced their gene expression in mice where it was correlated with humerus trabecular bone density. High-density polymorphisms were selected to cover the entire gene variability and 231 polymorphisms were genotyped in a first sample of 709 premenopausal women. Positive associations were retested in a second, independent, sample of 673 premenopausal women. Ten polymorphisms remained associated with BMD in the combined samples and one was further associated in a large sample of postmenopausal women (1401 women). This associated polymorphism was located in the gene CSF3R (granulocyte colony stimulating factor receptor) that had never been associated with BMD before. The results reported in this study suggest a role for CSF3R in the determination of bone density in women. Copyright © 2010 Elsevier Inc. All rights reserved.

The Mice Drawer System Tissue Sharing Program (MDS-TSP): osteobiology in microgravity

NASA Astrophysics Data System (ADS)

Ruggiu, Alessandra; Cancedda, Ranieri; Biticchi, Roberta; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Tasso, Roberta; Tavella, Sara

The capacity of bone tissue to alter its mass and architecture in response to mechanical request has long been known. Bone not only develops as a structure designed specifically for mechanical demands, but it can adapt during life toward more efficient mechanical performance. In partic-ular, the skeletal effects of microgravity result in the development of an osteoporotic phenotype with several bone defects including a bone mass decrease resembling the bone modifications occurring in elder people and in bed rest conditions. This is particularly true for weight bearing bones such as spine, femur and tibiae. In contrast non-weight bearing bones like calvaria etc didn't show bone mineral density decrease in weightlessness. Given the interest of our labora-tory in the microgravity induced skeleton alterations, we focused our attention on a transgenic mouse overexpressing pleiotrophin (PTN) under the control of the bone specific human os-teocalcin promoter. This protein is a heparin-binding cytokine with different functions. In particular PTN-transgenic mice (PTN-Tg) show an increase in the bone mass and mineral-ization, with a calcium content/mg bone of 10We used this mouse model in the MDS flight experiment to study the PTN potential role in counteracting bone loss in microgravity. Three PTN-transgenic mice (Tg) and three wild type (Wt) mice were housed in the MDS (Mouse Drawer System) at the ISS for three months. During these three months two wt and one tg mice died and therefore could be only frozen for subsequent skeletal analysis. The other three mice, daily checked for their health status, were viable and in good condition throughout the all three months at the ISS. At the end of November 2009 the three mice came back to Earth and after blood collection were immediately sacrificed and the different bones isolated. From blood cell analysis no major hematological alterations were noticed in the blood cell count except a slight increase in the number of erythrocytes. The serum collected from these mice is being used in a Luminex panel assay for several cytokine and bone metabolism markers. A ground replica of the flight experiment ("ground control") was performed at the University of Genova from November 2009 to the second week of February 2010 during which we collected the bone samples. To study the microgravity effects on both wt and PTN-Tg mice we are performing morphological analysis by classical histological technique. A finer microarchitectural study by synchrotron and bench microCT has been initiated both at the Grenoble and the Trieste facil-ities. With this last technique we are analyzing both weight and non-weight bearing bones and we are evaluating bone mineral density, mineralization amount, trabecular architecture. We are also in the process of obtaining a holotomographic reconstruction of the trabecular and cortical bone from both the flight and the ground control mice. In addition we extracted RNA from long bones and bone marrow of the same mice and we are performing Real-time PCR analysis to determine the expression of bone marker such as osteocalcin, runx2, bone sialoprotein and of markers of bone turnover such as RankL, TRAP, cathepsin K, IL6 in the different animals.

Influence of physical activity on tibial bone material properties in laying hens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Navarro, A. B.; McCormack, H. M.; Fleming, R. H.

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as corticalmore » and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.« less

Influence of physical activity on tibial bone material properties in laying hens

DOE PAGES

Rodriguez-Navarro, A. B.; McCormack, H. M.; Fleming, R. H.; ...

2017-11-03

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as corticalmore » and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.« less

Social networking between cells of the foetal skeleton: the importance of thyroid hormones.

PubMed

Farquharson, Colin

2011-08-01

In this issue of Journal of Endocrinology, Lanham et al. investigated the effects of hypothyroidism on the developing skeleton of the ovine foetus in utero. Their analyses indicated that, following thyroidectomy, bone growth, structure and mechanical properties were all altered at late gestation or at term. Adrenalectomy, whilst preventing the prepartum rise in triiodothyronine, did not modify skeletal development. The hypothyroid-mediated skeletal defects of the developing foetus described in this study may have clinical implications for bone health in later life.

Fat, Sugar, and Bone Health: A Complex Relationship

PubMed Central

Tian, Li; Yu, Xijie

2017-01-01

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation between dietary nutrition and bone health might provide a basis for the development of strategies to improve bone health by modifying nutritional components. PMID:28513571

Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

PubMed

Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

2015-05-01

The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in vivo. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Fat, Sugar, and Bone Health: A Complex Relationship.

PubMed

Tian, Li; Yu, Xijie

2017-05-17

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation between dietary nutrition and bone health might provide a basis for the development of strategies to improve bone health by modifying nutritional components.

Comparison of the bone regeneration ability between stem cells from human exfoliated deciduous teeth, human dental pulp stem cells and human bone marrow mesenchymal stem cells.

PubMed

Nakajima, Kengo; Kunimatsu, Ryo; Ando, Kazuyo; Ando, Toshinori; Hayashi, Yoko; Kihara, Takuya; Hiraki, Tomoka; Tsuka, Yuji; Abe, Takaharu; Kaku, Masato; Nikawa, Hiroki; Takata, Takashi; Tanne, Kazuo; Tanimoto, Kotaro

2018-03-11

Cleft lip and palate is the most common congenital anomaly in the orofacial region. Autogenous iliac bone graft, in general, has been employed for closing the bone defect at the alveolar cleft. However, such iliac bone graft provides patients with substantial surgical and psychological invasions. Consequently, development of a less invasive method has been highly anticipated. Stem cells from human exfoliated deciduous teeth (SHED) are a major candidate for playing a significant role in tissue engineering and regenerative medicine. The aim of this study was to elucidate the nature of bone regeneration by SHED as compared to that of human dental pulp stem cells (hDPSCs) and bone marrow mesenchymal stem cells (hBMSCs). The stems cells derived from pulp tissues and bone marrow were transplanted with a polylactic-coglycolic acid barrier membrane as a scaffold, for use in bone regeneration in an artificial bone defect of 4 mm in diameter in the calvaria of immunodeficient mice. Three-dimensional analysis using micro CT and histological evaluation were performed. Degree of bone regeneration with SHED relative to the bone defect was almost equivalent to that with hDPSCs and hBMSCs 12 weeks after transplantation. The ratio of new bone formation relative to the pre-created bone defect was not significantly different among groups with SHED, hDPSCs and hBMSCs. In addition, as a result of histological evaluation, SHED produced the largest osteoid and widely distributed collagen fibers compared to hDPSCs and hBMSCs groups. Thus, SHED transplantation exerted bone regeneration ability sufficient for the repair of bone defect. The present study has demonstrated that SHED is one of the best candidate as a cell source for the reconstruction of alveolar cleft due to the bone regeneration ability with less surgical invasion. Copyright © 2018 Elsevier Inc. All rights reserved.

Correspondence between theoretical models and dual energy x-ray absorptiometry measurements of femoral cross-sectional growth during adolescence

NASA Technical Reports Server (NTRS)

van der Meulen, M. C.; Marcus, R.; Bachrach, L. K.; Carter, D. R.

1997-01-01

We have developed an analytical model of long bone cross-sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9-26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross-sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.

The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss.

PubMed

Shinohara, Masahiro; Chang, Betty Y; Buggy, Joseph J; Nagai, Yusuke; Kodama, Tatsuhiko; Asahara, Hiroshi; Takayanagi, Hiroshi

2014-03-01

Bone-resorbing osteoclasts play an essential role in normal bone homeostasis, as well as in various bone disorders such as osteoporosis and rheumatoid arthritis. Previously we showed that the Tec family of tyrosine kinases is essential for the differentiation of osteoclasts and the inhibition of Btk is a promising strategy for the prevention of the bone loss in osteoclast-associated bone disorders. Here we demonstrate that an orally available Btk inhibitor, ibrutinib (PCI-32765), suppresses osteoclastic bone resorption by inhibiting both osteoclast differentiation and function. Ibrutinib downregulated the expression of NFATc1, the key transcription factor for osteoclastogenesis, and disrupted the formation of the actin ring in mature osteoclasts. In addition, genome-wide screening revealed that Btk regulates the expression of the genes involved in osteoclast differentiation and function in both an NFATc1-dependent and -independent manner. Finally, we showed that ibrutinib administration ameliorated the bone loss that developed in a RANKL-induced osteoporosis mouse model. Thus, this study suggests ibrutinib to be a promising therapeutic agent for osteoclast-associated bone diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

Automatic bone detection and soft tissue aware ultrasound-CT registration for computer-aided orthopedic surgery.

PubMed

Wein, Wolfgang; Karamalis, Athanasios; Baumgartner, Adrian; Navab, Nassir

2015-06-01

The transfer of preoperative CT data into the tracking system coordinates within an operating room is of high interest for computer-aided orthopedic surgery. In this work, we introduce a solution for intra-operative ultrasound-CT registration of bones. We have developed methods for fully automatic real-time bone detection in ultrasound images and global automatic registration to CT. The bone detection algorithm uses a novel bone-specific feature descriptor and was thoroughly evaluated on both in-vivo and ex-vivo data. A global optimization strategy aligns the bone surface, followed by a soft tissue aware intensity-based registration to provide higher local registration accuracy. We evaluated the system on femur, tibia and fibula anatomy in a cadaver study with human legs, where magnetically tracked bone markers were implanted to yield ground truth information. An overall median system error of 3.7 mm was achieved on 11 datasets. Global and fully automatic registration of bones aquired with ultrasound to CT is feasible, with bone detection and tracking operating in real time for immediate feedback to the surgeon.

The Oxysterol, 27-Hydroxycholesterol, Links Cholesterol Metabolism to Bone Homeostasis Through Its Actions on the Estrogen and Liver X Receptors

PubMed Central

Nelson, Erik R.; DuSell, Carolyn D.; Wang, Xiaojuan; Howe, Matthew K.; Evans, Glenda; Michalek, Ryan D.; Umetani, Michihisa; Rathmell, Jeffrey C.; Khosla, Sundeep; Gesty-Palmer, Diane

2011-01-01

Osteoporosis and age-related bone loss are important public health concerns. Therefore, there is a high level of interest in the development of medical interventions and lifestyle changes that reduce the incidence of osteoporosis and age-related bone loss. Decreased bone mineral density is associated with high cholesterol, and patients on statins have increased bone mineral densities, strongly implicating cholesterol as a negative regulator of bone homeostasis. In this study, using both molecular and pharmacological approaches, we have been able to demonstrate that the primary cholesterol metabolite, 27-hydroxycholesterol, through its actions on both estrogen receptors and liver X receptors, decreases osteoblast differentiation and enhances osteoclastogenesis, resulting in increased bone resorbtion in mice. Induction of the short heterodimer partner protein by estrogens in osteoblasts can attenuate the liver X receptor-mediated actions of 27-hydroxycholesterol in bone. These data establish a mechanistic link between cholesterol and bone quality, highlight an unexpected target of estrogens in osteoblasts, and define a signaling axis, the therapeutic exploitation of which is likely to yield novel antiosteoporotic drugs. PMID:21933863

Wise Regulates Bone Deposition through Genetic Interactions with Lrp5

PubMed Central

Ellies, Debra L.; Economou, Androulla; Viviano, Beth; Rey, Jean-Philippe; Paine-Saunders, Stephenie; Krumlauf, Robb; Saunders, Scott

2014-01-01

In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise−/− mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development. PMID:24789067

Wise regulates bone deposition through genetic interactions with Lrp5.

PubMed

Ellies, Debra L; Economou, Androulla; Viviano, Beth; Rey, Jean-Philippe; Paine-Saunders, Stephenie; Krumlauf, Robb; Saunders, Scott

2014-01-01

In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development.

Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

NASA Technical Reports Server (NTRS)

Wolinsky, Ira

1987-01-01

Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

Can we improve fixation and outcomes? Use of bone substitutes.

PubMed

Moroni, Antonio; Larsson, Sune; Hoang Kim, Amy; Gelsomini, Letizia; Giannoudis, Peter V

2009-07-01

Hip fractures secondary to osteoporosis are common in the elderly. Stabilizing these fractures until union is achieved is a challenge due to poor bone stock and insufficient purchase of the implant to the bone. The reported high rate of complications has prompted extensive research in the development of fixation techniques. Furthermore, manipulation of both the local fracture environment in terms of application of growth factors, scaffolds, and mesenchymal cells and the systemic administration of agents promoting bone formation and bone strength has been considered as a treatment option with promising results. There are only a few evidence-based studies reporting on fixation augmentation techniques. This article reports on the efficacy of bone graft substitutes for the fixation of hip fractures, in particular calcium phosphates, which have been used as granules, cements, and implant coatings.

The effect of down regulation of calcineurin Aα by lentiviral vector-mediated RNAi on the biological behavior of small-cell lung cancer and its bone metastasis.

PubMed

Ma, Ning-Qiang; Liu, Li-Li; Min, Jie; Wang, Jun-Wei; Jiang, Wei-Feng; Liu, Yan; Feng, Yan-Guo; Su, Hai-Chuan; Feng, Ying-Ming; Zhang, He-Long

2011-12-01

Bone is the third most common site of cancer metastasis. Over 30 to 40% of lung cancers can develop skeletal metastasis and no effective curative therapy exists in clinic cases. Previously we screened the different expression of proteins between SBC-5 cells and SBC-3 cells by proteomic study methods (MALDI-TOF/TOF-MS) and found that calcineurin (hereafter referred as Cn) overexpresses in SBC-5 which has special priority in metastasis to bone in a multiple-organ metastasis mice model. However the roles of Cn in osteotropism of SCLC remain to be elucidated. At present study, we decrease CnAα expression in SBC-5 by lentiviral vector-mediated RNAi and found that down regulation of CnAα gene expression can decrease the proliferation and colony formation rate, impede the cell cycle progression, reduce the cell migration and invasion, and inhibit cells adhering to bone matrix, but not change the apoptosis rate of SBC-5 in vitro. In vivo down or up regulation of CnAα gene expression can only decrease or increase the bone metastasis rate, but not affect the metastasis rate to the visceral organs. Our research reveals that CnAα is closely related to the osteotropism metastasis of SCLC and a candidate tumor promotor gene for developing bone metastases.

The functional activity of bone tissue cells under space flight conditions.

NASA Astrophysics Data System (ADS)

Rodionova, N. V.; Polkovenko, O. V.; Oganov, V. S.; Nesterenko, O. N.

The space flight conditions affect considerably the state of bone tissue leading to the development of osteoporosis and osteopenia Many aspects of reactions of bone tissue cells still remain unclear until now With the use of electron microscopy we studied the samples gathered from the femoral bone epiphyses and metaphyses of rats flown on board the space laboratory Spacelab -- 2 during 2 weeks It was established that under microgravity conditions there occur remodelling processes in a spongy bone related with a deficit of support load In this work the main attention is focused on studying the ultrastructure of osteogenetic cells and osteoclasts The degree of differentiation and functional state are evaluated according to the degree of development of organelles for specific biosynthesis rough endoplasmic reticulum RER Golgy complex GC as well as the state of mitochondria and cell nucleus As compared with a synchronous control the population of osteogenetic cells from zones of bone reconstruction shows a decrease in the number of functionally active forms We can judge of this from the reduction of a specific volume of RER GC mitochondria in osteoblasts RER loses architectonics typical for osteoblasts and as against the control is represented by short narrow canaliculi distributed throughout the cytoplasm some canals disintegrate GC is slightly pronounced mitochondria become smaller in size and acquire an optically dark matrix These phenomena are supposed to be associated with the desorganization of microtubules and

Sigma-1 Receptor Antagonist BD1047 Reduces Mechanical Allodynia in a Rat Model of Bone Cancer Pain through the Inhibition of Spinal NR1 Phosphorylation and Microglia Activation

PubMed Central

Zhu, Shanshan; Wang, Chenchen; Han, Yuan; Song, Chao; Hu, Xueming; Liu, Yannan

2015-01-01

Previous studies have demonstrated that sigma-1 receptor plays important roles in the induction phase of rodent neuropathic pain; however, whether it is involved in bone cancer pain (BCP) and the underlying mechanisms remain elusive. The aim of this study was to examine the potential role of the spinal sigma-1 receptor in the development of bone cancer pain. Walker 256 mammary gland carcinoma cells were implanted into the intramedullary space of the right tibia of Sprague-Dawley rats to induce ongoing bone cancer-related pain behaviors; our findings indicated that, on days 7, 10, 14, and 21 after operation, the expression of sigma-1 receptor in the spinal cord was higher in BCP rats compared to the sham rats. Furthermore, intrathecal injection of 120 nmol of sigma-1 receptor antagonist BD1047 on days 5, 6, and 7 after operation attenuated mechanical allodynia as well as the associated induction of c-Fos and activation of microglial cells, NR1, and the subsequent Ca2+-dependent signals of BCP rats. These results suggest that sigma-1 receptor is involved in the development of bone cancer pain and that targeting sigma-1 receptor may be a new strategy for the treatment of bone cancer pain. PMID:26696751

Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: an experimental study in rabbits.

PubMed

Athanasiou, Vasilis T; Papachristou, Dionysios J; Panagopoulos, Andreas; Saridis, Alkis; Scopa, Chrisoula D; Megas, Panagiotis

2010-01-01

Different types of bone-graft substitutes have been developed and are on the market worldwide to eliminate the drawbacks of autogenous grafting. This experimental animal study was undertaken to evaluate the different histological properties of various bone graft substitutes utilized in this hospital. Ninety New Zealand white rabbits were divided into six groups of 15 animals. Under general anesthesia, a 4.5 mm-wide hole was drilled into both the lateral femoral condyles of each rabbit, for a total of 180 condyles for analysis. The bone defects were filled with various grafts, these being 1) autograft, 2) DBM crunch allograft (Grafton), 3) bovine cancellous bone xenograft (Lubboc), 4) calcium phosphate hydroxyapatite substitute (Ceraform), 5) calcium sulfate substitute (Osteoset), and 6) no filling (control). The animals were sacrificed at 1, 3, and 6 months after implantation and tissue samples from the implanted areas were processed for histological evaluation. A histological grading scale was designed to determine the different histological parameters of bone healing. The highest histological grades were achieved with the use of cancellous bone autograft. Bovine xenograft (Lubboc) was the second best in the histological scale grading. The other substitutes (Grafton, Ceraform, Osteoset) had similar scores but were inferior to both allograft and xenograft. Bovine xenograft showed better biological response than the other bone graft substitutes; however, more clinical studies are necessary to determine its overall effectiveness.

Experimental and numerical characterisation of the elasto-plastic properties of bovine trabecular bone and a trabecular bone analogue.

PubMed

Kelly, Nicola; McGarry, J Patrick

2012-05-01

The inelastic pressure dependent compressive behaviour of bovine trabecular bone is investigated through experimental and computational analysis. Two loading configurations are implemented, uniaxial and confined compression, providing two distinct loading paths in the von Mises-pressure stress plane. Experimental results reveal distinctive yielding followed by a constant nominal stress plateau for both uniaxial and confined compression. Computational simulation of the experimental tests using the Drucker-Prager and Mohr-Coulomb plasticity models fails to capture the confined compression behaviour of trabecular bone. The high pressure developed during confined compression does not result in plastic deformation using these formulations, and a near elastic response is computed. In contrast, the crushable foam plasticity models provide accurate simulation of the confined compression tests, with distinctive yield and plateau behaviour being predicted. The elliptical yield surfaces of the crushable foam formulations in the von Mises-pressure stress plane accurately characterise the plastic behaviour of trabecular bone. Results reveal that the hydrostatic yield stress is equal to the uniaxial yield stress for trabecular bone, demonstrating the importance of accurate characterisation and simulation of the pressure dependent plasticity. It is also demonstrated in this study that a commercially available trabecular bone analogue material, cellular rigid polyurethane foam, exhibits similar pressure dependent yield behaviour, despite having a lower stiffness and strength than trabecular bone. This study provides a novel insight into the pressure dependent yield behaviour of trabecular bone, demonstrating the inadequacy of uniaxial testing alone. For the first time, crushable foam plasticity formulations are implemented for trabecular bone. The enhanced understanding of the inelastic behaviour of trabecular bone established in this study will allow for more realistic simulation of orthopaedic device implantation and failure. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of the software tool for generation and visualization of the finite element head model with bone conduction sounds

NASA Astrophysics Data System (ADS)

Nikolić, Dalibor; Milošević, Žarko; Saveljić, Igor; Filipović, Nenad

2015-12-01

Vibration of the skull causes a hearing sensation. We call it Bone Conduction (BC) sound. There are several investigations about transmission properties of bone conducted sound. The aim of this study was to develop a software tool for easy generation of the finite element (FE) model of the human head with different materials based on human head anatomy and to calculate sound conduction through the head. Developed software tool generates a model in a few steps. The first step is to do segmentation of CT medical images (DICOM) and to generate a surface mesh files (STL). Each STL file presents a different layer of human head with different material properties (brain, CSF, different layers of the skull bone, skin, etc.). The next steps are to make tetrahedral mesh from obtained STL files, to define FE model boundary conditions and to solve FE equations. This tool uses PAK solver, which is the open source software implemented in SIFEM FP7 project, for calculations of the head vibration. Purpose of this tool is to show impact of the bone conduction sound of the head on the hearing system and to estimate matching of obtained results with experimental measurements.

The effects of strontium on bone mineral: A review on current knowledge and microanalytical approaches.

PubMed

Querido, William; Rossi, Andre L; Farina, Marcos

2016-01-01

The interest in effects of strontium (Sr) on bone has greatly increased in the last decade due to the development of the promising drug strontium ranelate. This drug is used for treating osteoporosis, a major bone disease affecting hundreds of millions of people worldwide, especially postmenopausal women. The novelty of strontium ranelate compared to other treatments for osteoporosis is its unique effect on bone: it simultaneously promotes bone formation by osteoblasts and inhibits bone resorption by osteoclasts. Besides affecting bone cells, treatment with strontium ranelate also has a direct effect on the mineralized bone matrix. Due to the chemical similarities between Sr and Ca, a topic that has long been of particular interest is the incorporation of Sr into bones replacing Ca from the mineral phase, which is composed by carbonated hydroxyapatite nanocrystals. Several groups have analyzed the mineral produced during treatment; however, most analysis were done with relatively large samples containing numerous nanocrystals, resulting thus on data that represents an average of many crystalline domains. The nanoscale analysis of the bone apatite crystals containing Sr has only been described in a few studies. In this study, we review the current knowledge on the effects of Sr on bone mineral and discuss the methodological approaches that have been used in the field. In particular, we focus on the great potential that advanced microscopy and microanalytical techniques may have on the detailed analysis of the nanostructure and composition of bone apatite nanocrystals produced during treatment with strontium ranelate. Copyright © 2015. Published by Elsevier Ltd.

Analysis of relevant proteins from bone graft harvested using the reamer irrigator and aspirator system (RIA) versus iliac crest (IC) bone graft and RIA waste water.

PubMed

Crist, Brett D; Stoker, Aaron M; Stannard, James P; Cook, James L

2016-08-01

Femoral reaming using a Reamer Irrigator Aspirator (RIA) can produce greater than three liters of waste water per procedure, which contains cells and proteins that could promote bone healing. This purpose of this study was to determine the protein profile of RIA waste water and compare protein synthesis by cells harvested via RIA versus iliac crest (IC) bone graft. Bone graft was collected from 30 patients-15 using RIA from the femur and 15 harvested from the iliac crest. Waste water collected during the RIA procedure was analyzed in 12 patients. Cells from each graft were cultured in monolayer using growth media for 14days and inductive media for the next 14days. Media samples were collected on days 14, 21, and 28. Proteins for analysis were chosen based on their potential in bone healing, pro-inflammatory, and anti-inflammatory processes. Proteins present in RIA waste water indicate the potential for clinical use of this filtrate as an adjunct for enhancing bone production, healing, and remodeling. Similarly, cells cultured from RIA bone graft harvests compared favorably to those from iliac crest bone grafts with respect to their potential to aid in bone healing. RIA waste water has potential to serve as an autogenic and allogenic enhancer for bone healing. Continued development of processing protocols for viable commercial use of the waste water and pre-clinical studies designed to evaluate RIA waste water products for bone healing are ongoing. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue.

PubMed

Babur, Betul Kul; Futrega, Kathryn; Lott, William B; Klein, Travis Jacob; Cooper-White, Justin; Doran, Michael Robert

2015-09-01

Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8-14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

Computation of bone remodelling after Duracon knee arthroplasty using a thermodynamic-based model.

PubMed

Bougherara, H; Nazgooei, S; Sayyidmousavi, A; Marsik, F; Marík, I A

2011-07-01

The present study utilizes a recently developed literature model for the bone remodelling process to predict the evolution of bone density following Duracon total knee arthroplasty (TKA). In this model, which is based on chemical kinetics and irreversible thermodynamics, bone is treated as a self-organizing system capable of exchanging matter, energy, and entropy with its surroundings. Unlike previous models in which mechanical loading is regarded as the only stimulus for bone remodelling, the present model establishes a unique coupling between mechanical loading and the chemical reactions involved in the process of bone remodelling. This model was incorporated into the finite element software ANSYS by means of a macro to compute density distribution in distal femoral bone both before and after TKA. Consistent with dual-energy X-ray absorptiometry (DEXA) scans reported in the literature, the results showed that the most severe bone loss occurs in the anterior region of the distal femur and that there is more bone resorption in the lateral than the medial condyle following TKA. Furthermore, the bone density distribution predicted using the present model showed a gradual and uniform pattern and thus a more realistic bone evolution contrary to the strain energy density model, where there is no gradual bone density evolution.

The risk of avascular necrosis following chevron osteotomy: a prospective study using bone scintigraphy.

PubMed

Shariff, Raheel; Attar, Fahad; Osarumwene, Donald; Siddique, Rehan; Attar, Gulam Dastagir

2009-04-01

Controversy exists with regard to the effects of chevron osteotomy on blood supply and subsequent development of avascular necrosis (AVN) of the first metatarsal head. The aim of this study was to assess the incidence of avascular necrosis in our centre following chevron osteotomy for hallux valgus, using bone scintigraphy. Thirty nine patients who had a chevron osteotomy for treatment of hallux valgus were prospectively studied. Mean follow-up was 14 months. Bone scintigraphy was used to assess metatarsal head perfusion at an average 8.5 weeks post operatively. Three patients (7.7%) showed abnormal bone scan around the metatarsal head. Further evaluation of these patients did not show any sign of AVN. We conclude there appears to be a risk of circulatory disturbance to the metatarsal head following chevron osteotomy of the first metarsal (7.7% in this study); however this does not translate into clinically significant AVN.

Phenotypic characterization of Grm1crv4 mice reveals a functional role for the type 1 metabotropic glutamate receptor in bone mineralization.

PubMed

Musante, Ilaria; Mattinzoli, Deborah; Otescu, Lavinia Alexandra; Bossi, Simone; Ikehata, Masami; Gentili, Chiara; Cangemi, Giuliana; Gatti, Cinzia; Emionite, Laura; Messa, Piergiorgio; Ravazzolo, Roberto; Rastaldi, Maria Pia; Riccardi, Daniela; Puliti, Aldamaria

2017-01-01

Recent increasing evidence supports a role for neuronal type signaling in bone. Specifically glutamate receptors have been found in cells responsible for bone remodeling, namely the osteoblasts and the osteoclasts. While most studies have focused on ionotropic glutamate receptors, the relevance of the metabotropic glutamate signaling in bone is poorly understood. Specifically type 1 metabotropic glutamate (mGlu1) receptors are expressed in bone, but the effect of its ablation on skeletal development has never been investigated. Here we report that Grm1 crv4/crv4 mice, homozygous for an inactivating mutation of the mGlu1 receptor, and mainly characterized by ataxia and renal dysfunction, exhibit decreased body weight, bone length and bone mineral density compared to wild type (WT) animals. Blood analyses of the affected mice demonstrate the absence of changes in circulating factors, such as vitamin D and PTH, suggesting renal damage is not the main culprit of the skeletal phenotype. Cultures of osteoblasts lacking functional mGlu1 receptors exhibit less homogeneous collagen deposition than WT cells, and present increased expression of osteocalcin, a marker of osteoblast maturation. These data suggest that the skeletal damage is directly linked to the absence of the receptor, which in turn leads to osteoblasts dysfunction and earlier maturation. Accordingly, skeletal histomorphology suggests that Grm1 crv4/crv4 mice exhibit enhanced bone maturation, resulting in premature fusion of the growth plate and shortened long bones, and further slowdown of bone apposition rate compared to the WT animals. In summary, this work reveals novel functions of mGlu1 receptors in the bone and indicates that in osteoblasts mGlu1 receptors are necessary for production of normal bone matrix, longitudinal bone growth, and normal skeletal development. Copyright © 2016 Elsevier Inc. All rights reserved.

Deposition of collagen type I onto skeletal endothelium reveals a new role for blood vessels in regulating bone morphology

PubMed Central

Ben Shoham, Adi; Rot, Chagai; Stern, Tomer; Krief, Sharon; Akiva, Anat; Dadosh, Tali; Sabany, Helena; Lu, Yinhui; Kadler, Karl E.

2016-01-01

Recently, blood vessels have been implicated in the morphogenesis of various organs. The vasculature is also known to be essential for endochondral bone development, yet the underlying mechanism has remained elusive. We show that a unique composition of blood vessels facilitates the role of the endothelium in bone mineralization and morphogenesis. Immunostaining and electron microscopy showed that the endothelium in developing bones lacks basement membrane, which normally isolates the blood vessel from its surroundings. Further analysis revealed the presence of collagen type I on the endothelial wall of these vessels. Because collagen type I is the main component of the osteoid, we hypothesized that the bone vasculature guides the formation of the collagenous template and consequently of the mature bone. Indeed, some of the bone vessels were found to undergo mineralization. Moreover, the vascular pattern at each embryonic stage prefigured the mineral distribution pattern observed one day later. Finally, perturbation of vascular patterning by overexpressing Vegf in osteoblasts resulted in abnormal bone morphology, supporting a role for blood vessels in bone morphogenesis. These data reveal the unique composition of the endothelium in developing bones and indicate that vascular patterning plays a role in determining bone shape by forming a template for deposition of bone matrix. PMID:27621060

The Role of Three-Dimensional Scaffolds in Treating Long Bone Defects: Evidence from Preclinical and Clinical Literature-A Systematic Review.

PubMed

Roffi, Alice; Krishnakumar, Gopal Shankar; Gostynska, Natalia; Kon, Elizaveta; Candrian, Christian; Filardo, Giuseppe

2017-01-01

Long bone defects represent a clinical challenge. Bone tissue engineering (BTE) has been developed to overcome problems associated with conventional methods. The aim of this study was to assess the BTE strategies available in preclinical and clinical settings and the current evidence supporting this approach. A systematic literature screening was performed on PubMed database, searching for both preclinical (only on large animals) and clinical studies. The following string was used: "(Scaffold OR Implant) AND (Long bone defect OR segmental bone defect OR large bone defect OR bone loss defect)." The search retrieved a total of 1573 articles: 51 preclinical and 4 clinical studies were included. The great amount of preclinical papers published over the past few years showed promising findings in terms of radiological and histological evidence. Unfortunately, this in vivo situation is not reflected by a corresponding clinical impact, with few published papers, highly heterogeneous and with small patient populations. Several aspects should be further investigated to translate positive preclinical findings into clinical protocols: the identification of the best biomaterial, with both biological and biomechanical suitable properties, and the selection of the best choice between cells, GFs, or their combination through standardized models to be validated by randomized trials.

Harold Goldstein (R) and Dan Leiser (L) discuss bone implant development in the the Shuttle Tile

NASA Technical Reports Server (NTRS)

1993-01-01

Harold Goldstein (R) and Dan Leiser (L) discuss bone implant development in the the Shuttle Tile Laboratory N-242. A spin-off of Ames research on both bone density in microgravity and on thermal protection foams is the bone-growth implant shown in 1993.

Infant formula increases bone turnover favoring bone formation

USDA-ARS?s Scientific Manuscript database

In the first year of life, the major infant food choices have traditionally been breast milk (BM), cow's milk formula (MF), or soy formula (SF). Studies examining the effects of infant formula on early life skeletal development are extremely limited. We have enrolled 120 healthy 6-month-old infants ...

Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model

PubMed Central

Bhatta, Anil; Sangani, Rajnikumar; Kolhe, Ravindra; Toque, Haroldo A.; Cain, Michael; Wong, Abby; Howie, Nicole; Shinde, Rahul; Elsalanty, Mohammed; Yao, Lin; Chutkan, Norman; Hunter, Monty; Caldwell, Ruth B.; Isales, Carlos; Caldwell, R. William; Fulzele, Sadanand

2016-01-01

A balanced diet is crucial for healthy development and prevention of musculoskeletal related diseases. Diets high in fat content are known to cause obesity, diabetes and a number of other disease states. Our group and others have previously reported that activity of the urea cycle enzyme arginase is involved in diabetes-induced dysregulation of vascular function due to decreases in nitric oxide formation. We hypothesized that diabetes may also elevate arginase activity in bone and bone marrow, which could lead to bone-related complications. To test this we determined the effects of diabetes on expression and activity of arginase, in bone and bone marrow stromal cells (BMSCs). We demonstrated that arginase 1 is abundantly present in the bone and BMSCs. We also demonstrated that arginase activity and expression in bone and bone marrow is up-regulated in models of diabetes induced by HFHS diet and streptozotocin (STZ). HFHS diet down-regulated expression of healthy bone metabolism markers (BMP2, COL-1, ALP, and RUNX2) and reduced bone mineral density, bone volume and trabecular thickness. However, treatment with an arginase inhibitor (ABH) prevented these bone-related complications of diabetes. In-vitro study of BMSCs showed that high glucose treatment increased arginase activity and decreased nitric oxide production. These effects were reversed by treatment with an arginase inhibitor (ABH). Our study provides evidence that deregulation of L-arginine metabolism plays a vital role in HFHS diet-induced diabetic complications and that these complications can be prevented by treatment with arginase inhibitors. The modulation of L-arginine metabolism in disease could offer a novel therapeutic approach for osteoporosis and other musculoskeletal related diseases. PMID:26704078

CCN3 Protein Participates in Bone Regeneration as an Inhibitory Factor*

PubMed Central

Matsushita, Yuki; Sakamoto, Kei; Tamamura, Yoshihiro; Shibata, Yasuaki; Minamizato, Tokutaro; Kihara, Tasuku; Ito, Masako; Katsube, Ken-ichi; Hiraoka, Shuichi; Koseki, Haruhiko; Harada, Kiyoshi; Yamaguchi, Akira

2013-01-01

CCN3, a member of the CCN protein family, inhibits osteoblast differentiation in vitro. However, the role of CCN3 in bone regeneration has not been well elucidated. In this study, we investigated the role of CCN3 in bone regeneration. We identified the Ccn3 gene by microarray analysis as a highly expressed gene at the early phase of bone regeneration in a mouse bone regeneration model. We confirmed the up-regulation of Ccn3 at the early phase of bone regeneration by RT-PCR, Western blot, and immunofluorescence analyses. Ccn3 transgenic mice, in which Ccn3 expression was driven by 2.3-kb Col1a1 promoter, showed osteopenia compared with wild-type mice, but Ccn3 knock-out mice showed no skeletal changes compared with wild-type mice. We analyzed the bone regeneration process in Ccn3 transgenic mice and Ccn3 knock-out mice by microcomputed tomography and histological analyses. Bone regeneration in Ccn3 knock-out mice was accelerated compared with that in wild-type mice. The mRNA expression levels of osteoblast-related genes (Runx2, Sp7, Col1a1, Alpl, and Bglap) in Ccn3 knock-out mice were up-regulated earlier than those in wild-type mice, as demonstrated by RT-PCR. Bone regeneration in Ccn3 transgenic mice showed no significant changes compared with that in wild-type mice. Phosphorylation of Smad1/5 was highly up-regulated at bone regeneration sites in Ccn3 KO mice compared with wild-type mice. These results indicate that CCN3 is up-regulated in the early phase of bone regeneration and acts as a negative regulator for bone regeneration. This study may contribute to the development of new strategies for bone regeneration therapy. PMID:23653360

Optimal parameters to avoid thermal necrosis during bone drilling: A finite element analysis.

PubMed

Mediouni, Mohamed; Schlatterer, Daniel R; Khoury, Amal; Von Bergen, Tobias; Shetty, Sunil H; Arora, Manit; Dhond, Amit; Vaughan, Neil; Volosnikov, Alexander

2017-11-01

The drilling bone may potentially cause excessive frictional heat, which can lead to local bone necrosis. This heat generation and local necrosis has been suggested to contribute to the resorption of bone around the placed screws, ending in loss of screw purchase in the bone and inadvertent loosening and/or the bone-implant construct. In vivo studies on this subject have inherent obstacles not the least of which is controlling the variables and real time bone temperature data acquisition. Theoretical models can be generated using computer software and the inclusion of known constants for the mechanical properties of metal and bone. These known Data points for the variables (drill bit and bone) enables finite element analysis of various bone drilling scenarios. An elastic-plastic three-dimensional (3D) acetabular bone mode was developed and finite element model analysis (FEA) was applied to various simulated drilling procedures. The FEA results clearly indicate that the depth of drilling and the drill speed both have a significant effect on the temperature during drilling procedures. The reduction of the feeding speed leads to a reduction in bone temperature. Our data suggests that reducing the feeding speed regardless of RPMs and pressure applied could be a simple useful and effective way to reduce drilling temperatures. This study is the first step in helping any surgeon who drills bone and places screws to better understand the ideal pressure to apply and drill speed to employ and advance rate to avoid osteonecrosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2386-2391, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Skeletal development of mice lacking bone sialoprotein (BSP)--impairment of long bone growth and progressive establishment of high trabecular bone mass.

PubMed

Bouleftour, Wafa; Boudiffa, Maya; Wade-Gueye, Ndeye Marième; Bouët, Guénaëlle; Cardelli, Marco; Laroche, Norbert; Vanden-Bossche, Arnaud; Thomas, Mireille; Bonnelye, Edith; Aubin, Jane E; Vico, Laurence; Lafage-Proust, Marie Hélène; Malaval, Luc

2014-01-01

Adult Ibsp-knockout mice (BSP-/-) display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn)/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice, while impairing primary mineralization.