In vivo response to starch-based scaffolds designed for bone tissue engineering applications.

PubMed

Salgado, A J; Coutinho, O P; Reis, R L; Davies, J E

2007-03-15

Our purpose was to evaluate the in vivo endosseous response to three starch-based scaffolds implanted in rats (n = 54). We implanted the three scaffold groups; a 50/50 (wt %) blend of corn starch and ethylene-vinyl alcohol (SEVA-C), the same composition coated with a biomimetic calcium phosphate (Ca-P) layer (SEVA-C/CaP), and a 50/50 (wt %) blend of corn starch and cellulose acetate (SCA), all produced by extrusion with blowing agents, into distal femurs proximal to the epiphyseal plate, for 1, 3, or 6 weeks. Our results showed that at 1 week considerable reparative bone formed around all scaffold groups, although the bone was separated from the scaffold by an intervening soft tissue interfacial zone that comprised two distinct compartments: the surface of the scaffold was occupied by multinucleate giant cells and the compartment between these cells and the surrounding bone was occupied by a streaming fibrous-like tissue. The extracellular matrix of the latter was continuous with the extracellular bone matrix itself, labeled positively for osteocalcin and appeared mineralized by back-scattered electron imaging. All three scaffolds showed a similar tissue response, with the soft tissue interface diminishing with time. No bone contact was observed with SEVA-C at any time point, only transitory bone contact was observed with SEVA-C/CaP at 3 weeks, but SCA exhibited direct bone contact at 6 weeks where 56.23 +/- 6.46% of the scaffold surface was occupied by bone. We conclude that all materials exhibited a favorable bony response and that the rapidly forming initial "connective tissue" seen around all scaffolds was a very early form of bone formation.

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.

Preliminary evidence of early bone resorption in a sheep model of acute burn injury: an observational study.

PubMed

Klein, Gordon L; Xie, Yixia; Qin, Yi-Xian; Lin, Liangjun; Hu, Minyi; Enkhbaatar, Perenlei; Bonewald, Lynda F

2014-03-01

nearly twice that of the controls. Moreover, whole blood ionized Ca measured at 3- to 6-h intervals over the first 24 h in both burn and control sheep showed a 6 % reduction versus baseline in the burned sheep with <1 % reduction in the control animals. This sheep model was previously used to demonstrate upregulation of the parathyroid calcium-sensing receptor within the timeframe of the present study. Because both early bone resorption, supported by this study, and calcium-sensing receptor upregulation, consistent with the observed reduction in blood ionized Ca, are mediated by proinflammatory cytokines that are present as part of the post-burn systemic inflammatory response, we may postulate that post-burn upregulation of the parathyroid calcium-sensing receptor may be an adaptive response to clear the blood of excess calcium liberated by cytokine-mediated bone resorption.

Early matrix change of a nanostructured bone grafting substitute in the rat.

PubMed

Xu, Weiguo; Holzhüter, Gerd; Sorg, Heiko; Wolter, Daniel; Lenz, Solvig; Gerber, Thomas; Vollmar, Brigitte

2009-11-01

A nanocrystalline bone substitute embedded in a highly porous silica gel matrix (NanoBone) has previously been shown to bridge bone defects by an organic matrix. As the initial host response on the bone graft substitute might be a determinant for subsequent bone formation, our present purpose was to characterize the early tissue reaction on this biomaterial. After implantation of 80 mg of NanoBone into the adipose neck tissue of a total of 35 rats, grafts were harvested for subsequent analysis at days 3, 6, 9, 12, and 21. The biomaterial was found encapsulated by granulation tissue which partly penetrated the implant at day 3 and completely pervaded the graft at day 12 on implantation. Histology revealed tartrate-resistant acid phosphatase (TRAP)-positive giant cells covering the biomaterial. ED1 (CD68) immunopositivity of these cells further indicated their osteoclast-like phenotype. Scanning electron microscopy revealed organic tissue components within the periphery of the graft already at day 9, whereas the central hematoma region still presented the silica-surface of the biomaterial. Energy dispersive X-ray spectroscopy further demonstrated that the silica gel was degraded faster in the peripheral granulation tissue than in the central hematoma and was replaced by organic host components by day 12. In conclusion, the silica gel matrix is rapidly replaced by carbohydrate macromolecules. This might represent a key step in the process of graft degradation on its way toward induction of bone formation. The unique composition and structure of this nanoscaled biomaterial seem to support its degradation by host osteoclast-like giant cells.

Reduced limbic and hypothalamic volumes correlate with bone density in early Alzheimer's disease.

PubMed

Loskutova, Natalia; Honea, Robyn A; Brooks, William M; Burns, Jeffrey M

2010-01-01

Accelerated bone loss is associated with Alzheimer's disease (AD). Although the central nervous system plays a direct role in regulating bone mass, primarily through the actions of the hypothalamus, there is little work investigating the possible role of neurodegeneration in bone loss. In this cross-sectional study, we examined the association between bone mineral density (BMD) and neuroimaging markers of neurodegeneration (i.e., global and regional measures of brain volume) in early AD and non-demented aging. Fifty-five non-demented and 63 early AD participants underwent standard neurological and neuropsychological assessment, structural MRI scanning, and dual energy x-ray absorptiometry. In early AD, voxel-based morphometry analyses demonstrated that low BMD was associated with low volume in limbic grey matter (GM) including the hypothalamus, cingulate, and parahippocampal gyri and in the left superior temporal gyrus and left inferior parietal cortex. No relationship between BMD and regional GM volume was found in non-demented controls. The hypothesis-driven region of interest analysis further isolating the hypothalamus demonstrated a positive relationship between BMD and hypothalamic volume after controlling for age and gender in the early AD group but not in non-demented controls. These results demonstrate that lower BMD is associated with lower hypothalamic volume in early AD, suggesting that central mechanisms of bone remodeling may be disrupted by neurodegeneration.

Mechanical response tissue analyzer for estimating bone strength

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Steele, Charles; Mauriello, Anthony

1991-01-01

One of the major concerns for extended space flight is weakness of the long bones of the legs, composed primarily of cortical bone, that functions to provide mechanical support. The strength of cortical bone is due to its complex structure, described simplistically as cylinders of parallel osteons composed of layers of mineralized collagen. The reduced mechanical stresses during space flight or immobilization of bone on Earth reduces the mineral content, and changes the components of its matrix and structure so that its strength is reduced. Currently, the established clinical measures of bone strength are indirect. The measures are based on determinations of mineral density by means of radiography, photon absorptiometry, and quantitative computer tomography. While the mineral content of bone is essential to its strength, there is growing awareness of the limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially osteoporosis. Other experimental methods in clinical trials that more directly evaluate the physical properties of bone, and do not require exposure to radiation, include ultrasound, acoustic emission, and low-frequency mechanical vibration. The last method can be considered a direct measure of the functional capacity of a long bone since it quantifies the mechanical response to a stimulus delivered directly to the bone. A low frequency vibration induces a response (impedance) curve with a minimum at the resonant frequency, that a few investigators use for the evaluation of the bone. An alternative approach, the method under consideration, is to use the response curve as the basis for determination of the bone bending stiffness EI (E is the intrinsic material property and I is the cross-sectional moment of inertia) and mass, fundamental mechanical properties of bone.

[Local injection of exogenous nerve growth factor improves early bone maturation of implants].

PubMed

Yao, Yang; Du, Yu; Gu, Xia; Guang, Meng-Kai; Huang, Bo; Gong, Ping

2018-04-01

To investigate the effects of nerve growth factor (NGF) in the osteogenic action of implants and the maturation and reconstruction changes in bone tissues in the early stage of osseointegration. The mouse implant model was established by placing titanium in the femoral head of the mouse and locally injecting NGF in the implant zone. On 1, 2 and 4 weeks after operation, stain samples were collected from animals using hematoxylin-eosin (HE) staining and Masson staining. The effect of NGF on the bone maturation was compared at different time points of early stage osseointegration. The results of HE and Masson staining indicated that the local injection of external NGF can up-regulate bone mass, amount of bone trabecula, and bone maturity in the mouse model. The mature bone rate in treatment group of 1 week and 4 weeks after operation were significantly higher than those in the control group (P<0.05). NGF can shorten the period of bone maturation.

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.

Fossil traces of the bone-eating worm Osedax in early Oligocene whale bones

PubMed Central

Kiel, Steffen; Goedert, James L.; Kahl, Wolf-Achim; Rouse, Greg W.

2010-01-01

Osedax is a recently discovered group of siboglinid annelids that consume bones on the seafloor and whose evolutionary origins have been linked with Cretaceous marine reptiles or to the post-Cretaceous rise of whales. Here we present whale bones from early Oligocene bathyal sediments exposed in Washington State, which show traces similar to those made by Osedax today. The geologic age of these trace fossils (∼30 million years) coincides with the first major radiation of whales, consistent with the hypothesis of an evolutionary link between Osedax and its main food source, although older fossils should certainly be studied. Osedax has been destroying bones for most of the evolutionary history of whales and the possible significance of this “Osedax effect” in relation to the quality and quantity of their fossils is only now recognized. PMID:20424110

Using cell and organ culture models to analyze responses of bone cells to mechanical stimulation.

PubMed

Pitsillides, Andrew A; Rawlinson, Simon C F

2012-01-01

Bone cells of the osteoblastic lineage are responsive to the local mechanical environment. Through integration of a number of possible loading-induced regulatory stimuli, osteocyte, osteoblast, and osteoclast behaviour is organized to fashion a skeletal element of sufficient strength and toughness to resist fracture and crack propagation. Early pre-osteogenic responses had been determined in vivo and this led to the development of bone organ culture models to elucidate other pre-osteogenic responses where osteocytes and osteoblasts retain the natural orientation, connections and attachments to their native extracellular matrix. The application of physiological mechanical loads to bone in these organ culture models generates the regulatory stimuli. As a consequence, these experiments can be used to illustrate the distinctive mechanisms by which osteocytes and osteoblasts respond to mechanical loads and also differences in these responses, suggesting co-ordinated and cooperatively between cell populations. Organ explant cultures are awkward to maintain, and have a limited life, but length of culture times are improving. Monolayer cultures are much easier to maintain and permit the application of a particular mechanical stimulation to be studied in isolation; mainly direct mechanical strain or fluid shear strains. These allow for the response of a single cell type to the applied mechanical stimulation to be monitored precisely.The techniques that can be used to apply mechanical strain to bone and bone cells have not advanced greatly since the first edition. The output from such experiments has, however, increased substantially and their importance is now more broadly accepted. This suggests a growing use of these approaches and an increasing awareness of the importance of the mechanical environment in controlling normal bone cell behaviour. We expand the text to include additions and modifications made to the straining apparatus and update the research cited to

The incidence of bone metastasis after early-stage breast cancer in Canada.

PubMed

Liede, Alexander; Jerzak, Katarzyna J; Hernandez, Rohini K; Wade, Sally W; Sun, Ping; Narod, Steven A

2016-04-01

Current information on the incidence and prevalence of bone metastases in women with breast cancer is scarce. This study examined the occurrence and predictors of bone metastases, as well as post-metastasis survival in a prospective cohort of Canadian women with breast cancer. We included women treated for early-stage (stage I, II, or III) breast cancer at the Henrietta Banting Breast Centre (HBBC) in Toronto, Canada between 1987 and 2000. Data were abstracted from medical records and pathology reports in the HBBC database; follow-up extended to end of data availability or August 31, 2015. Actuarial survival analyses provided cumulative incidence of bone metastases at 5, 10, and 15 years after breast cancer diagnosis. Kaplan-Meier curves describe breast cancer mortality. Regression models assessed patient, tumor, and treatment characteristics as predictors of bone metastases with all-cause mortality as a competing risk. Among 2097 women studied, the 5-, 10-, and 15-year probability of bone metastasis was 6.5, 10.3, and 11.3 % for the first recurrence, and 8.4, 12.5, and 13.6 % for any bone recurrence. At median follow-up (12.5 years), 13.2 % of patients had bone metastases. Median survival was 1.6 years following bone metastasis, and shorter if both bone and visceral metastases occurred. Advanced age and adjuvant treatment with tamoxifen were protective against bone metastasis. In this representative cohort of women diagnosed with early-stage breast cancer in Ontario, Canada, with long follow-up, the incidence of bone metastases was consistent with longitudinal studies from the United Kingdom, Denmark, and the US.

Dissolution behavior and early bone apposition of calcium phosphate-coated machined implants

PubMed Central

Hwang, Ji-Wan; Lee, Eun-Ung; Lee, Jung-Seok; Jung, Ui-Won; Lee, In-Seop

2013-01-01

Purpose Calcium phosphate (CaP)-coated implants promote osseointegration and survival rate. The aim of this study was to (1) analyze the dissolution behavior of the residual CaP particles of removed implants and (2) evaluate bone apposition of CaP-coated machined surface implants at the early healing phase. Methods Mandibular premolars were extracted from five dogs. After eight weeks, the implants were placed according to drilling protocols: a nonmobile implant (NI) group and rotational implant (RI) group. For CaP dissolution behavior analysis, 8 implants were removed after 0, 1, 2, and 4 weeks. The surface morphology and deposition of the coatings were observed. For bone apposition analysis, block sections were obtained after 1-, 2-, and 4-week healing periods and the specimens were analyzed. Results Calcium and phosphorus were detected in the implants that were removed immediately after insertion, and the other implants were composed mainly of titanium. There were no notable differences between the NI and RI groups in terms of the healing process. The bone-to-implant contact and bone density in the RI group showed a remarkable increase after 2 weeks of healing. Conclusions It can be speculated that the CaP coating dissolves early in the healing phase and chemically induces early bone formation regardless of the primary stability. PMID:24455442

Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray

PubMed Central

Chen, YuXian; Shen, Jun; Lu, HuaDing; Zeng, Chun; Ren, JianHua; Zeng, Hua; Li, ZhiFu; Chen, ShaoMing; Cai, DaoZhang; Zhao, Qing

2012-01-01

Osteoarthritis (OA) is a degenerative joint disease that affects both cartilage and bone. A better understanding of the early molecular changes in subchondral bone may help elucidate the pathogenesis of OA. We used microarray technology to investigate the time course of molecular changes in the subchondral bone in the early stages of experimental osteoarthritis in a rat model. We identified 2,234 differentially expressed (DE) genes at 1 week, 1,944 at 2 weeks and 1,517 at 4 weeks post-surgery. Further analyses of the dysregulated genes indicated that the events underlying subchondral bone remodeling occurred sequentially and in a time-dependent manner at the gene expression level. Some of the identified dysregulated genes that were identified have suspected roles in bone development or remodeling; these genes include Alp, Igf1, Tgf β1, Postn, Mmp3, Tnfsf11, Acp5, Bmp5, Aspn and Ihh. The differences in the expression of these genes were confirmed by real-time PCR, and the results indicated that our microarray data accurately reflected gene expression patterns characteristic of early OA. To validate the results of our microarray analysis at the protein level, immunohistochemistry staining was used to investigate the expression of Mmp3 and Aspn protein in tissue sections. These analyses indicate that Mmp3 protein expression completely matched the results of both the microarray and real-time PCR analyses; however, Aspn protein expression was not observed to differ at any time. In summary, our study demonstrated a simple method of separation of subchondral bone sample from the knee joint of rat, which can effectively avoid bone RNA degradation. These findings also revealed the gene expression profiles of subchondral bone in the rat OA model at multiple time points post-surgery and identified important DE genes with known or suspected roles in bone development or remodeling. These genes may be novel diagnostic markers or therapeutic targets for OA. PMID:22384228

Childhood growth predicts higher bone mass and greater bone area in early old age: findings among a subgroup of women from the Helsinki Birth Cohort Study.

PubMed

Mikkola, T M; von Bonsdorff, M B; Osmond, C; Salonen, M K; Kajantie, E; Cooper, C; Välimäki, M J; Eriksson, J G

2017-09-01

We examined the associations between childhood growth and bone properties among women at early old age. Early growth in height predicted greater bone area and higher bone mineral mass. However, information on growth did not improve prediction of bone properties beyond that predicted by body size at early old age. We examined the associations between body size at birth and childhood growth with bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) in early old age. A subgroup of women (n = 178, mean 60.4 years) from the Helsinki Birth Cohort Study, born 1934-1944, participated in dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and hip. Height and weight at 0, 2, 7, and 11 years, obtained from health care records, were reconstructed into conditional variables representing growth velocity independent of earlier growth. Weight was adjusted for corresponding height. Linear regression models were adjusted for multiple confounders. Birth length and growth in height before 7 years of age were positively associated with femoral neck area (p < 0.05) and growth in height at all age periods studied with spine bone area (p < 0.01). Growth in height before the age of 7 years was associated with BMC in the femoral neck (p < 0.01) and birth length and growth in height before the age of 7 years were associated with BMC in the spine (p < 0.05). After entering adult height into the models, nearly all associations disappeared. Weight gain during childhood was not associated with bone area or BMC, and aBMD was not associated with early growth. Optimal growth in height in girls is important for obtaining larger skeleton and consequently higher bone mass. However, when predicting bone mineral mass among elderly women, information on early growth does not improve prediction beyond that predicted by current height and weight.

3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep.

PubMed

Ding, Ming; Henriksen, Susan S; Martinetti, Roberta; Overgaard, Søren

2017-11-01

Early fixation of total joint arthroplasties is crucial for ensuring implant survival. An alternative bone graft material in revision surgery is needed to replace the current gold standard, allograft, seeing that the latter is associated with several disadvantages. The incubation of such a construct in a perfusion bioreactor has been shown to produce viable bone graft materials. This study aimed at producing larger amounts of viable bone graft material (hydroxyapatite 70% and β-tricalcium-phosphate 30%) in a novel perfusion bioreactor. The abilities of the bioreactor-activated graft material to induce early implant fixation were tested in a bilateral implant defect model in sheep, with allograft as the control group. Defects were bilaterally created in the distal femurs of the animals, and titanium implants were inserted. The concentric gaps around the implants were randomly filled with either allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while no significant differences between groups were found regarding early implant fixation. The microarchitecture of the bone formed by the synthetic graft materials resembled that of allograft. Histomorphometry revealed that allograft induced significantly more bone and less fibrous tissue (p < 0.05). In conclusion, bone formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2465-2476, 2017. © 2016 Wiley Periodicals, Inc.

Searching early bone metastasis on plain radiography by using digital imaging processing

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

Jaramillo-Nunez, A.; Perez-Meza, M.; Universidad de la Sierra Sur, C. P. 70800, Miahuatlan, Oax.

2012-10-23

Some authors mention that it is not possible to detect early bone metastasis on plain radiography. In this work we use digital imaging processing to analyze three radiographs taken from a patient with bone metastasis discomfort on the right shoulder. The time period among the first and second radiography was approximately one month and between the first and the third one year. This procedure is a first approach in order to know if in this particular case it was possible to detect an early bone metastasis. The obtained results suggest that by carrying out a digital processing is possible tomore » detect the metastasis since the radiography contains the information although visually it is not possible to observe it.« less

Does estrogen play a role in response to adjuvant bone-targeted therapies?

PubMed Central

Russell, Kent; Amir, Eitan; Paterson, Alexander; Josse, Robert; Addison, Christina; Kuchuk, Iryna; Clemons, Mark

2013-01-01

Bone remains the most common site of breast cancer recurrence. The results of population studies, pre-clinical research and clinical studies in patients with metastatic disease provided a rationale for testing bone-targeted agents in the adjuvant setting. Despite the initial optimism, results from eight prospectively designed, randomized control studies powered to assess the value of adjuvant bone-targeted therapy in early breast cancer are conflicting. Data have shown that, where benefit exists, it tends to be in women with a “low estrogen environment”, either through menopause or suppression of ovarian function. In this manuscript, we review clinical data supporting the hypothesis that estrogen levels may play a part in explaining the response of patients to bone-targeted agents in the adjuvant setting. The results presented to date suggest that there may be data supporting a unifying role for estrogen in adjuvant trials. However, in the absence of any prospective randomized trials in which estrogen data has been systematically collected we cannot specifically answer this question. We await the results of the Oxford overview analysis of individual patient data with interest. PMID:26909288

Clavicular bone tunnel malposition leads to early failures in coracoclavicular ligament reconstructions.

PubMed

Cook, Jay B; Shaha, James S; Rowles, Douglas J; Bottoni, Craig R; Shaha, Steven H; Tokish, John M

2013-01-01

Modern techniques for the treatment of acromioclavicular (AC) joint dislocations have largely centered on free tendon graft reconstructions. Recent biomechanical studies have demonstrated that an anatomic reconstruction with 2 clavicular bone tunnels more closely matches the properties of native coracoclavicular (CC) ligaments than more traditional techniques. No study has analyzed tunnel position in regard to risk of early failure. To evaluate the effect of clavicular tunnel position in CC ligament reconstruction as a risk of early failure. Case series; Level of evidence, 4. A retrospective review was performed of a consecutive series of CC ligament reconstructions performed with 2 clavicular bone tunnels and a free tendon graft. The population was largely a young, active-duty military group of patients. Radiographs were analyzed for the maintenance of reduction and location of clavicular bone tunnels using a picture archiving and communication system. The distance from the lateral border of the clavicle to the center of each bone tunnel was divided by the total clavicular length to establish a ratio. Medical records were reviewed for operative details and functional outcome. Failure was defined as loss of intraoperative reduction. The overall failure rate was 28.6% (8/28) at an average of 7.4 weeks postoperatively. Comparison of bone tunnel position showed that medialized bone tunnels were a significant predictor for early loss of reduction for the conoid (a ratio of 0.292 vs 0.248; P = .012) and trapezoid bone tunnels (a ratio of 0.171 vs 0.128; P = .004); this correlated to an average of 7 to 9 mm more medial in the reconstructions that failed. Reconstructions performed with a conoid ratio of ≥0.30 were significantly more likely to fail (5/5, 100%) than were those performed lateral to a ratio of 0.30 (3/23, 13.0%) (P < .01). There were no failures when the conoid ratio was <0.25 (0/10, 0%). Conoid tunnel placement was also statistically significant for

EARLY COMPLICATIONS IN THE ORTHOPEDIC TREATMENT OF BONE METASTASES.

PubMed

Teixeira, Luiz Eduardo Moreira; Miranda, Ricardo Horta; Ghedini, Daniel Ferreira; Aguilar, Rafael Bazílio; Novais, Eduardo Nilo Vasconcelos; de Abreu E Silva, Guilherme Moreira; Araújo, Ivana Duval; de Andrade, Marco Antônio Percope

2009-01-01

To assess the early complications in the orthopedic treatment of metastatic bone lesions and the factors associated with these complications. There were assessed, retrospectively, 64 patients that underwent surgical treatment for bone metastases, analyzing the complications that occurred in the pre-operative and early post- operative period and associating them with the tumor origin, type of procedure done, the need of blood reposition before the surgery, the need of new surgical procedures and the mortality due to the complications. Early complications in the treatment were observed in 17 (26.6%) patients, of which six (35.2%) ended up dying due to these complications. Regarding the type, 15 (23.8%) cases were due to surgical complications, four (6.3%) clinical and three (4.7%) patients showed clinical and surgical complications. There was no significant difference in the frequency of complications or mortality when assessed the type of reconstruction or affected region. The tumors with a renal origin needed more blood reposition and showed a bigger frequency of complications. The complications occurred in 26.6%. The complications are not related to the kind of treatment performed or to the region affected. The renal origin tumors showed a higher risk of hemorrhage.

Biomimetic materials for controlling bone cell responses.

PubMed

Drevelle, Olivier; Faucheux, Nathalie

2013-01-01

Bone defects that cannot "heal spontaneously during life" will become an ever greater health problem as populations age. Harvesting autografts has several drawbacks, such as pain and morbidity at both donor and acceptor sites, the limited quantity of material available, and frequently its inappropriate shape. Researchers have therefore developed alternative strategies that involve biomaterials to fill bone defects. These biomaterials must be biocompatible and interact with the surrounding bone tissue to allow their colonization by bone cells and blood vessels. The latest generation biomaterials are not inert; they control cell responses like adhesion, proliferation and differentiation. These biomaterials are called biomimetic materials. This review focuses on the development of third generation materials. We first briefly describe the bone tissue with its cells and matrix, and then how bone cells interact with the extracellular matrix. The next section covers the materials currently used to repair bone defects. Finally, we describe the strategies employed to modify the surface of materials, such as coating with hydroxyapatite and grafting biomolecules.

Bone metastasis target redox-responsive micell for the treatment of lung cancer bone metastasis and anti-bone resorption.

PubMed

Ye, Wei-Liang; Zhao, Yi-Pu; Cheng, Ying; Liu, Dao-Zhou; Cui, Han; Liu, Miao; Zhang, Bang-Le; Mei, Qi-Bing; Zhou, Si-Yuan

2018-01-16

In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and -15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis.

[Osteoclasts and early bone remodeling after orthodontic micro-implant placement].

PubMed

Zhang, Wei; Guo, Jia-jia; Zhu, Wen-qian; Tang, Guo-hua

2013-08-01

To observe the incidence of osteoclasts during early bone remodeling after orthodontic micro-implant placement. Twenty New Zealand rabbits were randomly allotted into 4 groups. One micro-implant was implanted proximal to the epiphyseal plate of the tibia. Animals were sacrificed on day 3, 7, 14 and 28 (n=5). The sequence of histological changes around the micro-implants were evaluated by hematoxylin and eosin (HE) staining. Osteoclasts were identified by TRAP staining. The differences of the number of the osteoclasts among each time point were analyzed by one way ANOVA with SPSS 19.0 software package. After 3 days of implantation, a large number of erythrocytes, inflammatory cells, mesenchymal cells and bone debris were seen at the implant bone interfaces. Few osteoclasts were observed. On day 7, granular woven bone was formed and some osteoclasts were found in the Howship's lacunae. New bone formation and mineralization were apparent on day 14. Meanwhile, large amounts of osteoclasts were found in the latticed woven bone. On day 28, woven trabeculae with lamellate structures connected to lamellar bone and fewer osteoclasts were identified. Semi-quantitative analysis showed that the number of the osteoclasts was at peak on day 14. There were significant differences among each time point (P<0.01). Osteoclast activity is closely related to bone formation and remodeling after micro-implant insertion.

Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

PubMed

Passeron, Thierry; Salhi, Aicha; Mazer, Jean-Michel; Lavogiez, Céline; Mazereeuw-Hautier, Juliette; Galliot, Chrystèle; Collet-Villette, Anne-Marie; Labreze, Christine; Boon, Laurence; Hardy, Jean-Philippe; Fayard, Virginie; Livideanu, Cristina Bulai; Toubel, Gérard; Georgescou, Gabriela; Gral, Nathalie; Maza, Aude; Lacour, Jean-Philippe

2016-07-01

There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). We sought to characterize patients with hypertrophic PWS presenting during childhood. Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

[Bone marrow stromal damage mediated by immune response activity].

PubMed

Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

1994-01-01

The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

EARLY COMPLICATIONS IN THE ORTHOPEDIC TREATMENT OF BONE METASTASES

PubMed Central

Teixeira, Luiz Eduardo Moreira; Miranda, Ricardo Horta; Ghedini, Daniel Ferreira; Aguilar, Rafael Bazílio; Novais, Eduardo Nilo Vasconcelos; de Abreu e Silva, Guilherme Moreira; Araújo, Ivana Duval; de Andrade, Marco Antônio Percope

2015-01-01

Objective: To assess the early complications in the orthopedic treatment of metastatic bone lesions and the factors associated with these complications. Method: There were assessed, retrospectively, 64 patients that underwent surgical treatment for bone metastases, analyzing the complications that occurred in the pre-operative and early post- operative period and associating them with the tumor origin, type of procedure done, the need of blood reposition before the surgery, the need of new surgical procedures and the mortality due to the complications. Results: Early complications in the treatment were observed in 17 (26.6%) patients, of which six (35.2%) ended up dying due to these complications. Regarding the type, 15 (23.8%) cases were due to surgical complications, four (6.3%) clinical and three (4.7%) patients showed clinical and surgical complications. There was no significant difference in the frequency of complications or mortality when assessed the type of reconstruction or affected region. The tumors with a renal origin needed more blood reposition and showed a bigger frequency of complications. Conclusion: The complications occurred in 26.6%. The complications are not related to the kind of treatment performed or to the region affected. The renal origin tumors showed a higher risk of hemorrhage. PMID:27077063

Diagnostic role of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for early and atypical bone metastases.

PubMed

Chen, Xiao-Liang; Li, Qian; Cao, Lin; Jiang, Shi-Xi

2014-01-01

The bone metastasis appeared early before the bone imaging for most of the above patients. (99)Tc(m)-MDP ((99)Tc(m) marked methylene diphosphonate) bone imaging could diagnosis the bone metastasis with highly sensitivity, but with lower specificity. The aim of this study is to explore the diagnostic value of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for the early period atypical bone metastases. 15 to 30 mCi (99)Tc(m)-MDP was intravenously injected to the 34 malignant patients diagnosed as doubtful early bone metastases. SPECT, CT and SPECT/CT images were captured and analyzed consequently. For the patients diagnosed as early period atypical bone metastases by SPECT/CT, combining the SPECT/CT and MRI together as the SPECT/MRI integrated image. The obtained SPECT/MRI image was analyzed and compared with the pathogenic results of patients. The results indicated that 34 early period doubtful metastatic focus, including 34 SPECT positive focus, 17 focus without special changes by using CT method, 11 bone metastases focus by using SPECT/CT method, 23 doubtful bone metastases focus, 8 doubtful bone metastases focus, 14 doubtful bone metastases focus and 2 focus without clear image. Totally, SPECT/CT combined with SPECT/MRI method diagnosed 30 bone metastatic focus and 4 doubtfully metastatic focus. In conclusion, (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging shows a higher diagnostic value for the early period bone metastases, which also enhances the diagnostic accuracy rate.

Sclerostin's role in bone's adaptive response to mechanical loading.

PubMed

Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2017-03-01

Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss. However, while sclerostin up-regulation appears to be necessary for the loss of bone with disuse, the role of sclerostin in the osteogenic response to loading is more complex. While mice unable to down-regulate sclerostin do not gain bone with loading, Sost knockout mice have an enhanced osteogenic response to loading. The molecular mechanisms by which osteocytes sense and transduce loading-related stimuli into changes in sclerostin expression remain unclear but include several, potentially interlinked, signalling cascades involving periostin/integrin, prostaglandin, estrogen receptor, calcium/NO and Igf signalling. Deciphering the mechanisms by which changes in the mechanical environment regulate sclerostin production may lead to the development of therapeutic strategies that can reverse the skeletal structural deterioration characteristic of disuse and age-related osteoporosis and enhance bones' functional adaptation to loading. By enhancing the osteogenic potential of the context in which individual therapies such as sclerostin antibodies act it may become possible to both prevent and reverse the age-related skeletal structural deterioration characteristic of osteoporosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Increasing Bone Mass and Bone Strength in Individuals with Chronic Spinal Cord Injury: Maximizing Response to Therapy

DTIC Science & Technology

2017-10-01

Award Number: W81XWH-16-1-0763 TITLE: Increasing Bone Mass and Bone Strength in Individuals with Chronic Spinal Cord Injury: Maximizing Response...TYPE Annual 3. DATES COVERED (From - To) 30 Sep 2016-29 Sep 2017 5a. CONTRACT NUMBER Increasing Bone Mass and Bone Strength in Individuals with...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Rapid bone loss is a universal

Estimating the strength of bone using linear response

NASA Astrophysics Data System (ADS)

Gunaratne, Gemunu H.

2002-12-01

Accurate diagnostic tools are required for effective management of osteoporosis; one method to identify additional diagnostics is to search for observable consequences of bone loss. An analysis of a model system is used to show that weakening of a bone is accompanied by a reduction of the fraction of the bone that participates in load transmission. On the basis of this observation, it is argued that the ratio Γ of linear responses of a network to dc and high-frequency ac driving can be used as a surrogate for their strength. Protocols needed to obtain Γ for bone samples are discussed.

Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

NASA Astrophysics Data System (ADS)

Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

2016-06-01

Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

A Prospective Study of Bone Tumor Response Assessment in Metastatic Breast Cancer

PubMed Central

Hayashi, Naoki; Costelloe, Colleen M.; Hamaoka, Tsuyoshi; Wei, Caimiao; Niikura, Naoki; Theriault, Richard L.; Hortobagyi, Gabriel N.; Madewell, John E.; Ueno, Naoto T.

2013-01-01

In this pilot study, we prospectively compared the response of bone metastasis assessed by our MD Anderson (MDA) bone tumor response criteria (computed tomography [CT], plain radiography [XR], and skeletal scintigraphy [SS]) with the response assessed by the World Health Organization (WHO) criteria (XR and SS). Both MDA and WHO criteria predicted progression-free survival (PFS) of patients at 6 months but not at an earlier time point. Background In our previous study, new MD Anderson (MDA) bone tumor response criteria (based on computed tomography [CT], plain radiography [XR], and skeletal scintigraphy [SS]) predicted progression-free survival (PFS) better than did World Health Organization (WHO) bone tumor response criteria (plain radiography [XR] and SS) among patients with breast cancer and bone-only metastases. In this pilot study, we tested whether MDA criteria could reveal bone metastasis response earlier than WHO criteria in patients with newly diagnosed breast cancer with osseous and measurable nonosseous metastases. Methods We prospectively analyzed bone metastasis response using each imaging modality and set of bone response criteria to distinguish progressive disease (PD) from non-PD and their association with PFS and overall survival (OS). We also compared the response of osseous metastases assessed by both criteria with the response of nonosseous measurable lesions. Results The median follow-up period was 26.7 months (range, 6.1–53.3 months) in 29 patients. PFS rates differed at 6 months based on the classification of PD or non-PD using either set of criteria (MDA, P = .002; WHO, P = .014), but these rates, as well as OS, did not differ at 3 months. Response in osseous metastases by either set of criteria did not correlate with the response in nonosseous metastases. Conclusion MDA and WHO criteria predicted PFS of patients with osseous metastases at 6 months but not at an earlier time point. We plan a well-powered study to determine the role of MDA

Early bone anchorage to micro- and nano-topographically complex implant surfaces in hyperglycemia.

PubMed

Ajami, Elnaz; Bell, Spencer; Liddell, Robert S; Davies, John E

2016-07-15

The aim of this work was to investigate the effect of implant surface design on early bone anchorage in the presence of hyperglycemia. 108 Wistar rats were separated into euglycemic (EG) controls and STZ-treated hyperglycemic (HG) groups, and received bilateral femoral custom rectangular implants of two surface topographies: grit blasted (GB) and grit-blast with a superimposed calcium phosphate nanotopography (GB-DCD). The peri-implant bone was subjected to a tensile disruption test 5, 7, and 9days post-operatively (n=28/time point); the force was measured; and the residual peri-implant bone was observed by scanning electron microscopy (SEM). Disruption forces at 5days were not significantly different from zero for the GB implants (p=0.24) in either metabolic group; but were for GB+DCD implants in both metabolic groups (p<0.001). Contact osteogenesis was greater on GB-DCD than the GB surface. The nano-and micro-surfaced implants showed significantly different disruption forces at all time points (e.g. >15N and <5N respectively at 9days). Such differences were not seen within the GB implants, as all values were very low (<5N). Even in hyperglycemia the GB-DCD surface outperformed the GB surfaces in both metabolic groups. Significantly, SEM of peri-implant bone showed compromised intra-fibrillar collagen mineralization in hyperglycemia, while inter-fibrillar and cement line mineralization remained unaffected. Enhanced bone anchorage to the implant surfaces was observed on the nanotopographically complex surface independent of metabolic group. The compromised intra-fibrillar mineralization observed provides a mechanism by which early bone mineralization is affected in hyperglycemia. It is generally accepted that the hyperglycemia associated with diabetes mellitus compromises bone quality, although the mechanism by which this occurs is unknown. Uncontrolled hyperglycemia is therefore a contra-indication for bone implant placement. It is also known that nano

Monitoring tissue inflammation and responses to drug treatments in early stages of mice bone fracture using 50 MHz ultrasound

PubMed Central

Chen, Yen-Chu; Lin, Yi-Hsun; Wang, Shyh-Hau; Lin, Shih-Ping; Shung, K. Kirk; Wu, Chia-Ching

2014-01-01

Bone fracture induces moderate inflammatory responses that are regulated by cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LO) for initiating tissue repair and bone formation. Only a handful of non-invasive techniques focus on monitoring acute inflammation of injured bone currently exists. In the current study, we monitored in vivo inflammation levels during the initial 2 weeks of the inflammatory stage after mouse bone fracture utilizing 50 MHz ultrasound. The acquired ultrasonic images were correlated well with histological examinations. After the bone fracture in the tibia, dynamic changes in the soft tissue at the medial-posterior compartment near the fracture site were monitored by ultrasound on the days of 0, 2, 4, 7, and 14. The corresponding echogenicity increased on the 2nd, 4th, and 7th day, and subsequently declined to basal levels after the 14th day. An increase of cell death was identified by the positive staining of deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and was consistent with ultrasound measurements. The increases of both COX-2 and Leukotriene B4 receptor 1 (BLT1, 5- LO-relative receptor), which are regulators for tissue inflammation, in the immunohistochemistry staining revealed their involvement in bone fracture injury. Monitoring the inflammatory response to various non-steroidal anti-inflammatory drugs (NSAIDs) treatments was investigated by treating injured mice with a daily oral intake of aspirin (Asp), indomethacin (IND), and a selective COX-2 inhibitor (SC-236). The Asp treatment significantly reduced fracture-increased echogenicity (hyperechogenicity, p < 0.05) in ultrasound images as well as inhibited cell death, and expression of COX-2 and BLT1. In contrast, treatment with IND or SC-236 did not reduce the hyperechogenicity, as confirmed by cell death (TUNEL) and expression levels of COX-2 or BLT1. Taken together, the current study reports the feasibility of a noninvasive ultrasound method capable of monitoring

Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm.

PubMed

Fewtrell, Mary S; Williams, Jane E; Singhal, Atul; Murgatroyd, Peter R; Fuller, Nigel; Lucas, Alan

2009-07-01

Preterm infants are at risk of metabolic bone disease due to inadequate mineral intake with unknown consequences for later bone health. To test the hypotheses that (1) early diet programs peak bone mass and bone turnover; (2) human milk has a beneficial effect on these outcomes; (3) preterm subjects have reduced peak bone mass compared to population reference data. 20 year follow-up of 202 subjects (43% male; 24% of survivors) who were born preterm and randomized to: (i) preterm formula versus banked breast milk or (ii) preterm versus term formula; as sole diet or supplement to maternal milk. Outcome measures were (i) anthropometry; (ii) hip, lumbar spine (LS) and whole body (WB) bone mineral content (BMC) and bone area (BA) measured using DXA; (iii) bone turnover markers. Infant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving >90% human milk had significantly higher WBBA (by 3.5%, p=0.01) and BMC (by 4.8%, p=0.03) than those receiving <10%. Compared to population data, subjects had significantly lower height SDS (-0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS (-0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight <1250 g (height SDS -0.81 (0.95), LSBMD SDS -0.61 (1.3)). Infant dietary randomization group did not affect peak bone mass or turnover suggesting the observed reduced final height and LS bone mass, most marked in growth restricted subjects with the lowest birthweight, may not be related to sub-optimal early nutrition. The higher WB bone mass associated with human milk intake, despite its low nutrient content, may reflect non-nutritive factors in breast milk. These findings may have implications for later osteoporosis risk and require further investigation.

Effects of early and late treatments of low-intensity, high-frequency mechanical vibration on bone parameters in rats.

PubMed

Sasso, Gisela Rodrigues da Silva; Florencio-Silva, Rinaldo; Santos, Miriam Aparecida; Teixeira, Cristiane de Paula; Simões, Manuel de Jesus; Katchburian, Eduardo; Reginato, Rejane Daniele; Daniele Reginato, Rejane

2015-01-01

Low-intensity, high-frequency mechanical vibration (LHMV) has shown to increase bone formation. However, studies comparing the effectiveness of early- and late-treatments of LHMV to counteract bone loss have not been documented. This study was designed to compare the effects of early- and late-treatments of LHMV (at 30 Hz/0.6 g, 20 min per day/five days per week, for 12 weeks) on bone parameters in ovariectomized (Ovx) rats. Thirty days after ovariectomy, 40 adult rats were randomly divided into four groups: GI (early control group); GII treated with LHMV 3 weeks after Ovx (early treatment); GIII (late control group) and GIV treated with LHMV twelve weeks after Ovx (late treatment). Bone mineral density (BMD) was analyzed before Ovx and after treatments. Then, animals were killed, and the femurs were collected and their length and diaphysis diameter were measured; the distal femurs were taken and processed for histomorphometry and polarized light microscopy for collagen fibers analysis or subjected to immunohistochemistry of cleaved caspase-3 in osteocytes. Statistical analysis was done by ANOVA followed by the Bonferroni post hoc test (p < 0.05). BMD was similar among the groups before Ovx, but after treatments, it was significantly higher in GII and GIV compared with their control groups (p < 0.05). Femur length and cortical bone thickness were similar among the groups, but the diaphysis diameter of GII was higher compared with GI. Trabecular bone area was higher in the vibrated groups, but it was greater in GII (p < 0.05). Also, the vibrated groups showed the higher content collagen fibers and lower presence apoptotic osteocytes (positive caspase-3 immunoreactivity) when compared with the other groups (p < 0.05). These results suggest that both early- and late-treatments with LHMV counteract bone loss, being the early treatment more effective than the late treatment.

Early arthritis induces disturbances at bone nanostructural level reflected in decreased tissue hardness in an animal model of arthritis

PubMed Central

Cascão, Rita; Finnilä, Mikko A. J.; Lopes, Inês P.; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João E.

2018-01-01

Introduction Arthritis induces joint erosions and skeletal bone fragility. Objectives The main goal of this work was to analyze the early arthritis induced events at bone architecture and mechanical properties at tissue level. Methods Eighty-eight Wistar rats were randomly housed in experimental groups, as follows: adjuvant induced arthritis (AIA) (N = 47) and a control healthy group (N = 41). Rats were monitored during 22 days for the inflammatory score, ankle perimeter and body weight and sacrificed at different time points (11 and 22 days post disease induction). Bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. Results At bone tissue level, measured by nanoindentation, there was a reduction of hardness in the arthritic group, associated with an increase of the ratio of bone concentric to parallel lamellae and of the area of the osteocyte lacuna. In addition, increased bone turnover and changes in the microstructure and mechanical properties were observed in arthritic animals, since the early phase of arthritis, when compared with healthy controls. Conclusion We have shown in an AIA rat model that arthritis induces very early changes at bone turnover, structural degradation and mechanical weakness. Bone tissue level is also affected since the early phase of arthritis, characterized by decreased tissue hardness associated with changes in bone lamella organization and osteocyte lacuna surface. These observations highlight the pertinence of immediate control of inflammation in the initial stages of arthritis. PMID:29315314

FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?

PubMed

Georgi, Thomas Walter; Kluge, Regine; Kurch, Lars; Chavdarova, Lidia; Hasenclever, Dirk; Stoevesandt, Dietrich; Pelz, Tanja; Landman-Parker, Judith; Wallace, Hamish; Karlen, Jonas; Fernandez-Teijeiro, Ana; Cepelova, Michaela; Fossa, Alexander; Balwierz, Walentyna; Attarbaschi, Andishe; Ammann, Roland A; Pears, Jane; Hraskova, Andrea; Uyttebroeck, Anne; Beishuizen, Auke; Dieckmann, Karin; Leblanc, Thierry; Daw, Stephen; Baumann, Julia; Körholz, Dieter; Sabri, Osama; Mauz-Körholz, Christine

2018-04-13

Purpose: This study focused on skeletal involvement in FDG-PET (PET) in Hodgkin lymphoma (HL). We aimed at a systematic evaluation of the different types of skeletal involvement and their PET response after two cycles of chemotherapy (PET-2), to answer the question whether the current PET response criterion for skeletal involvement is suitable. A secondary objective was to observe the influence of initial uptake intensity and metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: Initial PET scans (PET-0) of 1068 pediatric HL patients from the EuroNet-PHL-C1 (C1) trial were evaluated by central review for skeletal involvement. Three types of skeletal lesions were distinguished: skeletal lesions detected only in PET (PETonly), bone marrow (BM) lesions confirmed by MRI or BM biopsy and bone lesions. Uptake intensity (measured as qPET value) and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response in PET-2 of skeletal and nodal involvement were compared. Results: 139/1068 (13%) C1 patients showed skeletal involvement (44/139 PETonly patients, 32/139 BM patients and 63/139 bone patients). 101/139 (73%) patients became PET-2 negative in the skeleton while lymph node involvement was PET-2 negative in 94/139 (68%) patients. Highest skeletal PET-2 negative rate was seen in 42/44 (95%) PETonly patients, followed by 22/32 (69%) BM patients and 37/63 (59%) bone patients. Skeletal lesions who became PET-2 negative showed lower median values for initial qPET (2.74) and MTV (2ml) than lesions who remained PET-2 positive (3.84; 7ml). Conclusion: In this study with pediatric HL patients, the complete response rate in PET-2 of skeletal and nodal involvement was similar. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion - comparison with the local skeletal background - is well suited. Initial uptake intensity and MTV of

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

PubMed

Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis

2011-08-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia

PubMed Central

Yadav, Manisha C.; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L.; Whyte, Michael P.; Crine, Philippe; Millán, José Luis

2011-01-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD10, renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2−/−) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2−/− mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2 mg/kg for 43 days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED80 (the dose prevents the bone defects in 80% of mice) was 3.2, 2.8 and 2.9 mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PPi concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. PMID:21458605

Early fixation of cobalt-chromium based alloy surgical implants to bone using a tissue-engineering approach.

PubMed

Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

2012-01-01

To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation.

Early Fixation of Cobalt-Chromium Based Alloy Surgical Implants to Bone Using a Tissue-engineering Approach

PubMed Central

Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

2012-01-01

To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation. PMID:22754313

The response of bone, articular cartilage and tendon to exercise in the horse

PubMed Central

Firth, Elwyn C

2006-01-01

Horses can gallop within hours of birth, and may begin training for athletic competition while still growing. This review cites studies on the effects of exercise on bone, tendon and articular cartilage, as detected by clinical and research imaging techniques, tissue biochemical analysis and microscopy of various kinds. For bone, alterations in bone mineral content, mineral density and the morphology of the mineralized tissue are the most common end-points. Apparent bone density increases slightly after athletic training in the cortex, but substantially in the major load paths of the epiphyses and cuboidal bones, despite the lower material density of the new bone, which is deposited subperiosteally and on internal surfaces without prior osteoclastic resorption. With training of greater intensity, adaptive change is supervened by patho-anatomical change in the form of microdamage and frank lesions. In tendon, collagen fibril diameter distribution changes significantly during growth, but not after early training. The exact amount and type of protracted training that does cause reduction in mass average diameter (an early sign of progressive microdamage) have not been defined. Training is associated with an increase in the cross-sectional area of some tendons, possibly owing to slightly greater water content of non-collagenous or newly synthesized matrix. Early training may be associated with greater thickness of hyaline but not calcified articular cartilage, at least in some sites. The age at which adaptation of cartilage to biomechanical influences can occur may thus extend beyond very early life. However, cartilage appears to be the most susceptible of the three tissues to pathological alteration. The effect of training exercise on the anatomical or patho-anatomical features of connective tissue structures is affected by the timing, type and amount of natural or imposed exercise during growth and development which precedes the training. PMID:16637875

Relation of adrenal-derived steroids with bone maturation, mineral density and geometry in healthy prepubertal and early pubertal boys.

PubMed

Vandewalle, S; Taes, Y; Fiers, T; Toye, K; Van Caenegem, E; Kaufman, J-M; De Schepper, J

2014-12-01

Little is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys. To study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys. 98 healthy prepubertal and early pubertal boys (aged 6-14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand. Adrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD). In healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys. Copyright © 2014 Elsevier Inc. All rights reserved.

Multiscale biomechanical responses of adapted bone-periodontal ligament-tooth fibrous joints

PubMed Central

Jang, Andrew T.; Merkle, Arno; Fahey, Kevin; Gansky, Stuart A.; Ho, Sunita P.

2015-01-01

Reduced functional loads cause adaptations in organs. In this study, temporal adaptations of bone-ligament-tooth fibrous joints to reduced functional loads were mapped using a holistic approach. Systematic studies were performed to evaluate organ-level and tissue-level adaptations in specimens harvested periodically from rats given powder food for 6 months (N = 60 over 8,12,16,20, and 24 weeks). Bone-periodontal ligament (PDL)-tooth fibrous joint adaptation was evaluated by comparing changes in joint stiffness with changes in functional space between the tooth and alveolar bony socket. Adaptations in tissues included mapping changes in the PDL and bone architecture as observed from collagen birefringence, bone hardness and volume fraction in rats fed soft foods (soft diet, SD) compared to those fed hard pellets as a routine diet (hard diet, HD). In situ biomechanical testing on harvested fibrous joints revealed increased stiffness in SD groups (SD:239-605 N/mm) (p<0.05) at 8 and 12 weeks. Increased joint stiffness in early development phase was due to decreased functional space (at 8wks change in functional space was −33 µm, at 12wks change in functional space was −30 µm) and shifts in tissue quality as highlighted by birefringence, architecture and hardness. These physical changes were not observed in joints that were well into function, that is, in rodents older than 12 weeks of age. Significant adaptations in older groups were highlighted by shifts in bone growth (bone volume fraction 24wks: Δ-0.06) and bone hardness (8wks: Δ−0.04 GPa, 16 wks: Δ−0.07 GPa, 24wks: Δ−0.06 GPa). The response rate (N/s) of joints to mechanical loads decreased in SD groups. Results from the study showed that joint adaptation depended on age. The initial form-related adaptation (observed change in functional space) can challenge strain-adaptive nature of tissues to meet functional demands with increasing age into adulthood. The coupled effect between functional space in

Bone response to a titanium aluminium nitride coating on metallic implants.

PubMed

Freeman, C O; Brook, I M

2006-05-01

The design, surface characteristics and strength of metallic implants are dependant on their intended use and clinical application. Surface modifications of materials may enable reduction of the time taken for osseointegration and improve the biological response of bio-mechanically favourable metals and alloys. The influence of a titanium aluminium nitride (TAN) coating on the response of bone to commercially pure titanium and austenitic 18/8 stainless steel wire is reported. TAN coated and plain rods of stainless steel and commercially pure titanium were implanted into the mid-shaft of the femur of Wistar rats. The femurs were harvested at four weeks and processed for scanning electron and light microscopy. All implants exhibited a favourable response in bone with no evidence of fibrous encapsulation. There was no significant difference in the amount of new bone formed around the different rods (osseoconduction), however, there was a greater degree of shrinkage separation of bone from the coated rods than from the plain rods (p = 0.017 stainless steel and p = 0.0085 titanium). TAN coating may result in reduced osseointegration between bone and implant.

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

Testosterone regulates bone response to inflammation.

PubMed

Steffens, J P; Herrera, B S; Coimbra, L S; Stephens, D N; Rossa, C; Spolidorio, L C; Kantarci, A; Van Dyke, T E

2014-03-01

This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48 h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1β expression was increased in the L group (p<0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100 nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10 nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function. © Georg Thieme Verlag KG Stuttgart · New York.

Rictor is required for optimal bone accrual in response to anti-sclerostin therapy in the mouse.

PubMed

Sun, Weiwei; Shi, Yu; Lee, Wen-Chih; Lee, Seung-Yon; Long, Fanxin

2016-04-01

Wnt signaling has emerged as a major target pathway for the development of novel bone anabolic therapies. Neutralizing antibodies against the secreted Wnt antagonist sclerostin (Scl-Ab) increase bone mass in both animal models and humans. Because we have previously shown that Rictor-dependent mTORC2 activity contributes to Wnt signaling, we test here whether Rictor is required for Scl-Ab to promote bone anabolism. Mice with Rictor deleted in the early embryonic limb mesenchyme (Prx1-Cre;Rictor(f/f), hereafter RiCKO) were subjected to Scl-Ab treatment for 5weeks starting at 4months of age. In vivo micro-computed tomography (μCT) analyses before the treatment showed that the RiCKO mice displayed normal trabecular, but less cortical bone mass than the littermate controls. After 5weeks of treatment, Scl-Ab dose-dependently increased trabecular and cortical bone mass in both control and RiCKO mice, but the increase was significantly blunted in the latter. Dynamic histomorphometry revealed that the RiCKO mice formed less bone than the control in response to Scl-Ab. In addition, the RiCKO mice possessed fewer osteoclasts than normal under the basal condition and exhibited lesser suppression in osteoclast number by Scl-Ab. Consistent with the fewer osteoclasts in vivo, bone marrow stromal cells (BMSC) from the RiCKO mice expressed less Rankl but normal levels of Opg or M-CSF, and were less effective than the control cells in supporting osteoclastogenesis in vitro. The reliance of Rankl on Rictor appeared to be independent of Wnt-β-catenin or Wnt-mTORC2 signaling as Wnt3a had no effect on Rankl expression by BMSC from either control or RICKO mice. Overall, Rictor in the limb mesenchymal lineage is required for the normal response to the anti-sclerostin therapy in both bone formation and resorption. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanotransduction and the functional response of bone to mechanical strain

NASA Technical Reports Server (NTRS)

Duncan, R. L.; Turner, C. H.

1995-01-01

Mechanotransduction plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo. In bone, the process of mechanotransduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch. In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through the integrin-cytoskeleton-nuclear matrix structure, stretch-activated cation channels within the cell membrane, G protein-dependent pathways, and linkage between the cytoskeleton and the phospholipase C or phospholipase A pathways. The tight interaction of each of these pathways would suggest that the entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal. In the transmission of signal, osteoblasts, osteocytes, and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction. In the effector cell response, the effects of mechanical loading are dependent upon the

[Early application of the antibiotic-laden bone cement (ALBC) combined with the external fixation support in treating the open fractures of lower limbs complicated with bone defect].

PubMed

Xiao, Jian; Mao, Zhao-Guang; Zhu, Hui-Hua; Guo, Liang

2017-03-25

To discuss the curative effect of the early application of the antibiotic-laden bone cement (ALBC) combined with the external fixation support in treating the open fractures of lower limbs complicated with bone defect. From December 2013 to January 2015, 36 cases of lower limb open comminuted fractures complicated with bone defects were treated by the vancomycin ALBC combined with the external fixation support, including 26 males and 10 females with an average age of 38.0 years old ranging from 19 to 65 years old. The included cases were all open fractures of lower limbs complicated with bone defects with different degree of soft tissue injuries. Among them, 25 cases were tibial fractures, 11 cases were femoral fractures. The radiographs indicated a presence of bone defects, which ranged from 3.0 to 6.1 cm with an average of 4.0 cm. The Gustilo classification of open fractures:24 cases were type IIIA, 12 cases were typr IIIB. The percentage of wound infection, bone grafting time, fracture healing time and postoperative joint function of lower limb were observed. The function of injured limbs was evaluated at 1 month after the clinical healing of fracture based on Paley evaluation criterion. All cases were followed up for 3 to 24 months with an average of (6.0±3.0) months. The wound surface was healed well, neither bone infections nor unhealed bone defects were presented. The reoperation of bone grafting was done at 6 weeks after the patients received an early treatment with ALBC, some of them were postponed to 8 weeks till the approximate healing of fractures, the treatment course lasted for 4 to 8 months with an average of(5.5±1.5) months. According to Paley and other grading evaluations of bone and function, there were 27 cases as excellent, 5 cases as good, 3 cases as ordinary. The ALBC combined with external fixation support was an effective method for early treatment to treat the traumatic lower limb open fractures complicated with bone defects. This method

Interpretation and classification of bone scintigraphic findings in stress fractures.

PubMed

Zwas, S T; Elkanovitch, R; Frank, G

1987-04-01

A new system for classification of stress fractures identified by bone scintigraphy was developed and divided into four grades according to lesion dimension, bone extension, and tracer accumulation. The scintigraphic findings were evaluated for severity of lesions by extent of the visualized bone response, ranging from ill-defined cortical lesions with slightly increased activity (I) to well-defined intramedullary transcortical lesions with intensely increased activity (IV). Bone scintigraphies using [99mTc]MDP were obtained in 310 military recruits suspected of having stress fractures. In 235 patients, 391 stress fractures were diagnosed. Forty percent of the lesions were asymptomatic. Most of the lesions were in the tibiae (72%), and 87% of the patients had one or two lesions, while 13% had three to five lesions. Eighty-five percent of the lesions were classified as mild and showed early and more complete resolution on follow-up studies after treatment as compared to the severe grades. Furthermore, specific scintigraphic patterns have been introduced for distinguishing inflammatory shin-splints from stress fractures, allowing for their appropriate early treatment. Thus, early recognition of mild stress fracture scintigraphic patterns representing the beginning of pathologic bone response to stress enabled a prompt and effective treatment to prevent progression of lesions, protracted disability, and complications.

Evaluating the relationship between muscle and bone modeling response in older adults.

PubMed

Reider, Lisa; Beck, Thomas; Alley, Dawn; Miller, Ram; Shardell, Michelle; Schumacher, John; Magaziner, Jay; Cawthon, Peggy M; Barbour, Kamil E; Cauley, Jane A; Harris, Tamara

2016-09-01

Bone modeling, the process that continually adjusts bone strength in response to prevalent muscle-loading forces throughout an individual's lifespan, may play an important role in bone fragility with age. Femoral stress, an index of bone modeling response, can be estimated using measurements of DXA derived bone geometry and loading information incorporated into an engineering model. Assuming that individuals have adapted to habitual muscle loading forces, greater stresses indicate a diminished response and a weaker bone. The purpose of this paper was to evaluate the associations of lean mass and muscle strength with the femoral stress measure generated from the engineering model and to examine the extent to which lean mass and muscle strength account for variation in femoral stress among 2539 healthy older adults participating in the Health ABC study using linear regression. Mean femoral stress was higher in women (9.51, SD=1.85Mpa) than in men (8.02, SD=1.43Mpa). Percent lean mass explained more of the variation in femoral stress than did knee strength adjusted for body size (R(2)=0.187 vs. 0.055 in men; R(2)=0.237 vs. 0.095 in women). In models adjusted for potential confounders, for every percent increase in lean mass, mean femoral stress was 0.121Mpa lower (95% CI: -0.138, -0.104; p<0.001) in men and 0.139Mpa lower (95% CI: -0.158, -0.121; p<0.001) in women. The inverse association of femoral stress with lean mass and with knee strength did not differ by category of BMI. Results from this study provide insight into bone modeling differences as measured by femoral stress among older men and women and indicate that lean mass may capture elements of bone's response to load. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

How MMPs Impact Bone Responses to Metastatic Prostate Cancer

DTIC Science & Technology

2009-02-01

STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Using an animal model of prostate tumor...prostate tumor progression in the bone since no difference in osteolytic or osteoblastic responses between wild type and MMP-9 deficient animals were...described as the ‘vicious cycle’ (4). Using an animal model of 4 tumor progression in the bone, we have previously identified a group of enzymes known as

How MMPs Impact Bone Responses to Metastatic Prostate Cancer

DTIC Science & Technology

2010-02-01

13. SUPPLEMENTARY NOTES 14. ABSTRACT Using an animal model of prostate tumor progression in the bone we have previously shown that MMPs...in osteolytic or osteoblastic responses between wild type and MMP-9 deficient animals were detected by Faxitron, CT, SPECT and histomorphometry...as the ‘vicious cycle’ (4). Using an animal model of 2 tumor progression in the bone, we have previously identified a group of enzymes known as

Reduced bone mass in Dutch adolescents fed a macrobiotic diet in early life.

PubMed

Parsons, T J; van Dusseldorp, M; van der Vliet, M; van de Werken, K; Schaafsma, G; van Staveren, W A

1997-09-01

This study investigated the effect of a macrobiotic (vegan-type) diet, low in calcium and vitamin D, consumed in early life, on bone mineral during adolescence. Bone mineral content (BMC) and bone area were measured in 195 adolescents (103 girls, 92 boys) aged 9-15 years, using dual-energy X-ray absorptiometry. Ninety-three adolescents (43 girls, 50 boys) had followed a macrobiotic diet in childhood, and 102 (60 girls, 42 boys) were control subjects. After adjustment for bone area, weight, height, percent body lean, age, and puberty, BMC was significantly lower in macrobiotic subjects, in boys and girls, respectively, at the whole body, -3.4% and -2.5%, spine, -8.5% and -5.0%, femoral neck, -8.0% and -8.2%, midshaft radius, -6.8% and -5.6%, and also in girls, at the trochanter, -5.8% (p < 0.05). No group differences were observed at the wrist. Group differences were not explained by current calcium adjusted bone mass at age 9-15 years, observations which may hold important implications for fracture risk in later life.

Effect of carbohydrate feeding on the bone metabolic response to running

PubMed Central

Varley, Ian; Jones, Thomas W.; James, Ruth M.; Tang, Jonathan C. Y.; Fraser, William D.; Greeves, Julie P.

2015-01-01

Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO·kg body mass−1·h−1) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (V̇o2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P = 0.028; P1NP: P = 0.021; IL-6: P = 0.036), although there was no difference in the short-term response (β-CTX: P = 0.856; P1NP: P = 0.721; IL-6: P = 0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover. PMID:26251510

Is Animal Age a Factor In the Response of Bone to Spaceflight?

NASA Technical Reports Server (NTRS)

Morey-Holton, E. R.; Garetto, L. P.; Doty, S. B.; Halloran, B. P.; Turner, R. T.; Dalton, Bonnie (Technical Monitor)

2002-01-01

The rodent bone response to spaceflight may be influenced by a multitude of actors including flight duration, strain, and housing. Review of bone formation rates during spaceflight suggests that age may also play a role in the response. Weanling rats show fewer bone changes than older rats. To determine if the long bones of weanling rats were insensitive to weight-bearing, a hindlimb unloading experiment was conducted simultaneously with a 9d shuttle flight in 34d old group-housed male rats. All animals were injected with bone markers 7d and 1d before flight and euthanized at landing, 24hr, and 72hr following recovery. If no differences in body weight, bone length, or bone formation at the tibiofibular junction were noted at the different time points, data were combined for each group. No significant differences in body weight were found at any time period among the groups. The humerus, tibia, and femur elongated significantly during the flight period with no difference in lengths between groups at the end of the flight period. The group-housed flight rats showed no change in cortical bone formation rate compared to preflight values, flight controls, or vivarium controls. However, the hindlimb unloading group showed a significant 30% decrease in bone formation rate compared to all other groups. Individually-housed 38d old animals flown for 14d showed approx. 10% suppression of cortical growth. We speculate that the mechanical threshold required for cross-sectional bone growth is reached in group-house weanling rats during spaceflight, perhaps, through physical interactions, and that the weanling animals are sensitive to loading. However, the threshold is not fully reached in either singly-housed flight or hindlimb unloaded weanling rats. Older singly-housed flight animals appear to show equal or greater bone changes compared to hindlimb unloaded rats. We conclude that age, flight duration, strain, and housing have important roles in rodent skeletal responses to

Tumor Response After Stereotactic Body Radiation Therapy to Nonspine Bone Metastases: An Evaluation of Response Criteria

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

McDonald, Rachel; Probyn, Linda; Poon, Ian

Purpose: To evaluate the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and University of Texas MD Anderson (MDA) Cancer Center criteria in the setting of stereotactic body radiation therapy (SBRT) to nonspine bone metastases. Methods: Patients who were treated with SBRT to nonspine bone metastases were identified by retrospective chart review. An independent musculoskeletal radiologist evaluated response to treatment using computed tomography (CT) scans. Results: Thirty-three patients were treated to 42 nonspine bone metastases. The most common primary cancer cites were renal cell carcinoma (RCC) (33.3%), lung (24.2%), and prostate (18.2%). Bone metastases were either mainlymore » lytic (57.1%), mainly sclerotic (28.6%), or mixed (14.3%). When lytic and sclerotic lesions were evaluated according to RECIST 1.1, local control (LC) was 83%, 85%, 88%, and 80% for those with CT imaging between months 1 to 3, 4 to 6, 7 to 9, and 10 to 12, respectively. When evaluated by the MDA criteria by density, LC within each time period was slightly greater. Overall LC decreased considerably when evaluated by MDA in terms of size. Conclusions: Consensus definitions of response are required as they have implications on clinical trials and disease management. Without consistent response criteria, outcomes from clinical trials cannot be compared and treatment efficacy remains undetermined.« less

Accentuated Osteoclastic Response to Parathyroid Hormone Undermines Bone Mass Acquisition in Osteonectin-null Mice

PubMed Central

do Reis, Luciene Machado; Kessler, Catherine B.; Adams, Douglas J.; Lorenzo, Joseph; Jorgetti, Vanda; Delany, Anne M.

2008-01-01

Matricellular proteins play a unique role in the skeleton as regulators of bone remodeling, and the matricellular protein osteonectin (SPARC, BM-40) is the most abundant non-collagenous protein in bone. In the absence of osteonectin, mice develop progressive low turnover osteopenia, particularly affecting trabecular bone. Polymorphisms in a regulatory region of the osteonectin gene are associated with bone mass in a subset of idiopathic osteoporosis patients, and these polymorphisms likely regulate osteonectin expression. Thus it is important to determine how osteonectin gene dosage affects skeletal function. Moreover, intermittent administration of parathyroid hormone (PTH) (1-34) is the only anabolic therapy approved for the treatment of osteoporosis, and it is critical to understand how modulators of bone remodeling, such as osteonectin, affect skeletal response to anabolic agents. In this study, 10 week old female wild type, osteonectin-haploinsufficient, and osteonectin-null mice (C57Bl/6 genetic background) were given 80 μg/kg body weight/day PTH(1-34) for 4 weeks. Osteonectin gene dosage had a profound effect on bone microarchitecture. The connectivity density of trabecular bone in osteonectin-haploinsufficient mice was substantially decreased compared with that of wild type mice, suggesting compromised mechanical properties. Whereas mice of each genotype had a similar osteoblastic response to PTH treatment, the osteoclastic response was accentuated in osteonectin-haploinsufficient and osteonectin-null mice. Eroded surface and osteoclast number were significantly higher in PTH-treated osteonectin-null mice, as was endosteal area. In vitro studies confirmed that PTH induced the formation of more osteoclast-like cells in marrow from osteonectin-null mice compared with wild type. PTH treated osteonectin-null bone marrow cells expressed more RANKL mRNA compared with wild type. However, the ratio of RANKL:OPG mRNA was somewhat lower in PTH treated osteonectin

Changes in Mouse Bone Turnover in Response to Microgravity

NASA Technical Reports Server (NTRS)

Cheng-Campbell, M.; Blaber, E.; Almeida, E.

2016-01-01

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1a/p21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23% decrease in bone fraction (p=0.005) and 11.91% decrease in bone thickness (p=0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl/6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n=10) and vivarium controls (n=10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered

Premenopausal women with early breast cancer treated with estradiol suppression have severely deteriorated bone microstructure.

PubMed

Ramchand, Sabashini K; Seeman, Ego; Wang, Xiao-Fang; Ghasem-Zadeh, Ali; Francis, Prudence A; Ponnusamy, Evangeline J; Bardin, Michele S; Bui, Minh; Zebaze, Roger; Zajac, Jeffrey D; Grossmann, Mathis

2017-10-01

In premenopausal women with early estrogen-receptor-positive breast cancer, combined ovarian suppression and aromatase inhibition reduce estradiol production precipitously. The resulting unbalanced and rapid bone remodelling replaces older bone with less bone that is less fully mineralized. We hypothesized that these changes result in severe microstructural deterioration and reduced matrix mineralization density. Images of the distal radius and distal tibia were acquired using high-resolution peripheral quantitative computed tomography in a cross-sectional study of 27 premenopausal women, mean age 43.3years (range 30.4 to 53.7) with early breast cancer made estradiol deficient for 17months (range 6-120) using ovarian suppression and aromatase inhibition, 42 healthy age-matched premenopausal and 35 postmenopausal controls, mean age 62.6years (range 60.2 to 65.5). Cortical and trabecular microstructure were quantified using Strax software. Compared with premenopausal controls, the women with breast cancer had 0.75 SD (95% CI 0.21 to 1.29) lower distal radial trabecular bone volume due to 1.29 SD (0.71 to 1.87) fewer trabeculae. Cortical porosity was 1.25 SD (0.59 to 1.91) higher but cortical thickness was not reduced. Compared with postmenopausal controls 20years older, cases had comparable or lower trabecular bone volume and comparable cortical porosity and thickness. Matrix mineral density was 1.56 SD (0.90 to 2.22) lower than in premenopausal controls and 2.17 SD (1.50 to 2.84) lower than in postmenopausal controls. Results at the tibia were similar. The severe cortical porosity and trabecular deterioration associated with estradiol depletion and the longevity of premenopausal women with early breast cancer treated with endocrine therapy provide a compelling rationale to investigate the efficacy of antiresorptive therapy initiated at the time of breast cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Early caregiving and physiological stress responses.

PubMed

Luecken, Linda J; Lemery, Kathryn S

2004-05-01

Inadequate early caregiving has been associated with risks of stress-related psychological and physical illness over the life span. Dysregulated physiological stress responses may represent a mechanism linking early caregiving to health outcomes. This paper reviews evidence linking early caregiving to physiological responses that can increase vulnerability to stress-related illness. A number of high-risk family characteristics, including high conflict, divorce, abuse, and parental psychopathology, are considered in the development of stress vulnerability. Three theoretical pathways linking caregiving to physiological stress responses are outlined: genetic, psychosocial, and cognitive-affective. Exciting preliminary evidence suggests that early caregiving can impact long-term physiological stress responses. Directions for future research in this area are suggested.

The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells

PubMed Central

Wang, Hai; Yu, Cuijuan; Gao, Xia; Welte, Thomas; Muscarella, Aaron M.; Tian, Lin; Zhao, Hong; Zhao, Zhen; Du, Shiyu; Tao, Jianning; Lee, Brendan; Westbrook, Thomas F.; Wong, Stephen T. C.; Jin, Xin; Rosen, Jeffrey M.; Osborne, C. Kent; Zhang, Xiang H.-F.

2014-01-01

Summary Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We further elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human datasets analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases. Significance In advanced stages, breast cancer bone metastases are driven by paracrine crosstalk among cancer cells, osteoblasts, and osteoclasts, which constitute a vicious osteolytic cycle. Current therapies targeting this process limit tumor progression, but do not improve patient survival. On the other hand, bone micrometastases may remain indolent for years before activating the vicious cycle, providing a therapeutic opportunity to prevent macrometastases. Here, we show that bone colonization is initiated in a microenvironment niche exhibiting active osteogenesis. Cancer and osteogenic cells form heterotypic adherens junctions, which enhance mTOR activity and drive early-stage bone colonization prior to osteolysis. These results reveal a strong connection between osteogenesis and micrometastasis and suggest potential therapeutic targets to prevent bone macrometastases. PMID:25600338

Sink or swim? Bone density as a mechanism for buoyancy control in early cetaceans.

PubMed

Gray, Noel-Marie; Kainec, Kimberly; Madar, Sandra; Tomko, Lucas; Wolfe, Scott

2007-06-01

Previous analyses have shown that secondarily aquatic tetrapods, including whales, exhibit osteological adaptations to life in water as part of their complex buoyancy control systems. These structural specializations of bone span hyperostosis through osteoporosis. The past 15 years of paleontological effort has provided an unprecedented opportunity to examine the osteological transformation of whales as they make their transition to an obligate aquatic lifestyle over a 10-million-year period. It is hypothesized that whales manifest their osteological specialization in the same manner as extant semiaquatic and fully aquatic mammals. This study presents and analysis of the microstructural features of bone in early and late archaic cetaceans, and in a comparative sample of modern terrestrial, semiaquatic, and aquatic mammals. Bone histology was examined from the ribs of 10 fossilized individuals representing five early cetacean families, including Pakicetidae, Ambulocetidae, Protocetidae, Remintonocetidae, and Basilosauridae. Comparisons were then made with rib histology from nine genera of extant mammals including: Odocoileus (deer), Bos (cow), Equus (horse), Canis (dog), Lutra (river otter), Enhydra (sea otter), Choeropsis (pygmy hippo), Trichechus (sea cow), and Delphinus (dolphin). Results show that the transition from terrestrial, to semiaquatic, to obligate aquatic locomotion in archaeocetes involved a radical shift in bone function achieved by means of profound changes at the microstructural level. A surprising finding was that microstructural change predates gross anatomical shift in archaeocetes associated with swimming. Histological analysis shows that high bone density is an aquatic specialization that provides static buoyancy control (ballast) for animals living in shallow water, while low bone density is associated with dynamic buoyancy control for animals living in deep water. Thus, there was a shift from the typical terrestrial form, to osteopetrosis

Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

PubMed

Ferrari, Serge L; Chevalley, Thierry; Bonjour, Jean-Philippe; Rizzoli, René

2006-04-01

Whether peak bone mass is low among children with fractures remains uncertain. In a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures. Among those, BMC gain at multiple sites and vertebral bone size at pubertal maturity were significantly decreased. Hence, childhood fractures may be markers of low peak bone mass acquisition and persistent skeletal fragility. Fractures in childhood may result from a deficit in bone mass accrual during rapid longitudinal growth. Whether low bone mass persists beyond this period however remains unknown. BMC at the spine, radius, hip, and femur diaphysis was prospectively measured over 8.5 years in 125 girls using DXA. Differences in bone mass and size between girls with and without fractures were analyzed using nonparametric tests. The contribution of genetic factors was evaluated by mother-daughter correlations and that of calcium intake by Cox proportional hazard models. Fifty-eight fractures occurred in 42 among 125 girls (cumulative incidence, 46.4%), one-half of all fractures affecting the forearm and wrist. Girls with and without fractures had similar age, height, weight. and calcium intake at all time-points. Before and during early puberty, BMC and width of the radius diaphysis was lower in the fracture compared with no-fracture group (p < 0.05), whereas aBMD and BMAD were similar in the two groups. At pubertal maturity (Tanner's stage 5, mean age +/- SD, 16.4 +/- 0.5 years), BMC at the ultradistal radius (UD Rad.), femur trochanter, and lumbar spine (LS), and LS projected bone area were all significantly lower in girls with fractures. Throughout puberty, BMC gain at these sites was also decreased in the fracture group (LS, -8.0%, p = 0.015; UD Rad., -12.0%, p = 0.004; trochanter, -8.4%, p = 0.05 versus no fractures). BMC was highly correlated between prepuberty and pubertal maturity (R = 0.54-0.81) and between mature daughters and their mothers (R = 0.32-0.46). Calcium intake was not related to

Growth plate-derived hedgehog-signal-responsive cells provide skeletal tissue components in growing bone.

PubMed

Haraguchi, Ryuma; Kitazawa, Riko; Imai, Yuuki; Kitazawa, Sohei

2018-04-01

Longitudinal bone growth progresses by continuous bone replacement of epiphyseal cartilaginous tissue, known as "growth plate", produced by columnar proliferated- and differentiated-epiphyseal chondrocytes. The endochondral ossification process at the growth plate is governed by paracrine signals secreted from terminally differentiated chondrocytes (hypertrophic chondrocytes), and hedgehog signaling is one of the best known regulatory signaling pathways in this process. Here, to investigate the developmental relationship between longitudinal endochondral bone formation and osteogenic progenitors under the influence of hedgehog signaling at the growth plate, genetic lineage tracing was carried out with the use of Gli1 CreERT2 mice line to follow the fate of hedgehog-signal-responsive cells during endochondral bone formation. Gli1 CreERT2 genetically labeled cells are detected in hypertrophic chondrocytes and osteo-progenitors at the chondro-osseous junction (COJ); these progeny then commit to the osteogenic lineage in periosteum, trabecular and cortical bone along the developing longitudinal axis. Furthermore, in ageing bone, where longitudinal bone growth ceases, hedgehog-signal responsiveness and its implication in osteogenic lineage commitment is significantly weakened. These results show, for the first time, evidence of the developmental contribution of endochondral progenitors under the influence of epiphyseal chondrocyte-derived secretory signals in longitudinally growing bone. This study provides a precise outline for assessing the skeletal lineage commitment of osteo-progenitors in response to growth-plate-derived regulatory signals during endochondral bone formation.

Determinants of bone and blood lead concentrations in the early postpartum period

PubMed Central

Brown, M. J.; Hu, H.; Gonzales-Cossio, T.; Peterson, K.; Sanin, L.; Kageyama, M. d.; Palazuelos, E.; Aro, A.; Schnaas, L.; Hernandez-Avila, M.

2000-01-01

OBJECTIVE—This study investigated determinants of bone and blood lead concentrations in 430 lactating Mexican women during the early postpartum period and the contribution of bone lead to blood lead.
METHODS—Maternal venous lead was measured at delivery and postpartum, and bone lead concentrations, measured with in vivo K-x ray fluorescence, were measured post partum. Data on environmental exposure, demographic characteristics, and maternal factors related to exposure to lead were collected by questionnaire. Linear regression was used to examine the relations between bone and blood lead, demographics, and environmental exposure variables.
RESULTS—Mean (SD) blood, tibial, and patellar lead concentrations were 9.5 (4.5) µg/dl, 10.2 (10.1) µg Pb/g bone mineral, and 15.2 (15.1) µg Pb/g bone mineral respectively. These values are considerably higher than values for women in the United States. Older age, the cumulative use of lead glazed pottery, and higher proportion of life spent in Mexico City were powerful predictors of higher bone lead concentrations. Use of lead glazed ceramics to cook food in the past week and increased patellar lead concentrations were significant predictors of increased blood lead. Patellar lead concentrations explained one third of the variance accounted for by the final blood lead model. Women in the 90th percentile for patella lead had an untransformed predicted mean blood lead concentration 3.6 µg/dl higher than those in the 10th percentile.
CONCLUSIONS—This study identified the use of lead glazed ceramics as a major source of cumulative exposure to lead, as reflected by bone lead concentrations, as well as current exposure, reflected by blood lead, in Mexico. A higher proportion of life spent in Mexico City, a proxy for exposure to leaded gasoline emissions, was identified as the other major source of cumulative lead exposure. The influence of bone lead on blood lead coupled with the long half life of lead in bone has

Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

PubMed

Rougraff, Bruce T; Kling, Thomas J

2002-06-01

The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

Aging Periosteal Progenitor Cells have Reduced Regenerative Responsiveness to Bone Injury and to the Anabolic Actions of PTH 1-34 Treatment

PubMed Central

Yukata, Kiminori; Xie, Chao; Li, Tian-Fang; Takahata, Masahiko; Hoak, Donna; Kondabolu, Sirish; Zhang, Xinping; Awad, Hani A.; Schwarz, Edward M.; Beck, Christopher A.; Jonason, Jennifer H.; O’Keefe, Regis J.

2014-01-01

A stabilized tibia fracture model was used in young (8-week old) and aged (1-year old) mice to define the relative bone regenerative potential and the relative responsiveness of the periosteal progenitor population with aging and PTH 1-34 (PTH) systemic therapy. Bone regeneration was assessed through gene expressions, radiographic imaging, histology/histomorphometry, and biomechanical testing. Radiographs and microCT showed increased calcified callus tissue and enhanced bone healing in young compared to aged mice. A key mechanism involved reduced proliferation, expansion, and differentiation of periosteal progenitor cell populations in aged mice. The experiments showed that PTH increased calcified callus tissue and torsional strength with a greater response in young mice. Histology and quantitative histomorphometry confirmed that PTH increased callus tissue area due primarily to an increase in bone formation, since minimal changes in cartilage and mesenchyme tissue area occurred. Periosteum examined at 3, 5, and 7 days showed that PTH increased cyclin D1 expression, the total number of cells in the periosteum, and width of the periosteal regenerative tissue. Gene expression showed that aging delayed differentiation of both bone and cartilage tissues during fracture healing. PTH resulted in sustained Col10a1 expression consistent with delayed chondrocyte maturation, but otherwise minimally altered cartilage gene expression. In contrast, PTH 1-34 stimulated expression of Runx2 and Osterix, but resulted in reduced Osteocalcin. β-catenin staining was present in mesenchymal chondroprogenitors and chondrocytes in early fracture healing, but was most intense in osteoblastic cells at later times. PTH increased active β-catenin staining in the osteoblast populations of both young and aged mice, but had a lesser effect in cartilage. Altogether the findings show that reduced fracture healing in aging involves decreased proliferation and differentiation of stem cells lining

PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis.

PubMed

Orth, P; Cucchiarini, M; Wagenpfeil, S; Menger, M D; Madry, H

2014-06-01

To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral density of the subarticular spongiosa (P = 0.001). Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Early detection of disease program: Evaluation of the cellular immune response

NASA Technical Reports Server (NTRS)

Criswell, B. S.; Knight, V.; Martin, R. R.; Kasel, J. A.

1974-01-01

The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.

Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

PubMed

Scott, Naomi M; Ng, Royce L X; McGonigle, Terence A; Gorman, Shelley; Hart, Prue H

2015-11-01

During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

Early bone growth on the surface of titanium implants in rat femur is enhanced by an amorphous diamond coating.

PubMed

Jaatinen, Jarkko J P; Korhonen, Rami K; Pelttari, Alpo; Helminen, Heikki J; Korhonen, Hannu; Lappalainen, Reijo; Kröger, Heikki

2011-08-01

Amorphous diamond (AD) is a durable and compatible biomaterial for joint prostheses. Knowledge regarding bone growth on AD-coated implants and their early-stage osseointegration is poor. We investigated bone growth on AD-coated cementless intramedullary implants implanted in rats. Titanium was chosen as a reference due to its well-known performance. We placed AD-coated and non-coated titanium implants (R(a) ≈ 0.2 μm) into the femoral bone marrow of 25 rats. The animals were divided in 2 groups according to implant coating and they were killed after 4 or 12 weeks. The osseointegration of the implants was examined from hard tissue specimens by measuring the new bone formation on their surface. 4 weeks after the operation, the thickness of new bone in the AD-coated group was greater than that in the non-coated group (15.3 (SD 7.1) μm vs. 7.6 (SD 6.0) μm). 12 weeks after the operation, the thickness of new bone was similar in the non-coated group and in the AD-coated group. We conclude that AD coating of femoral implants can enhance bone ongrowth in rats in the acute, early stage after the operation and might be an improvement over earlier coatings.

The molecular response of bone to growth hormone during skeletal unloading: regional differences

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Harris, J.; Halloran, B. P.; Currier, P. A.; Tanner, S.; Morey-Holton, E.

1995-01-01

Hind limb elevation of the growing rat provides a good model for the skeletal changes that occur during space flight. In this model the bones of the forelimbs (normally loaded) are used as an internal control for the changes that occur in the unloaded bones of the hind limbs. Previous studies have shown that skeletal unloading of the hind limbs results in a transient reduction of bone formation in the tibia and femur, with no change in the humerus. This fall in bone formation is accompanied by a fall in serum osteocalcin (bone Gla protein, BGP) and bone BGP messenger RNA (mRNA) levels, but a rise in bone insulin-like growth factor-I (IGF-I) protein and mRNA levels and resistance to the skeletal growth-promoting actions of IGF-I. To determine whether skeletal unloading also induced resistance to GH, we evaluated the response of the femur and humerus of sham and hypophysectomized rats, control and hind limb elevated, to GH (two doses), measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and alpha 1(1)-procollagen (coll). Hypophysectomy (HPX) decreased the mRNA levels of IGF-I, BGP, and coll in the femur, but was either less effective or had the opposite effect in the humerus. GH at the higher dose (500 micrograms/day) restored these mRNA levels to or above the sham control values in the femur, but generally had little or no effect on the humerus. RAP mRNA levels were increased by HPX, especially in the femur. The lower dose of GH (50 micrograms/day) inhibited this rise in RAP, whereas the higher dose raised the mRNA levels and resulted in the appearance of additional transcripts not seen in controls. As for the other mRNAs, RAP mRNA in the humerus was less affected by HPX or GH than that in the femur. Hind limb elevation led to an increase in IGF-I, coll, and RAP mRNAs and a reduction in BGP mRNA in the femur and either had no effect or potentiated the response of these mRNAs to GH. We conclude that GH stimulates a number of markers of bone

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

Anabolic Responses of an Adult Cancellous Bone Site to Prostaglandin E2 in the Rat

NASA Technical Reports Server (NTRS)

Ito, Hiroshi; Ke, Hua Zhu; Jee, Webster S. S.; Sakou, Takashi

1993-01-01

The objects of this study were to determine: (1) the response of a non-growing cancellous bone site to daily prostaglandin E2 (PGE2) administration; and (2) the differences in the effects of daily PGE2, administration in growing (proximal tibial metaphysis, PTM) and non-growing cancellous bone sites (distal tibial metaphysis, DTM). Seven-month-old male Sprague-Dawley rats were given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg per day for 60, 120 and 180 days. The static and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified distal tibial metaphyses (DTM). No age-related changes were found in static and dynamic histomorphometry of DTM cancellous bone between 7 and 13 months of age. The DTM of 7-month-old (basal controls) rats consisted of a 24.5 +/- 7.61%-metaphyseal cancellous bone mass, and a thick trabeculae (92 +/- 12 micro-m). It also had a very low tissue-base bone formation rate (3.0 +/- 7.31%/year). Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased trabecular bone mass and improved architecture (increased trabecular bone area, width and number, and decreased trabecular separation); (2) increased trabecular interconnections: (3) increased bone formation parameters; and (4) decreased eroded perimeter. A new steady state with more cancellous bone mass and higher bone turnover was observed from day 60 onward, The elevated bone mass induced by the first 60 days of PGE2 treatment was maintained by another 60 and 120 days with continuous daily PGE2 treatment. When these findings were compared to those previously reported for the PTM, we found that the DTM was much more responsive to PGE2 treatment than the PTM. Percent trabecular bone area and tissue based bone formation rate increased significantly more in DTM as compared to PTM after the 60 days of 6 mg PGE2 treatment. These observations indicate that a non

Synergy of bone marrow transplantation and curcumin ensue protective effects at early onset of diabetes in mice.

PubMed

Arivazhagan, Arivarasan; Krishna, Soni; Yadav, Shivangi; Shah, Harshit Rajesh; Kumar, Pravir; Ambasta, Rashmi Kumar

2015-07-01

The aim of this study was to investigate the early onset effects of diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice. In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and Caspase-3 antibodies. The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells. This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

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

Bone-specific gene expression patterns and whole bone tissue of female mice are programmed by early life exposure to soy isoflavones and folic acid.

PubMed

Kaludjerovic, Jovana; Ward, Wendy E

2015-10-01

Female mice exposed to soy isoflavones (ISO) during early postnatal life have improved bone outcomes at adulthood. Since long-lasting effects may be mediated by DNA methylation, we hypothesized that providing supplemental folic acid (FA), a methyl donor, during early life, would enhance the positive effect of ISO to bone health. Bone-specific gene expression patterns were studied to understand potential mechanisms. CD-1 dams (n=36) were randomized to adequate or supplemental levels of FA (2 or 8 mg/kg diet) during pregnancy and lactation, and offspring received corn oil or ISO (7 mg/kg body weight/d) from postnatal day 1 to 10. From weaning, pups were fed an adequate FA diet and were studied to 4 months of age. Female offspring exposed to supplemental FA+ISO had higher bone mineral density (BMD), trabecular connectivity and peak load at the lumbar spine compared to females exposed to adequate FA. Female offspring exposed to adequate FA+ISO or supplemental FA had higher (P<.05) BMD and greater resistance to fracture at the lumbar spine and the femur; higher trabecular connectivity at the lumbar spine; and lower expression of DNA methyltransferase 3a (Dnmt3a) and neuropeptide Y (NPY) in the femur compared to mice exposed to adequate FA. In addition, only mice exposed to adequate FA+ISO had microstructural improvements at the femur neck and higher serum osteoprotegrin (OPG) and insulin growth factor-I (IGF-I). In summary, exposure to supplemental FA did not enhance the positive effect of ISO in bone. However, exposure to adequate FA+ISO or supplemental FA improved bone at least in part by suppressing Dnmt3a and NPY. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy.

PubMed

de Bakker, Chantal M J; Altman, Allison R; Tseng, Wei-Ju; Tribble, Mary Beth; Li, Connie; Chandra, Abhishek; Qin, Ling; Liu, X Sherry

2015-04-01

Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r=0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed. Copyright © 2014 Elsevier Inc. All rights reserved.

Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone.

PubMed

Krivic, A; Majerovic, M; Jelic, I; Seiwerth, S; Sikiric, P

2008-05-01

In the presented study we compared the effect of stable peptide BPC 157 and methylprednisolone on early functional recovery after Achilles tendon to bone transection in a rat model before collagen healing started. Surgical transection of the right Achilles tendon to bone area was performed in seventy two Wistar Albino male rats. Healing Achilles tendon edges were harvested at days 1-4 following the transection. Using Achilles functional index (AFI), myeloperoxidase activity, histological inflammatory cell influx and vascular index early functional recovery was evaluated. Agents (stable peptide BPC 157 10 microg methylprednisolone 5 mg, normal saline 5 ml) were given alone (/kg b.w., intraperitoneally, once daily, first 30 min after surgery, last 24 h before analysis). Control group received normal saline 5 ml/kg. BPC 157 improved functional recovery (AFI values increased at all time points, p <0.05) by anti-inflammatory (decreased myeloperoxidase (MPO) activity and histological inflammatory cell influx, p <0.05) and increased new blood vessel formation (increased vascular index, p <0.05). Methyprednisolone decreased MPO activity and histological inflammatory cell influx, (p <0.05) but also decreased new blood vessel formation and did not affect early functional recovery. Stable peptide BPC 157 with combined anti-inflammatory action and induction of early new blood vessel formation facilitates early functional recovery in Achilles tendon to bone healing.

Adiposity is associated with early reduction in bone mass in pediatric inflammatory bowel disease.

PubMed

Setty-Shah, Nithya; Maranda, Louise; Nwosu, Benjamin Udoka

2016-01-01

The effect of adiposity on bone mass in the early phases of inflammatory bowel disease (IBD) in children and adolescents is unclear. The aim of this study was to determine the role of adiposity on bone mass in the first 3 y of diagnosis of IBD. The expected result is that increased adiposity will be associated with increased bone mass in both the controls and IBD subjects. Height-adjusted bone mineral density (BMD) z-scores of 25 subjects, age 13.97 ± 2.70 y, diagnosed with IBD for <4 y were compared to 24 controls, age 13.65 ± 2.60 y. Overweight was defined as BMI of ≥85th but <95th percentile, and obesity as BMI ≥95th percentile. Severity of IBD was determined by the Pediatric Crohn's Disease Activity Index and Lichtiger Colitis Activity Index. Before stratification by BMI criterion, height-adjusted BMD z-scores were not significantly lower in IBD subjects versus controls for both the femoral neck (-0.8 ± 1.1 versus -0.06 ± 1.1, P = 0.070) and lumbar vertebrae (-0.4 ± 1.2 versus 0.2 ± 1.2, P = 0.086). Following stratification, height-adjusted BMD z-scores were significantly lower in the overweight/obese IBD subjects versus overweight/obese controls for femoral neck (-0.9 ± 0.9 versus 0.3 ± 1.3, P = 0.032); and non-significantly lower for the lumbar spine z-score (-0.4 ± 1.6 versus 0.5 ± 1.3, P = 0.197). BMD z-score had no relationship with the duration of disease, steroid therapy, and the severity of disease. Adiposity was associated with reduced bone mass in the early phases of IBD, but with increased bone mass in the controls. Copyright © 2016 Elsevier Inc. All rights reserved.

Short Stature, Accelerated Bone Maturation, and Early Growth Cessation Due to Heterozygous Aggrecan Mutations

PubMed Central

Nilsson, Ola; Guo, Michael H.; Dunbar, Nancy; Popovic, Jadranka; Flynn, Daniel; Jacobsen, Christina; Lui, Julian C.; Hirschhorn, Joel N.; Baron, Jeffrey

2014-01-01

Context: Many children with idiopathic short stature have a delayed bone age. Idiopathic short stature with advanced bone age is far less common. Objective: The aim was to identify underlying genetic causes of short stature with advanced bone age. Setting and Design: We used whole-exome sequencing to study three families with autosomal-dominant short stature, advanced bone age, and premature growth cessation. Results: Affected individuals presented with short stature [adult heights −2.3 to −4.2 standard deviation scores (SDS)] with histories of early growth cessation or childhood short stature (height SDS −1.9 to −3.5 SDS), advancement of bone age, and normal endocrine evaluations. Whole-exome sequencing identified novel heterozygous variants in ACAN, which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The variants were present in all affected, but in no unaffected, family members. In Family 1, a novel frameshift mutation in exon 3 (c.272delA) was identified, which is predicted to cause early truncation of the aggrecan protein. In Family 2, a base-pair substitution was found in a highly conserved location within a splice donor site (c.2026+1G>A), which is also likely to alter the amino acid sequence of a large portion of the protein. In Family 3, a missense variant (c.7064T>C) in exon 14 affects a highly conserved residue (L2355P) and is strongly predicted to perturb protein function. Conclusions: Our study demonstrates that heterozygous mutations in ACAN can cause a mild skeletal dysplasia, which presents clinically as short stature with advanced bone age. The accelerating effect on skeletal maturation has not previously been noted in the few prior reports of human ACAN mutations. Our findings thus expand the spectrum of ACAN defects and provide a new molecular genetic etiology for the unusual child who presents with short stature and accelerated skeletal maturation. PMID:24762113

Bone Metabolism on ISS Missions

NASA Technical Reports Server (NTRS)

Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

2014-01-01

Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those

Maturity- and sex-related changes in tibial bone geometry, strength and bone-muscle strength indices during growth: a 20-month pQCT study.

PubMed

Macdonald, Heather M; Kontulainen, Saija A; Mackelvie-O'Brien, Kerry J; Petit, Moira A; Janssen, Patricia; Khan, Karim M; McKay, Heather A

2005-06-01

During growth, bone strength is conferred through subtle adaptations in bone mass and geometry in response to muscle forces. Few studies have examined the changes in bone geometry, strength and the bone-muscle strength relationship across maturity in boys and girls. Our aims were to describe (i) 20-month changes in bone geometry and strength at the tibial midshaft across three maturity groups of boys and girls, (ii) differences in these adaptations between sexes at the same approximate level of maturity and (iii) the bone-muscle strength relationship across maturity groups of boys and girls and between sexes. We used peripheral quantitative computed tomography (pQCT, Stratec XCT-2000) to measure change in total bone cross-sectional area (ToA, mm(2)), cortical area (CoA, mm(2)), average cortical thickness (C.Th., mm), section modulus (mm(3)) and muscle cross-sectional area (mm(2)) at the tibial midshaft (50% site) in 128 EARLY-, PERI- and POST-pubertal girls (n = 69, 11.9 +/- 0.6 years) and boys (n = 59, 12.0 +/- 0.6 years) across 20 months. We also calculated two bone-muscle strength indices (BMSI) for compression (CoA/MCSA) and bending [strength index/MCSA; where strength index = Z / (tibial length / 2)]. EARLY boys and girls had smaller ToA at baseline than same sex PERI or POST participants. There were no sex differences in ToA or CoA at baseline; however, boys increased both parameters significantly more than girls in every maturity group (8.5-11.1%, P < 0.01). These changes in bone geometry conferred greater gains in bone strength for boys compared with girls in each maturity group (13.8-15.6%, P < 0.01). Baseline BMSIs did not differ between sexes for EARLY and PERI groups, whereas BMSIs were significantly higher for POST boys compared with POST girls (P < 0.05). BMSIs decreased for EARLY and PERI girls (-7.4-(-1.1%)) whereas the ratios remained stable for EARLY and PERI boys (-0.6-2.5%). This sex difference in BMSI change was due to a relatively greater

Miscellaneous indications in bone scintigraphy: metabolic bone diseases and malignant bone tumors.

PubMed

Cook, Gary J R; Gnanasegaran, Gopinath; Chua, Sue

2010-01-01

The diphosphonate bone scan is ideally suited to assess many global, focal or multifocal metabolic bone disorders and there remains a role for conventional bone scintigraphy in metabolic bone disorders at diagnosis, investigation of complications, and treatment response assessment. In contrast, the role of bone scintigraphy in the evaluation of primary malignant bone tumors has reduced with the improvement of morphologic imaging, such as computed tomography and magnetic resonance imaging. However, an increasing role for (18)F-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography is emerging as a functional assessment at diagnosis, staging, and neoadjuvant treatment response assessment.

Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity.

PubMed

Zerofsky, Melissa; Ryder, Mark; Bhatia, Suruchi; Stephensen, Charles B; King, Janet; Fung, Ellen B

2016-10-01

Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children's Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency. © 2015 John Wiley & Sons Ltd.

Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity

PubMed Central

Zerofsky, Melissa; Ryder, Mark; Bhatia, Suruchi; Stephensen, Charles B.; King, Janet; Fung, Ellen B.

2015-01-01

Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children’s Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency. PMID:25850574

Dried Plum Protects From Radiation-Induced Bone Loss by Attenuating Pro-Osteoclastic and Oxidative Stress Responses

NASA Technical Reports Server (NTRS)

Globus, Ruth

2015-01-01

Future space explorations beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure plays a major role in progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Our long-term goals are to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures. We had previously reported that exposure to low or high-LET radiation correlates with an acute increase in the expression of pro-osteoclastic and oxidative stress genes in bone during the early response to radiation followed by pathological changes in skeletal structure. We then conducted systematic screening for potential countermeasures against bone loss where we tested the ability of various antioxidants to mitigate the radiation-induced increase in expression of these markers. For the screen, 16-week old C57Bl6J mice were treated with a dietary antioxidant cocktail, injectable DHLA or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs radiation and one day later, marrow cells were collected and the relevant genes analyzed for expression levels. Among the candidate countermeasures tested, DP was most effective in reducing the expression of genes associated with bone loss. Furthermore, analysis of skeletal structure by microcomputed tomography (microCT) revealed that DP also prevents the radiation-induced deterioration in skeletal microarchitecture as indicated by parameters such as percent bone volume (BVTV), trabecular spacing and trabecular number. We also found that DP has similar protective effects on skeletal structure in a follow-up study using 1 Gy of

IGF-1 Receptor Expression on Circulating Osteoblast Progenitor Cells Predicts Tissue-Based Bone Formation Rate and Response to Teriparatide in Premenopausal Women With Idiopathic Osteoporosis.

PubMed

Cohen, Adi; Kousteni, Stavroula; Bisikirska, Brygida; Shah, Jayesh G; Manavalan, J Sanil; Recker, Robert R; Lappe, Joan; Dempster, David W; Zhou, Hua; McMahon, Donald J; Bucovsky, Mariana; Kamanda-Kosseh, Mafo; Stubby, Julie; Shane, Elizabeth

2017-06-01

We have previously reported that premenopausal women with idiopathic osteoporosis (IOP) have profound microarchitectural deficiencies and heterogeneous bone remodeling. Those with the lowest bone formation rate have higher baseline serum insulin-like growth factor-1 (IGF-1) levels and less robust response to teriparatide. Because IGF-1 stimulates bone formation and is critical for teriparatide action on osteoblasts, these findings suggest a state of IGF-1 resistance in some IOP women. To further investigate the hypothesis that osteoblast and IGF-1-related mechanisms mediate differential responsiveness to teriparatide in IOP, we studied circulating osteoblast progenitor (COP) cells and their IGF-1 receptor (IGF-1R) expression. In premenopausal women with IOP, peripheral blood mononuclear cells (PBMCs) were obtained at baseline (n = 25) and over 24 months of teriparatide treatment (n = 11). Flow cytometry was used to identify and quantify COPs (non-hematopoetic lineage cells expressing osteocalcin and RUNX2) and to quantify IGF-1R expression levels. At baseline, both the percent of PBMCs that were COPs (%COP) and COP cell-surface IGF-1R expression correlated directly with several histomorphometric indices of bone formation in tetracycline-labeled transiliac biopsies. In treated subjects, both %COP and IGF-1R expression increased promptly after teriparatide, returning toward baseline by 18 months. Although neither baseline %COP nor increase in %COP after 3 months predicted the bone mineral density (BMD) response to teriparatide, the percent increase in IGF-1R expression on COPs at 3 months correlated directly with the BMD response to teriparatide. Additionally, lower IGF-1R expression after teriparatide was associated with higher body fat, suggesting links between teriparatide resistance, body composition, and the GH/IGF-1 axis. In conclusion, these assays may be useful to characterize bone remodeling noninvasively and may serve to predict early response to

Increased vertebral bone mineral in response to reduced exercise in amenorrheic runners.

PubMed

Lindberg, J S; Powell, M R; Hunt, M M; Ducey, D E; Wade, C E

1987-01-01

Seven female runners found to have exercise-induced amenorrhea and decreased bone mineral were reevaluated after 15 months. During the 15-month period, four runners took supplemental calcium and reduced their weekly running distance by 43%, resulting in an average 5% increase in body weight, increased estradiol levels and eumenorrhea. Bone mineral content increased from 1.003+/-0.097 to 1.070+/-0.089 grams per cm.(2) Three runners continued to have amenorrhea, with no change in running distance or body weight. Estradiol levels remained abnormally low and there was no significant change in the bone mineral content, although all three took supplemental calcium. We found that early osteopenia associated with exercise-induced menstrual dysfunction improved when runners reduced their running distance, gained weight and became eumenorrheic.

Increased Vertebral Bone Mineral in Response to Reduced Exercise in Amenorrheic Runners

PubMed Central

Lindberg, Jill S.; Hunt, Marjorie M.; Wade, Charles E.; Powell, Malcolm R.; Ducey, Diane E.

1987-01-01

Seven female runners found to have exercise-induced amenorrhea and decreased bone mineral were reevaluated after 15 months. During the 15-month period, four runners took supplemental calcium and reduced their weekly running distance by 43%, resulting in an average 5% increase in body weight, increased estradiol levels and eumenorrhea. Bone mineral content increased from 1.003±0.097 to 1.070±0.089 grams per cm.2 Three runners continued to have amenorrhea, with no change in running distance or body weight. Estradiol levels remained abnormally low and there was no significant change in the bone mineral content, although all three took supplemental calcium. We found that early osteopenia associated with exercise-induced menstrual dysfunction improved when runners reduced their running distance, gained weight and became eumenorrheic. ImagesFigure 1. PMID:3825107

The use of a magnesium-based bone adhesive for flexor tendon-to-bone healing

PubMed Central

Stavros, Thomopoulos; Emmanouil, Zampiakis; Rosalina, Das; Hyun-Min, Kim; J., Silva, Matthew; Necat, Havlioglu; H., Gelberman, Richard

2010-01-01

Purpose Our previous studies in a canine animal model demonstrated that the flexor tendon-to-bone insertion site has a poor capacity to heal. Magnesium based adhesives have the potential to improve tendon-to-bone healing. Therefore, we hypothesized that magnesium based bone adhesive (MBA) will improve the tendon-to-bone biomechanical properties initially and in the early period after repair. Methods Flexor digitorum profundus tendons were injured and repaired into bone tunnels in the distal phalanges of dogs. The bone tunnels were either filled with MBA prior to completing the repair or left empty (CTL). Histologic appearance, tensile properties, range of motion, and bone density were examined at time zero and 21 days after the repair. Results There was no histologic evidence of acute inflammation. There appeared to be more mast cells in the MBA group than in the CTL group. Chronic inflammatory infiltrate and fibrosis was slightly higher in the MBA group compared to the CTL group. Tensile properties at time zero were significantly higher in the MBA group compared to the CTL group. However, tensile properties were significantly lower in the MBA group compared to the CTL group at 21 days. Range of motion and bone density were significantly lower in the MBA and CTL groups compared to normal (i.e., uninjured) at 21 days; no differences were seen when comparing MBA to CTL. Conclusions We found that the initial biomechanical properties of flexor tendon-to-bone repairs can be improved with MBA. However, MBA use in vivo led to a decrease in the biomechanical properties of the repair. There was no effect of MBA on bone density or range of motion in the early period after repair. Our histologic analysis suggests that the poor healing in the MBA group may have been due to an allergic response or to increased chronic inflammation due to the foreign material. PMID:19643291

DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis.

PubMed

Clines, Katrina L; Clines, Gregory A

2018-05-14

Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis. LnCaP, C4-2B, LuCaP23.1, T47D, ZR-75-1, MCF-7, ARCaP and ARCaP M cancer cells that generate osteoblastic, mixed or no bone lesions had the lowest DKK1 expression. The cell lines with negligible expression, LnCaP, C4-2B and T47D, exhibited methylation of the DKK1 promoter. Canonical Wnt signaling activity was then determined and found in all cell lines tested, even in the MDA-MB-231 and PC3 cell lines despite sizeable amounts of DKK1 protein expression expected to block canonical Wnt signaling. A mechanism of DKK1 resistance in the osteolytic cell lines was investigated and determined to be at least partially due to down-regulation of the DKK1 receptors Kremen1 and Kremen2 in the MDA-MB-231 and PC3 cell lines. Combined DKK1 and Kremen expression in cancer cells may serve as predictive markers of the osteoblastic response of breast and prostate cancer bone metastasis. Published by Elsevier Inc.

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Iwaniec, U.; Wu, H.

2011-01-01

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal

Calcium phosphate compatible bone cement: Characterization, bonding properties and tissue response

NASA Astrophysics Data System (ADS)

Roemhildt, Maria Lynn

A novel, inorganic, bone cement, containing calcium phosphate, developed for implant fixation was evaluated. Setting properties were determined over a range of temperatures. The flow of the cement was greatly increased by application of vibration. Changes in the cement during hydration and aging were evaluated. Compressive strength of the cement over time was studied under simulated physiological conditions from 1 hour to 1 year after setting. After 1 day, this cement had equivalent compressive strength to commercially used PMMA cement. The strength was found to increase over 1 month and high strength was maintained up to 1 year. The shear strength of the cement-metal interface was studied in vitro using a pull-out test. Prepared specimens were stored under physiological conditions and tested at 4 hours, 24 hours, and 60 days. Comparable interfacial shear strength values were found at 4 hours, 24 hours and 60 days for the experimental cement and were not significantly different from values obtained for PMMA cement. In vivo tissue response was evaluated after cement implantation in the femoral medullary canal in canines. Tissue response and bonding at the cement-bone interface were evaluated at 2, 6, and 12 weeks. Cortical bone was found in direct contact with the OC-cement and was healthy. The strength of the cement-bone interface, measured using a push-out test, was significantly higher for the experimental cement than for commercial PMMA bone cement.

False-positive diagnosis of disease progression by magnetic resonance imaging for response assessment in prostate cancer with bone metastases: A case report and review of the pitfalls of images in the literature

PubMed Central

YU, YI-SHAN; LI, WAN-HU; LI, MING-HUAN; MENG, XUE; KONG, LI; YU, JIN-MING

2015-01-01

Bone metastases are common in prostate cancer. However, differentiating neoplastic from non-neoplastic alterations of bone on images is challenging. In the present report, a rare case of bone marrow reconversion on magnetic resonance imaging (MRI) assessment, which may lead to a false-positive diagnosis of disease progression of bone metastases in hormone-resistant prostate cancer, is presented. Furthermore, a review of the literature regarding the pitfalls of images for response assessment, including the ‘flare’ phenomenon on bone scintigraphy, computed tomography (CT), positron emission tomography/CT and marrow reconversion on MRI is also provided. These inaccuracies, which may lead to a premature termination of an efficacious treatment, should be carefully considered by the radiologists and oncologists involved in clinical trials. The case reported in the present study showed how to assess the early therapeutic response and select the appropriate treatment for the patient when these pitfalls are encountered on clinical images. PMID:26788174

Time course of disassociation of bone formation signals with bone mass and bone strength in sclerostin antibody treated ovariectomized rats.

PubMed

Ma, Yanfei L; Hamang, Matthew; Lucchesi, Jonathan; Bivi, Nicoletta; Zeng, Qianqiang; Adrian, Mary D; Raines, Sarah E; Li, Jiliang; Kuhstoss, Stuart A; Obungu, Victor; Bryant, Henry U; Krishnan, Venkatesh

2017-04-01

Sclerostin antibodies increase bone mass by stimulating bone formation. However, human and animal studies show that bone formation increases transiently and returns to pre-treatment level despite ongoing antibody treatment. To understand its mechanism of action, we studied the time course of bone formation, correlating the rate and extent of accrual of bone mass and strength after sclerostin antibody treatment. Ovariectomized (OVX) rats were treated with a sclerostin-antibody (Scle-ab) at 20mg/kg sc once weekly and sacrificed at baseline and 2, 3, 4, 6, and 8weeks post-treatment. In Scle-ab treated rats, serum PINP and OCN rapidly increased at week 1, peaked around week 3, and returned to OVX control levels by week 6. Transcript analyses from the distal femur revealed an early increase in bone formation followed by a sustained decrease in bone resorption genes. Lumbar vertebral (LV) osteoblast surface increased 88% by week 2, and bone formation rate (BFR/BS) increased 138% by week 4. Both parameters were below OVX control by week 8. Bone formation was primarily a result of modeling based formation. Endocortical and periosteal BFR/BS peaked around week 4 at 313% and 585% of OVX control, respectively. BFR/BS then declined but remained higher than OVX control on both surfaces through week 8. Histomorphometric analyses showed LV-BV/TV did not further increase after week 4, while BMD continued to increase at LV, mid femur (MF), and femoral neck (FN) through week 8. Biomechanical tests showed a similar improvement in bone strength through 8weeks in MF and FN, but bone strength plateaued between weeks 6 and 8 for LV. Our data suggest that bone formation with Scle-ab treatment is rapid and modeling formation dominated in OVX rats. Although transient, the bone formation response persists longer in cortical than trabecular bone. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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.

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study.

PubMed

Naylor, K E; Jacques, R M; Paggiosi, M; Gossiel, F; Peel, N F A; McCloskey, E V; Walsh, J S; Eastell, R

2016-01-01

We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication. Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers. Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomised to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for each marker was derived within the study population, whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years). Over 70 % of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63 % (difference 13 %, 95 % CI 0 to 27.1, P = 0.049) and good compliance -67 % (difference 15.9 %, 95 % CI 6.3 to 25.5, P = 0.001). Responders had a greater increase in spine bone density compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI 1.6 to 6.3, P = 0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate. Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD, and we suggest that biochemical assessment of response is a useful tool for the management of women with

Micromotion-induced strain fields influence early stages of repair at bone-implant interfaces

PubMed Central

Wazen, Rima M.; Currey, Jennifer A.; Guo, Hongqiang; Brunski, John B.; Helms, Jill A.; Nanci, Antonio

2013-01-01

Implant loading can create micromotion at the bone-implant interface. The interfacial strain associated with implant micromotion could contribute to regulating the tissue healing response. Excessive micromotion can lead to fibrous encapsulation and implant loosening. Our objective was to characterize the influence of interfacial strain on bone regeneration around implants in mouse tibiae. A micromotion system was used to create strain under conditions of (1) no initial contact between implant and bone, and (2) a direct bone-implant contact. Pin- and screw-shaped implants were subjected to displacements of 150 μm or 300 μm, 60 cycles/day, for 7 days. Pin-shaped implants placed in 5 animals were subjected to 3 sessions of 150 μm displacement per day, with 60 cycles per session. Control implants in both types of interfaces were stabilized throughout the healing period. Experimental strain analyses, microtomography, image-based displacement mapping, and finite element simulations were used to characterize interfacial strain fields. Calcified tissue sections were prepared and stained with Goldner to evaluate tissue reaction in higher and lower strain regions. In stable implants, bone formation occurred consistently around the implants. In implants subjected to micromotion, bone regeneration was disrupted in areas of high strain concentrations (e.g. > 30%), whereas lower strain values were permissive of bone formation. Increasing implant displacement or number of cycles per day also changed the strain distribution and disturbed bone healing. These results indicate that not only implant micromotion but also the associated interfacial strain field contributes to regulating the interfacial mechanobiology at healing bone-implant interfaces. PMID:23337705

Bone Metabolism after Bariatric Surgery

PubMed Central

Yu, Elaine W.

2014-01-01

Bariatric surgery is a popular and effective treatment for severe obesity, but may have negative effects on the skeleton. This review summarizes changes in bone density and bone metabolism from animal and clinical studies of bariatric surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts from obesity and weight loss are also considered. Despite challenges in bone density imaging, the preponderance of evidence suggests that bariatric surgery procedures have negative skeletal effects that persist beyond the first year of surgery, and that these effects vary by surgical type. The long-term clinical implications and current clinical recommendations are presented. Further study is required to determine mechanisms of bone loss after bariatric surgery. Although early studies focused on calcium/vitamin D metabolism and mechanical unloading of the skeleton, it seems likely that surgically-induced changes in the hormonal and metabolic profile may be responsible for the skeletal phenotypes observed after bariatric surgery. PMID:24677277

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

Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

PubMed

Hinton, Pamela S

2016-08-01

Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

Effect of oxygen plasma etching on pore size-controlled 3D polycaprolactone scaffolds for enhancing the early new bone formation in rabbit calvaria.

PubMed

Kook, Min-Suk; Roh, Hee-Sang; Kim, Byung-Hoon

2018-05-02

This study was to investigate the effects of O 2 plasma-etching of the 3D polycaprolactone (PCL) scaffold surface on preosteoblast cell proliferation and differentiation, and early new bone formation. The PCL scaffolds were fabricated by 3D printing technique. After O 2 plasma treatment, surface characterizations were examined by scanning electron microscopy, atomic force microscopy, and contact angle. MTT assay was used to determine cell proliferation. To investigate the early new bone formation, rabbits were sacrificed at 2 weeks for histological analyses. As the O 2 plasma etching time is increased, roughness and hydrophilicity of the PCL scaffold surface increased. The cell proliferation and differentiation on plasma-etched samples was significantly increased than on untreated samples. At 2 weeks, early new bone formation in O 2 plasma-etched PCL scaffolds was the higher than that of untreated scaffolds. The O 2 plasma-etched PCL scaffolds showed increased preosteoblast differentiation as well as increased new bone formation.

Exercise does not enhance aged bone's impaired response to artificial loading in C57Bl/6 mice.

PubMed

Meakin, Lee B; Udeh, Chinedu; Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2015-12-01

Bones adapt their structure to their loading environment and so ensure that they become, and are maintained, sufficiently strong to withstand the loads to which they are habituated. The effectiveness of this process declines with age and bones become fragile fracturing with less force. This effect in humans also occurs in mice which experience age-related bone loss and reduced adaptation to loading. Exercise engenders many systemic and local muscular physiological responses as well as engendering local bone strain. To investigate whether these physiological responses influence bones' adaptive responses to mechanical strain we examined whether a period of treadmill exercise influenced the adaptive response to an associated period of artificial loading in young adult (17-week) and old (19-month) mice. After treadmill acclimatization, mice were exercised for 30 min three times per week for two weeks. Three hours after each exercise period, right tibiae were subjected to 40 cycles of non-invasive axial loading engendering peak strain of 2250 με. In both young and aged mice exercise increased cross-sectional muscle area and serum sclerostin concentration. In young mice it also increased serum IGF1. Exercise did not affect bone's adaptation to loading in any measured parameter in young or aged bone. These data demonstrate that a level of exercise sufficient to cause systemic changes in serum, and adaptive changes in local musculature, has no effect on bone's response to loading 3h later. This study provides no support for the beneficial effects of exercise on bone in the elderly being mediated by systemic or local muscle-derived effects rather than local adaptation to altered mechanical strain. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Exaggerated inflammatory response after use of recombinant bone morphogenetic protein in recurrent unicameral bone cysts.

PubMed

MacDonald, Kevin M; Swanstrom, Morgan M; McCarthy, James J; Nemeth, Blaise A; Guliani, Teresa A; Noonan, Kenneth J

2010-03-01

Recurrent unicameral bone cysts (UBCs) can result in significant morbidity during a child's physical and emotional development. Multiple treatment options are available and a review of the literature fails to clearly define the optimal treatment for UBCs. Recombinant bone morphogenetic protein (BMP) has been used with success in other disorders of poor bone formation. This manuscript is the first to report on the use of recombinant BMP in the treatment of UBCs. Three patients with recurrent UBCs underwent revision surgery with recombinant BMP. Radiographic and medical review was performed and is reported here. In these patients, the use of BMP failed to fully resolve their UBC; 2 patients had complete recurrence that required further surgery. In addition to poor radiographic results, all patients developed exaggerated inflammatory responses in the acute postoperative period. Each child developed clinically significant limb swelling and pain that mimicked infection. On the basis of our poor radiographic results and a paradoxical clinical result, we no longer recommend the use of recombinant BMP in the manner reported here for the treatment of recurrent UBCs. Level IV, case series.

Comparison of dental implant stabilities by impact response and resonance frequencies using artificial bone.

PubMed

Kim, Dae-Seung; Lee, Woo-Jin; Choi, Soon-Chul; Lee, Sam-Sun; Heo, Min-Suk; Huh, Kyung-Hoe; Kim, Tae-Il; Yi, Won-Jin

2014-06-01

We compared implant stability as determined by the peak frequency from the impact response with the implant stability quotient (ISQ) by resonance frequency analysis (RFA) in various artificial bone conditions. The clinical bone conditions were simulated using an artificial bone material with different cortical thicknesses and trabecular densities. The artificial bone material was solid, rigid polyurethane. The polyurethane foam of 0.8g/cm(3) density was used for the cortical bone layer, and that of 0.08, 0.16, 0.24, 0.32, and 0.48g/cm(3) densities for the trabecular bone layer. The cortical bone material of 4 different thicknesses (1.4, 1.6, 1.8, and 2.0mm) was attached to the trabecular bone with varying density. Two types of dental implants (10 and 13mm lengths of 4.0mm diameter) were placed into the artificial bone blocks. An inductive sensor was used to measure the vibration caused by tapping the adapter-implant assembly. The peak frequency of the power spectrum of the impact response was used as the criterion for implant stability. The ISQ value was also measured for the same conditions. The stability, as measured by peak frequency (SPF) and ISQ value, increased as the trabecular density and the cortical density increased in linear regression analysis. The SPF and ISQ values were highly correlated with each other when the trabecular bone density and cortical bone thickness changed (Pearson correlation=0.90, p<0.01). The linear regression of the SPF with the cortical bone thickness showed higher goodness of fit (R(2) measure) than the ISQ value with the cortical bone thickness. The SPF could differentiate implantation conditions as many as the ISQ value when the trabecular bone density and the cortical density changed. However, the ISQ value was not consistent with the general stability tendency in some conditions. The SPF showed better consistency and differentiability with implant stability than the ISQ value by resonance frequency analysis in the various

A rational use of glucocorticoids in patients with early arthritis has a minimal impact on bone mass

PubMed Central

2010-01-01

Introduction Glucocorticoid (GC)-induced osteoporosis is a frequent complication in patients with rheumatoid arthritis. However, little information exists about the consequences of GC use in patients with early arthritis. Here we describe the variables underlying the use of GC in early arthritis, as well as its effect on bone-mineral density. Methods Data from 116 patients in our early arthritis register were analyzed (90 women; median age, 52.5 years, interquartile range (IQR, 38.5-66); 6-month median disease duration at entry (IQR, 4-9)). In this register, the clinical and treatment information was recorded systematically, including the cumulative GC dose. Lumbar spine, hip, and forearm bone-mineral density (BMD) measurements were performed at entry and after a 2-year follow-up. A multivariate analysis was performed to establish the variables associated with the use of GCs, as well as those associated with variations in BMD. Results Of the patients with early arthritis studied, 67% received GCs during the 2-year follow-up. GCs were more frequently prescribed to elderly patients, those with higher basal disease activity and disability, and patients with positive rheumatoid factor. When adjusted for these variables, GCs were less frequently prescribed to female patients. The use of GCs was associated with an increase of BMD in the ultradistal region of the forearm, although it induced a significant loss of BMD in the medial region of the forearm. No relevant effect of GC was noted on the BMD measured at other locations. Conclusions The frequent use of GCs as a "bridge therapy" in patients with early arthritis does not seem to be associated with relevant loss of bone mass. Moreover, cumulative GC administration might be associated with an increase of juxtaarticular BMD. PMID:20331862

Flexible intramedullary nailing for the treatment of unicameral bone cysts in long bones.

PubMed

Roposch, A; Saraph, V; Linhart, W E

2000-10-01

Unicameral bone cyst is characterized by its tenacity and risk of recurrence. Pathological fracture is common and is often the presenting symptom. The objective of the present study was to evaluate the results of flexible intramedullary nailing for the treatment of a unicameral bone cyst with or without a pathological fracture. Flexible intramedullary nailing for the treatment of a unicameral bone cyst was performed in thirty-two patients. Thirty of these patients presented with a pathological fracture; twenty-four were managed immediately with intramedullary nailing, and the other six had been managed conservatively at other clinics before they were referred to our department. The remaining two cysts were detected incidentally. The cyst was located in the humerus in twenty-one patients, in the femur in nine, and in the radius in two. The mean age of the patients at the time of surgery was 9.8 years, and the mean duration of follow-up was 53.7 months. Radiographic evaluation was performed according to the criteria of Capanna et al., and the cyst was classified as completely healed, healed with residual radiolucency (osteolysis), recurred, or having no response. The healing period ranged from three to 105 months. Fourteen cysts healed completely, and sixteen healed with residual radiolucent areas visible on radiographs. There was recurrence of two cysts that had healed with residual radiolucency. All of the cysts in the present study responded to treatment. A change of nails was necessary in nine patients, as the nails had become too short after bone growth. No major complications were observed. Flexible intramedullary nailing provides early stability, which allows early mobilization and thus obviates the need for a plaster cast and decreases the prevalence of the most common complication: a pathological fracture. This method of treatment also allows for an early return to normal activity.

Histological features of bone marrow in paediatric patients during the asymptomatic phase of early-stage Black African sickle cell anaemia.

PubMed

Mauriello, Alessandro; Giacobbi, Erica; Saggini, Andrea; Isgrò, Antonella; Facchetti, Simone; Anemona, Lucia

2017-04-01

Bone marrow histological features of sickle cell anaemia (SCA) patients during early stages and in the asymptomatic phase of the disease appear an interesting area of study, representing early-stage consequences of SCA with a close relation to its pathophysiology. Unfortunately, this field of research has never been specifically addressed before. Bone marrow biopsies from 26 consecutive Black African SCA patients (M:F=1.6:1; age 2-17 years), free of clinical signs of chronic bone marrow damage, with no recent history of symptomatic vaso-occlusive episodes, and waiting for haematopoietic stem cell transplantation (HSCT), underwent morphological, immunohistochemical and electron microscopy evaluation. Additional comparison with three bone marrow specimens from post-HSCT SCA patients and 10 bone marrow specimens from AS healthy carriers was performed. Bone marrow of SCA patients was normocellular or slighly hypercellular in all cases. Erythroid hyperplasia was a common feature. Myeloid lineage was slightly decreased with normal to slightly diminished neutrophilic granulocytes; CD68 positive monocytic-macrophagic cells appeared slightly increased, with a predominant CD163 positive M2/M(Hb) phenotype. A positive correlation was found between haemoglobin values and number of bone marrow erythroid cells (R 2 =0.15, p=0.05). Intravascular and interstitial clusters of erythroid sickle cells were found in bone marrow of pre-HSCT homozygous SS SCA patients, as well as heterozygous AS healthy carriers, and the single post-HSCT patient matched to an AS health carrier donor. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Bone scan in metabolic bone diseases. Review.

PubMed

Abdelrazek, Saeid; Szumowski, Piotr; Rogowski, Franciszek; Kociura-Sawicka, Agnieszka; Mojsak, Małgorzata; Szorc, Małgorzata

2012-08-25

Metabolic bone disease encompasses a number of disorders that tend to present a generalized involvement of the whole skeleton. The disorders are mostly related to increased bone turnover and increased uptake of radiolabelled diphosphonate. Skeletal uptake of 99mTc-labelled diphosphonate depends primarily upon osteoblastic activity, and to a lesser extent, skeletal vascularity. A bone scan image therefore presents a functional display of total skeletal metabolism and has valuable role to play in the assessment of patients with metabolic bone disorders. However, the bone scan appearances in metabolic bone disease are often non-specific, and their recognition depends on increased tracer uptake throughout the whole skeleton. It is the presence of local lesions, as in metastatic disease, that makes a bone scan appearance obviously abnormal. In the early stages, there will be difficulty in evaluating the bone scans from many patients with metabolic bone disease. However, in the more severe cases scan appearances can be quite striking and virtually diagnostic.

The quantitative assessment of peri-implant bone responses using histomorphometry and micro-computed tomography.

PubMed

Schouten, Corinne; Meijer, Gert J; van den Beucken, Jeroen J J P; Spauwen, Paul H M; Jansen, John A

2009-09-01

In the present study, the effects of implant design and surface properties on peri-implant bone response were evaluated with both conventional histomorphometry and micro-computed tomography (micro-CT), using two geometrically different dental implants (Screw type, St; Push-in, Pi) either or not surface-modified (non-coated, CaP-coated, or CaP-coated+TGF-beta1). After 12 weeks of implantation in a goat femoral condyle model, peri-implant bone response was evaluated in three different zones (inner: 0-500 microm; middle: 500-1000 microm; and outer: 1000-1500 microm) around the implant. Results indicated superiority of conventional histomorphometry over micro-CT, as the latter is hampered by deficits in the discrimination at the implant/tissue interface. Beyond this interface, both analysis techniques can be regarded as complementary. Histomorphometrical analysis showed an overall higher bone volume around St compared to Pi implants, but no effects of surface modification were observed. St implants showed lowest bone volumes in the outer zone, whereas inner zones were lowest for Pi implants. These results implicate that for Pi implants bone formation started from two different directions (contact- and distance osteogenesis). For St implants it was concluded that undersized implantation technique and loosening of bone fragments compress the zones for contact and distant osteogenesis, thereby improving bone volume at the interface significantly.

The temporal response of bone to unloading

NASA Technical Reports Server (NTRS)

Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

1984-01-01

Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Understanding bone responses in B-mode ultrasound images and automatic bone surface extraction using a Bayesian probabilistic framework

NASA Astrophysics Data System (ADS)

Jain, Ameet K.; Taylor, Russell H.

2004-04-01

The registration of preoperative CT to intra-operative reality systems is a crucial step in Computer Assisted Orthopedic Surgery (CAOS). The intra-operative sensors include 3D digitizers, fiducials, X-rays and Ultrasound (US). Although US has many advantages over others, tracked US for Orthopedic Surgery has been researched by only a few authors. An important factor limiting the accuracy of tracked US to CT registration (1-3mm) has been the difficulty in determining the exact location of the bone surfaces in the US images (the response could range from 2-4mm). Thus it is crucial to localize the bone surface accurately from these images. Moreover conventional US imaging systems are known to have certain inherent inaccuracies, mainly due to the fact that the imaging model is assumed planar. This creates the need to develop a bone segmentation framework that can couple information from various post-processed spatially separated US images (of the bone) to enhance the localization of the bone surface. In this paper we discuss the various reasons that cause inherent uncertainties in the bone surface localization (in B-mode US images) and suggest methods to account for these. We also develop a method for automatic bone surface detection. To do so, we account objectively for the high-level understanding of the various bone surface features visible in typical US images. A combination of these features would finally decide the surface position. We use a Bayesian probabilistic framework, which strikes a fair balance between high level understanding from features in an image and the low level number crunching of standard image processing techniques. It also provides us with a mathematical approach that facilitates combining multiple images to augment the bone surface estimate.

Bone Resorption Increases as Early as the Second Day in Head- Down Bed Rest

NASA Astrophysics Data System (ADS)

Heer, M.; Kamps, N.; Mika, C.; Boese, A.; Gerzer, R.

Long-term bed rest and space mission studies have shown that immobilization as well as microgravity induce increased bone resorption while bone formation tends to decrease. In order to analyze the kinetics of short-term changes in bone turnover we studied in a randomized, strictly controlled crossover design the effects of 6 days 6° head-down tilt bed rest (HDT) in 8 male healthy subjects (mean body weight (BW): 70.1 +/- 1.88 kg; mean age: 25.5 +/- 1.04 years) in our metabolic ward. Two days before arriving in the metabolic ward the subjects started with a diet consisting of an energy content of 10 MJ/d, 2000 mg Calcium/d, 400 i.U. Vitamin D, 200 mEq Na+ and 50 ml water/kg BW/d. The diet was continued in the metabolic ward. The metabolic ward period (11days) was divided into 3 parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers, namely C-telopeptide (CTX) and N-telopeptide (NTX). On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers (bone Alkaline Phosphatase (bAP), Procollagen-I-Propeptide (P-I-CP). Both study phases were identical with respect to environmental conditions, study protocol and diet. Urinary calcium excretion was as early as the first day in immobilization increased (p<0.01). CTX- and NTX-excretion stayed unchanged the first 24 hours in HDT compared to the control. But, already on the 2nd day of immobilization both bone resorption markers significantly increased. NTX-excretion was increased by 28.7 +/- 14.0% (p<0.05), while CTX-excretion rose by 17.8 +/- 8.3% (p<0.01). Both, the CTX- excretion as well as the calcium excretion keep the significantly higher level during the HDT period, and even continued through the first day of recovery. However, NTX excretion, descended from day

[Early mobilization. Competencies, responsibilities, milestones].

PubMed

Nydahl, P; Dewes, M; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Klas, K; Mende, H; Rothaug, O; Schuchhardt, D

2016-03-01

Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

[Musculoskeletal rehabilitation and bone. Musculoskeletal response to human space flight and physical countermeasures].

PubMed

Ohshima, Hiroshi

2010-04-01

The assembly of the Japanese Experiment Module "Kibo" to international space station was completed in 2009 and Koichi Wakata became the first Japanese station astronaut who spent more than 4 months in the station. Bone and muscle losses are significant medical concerns for long duration human space flight. Effective countermeasure program for bone loss and muscle atrophy is necessary to avoid post flight bone fracture and joint sprain after landing. The musculoskeletal response to human space flight and current physical countermeasure program for station astronauts are described.

Transplantation of Hepatocyte Growth Factor-Modified Dental Pulp Stem Cells Prevents Bone Loss in the Early Phase of Ovariectomy-Induced Osteoporosis.

PubMed

Kong, Fanxuan; Shi, Xuefeng; Xiao, Fengjun; Yang, Yuefeng; Zhang, Xiaoyan; Wang, Li-Sheng; Wu, Chu-Tse; Wang, Hua

2018-02-01

Investigations based on mesenchymal stem cells (MSCs) for osteoporosis have attracted attention recently. MSCs can be derived from various tissues, such as bone marrow, adipose, umbilical cord, placenta, and dental pulp. Among these, dental pulp-derived MSCs (DPSCs) and hepatocyte growth factor (HGF)-modified DPSCs (DPSCs-HGF) highly express osteogenic-related genes and have stronger osteogenic differentiation capacities. DPSCs have more benefits in treating osteoporosis. The purpose of this study was to investigate the roles of HGF gene-modified DPSCs in bone regeneration using a mouse model of ovariectomy (OVX)-induced bone loss. The HGF and luciferase genes were transferred into human DPSCs using recombinant adenovirus. These transduced cells were assayed for distribution or bone regeneration assay by transplantation into an OVX-induced osteoporosis model. By using bioluminogenic imaging, it was determined that some DPSCs could survive for >1 month in vivo. The DPSCs were mainly distributed to the lung in the early stage and to the liver in the late stage of OVX osteoporosis after administration, but they were scarcely distributed to the bone. The homing efficiency of DPSCs is higher when administrated in the early stage of a mouse OVX model. Micro-computed tomography indicated that DPSCs-Null or DPSCs-HGF transplantation significantly reduces OVX-induced bone loss in the trabecular bone of the distal femur metaphysis, and DPSCs-HGF show a stronger capacity to reduce bone loss. The data suggest that systemic infusion of DPSCs-HGF is a potential therapeutic approach for OVX-induced bone loss, which might be mediated by paracrine mechanisms.

Cross-sex pattern of bone mineral density in early onset gender identity disorder.

PubMed

Haraldsen, I R; Haug, E; Falch, J; Egeland, T; Opjordsmoen, S

2007-09-01

Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n=77; females, n=45). Male patients (n=12) received an oral dose of 50 mug ethinylestradiol daily for the first 3 months and 100 mug daily thereafter. Female patients (n=21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same-sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same-sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment.

Response Of Mineralizing And Non-Mineralizing Bone Cells To Fluid Flow: An In Vitro Model For Mechanotransruction

NASA Technical Reports Server (NTRS)

Makuch, Lauren A.

2004-01-01

Humans reach peak bone mass at age 30. After this point, we lose 1 to 2 percent of bone mass each decade. In the microgravity environment of space, astronauts lose bone mass at an accelerated rate of 1 to 2 percent each month. When astronauts travel to Mars, they may be in space for as long as 3 years. During this time, they may lose about half of their bone mass from weight-bearing bones. This loss may be irreversible. The drastic loss in bone that astronauts experience in space makes them much more vulnerable to fractures. In addition, the corresponding removal of calcium from bone results in higher levels of calcium in the blood, which increases the risk of developing kidney stones. Currently, studies are being conducted which investigate factors governing bone adaptation and mechanotransduction. Bone is constantly adapting in response to mechanical stimuli. Increased mechanical loading stimulates bone formation and suppresses bone resorption. Reduction in mechanical loading caused by bedrest, disuse, or microgravity results in decreased bone formation and possibly increased bone resorption. Osteoblasts and osteoclasts are the two main cell types that participate in bone remodeling. Osteoblasts are anabolic (bone-forming) cells and osteoclasts are catabolic (bone-resorbing) cells. In microgravity, the activity of osteoblasts slows down and the activity of osteoclasts may speed up, causing a loss of bone density. Mechanotransduction, the molecular mechanism by which mechanical stimuli are converted to biochemical signals, is not yet understood. Exposure of cells to fluid flow imposes a shear stress on the cells. Several studies have shown that the shear stress that results from fluid flow induces a cellular response similar to that induced by mechanical loading. Thus, fluid flow can be used as an in vitro model to simulate the mechanical stress that bone cells experience in vivo. Previous in vitro studies have shown that fluid flow induces several responses in

HYPERCALCURIA AND METABOLIC BONE DISEASE

PubMed Central

Rosenberg, Milton L.

1954-01-01

Hypercalcuria leading to nephrocalcinosis and nephrolithiasis may be secondary to a number of causes. In most instances, the history, physical examination, a few simple laboratory tests and x-ray study of the bones will reveal the true primary diagnosis. Specific treatment, if instituted early, will result in a satisfactory response and prevent the progression of renal complications. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:13209371

Effect of abutment height on interproximal implant bone level in the early healing: A randomized clinical trial.

PubMed

Blanco, Juan; Pico, Alexandre; Caneiro, Leticia; Nóvoa, Lourdes; Batalla, Pilar; Martín-Lancharro, Pablo

2018-01-01

The aim of this randomized clinical trial was to compare the effect on the interproximal implant bone loss (IBL) of two different heights (1 and 3 mm) of definitive abutments placed at bone level implants with a platform switched design. Twenty-two patients received forty-four implants (6.5-10 mm length and 3.5-4 mm diameter) to replace at least two adjacent missing teeth, one bridge set to each patient-two implants per bridge. Patients were randomly allocated, and two different abutment heights, 1 and 3 mm using only one abutment height per bridge, were used. Clinical and radiological measurements were performed at 3 and 6 months after surgery. Interproximal bone level changes were compared between treatment groups. The association between IBL and categorical variables (history of periodontitis, smoking, implant location, implant diameter, implant length, insertion torque, width of keratinized mucosa, bone density, gingival biotype and antagonist) was also performed. At 3 months, implants with a 1-mm abutment had significantly greater IBL (0.83 ± 0.19 mm) compared to implants with a 3-mm abutment (0.14 ± 0.08 mm). At 6 months, a greater IBL was observed at implants with 1-mm abutments compared to implants with 3-mm abutments (0.91 ± 0.19 vs. 0.11 ± 0.09 mm). The analysis of the relation between patient characteristics and clinical variables with IBL revealed no significant differences at any moment except for smoking. Abutment height is an important factor to maintain interproximal implant bone level in early healing. Short abutments led to a greater interproximal bone loss in comparison with long abutments after 6 months. Other variables except smoking showed no relation with interproximal bone loss in early healing. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Massage therapy during early postnatal life promotes greater lean mass and bone growth, mineralization, and strength in juvenile and young adult rats.

PubMed

Chen, H; Miller, S; Shaw, J; Moyer-Mileur, L

2009-01-01

The objects of this study were to investigate the effects of massage therapy during early life on postnatal growth, body composition, and skeletal development in juvenile and young adult rats. Massage therapy was performed for 10 minutes daily from D6 to D10 of postnatal life in rat pups (MT, n=24). Body composition, bone area, mineral content, and bone mineral density were measured by dual energy X-ray absorptiometry (DXA); bone strength and intrinsic stiffness on femur shaft were tested by three-point bending; cortical and cancellous bone histomorphometric measurements were performed at D21 and D60. Results were compared to age- and gender-matched controls (C, n=24). D21 body weight, body length, lean mass, and bone area were significantly greater in the MT cohort. Greater bone mineral content was found in male MT rats; bone strength and intrinsic stiffness were greater in D60 MT groups. At D60 MT treatment promoted bone mineralization by increasing trabecular mineral apposition rate in male and endosteal mineral surface in females, and also improved micro-architecture by greater trabeculae width in males and decreasing trabecular separation in females. In summary, massage therapy during early life elicited immediate and prolonged anabolic effects on postnatal growth, lean mass and skeletal developmental in a gender-specific manner in juvenile and young adult rats.

Regulation of bone morphogenetic proteins in early embryonic development

NASA Astrophysics Data System (ADS)

Yamamoto, Yukiyo; Oelgeschläger, Michael

2004-11-01

Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-β family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

SU-F-R-55: Early Detection of Treatment Induced Bone Marrow Injury During Chemoradiation Therapy Using Quantitative CT

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

Chen, X; Song, Y; Erickson, B

Purpose: Acute hematologic toxicity associated with bone marrow injury is a common complication of chemoradiation therapy (CRT) for pelvic malignancies. In this work, we investigate the feasibility of using quantitative CT to detect bone marrow injury during CRT. Methods: Daily CTs were acquired during routine CT-guided radiation therapy using a CT-on-rails for 15 cervical cancer patients. All patients treated with a radiation dose of 45.0 to 50.4 Gy in 1.8 Gy/fraction along with chemotherapy. For each patient, the contours of bone marrow were generated in L4, L5 and sacrum on the first daily CT and then populated to other dailymore » CTs by rigid registration using MIM (MIM Software Inc., Cleveland, OH) with manual editing if possible. A series of CT texture parameters, including Hunsfield Unit (HU) histogram, mean HU, entropy, energy, in bone marrow contours were calculated using MATLAB on each daily CT and were correlated with the completed blood counts (CBC) collected weekly for each patient. The correlations were analyzed with Pearson correlation tests. Results: For all patient data analyzed, mean HU in bone marrow decreased during CRT delivery. From the first to the last fraction the average mean HU reduction is 58.1 ± 13.6 HU (P<0.01). This decrease can be observed as early as after first 5 fractions and is strongly associated with the changes of most CBC quantities, such as the reductions of white and blood cell counts (r=0.97, P=0.001). The reduction of HU is spatially varied. Conclusion: Chemoradiation induced bone marrow injury can be detected during the delivery of CRT using quantitative CT. Chemoradiation results in reductions in mean HU, which are strongly associated with the change in the pretrial blood cell counts. Early detection of bone marrow injury with commonly available CT opens a door to improve bone marrow sparing, reducing risk of hematologic toxicity.« less

Evaluation of bone response to titanium-coated polymethyl methacrylate resin (PMMA) implants by X-ray tomography.

PubMed

Shalabi, Manal M; Wolke, Johannes G C; Cuijpers, Vincent M J I; Jansen, John A

2007-10-01

High-resolution three-dimensional data about the bone response to oral implants can be obtained by using microfocus computer tomography. However, a disadvantage is that metallic implants cause streaking artifacts due to scattering of X-rays, which prevents an accurate evaluation of the interfacial bone-to-implant contact. It has been suggested that the use of thin titanium coatings deposited on polymeric implants can offer an alternative option for analyzing bone contact using micro-CT imaging. Consequently, the aim of the current study was to investigate bone behavior to titanium-coated polymethylmethacrylate (PMMA) implants by micro-CT and histological evaluation. For the experiment titanium-coated PMMA implants were used. The implants had a machined threaded appearance and were provided with a 400-500 nm thick titanium coating. The implants were inserted in the right or left tibia of 10 goats. After an implantation period of 12 weeks the implants were retrieved and prepared for micro-computer tomography (microCT), light microscopy, and X-ray microanalysis. The micro-CT showed that the screw-threads and typical implant configuration were well maintained through the installation procedure. Overall, histological responses showed that the titanium-coated implants were well tolerated and caused no atypical tissue response. In addition, the bone was seen in direct contact with the titanium-coated layer. The X-ray microanalysis results confirmed the light microscopical data. In conclusion, the obtained results proof the final use of titanium-coated PMMA implants for evaluation of the bone-implant response using microCT. However, this study also confirms that for a proper analysis of the bone-implant interface the additional use of microscopical techniques is still required.

Influence of Exercise and Training on Critical Stages of Bone Growth and Development.

PubMed

Klentrou, Panagiota

2016-05-01

Although osteoporosis is considered a geriatric disease, factors affecting bone strength are most influential during child growth and development. This article reviews what is known and still unclear in terms of bone growth, development and adaptation relative to physical activity before and during puberty. Bone is responsive to certain exercise protocols early in puberty and less so in postpubertal years, where bone strength, rather than bone mass, being the outcome of interest. Mechanical loading and high impact exercise promote bone strength. Intense training before and during puberty, however, may negatively affect bone development. Future research should focus on increasing our mechanistic understanding of the manner by which diverse physical stressors alter the integrity of bone. Longitudinal studies that examine the extent to which muscle and bone are comodulated by growth in children are also recommended.

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.

Change in Mouse Bone Turnover in Response to Microgravity on RR-1

NASA Technical Reports Server (NTRS)

Cheng-Campbell, Margareth A.; Blaber, Elizabeth A.; Almeida, Eduardo A. C.

2016-01-01

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1ap21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23 decrease in bone fraction (p0.005) and 11.91 decrease in bone thickness (p0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n10) and vivarium controls (n10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37

Osteocyte physiology and response to fluid shear stress are impaired following exposure to cobalt and chromium: Implications for bone health following joint replacement

PubMed Central

Shah, Karan M.; Orton, Peter; Mani, Nick

2016-01-01

ABSTRACT The effects of metal ion exposure on osteocytes, the most abundant cell type in bone and responsible for coordinating bone remodeling, remain unclear. However, several studies have previously shown that exposure to cobalt (Co2+) and chromium (Cr3+), at concentrations equivalent to those found clinically, affect osteoblast and osteoclast survival and function. In this study, we tested the hypothesis that metal ions would similarly impair the normal physiology of osteocytes. The survival, dendritic morphology, and response to fluid shear stress of the mature osteocyte‐like cell‐line MLO‐Y4 following exposure to clinically relevant concentrations and combinations of Co and Cr ions were measured in 2D‐culture. Exposure of MLO‐Y4 cells to metal ions reduced cell number, increased dendrites per cell and increased dendrite length. We found that combinations of metal ions had a greater effect than the individual ions alone, and that Co2+ had a predominate effect on changes to cell numbers and dendrites. Combined metal ion exposure blunted the responses of the MLO‐Y4 cells to fluid shear stress, including reducing the intracellular calcium responses and modulation of genes for the osteocyte markers Cx43 and Gp38, and the signaling molecules RANKL and Dkk‐1. Finally, we demonstrated that in the late osteoblasts/early osteocytes cell line MLO‐A5 that Co2+ exposure had no effect on mineralization, but Cr3+ treatment inhibited mineralization in a dose‐dependent manner, without affecting cell viability. Taken together, these data indicate that metal exposure can directly affect osteocyte physiology, with potential implications for bone health including osseointegration of cementless components, and periprosthetic bone remodeling. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1716–1723, 2017. PMID:27673573

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

PubMed Central

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

Numerical assessment of bone remodeling around conventionally and early loaded titanium and titanium-zirconium alloy dental implants.

PubMed

Akça, Kıvanç; Eser, Atılım; Çavuşoğlu, Yeliz; Sağırkaya, Elçin; Çehreli, Murat Cavit

2015-05-01

The aim of this study was to investigate conventionally and early loaded titanium and titanium-zirconium alloy implants by three-dimensional finite element stress analysis. Three-dimensional model of a dental implant was created and a thread area was established as a region of interest in trabecular bone to study a localized part of the global model with a refined mesh. The peri-implant tissues around conventionally loaded (model 1) and early loaded (model 2) implants were implemented and were used to explore principal stresses, displacement values, and equivalent strains in the peri-implant region of titanium and titanium-zirconium implants under static load of 300 N with or without 30° inclination applied on top of the abutment surface. Under axial loading, principal stresses in both models were comparable for both implants and models. Under oblique loading, principal stresses around titanium-zirconium implants were slightly higher in both models. Comparable stress magnitudes were observed in both models. The displacement values and equivalent strain amplitudes around both implants and models were similar. Peri-implant bone around titanium and titanium-zirconium implants experiences similar stress magnitudes coupled with intraosseous implant displacement values under conventional loading and early loading simulations. Titanium-zirconium implants have biomechanical outcome comparable to conventional titanium implants under conventional loading and early loading.

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

Bone Tissue Response to Porous and Functionalized Titanium and Silica Based Coatings

PubMed Central

Chaudhari, Amol; Braem, Annabel; Vleugels, Jozef; Martens, Johan A.; Naert, Ignace; Cardoso, Marcio Vivan; Duyck, Joke

2011-01-01

Background Topography and presence of bio-mimetic coatings are known to improve osseointegration. The objective of this study was to evaluate the bone regeneration potential of porous and osteogenic coatings. Methodology Six-implants [Control (CTR); porous titanium coatings (T1, T2); thickened titanium (Ti) dioxide layer (TiO2); Amorphous Microporous Silica (AMS) and Bio-active Glass (BAG)] were implanted randomly in tibiae of 20-New Zealand white rabbits. The animals were sacrificed after 2 or 4 weeks. The samples were analyzed histologically and histomorphometrically. In the initial bone-free areas (bone regeneration areas (BRAs)), the bone area fraction (BAF) was evaluated in the whole cavity (500 µm, BAF-500), in the implant vicinity (100 µm, BAF-100) and further away (100–500 µm, BAF-400) from the implant. Bone-to-implant contact (BIC-BAA) was measured in the areas where the implants were installed in contact to the host bone (bone adaptation areas (BAAs)) to understand and compare the bone adaptation. Mixed models were used for statistical analysis. Principal Findings After 2 weeks, the differences in BAF-500 for different surfaces were not significant (p>0.05). After 4 weeks, a higher BAF-500 was observed for BAG than CTR. BAF-100 for AMS was higher than BAG and BAF-400 for BAG was higher than CTR and AMS. For T1 and AMS, the bone regeneration was faster in the 100-µm compared to the 400-µm zone. BIC-BAA for AMS and BAG was lower after 4 than 2 weeks. After 4 weeks, BIC-BAA for BAG was lower than AMS and CTR. Conclusions BAG is highly osteogenic at a distance from the implant. The porous titanium coatings didn't stimulate bone regeneration but allowed bone growth into the pores. Although AMS didn't stimulate higher bone response, it has a potential of faster bone growth in the vicinity compared to further away from the surface. BIC-BAA data were inconclusive to understand the bone adaptation. PMID:21935382

Androgen receptor stimulates bone sialoprotein (BSP) gene transcription via cAMP response element and activator protein 1/glucocorticoid response elements.

PubMed

Takai, Hideki; Nakayama, Youhei; Kim, Dong-Soon; Arai, Masato; Araki, Shouta; Mezawa, Masaru; Nakajima, Yu; Kato, Naoko; Masunaga, Hiroshi; Ogata, Yorimasa

2007-09-01

Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. Androgens are steroid hormones that are essential for skeletal development. The androgen receptor (AR) is a transcription factor and a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and prostate cell proliferation. To determine the molecular mechanism involved in the stimulation of bone formation, we have analyzed the effects of androgens and AR effects on BSP gene transcription. AR protein levels were increased after AR overexpression in ROS17/2.8 cells. BSP mRNA levels were increased by AR overexpression. However, the endogenous and overexpressed BSP mRNA levels were not changed by DHT (10(-8) M, 24 h). Whereas luciferase (LUC) activities in all constructs, including a short construct (nts -116 to +60), were increased by AR overexpression, the basal and LUC activities enhanced by AR overexpression were not induced by DHT (10(-8)M, 24 h). The effect of AR overexpression was abrogated by 2 bp mutations in either the cAMP response element (CRE) or activator protein 1 (AP1)/glucocorticoid response element (GRE). Gel shift analyses showed that AR overexpression increased binding to the CRE and AP1/GRE elements. Notably, the CRE-protein complexes were supershifted by phospho-CREB antibody, and CREB, c-Fos, c-Jun, and AR antibodies disrupted the complexes formation. The AP1/GRE-protein complexes were supershifted by c-Fos antibody and c-Jun, and AR antibodies disrupted the complexes formation. These studies demonstrate that AR stimulates BSP gene transcription by targeting the CRE and AP1/GRE elements in the promoter of the rat BSP gene.

Sensitivity and specificity of ultrasonography in early diagnosis of metatarsal bone stress fractures: a pilot study of 37 patients.

PubMed

Banal, Frédéric; Gandjbakhch, Frédérique; Foltz, Violaine; Goldcher, Alain; Etchepare, Fabien; Rozenberg, Sylvie; Koeger, Anne-Claude; Bourgeois, Pierre; Fautrel, Bruno

2009-08-01

To date, early diagnosis of stress fractures depends on magnetic resonance imaging (MRI) or bone scan scintigraphy, as radiographs are usually normal at onset of symptoms. These examinations are expensive or invasive, time-consuming, and poorly accessible. A recent report has shown the ability of ultrasonography (US) to detect early stress fractures. Our objective was to evaluate sensitivity and specificity of US versus dedicated MRI (0.2 Tesla), taken as the gold standard, in early diagnosis of metatarsal bone stress fractures. A case-control study from November 2006 to December 2007 was performed. All consecutive patients with mechanical pain and swelling of the metatarsal region for less than 3 months and with normal radiographs were included. US and dedicated MRI examinations of the metatarsal bones were performed the same day by experienced rheumatologists with expertise in US and MRI. Reading was undertaken blind to the clinical assessment and MRI/US results. Forty-one feet were analyzed on US and dedicated MRI from 37 patients (28 women, 9 men, mean age 52.7 +/- 14.1 yrs). MRI detected 13 fractures in 12 patients. Sensitivity of US was 83%, specificity 76%, positive predictive value 59%, and negative predictive value 92%. Positive likehood ratio was 3.45, negative likehood ratio 0.22. In cases of normal radiographs, US is indicated in the diagnosis of metatarsal bone stress fractures, as it is a low cost, noninvasive, rapid, and easy technique with good sensitivity and specificity. From these data, we propose a new imaging algorithm including US.

Remnant Woven Bone and Calcified Cartilage in Mouse Bone: Differences between Ages/Sex and Effects on Bone Strength

PubMed Central

Ip, Victoria; Toth, Zacharie; Chibnall, John; McBride-Gagyi, Sarah

2016-01-01

Introduction Mouse models are used frequently to study effects of bone diseases and genetic determinates of bone strength. Murine bones have an intracortical band of woven bone that is not present in human bones. This band is not obvious under brightfield imaging and not typically analyzed. Due to the band’s morphology and location it has been theorized to be remnant bone from early in life. Furthermore, lamellar and woven bone are well known to have differing mechanical strengths. The purpose of this study was to determine (i) if the band is from early life and (ii) if the woven bone or calcified cartilage contained within the band affect whole bone strength. Woven Bone Origin Studies In twelve to fourteen week old mice, doxycycline was used to label bone formed prior to 3 weeks old. Doxycycline labeling and woven bone patterns on contralateral femora matched well and encompassed an almost identical cross-sectional area. Also, we highlight for the first time in mice the presence of calcified cartilage exclusively within the band. However, calcified cartilage could not be identified on high resolution cone-beam microCT scans when examined visually or by thresholding methods. Mechanical Strength Studies Subsequently, three-point bending was used to analyze the effects of woven bone and calcified cartilage on whole bone mechanics in a cohort of male and female six and 13 week old Balb/C mice. Three-point bending outcomes were correlated with structural and compositional measures using multivariate linear regression. Woven bone composed a higher percent of young bones than older bones. However, calcified cartilage in older bones was twice that of younger bones, which was similar when normalized by area. Area and/or tissue mineral density accounted for >75% of variation for most strength outcomes. Percent calcified cartilage added significant predictive power to maximal force and bending stress. Calcified cartilage and woven bone could have more influence in genetic

Automated classification of mandibular cortical bone on dental panoramic radiographs for early detection of osteoporosis

NASA Astrophysics Data System (ADS)

Horiba, Kazuki; Muramatsu, Chisako; Hayashi, Tatsuro; Fukui, Tatsumasa; Hara, Takeshi; Katsumata, Akitoshi; Fujita, Hiroshi

2015-03-01

Findings on dental panoramic radiographs (DPRs) have shown that mandibular cortical index (MCI) based on the morphology of mandibular inferior cortex was significantly correlated with osteoporosis. MCI on DPRs can be categorized into one of three groups and has the high potential for identifying patients with osteoporosis. However, most DPRs are used only for diagnosing dental conditions by dentists in their routine clinical work. Moreover, MCI is not generally quantified but assessed subjectively. In this study, we investigated a computer-aided diagnosis (CAD) system that automatically classifies mandibular cortical bone for detection of osteoporotic patients at early stage. First, an inferior border of mandibular bone was detected by use of an active contour method. Second, regions of interest including the cortical bone are extracted and analyzed for its thickness and roughness. Finally, support vector machine (SVM) differentiate cases into three MCI categories by features including the thickness and roughness. Ninety eight DPRs were used to evaluate our proposed scheme. The number of cases classified to Class I, II, and III by a dental radiologist are 56, 25 and 17 cases, respectively. Experimental result based on the leave-one-out cross-validation evaluation showed that the sensitivities for the classes I, II, and III were 94.6%, 57.7% and 94.1%, respectively. Distribution of the groups in the feature space indicates a possibility of MCI quantification by the proposed method. Therefore, our scheme has a potential in identifying osteoporotic patients at an early stage.

Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response.

PubMed

Pizzi, Marco; Silver, Richard T; Barel, Ariella; Orazi, Attilio

2015-10-01

Recombinant interferon-α represents a well-established therapeutic option for the treatment of polycythemia vera and essential thrombocythemia. Recent studies also suggest a role for recombinant interferon-α in the treatment of 'early stage' primary myelofibrosis, but few studies have reported the bone marrow changes after clinically successful interferon therapy. The aim of the present study is to detail the histological responses to recombinant interferon-α in primary myelofibrosis and post-polycythemia vera/post-essential thrombocythemia myelofibrosis and to correlate these with clinical findings. We retrospectively studied 12 patients with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis, who had been treated with recombinant interferon-α. Six patients had received other prior cytoreductive therapies. Bone marrow biopsy was assessed for the following histological parameters: (i) cellularity; (ii) myeloid-to-erythroid ratio; (iii) megakaryocyte tight clusters; (iv) megakaryocyte and naked nuclei density; (v) megakaryocytic atypia; (vi) fibrosis; and (vii) the percentage of blasts. Clinical and laboratory data were included: (i) constitutional symptoms; (ii) splenomegaly, if present; and (iii) complete cell blood count. The clinical response to therapy was evaluated using the International Working Group for Myelofibrosis Research and Treatment/European LeukemiaNet response criteria. The Dynamic International Prognostic Scoring System (DIPSS) score was calculated before and after recombinant interferon-α administration. Successful interferon therapy for myelofibrosis was associated with a significant reduction of marrow fibrosis, cellularity, megakaryocyte density and naked nuclei density. The presence of JAK2(V617F) mutation correlated with improved DIPSS score. JAK2(V617F)-negative cases showed worsening of such score or evolution to acute myeloid leukemia. Cytogenetic analysis documented a normal karyotype in all

Short-term lower-body plyometric training improves whole body BMC, bone metabolic markers, and physical fitness in early pubertal male basketball players.

PubMed

Zribi, Anis; Zouch, Mohamed; Chaari, Hamada; Bouajina, Elyes; Ben Nasr, Hela; Zaouali, Monia; Tabka, Zouhair

2014-02-01

The effects of a 9-week lower-body plyometric training program on bone mass, bone markers and physical fitness was examined in 51 early pubertal male basketball players divided randomly into a plyometric group (PG: 25 participants) and a control group (CG: 26 participants). Areal bone mineral density (aBMD), bone mineral content (BMC), and bone area (BA) in the whole body, L2-L4 vertebrae, and in total hip, serum levels of osteocalcin (Oc) and C-terminal telopeptide fragment of Type I collagen (CTx), jump, sprint and power abilities were assessed at baseline and 9 weeks. Group comparisons were done by independent student's t-test between means and analyses of (ANOVA) and covariance (ANCOVA), adjusting for baseline values. PG experienced a significant increase in Oc (p < .01) and all physical fitness except for the 5-jump test. However, there was no improvement in aBMD, BMC and BA in any measured site, except in whole body BMC of the PG. A positive correlation was observed between percentage increase (Δ%) of physical fitness and those of (Oc) for the PG. In summary, biweekly sessions of lower body plyometric training program were successful for improving whole body BMC, bone formation marker (Oc) and physical fitness in early pubertal male basketball players.

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain.

PubMed

Pacheco-Costa, Rafael; Davis, Hannah M; Sorenson, Chad; Hon, Mary C; Hassan, Iraj; Reginato, Rejane D; Allen, Matthew R; Bellido, Teresita; Plotkin, Lilian I

2015-12-01

Connexin 43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43(ΔCT/fl)) were studied. Cx43(ΔCT/fl) mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43(fl/fl) controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43(ΔCT) is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43(ΔCT) mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43(ΔCT) were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. Copyright © 2015 Elsevier Inc. All rights reserved.

Exercise Effects on Fitness and Bone Mineral Density in Early Postmenopausal Women: 1-Year EFOPS Results.

ERIC Educational Resources Information Center

Kemmler, Wolfgang; Engelke, Klaus; Lauber, Dirk; Weineck, Juergen; Hensen, Johannes; Kalender, Willi A.

2002-01-01

Investigated the effect of intense exercise training on physical fitness, coronary heart disease, bone mineral density (BMD), and parameters related to quality of life in early postmenopausal women with osteopenia. Data on woman in control and exercise training groups indicated that the intense exercise training program was effective in improving…

Modulation by vitamin D status of the responsiveness of rat bone to gonadal steroids.

PubMed

Sömjen, D; Kaye, A M; Harell, A; Weisman, Y

1989-10-01

We have previously demonstrated that gonadal steroids stimulate [3H]thymidine incorporation and creatine kinase specific activity in skeletal tissues. In the present study we report that in 20-day-old vitamin D-deficient Wistar-derived rats, 17 beta-estradiol (E2; 5 micrograms/rat) or testosterone (50 micrograms/rat) failed to stimulate [3H]thymidine incorporation into diaphyses of long bones and that the response to these hormones in terms of increased creatine kinase specific activity was less than half the value in normally fed rats. Two daily ip injections of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3; 0.5 ng/g BW], but not 24,25-(OH)2D3 (5 ng/g BW), partially restored the biological responses to E2 in bone of 21-day-old vitamin D-deficient female rats. Vitamin D deficiency did not impair the responsiveness to gonadal steroids in the epiphysis of long bones, uterus, or prostate, in contrast to its effect on diaphysis. In 21-day-old normally fed female rats, neither vitamin D metabolite enhanced the response to E2. When cultures of rat epiphyseal cells were treated daily for 5 days with either 1,25-(OH)2D3 (1 nM) or 24,25-(OH)2D3 (10 nM), followed by E2 (30 nM) for 24 h, creatine kinase activity was significantly higher than in cultures treated daily for 5 days with vehicle alone, and then with E2. The same treatment of rat embryo calvaria bone cells showed that 1,25-(OH)2D3, but not 24,25-(OH)2D3, significantly increased the creatine kinase activity response to E2. These findings suggest that vitamin D metabolites selectively affect the biological responses of skeletal tissues to gonadal steroids.

A high concentration of recombinant human bone morphogenetic protein-2 induces low-efficacy bone regeneration in sinus augmentation: a histomorphometric analysis in rabbits.

PubMed

Hong, Ji-Youn; Kim, Min-Soo; Lim, Hyun-Chang; Lee, Jung-Seok; Choi, Seong-Ho; Jung, Ui-Won

2016-12-01

The aim of the study was to elucidate the efficacy of bone regeneration at the early stage of healing in rabbit sinuses grafted with a biphasic calcium phosphate (BCP) carrier soaked in a high concentration of recombinant human bone morphogenetic protein-2 (rhBMP-2). Both maxillary sinuses of eight male rabbits were used. The sinus on one side (assigned randomly) was grafted with BCP loaded with rhBMP-2 (1.5 mg/ml; test group) using a soaking method, while the other was grafted with saline-soaked BCP (control group). After a 2-week healing period, the sinuses were analyzed by micro-computed tomography and histomorphometry. The total augmented area and soft tissue space were significantly larger in the test group than in the control group, whereas the opposite was true for the area of residual material and newly formed bone. Most of the new bone in the test group was localized to the Schneiderian membrane (SM), while very little bone formation was observed in the window and center regions of the sinus. New bone was distributed evenly in the control group sinuses. Within the limitations of this study, it appeared that application of a high concentration of rhBMP-2 soaked onto a BCP carrier inhibited bone regeneration from the pristine bone and increased soft tissue swelling and inflammatory response at the early healing stage of sinus augmentation, although osteoinductive potential was found along the SM. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stimulating angiogenesis mitigates the unloading-induced reduction in osteogenesis in early-stage bone repair in rats

PubMed Central

Matsumoto, Takeshi; Sato, Shota

2015-01-01

Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced reduction in early-stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide-based contrast agent. Taking advantage of its absorption discontinuity at the K-absorption edge, vascular and bone images in the drill-hole defects were acquired by synchrotron radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10. The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU10 than in WB10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20–30, 30–40, and >40 μm were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 μm was smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf in the diameter ranges 10–20 and 20–30 μm was larger in DFOHU5 than in HU5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading. PMID:25780087

Stimulating angiogenesis mitigates the unloading-induced reduction in osteogenesis in early-stage bone repair in rats.

PubMed

Matsumoto, Takeshi; Sato, Shota

2015-03-01

Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced reduction in early-stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide-based contrast agent. Taking advantage of its absorption discontinuity at the K-absorption edge, vascular and bone images in the drill-hole defects were acquired by synchrotron radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10. The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU10 than in WB10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20-30, 30-40, and >40 μm were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 μm was smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf in the diameter ranges 10-20 and 20-30 μm was larger in DFOHU5 than in HU5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf

Repression of Osteoblast Maturation by ERRα Accounts for Bone Loss Induced by Estrogen Deficiency

PubMed Central

Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

2013-01-01

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency. PMID:23359549

Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

PubMed

Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

2013-01-01

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.

In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

NASA Astrophysics Data System (ADS)

McCanless, Jonathan D.

Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

In vivo measurement of mechanical properties of human long bone by using sonic sound

NASA Astrophysics Data System (ADS)

Hossain, M. Jayed; Rahman, M. Moshiur; Alam, Morshed

2016-07-01

Vibration analysis has evaluated as non-invasive techniques for the in vivo assessment of bone mechanical properties. The relation between the resonant frequencies, long bone geometry and mechanical properties can be obtained by vibration analysis. In vivo measurements were performed on human ulna as a simple beam model with an experimental technique and associated apparatus. The resonant frequency of the ulna was obtained by Fast Fourier Transformation (FFT) analysis of the vibration response of piezoelectric accelerometer. Both elastic modulus and speed of the sound were inferred from the resonant frequency. Measurement error in the improved experimental setup was comparable with the previous work. The in vivo determination of bone elastic response has potential value in screening programs for metabolic bone disease, early detection of osteoporosis and evaluation of skeletal effects of various therapeutic modalities.

Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

PubMed

Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

2016-08-01

Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

Early osteoblast responses to orthopedic implants: Synergy of surface roughness and chemistry of bioactive ceramic coating.

PubMed

Aniket; Reid, Robert; Hall, Benika; Marriott, Ian; El-Ghannam, Ahmed

2015-06-01

Pro-osteogenic stimulation of bone cells by bioactive ceramic-coated orthopedic implants is influenced by both surface roughness and material chemistry; however, their concomitant impact on osteoblast behavior is not well understood. The aim of this study is to investigate the effects of nano-scale roughness and chemistry of bioactive silica-calcium phosphate nanocomposite (SCPC50) coated Ti-6Al-4V on modulating early bone cell responses. Cell attachment was higher on SCPC50-coated substrates compared to the uncoated controls; however, cells on the uncoated substrate exhibited greater spreading and superior quality of F-actin filaments than cells on the SCPC50-coated substrates. The poor F-actin filament organization on SCPC50-coated substrates is thought to be due to the enhanced calcium uptake by the ceramic surface. Dissolution analyses showed that an increase in surface roughness was accompanied by increased calcium uptake, and increased phosphorous and silicon release, all of which appear to interfere with F-actin assembly and osteoblast morphology. Moreover, cell attachment onto the SCPC50-coated substrates correlated with the known adsorption of fibronectin, and was independent of surface roughness. High-throughput genome sequencing showed enhanced expression of extracellular matrix and cell differentiation related genes. These results demonstrate a synergistic relationship between bioactive ceramic coating roughness and material chemistry resulting in a phenotype that leads to early osteoblast differentiation. © 2014 Wiley Periodicals, Inc.

Modeling Hematopoiesis and Responses to Radiation Countermeasures in a Bone Marrow-on-a-Chip.

PubMed

Torisawa, Yu-Suke; Mammoto, Tadanori; Jiang, Elisabeth; Jiang, Amanda; Mammoto, Akiko; Watters, Alexander L; Bahinski, Anthony; Ingber, Donald E

2016-05-01

Studies on hematopoiesis currently rely on animal models because in vitro culture methods do not accurately recapitulate complex bone marrow physiology. We recently described a bone marrow-on-a-chip microfluidic device that enables the culture of living hematopoietic bone marrow and mimics radiation toxicity in vitro. In the present study, we used this microdevice to demonstrate continuous blood cell production in vitro and model bone marrow responses to potential radiation countermeasure drugs. The device maintained mouse hematopoietic stem and progenitor cells in normal proportions for at least 2 weeks in culture. Increases in the number of leukocytes and red blood cells into the microfluidic circulation also could be detected over time, and addition of erythropoietin induced a significant increase in erythrocyte production. Exposure of the bone marrow chip to gamma radiation resulted in reduction of leukocyte production, and treatment of the chips with two potential therapeutics, granulocyte-colony stimulating factor or bactericidal/permeability-increasing protein (BPI), induced significant increases in the number of hematopoietic stem cells and myeloid cells in the fluidic outflow. In contrast, BPI was not found to have any effect when analyzed using static marrow cultures, even though it has been previously shown to accelerate recovery from radiation-induced toxicity in vivo. These findings demonstrate the potential value of the bone marrow-on-a-chip for modeling blood cell production, monitoring responses to hematopoiesis-modulating drugs, and testing radiation countermeasures in vitro.

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

Angiogenesis after sintered bone implantation in rat parietal bone.

PubMed

Ohtsubo, S; Matsuda, M; Takekawa, M

2003-01-01

We studied the effect of bone substitutes on revascularization and the restart of blood supply after sintered bone implantation in comparison with synthetic hydroxyapatite implantation and fresh autogenous bone transplantation (control) in rat parietal bones. Methods for the study included the microvascular corrosion cast method and immunohistochemical techniques were also used. The revascularization of the control group was the same as that for usual wound healing in the observations of the microvascular corrosion casts. The sintered bone implantation group was quite similar to that of the control group. In the synthetic hydroxyapatite group, immature newly-formed blood vessels existed even on the 21st day after implantation and the physiological process of angiogenesis was interrupted. Immunohistochemically, vascular endothelial growth factor (VEGF), which activates angiogenesis, appeared at the early stages of both the control group and the sintered bone implantation group. VEGF reduced parallel with the appearance of the transforming growth factor factor-beta-1 (TGF-beta-1), which obstructs angiogenesis, and the angiogenesis passed gradually into the mature stage. In the hydroxyapatite implantation group, TGF-beta-1 appeared at the early stage of the implants. The appearance of VEGF lagged and it existed around the pores of hydroxyapatite even on the 21st day of the implantation. Proliferation and wandering of endothelial cells continued without any maturing of the vessels. These findings suggest that the structure and the components of the implant material affect angiogenesis after implantation as well as new bone formation.

Thermal processing of bone: in vitro response of mesenchymal cells to bone-conditioned medium.

PubMed

Sawada, K; Caballé-Serrano, J; Schuldt Filho, G; Bosshardt, D D; Schaller, B; Buser, D; Gruber, R

2015-08-01

The autoclaving, pasteurization, and freezing of bone grafts to remove bacteria and viruses, and for preservation, respectively, is considered to alter biological properties during graft consolidation. Fresh bone grafts release paracrine-like signals that are considered to support tissue regeneration. However, the impact of the autoclaving, pasteurization, and freezing of bone grafts on paracrine signals remains unknown. Therefore, conditioned medium was prepared from porcine cortical bone chips that had undergone thermal processing. The biological properties of the bone-conditioned medium were assessed by examining the changes in expression of target genes in oral fibroblasts. The data showed that conditioned medium obtained from bone chips that had undergone pasteurization and freezing changed the expression of adrenomedullin, pentraxin 3, BTB/POZ domain-containing protein 11, interleukin 11, NADPH oxidase 4, and proteoglycan 4 by at least five-fold in oral fibroblasts. Bone-conditioned medium obtained from autoclaved bone chips, however, failed to change the expression of the respective genes. Also, when bone-conditioned medium was prepared from fresh bone chips, autoclaving blocked the capacity of bone-conditioned medium to modulate gene expression. These in vitro results suggest that pasteurization and freezing of bone grafts preserve the release of biologically active paracrine signals, but autoclaving does not. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Decreased bone density in carriers and patients of an Israeli family with the osteoporosis-pseudoglioma syndrome.

PubMed

Lev, Dorit; Binson, Inga; Foldes, A Joseph; Watemberg, Nathan; Lerman-Sagie, Tally

2003-06-01

The osteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or early-onset blindness. Other manifestations include muscular hypotonia, ligamentous laxity, mild mental retardation and seizures. The gene responsible was recently identified to be the low density lipoprotein receptor-related family member LRP5 on chromosome 11q11-12. To measure bone density in two siblings with the OPPG syndrome as well as in their family members (parents and siblings). Bone mineral density was determined in the lumbar spine (antero-posterior), femoral neck, two-thirds distal forearm (> 95% cortical bone) and ultradistal forearm (predominantly trabecular bone) by dual-energy X-ray absorptiometry. The studies revealed osteoporotic changes both in the patients and the carriers. The findings demonstrate that OPPG carriers have reduced bone mass, which is a risk factor for development of early osteoporotic changes.

[Evaluation of early physiotherapy in patients after surgical treatment of cruciate ligament injury by bone-tendon-bone method].

PubMed

Klupiński, Kamil; Krekora, Katarzyna; Woldańska-Okońska, Marta

2014-01-01

Anterior cruciate ligament (ACL) is one of the most important structures of the knee joint. It has a stabilizing function and causes sliding movement between the articular surfaces. Most frequently there comes to the anterior cruciate ligament injury during practicing sports such as skiing, football, sports which require sudden turns and those which are associated with jumps for height like basketball and volleyball. The aim of study was to evaluate of the outcomes of complex physiotherapy after reconstruction of anterior cruciate ligament by bone -tendon-bone (BTB) method. The study involved 41 patients, 8 women and 33 men, aged 20 to 45 years, body height 1.60-1.90 cm and body weight 50-100 kg. The patients were divided into two groups. Group I included 26 patients (3 women and 23 men) after arthroscopic ACL reconstruction. Group II--control-group included 15 patients (5 women and 10 men) after ACL injury but not subjected to the ligament reconstruction. The patients from both groups underwent rehabilitation according to the same rehabilitation program suggested by the Medical Magnus Clinic in Lodz, which consisted in performing daily exercises in open and closed kinetic chains. All group I and II patients were examined three times: after surgery (before the start of the rehabilitation), in the sixth week of rehabilitation and 12 weeks afterwards. The clinical examination included: measurement of the range of movement in the knee joint, the measurement of musculoskeletal strength with Lovett scale, knee pain assessment using Visual Analog Scale (VAS), transpatellar anthropometric measurement of the knee joint, linear measurements of the thigh and shin (at two points: 5 and 10 cm above the patellar apex and at two points: 5 and 10 cm below the patellar base). Introduction of early highly specialized physiotherapy has been demonstrated to contribute to the improvement of the rehabilitation outcomes and to the shortening of the therapy. A statistically significant

Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: early treatment rescues bone lesions?

PubMed Central

Tomatsu, Shunji; Montaño, Adriana M.; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S.

2014-01-01

We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology (1). To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250 units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in liver and spleen, with detectable activity in bone and brain. Second, newborn ERT was conducted after tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th week were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in liver, spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than adult mice treated with ERT; however, hyaline and fibrous cartilage cells in femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mouse. PMID:24953405

Bone and Soft Tissue Response in Bone-Level Implants Restored with Platform Switching: A 5-Year Clinical Prospective Study.

PubMed

Lago, Laura; da Silva, Luis; Gude, Francisco; Rilo, Benito

The aim of this prospective study was to evaluate radiographic levels of peri-implant bone crest as well as soft tissue response, papilla height, and buccal mucosa recession, in bone-level implants restored with platform switching after 1-year and 5-year follow-ups. This prospective study called for the placement of 59 implants to obtain a target of 90% power. To compensate for possible dropouts, the sample size was adjusted to 67 implants. To assess marginal bone level changes, periapical radiographs were taken at baseline, 1 year, and 5 years after the definitive restorations. Peri-implant soft tissue modifications were evaluated by performing a photographic sequence at 15 days, 1 year, and 5 years after implant restoration. Parameters measured were: (1) distance from the tip of the papilla to the contact point and (2) apicocoronal crown length. A one-way analysis of variance (ANOVA rank test) was used to compare quantitative data among the three time points studied. Mean marginal bone level changes were as follows: -0.06 ± 0.32 mm from baseline to 1 year, -0.23 ± 0.38 mm from 1 to 5 years, and -0.28 ± 0.45 mm from baseline to 5 years. In bone-level outcomes, no statistically significant differences were found between baseline and 1 year, while the mean differences between 1 and 5 years and baseline and 5 years showed statistically significant differences. In the soft tissue analysis, the distance from the tip of the papilla to the contact point showed the following values: baseline, 2.08 mm; 1 year, 1.54 mm; 5 years, 1.31 mm. No statistically significant differences were found between baseline and 1 year, whereas statistically significant differences between 1 and 5 years and baseline and 5 years were found. Apicocoronal crown length measurements showed the following values: baseline, 9.44 mm; 1 year, 9.28 mm; 5 years, 9.81 mm. No significant differences were found between times studied. This prospective clinical study of 67 bone-level implants restored

Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer.

PubMed

Zidan, Jamal; Keidar, Zohar; Basher, Walid; Israel, Ora

2004-01-01

At the present time, tamoxifen is the most widely used anti-estrogen for adjuvant therapy and metastatic disease in postmenopausal women with breast cancer, a population at high risk for osteoporosis. This prospective study was designed to evaluate the effect of adjuvant tamoxifen on bone mineral density and all biochemical markers concomitantly in women with early-stage breast cancer in one study. Using dual-energy X-ray absorptiometry, prior to and 12 mo after tamoxifen treatment, bone mineral density in lumbar spine and femoral neck was measured in 44 women with T1-T2N0M0 estrogen-receptor-positive breast cancer receiving adjuvant treatment with tamoxifen 20 mg/d. Biomarkers that can affect bone mineral metabolism were measured before and after 3 and 12 mo of tamoxifen treatment. Bone mineral density was minimally increased in lumbar spine and femoral neck after 12 mo treatment with tamoxifen (p = 0.79 and 0.55, respectively). No differences were found in serum levels of calcium, phosphate, creatinine, ALAT, albumin, LDH, calcitonin, or estradiol. A significant decrease in osteocalcin levels was found after 3 and 12 mo (p < or = 0.01). TSH and PTH levels were increased (p < or = 0.05) after 3 mo, returning to baseline after 12 mo. In conclusion, tamoxifen has an estrogen-like effect on bone metabolism in postmenopausal women and is associated with preservation of bone mineral density in lumbar spine and femoral neck. Changes in serum concentration of biochemical markers may reflect decreased bone turnover or bone remodeling and add to the understanding of tamoxifen's effect on bone mineral density.

Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice

PubMed Central

McGee-Lawrence, Meghan E.; Carpio, Lomeli R.; Bradley, Elizabeth W.; Dudakovic, Amel; Lian, Jane B.; van Wijnen, Andre J.; Kakar, Sanjeev; Hsu, Wei; Westendorf, Jennifer J.

2014-01-01

Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/− mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/− mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2−/−:Runx2+/− mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/− mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2−/−:Runx2+/− calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/− and double mutant Axin2−/−:Runx2+/− mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/− mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2−/− mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. PMID:24973690

Raman spectroscopy of murine bone in response to simulated spaceflight conditions

NASA Astrophysics Data System (ADS)

Mandair, Gurjit S.; Bateman, Ted A.; Morris, Michael D.

2009-02-01

Astronauts exposed to spaceflight conditions can lose 1-2% of their bone mineral density per month from the weight-bearing portions of the skeletal system. Low bone mineral density, termed osteopenia, is the result of decreased bone formation and/or increased bone resorption. In this study, Raman spectroscopy is used to examine if the physicochemical composition of murine femurs is altered in response to simulated spaceflight conditions (hindlimb suspension). Female C57BL/6J mice, aged 53 days, were divided into ground control and simulated spaceflight groups for a period of 12 days, modeling the experiment profile of mice flown on Space Shuttle flight STS-108. After the study, the mice were sacrificed and femur specimens harvested. Mid-diaphysis sections were probed using near-infrared Raman microscopy. Spectra were collected at various anatomical sites (anterior, lateral, medial, and posterior quadrants) and/or cortical locations (periosteal, midosteal, and endosteal). Chemometric recovery of spectra was employed to reduce signal contributions from the epoxy embedding agent. Mean values for mineralization, carbonation, crystallinity, and other parameters associated with the matrix were estimated. Correlations between mineralization and carbonation were observed, despite the small absolute changes between the two groups. We present more detailed analysis of this data and comment on the prospects for Raman spectroscopic evaluation of bone quality in hindlimb suspended (HLS) specimens.

Recommendations for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma on behalf of the International Neuroblastoma Response Criteria Bone Marrow Working Group.

PubMed

Burchill, Susan A; Beiske, Klaus; Shimada, Hiroyuki; Ambros, Peter F; Seeger, Robert; Tytgat, Godelieve A M; Brock, Penelope R; Haber, Michelle; Park, Julie R; Berthold, Frank

2017-04-01

The current study was conducted to expedite international standardized reporting of bone marrow disease in children with neuroblastoma and to improve equivalence of care. A multidisciplinary International Neuroblastoma Response Criteria Bone Marrow Working Group was convened by the US National Cancer Institute in January 2012 with representation from Europe, North America, and Australia. Practical transferable recommendations to standardize the reporting of bone marrow disease were developed. To the authors' knowledge, the current study is the first to comprehensively present consensus criteria for the collection, analysis, and reporting of the percentage area of bone marrow parenchyma occupied by tumor cells in trephine-biopsies. The quantitative analysis of neuroblastoma content in bone marrow aspirates by immunocytology and reverse transcriptase-quantitative polymerase chain reaction are revised. The inclusion of paired-like homeobox 2b (PHOX2B) for immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction is recommended. Recommendations for recording bone marrow response are provided. The authors endorse the quantitative assessment of neuroblastoma cell content in bilateral core needle biopsies-trephines and aspirates in all children with neuroblastoma, with the exception of infants, in whom the evaluation of aspirates alone is advised. It is interesting to note that 5% disease is accepted as an internationally achievable level for disease assessment. The quantitative assessment of neuroblastoma cells is recommended to provide data from which evidence-based numerical criteria for the reporting of bone marrow response can be realized. This is particularly important in the minimal disease setting and when neuroblastoma detection in bone marrow is intermittent, where clinical impact has yet to be validated. The wide adoption of these harmonized criteria will enhance the ability to compare outcomes from different trials and facilitate

Early effects of zoledronic acid and teriparatide on bone microarchitecture, remodeling and collagen crosslinks: comparison between iliac crest and lumbar vertebra in ewes.

PubMed

Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D

2012-10-01

structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly only in LV1 (p<0.05) with a trend of increases in MS/BS and BFR/BS, compared to LV1-CTRL. In conclusion, in adult ewes, the bone mass, microarchitecture, remodeling and collagen crosslink content differ according to the bone site (iliac crest and vertebra). Furthermore, after 3 months, the responses to ZOL and TPTD were of different magnitude and delay between the two bone sites. The distinction of bone sites to study the early effects of anti-osteoporotic therapies appears meaningful in order to approach their site-specific anti-fracture efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

Bone modeling and cell-material interface responses induced by nickel-titanium shape memory alloy after periosteal implantation.

PubMed

Ryhänen, J; Kallioinen, M; Tuukkanen, J; Lehenkari, P; Junila, J; Niemelä, E; Sandvik, P; Serlo, W

1999-07-01

The purpose of this study was to evaluate the new bone formation, modeling and cell-material interface responses induced by nickel-titanium shape memory alloy after periosteal implantation. We used a regional acceleratory phenomenon (RAP) model, in which a periosteal contact stimulus provokes an adaptive modelling response. NiTi has thermal shape memory and superelasticity properties uncommon in other implant alloys. So far, there are insufficient data concerning the biocompatibility of NiTi as a bone implant. NiTi was compared to stainless steel (stst) and Ti-6Al-4V. The test implant was placed in contact with the intact femur periosteum, but it was not fixed inside the bone. Histomorphometry with digital image analysis was used to determine the bone formation and resorption parameters. The ultrastructural features of cell-material adhesion were analysed with scanning electron microscopy (FESEM). A typical peri-implant bone wall modelation was seen due to the normal RAP. The maximum new woven bone formation started earlier (2 weeks) in the Ti-6Al-4V group than in the NiTi (P < 0.01) group, but also decreased earlier, and at 8 weeks the NiTi (P < 0.05) and stst (P < 0.005) groups had greater cortical bone width. At 12 and 26 weeks no statistical differences were seen in the histomorphometric values. The histological response of the soft tissues around the NiTi implant was also clearly non-toxic and non-irritating. Cell adhesion and focal contacts were similar between the materials studied by FESEM. We conclude that NiTi had no negative effect on total new bone formation or normal RAP after periosteal implantation during a 26-week follow-up.

Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.

PubMed

Campbell, J Preston; Karolak, Matthew R; Ma, Yun; Perrien, Daniel S; Masood-Campbell, S Kathryn; Penner, Niki L; Munoz, Steve A; Zijlstra, Andries; Yang, Xiangli; Sterling, Julie A; Elefteriou, Florent

2012-07-01

Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress) or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.

Effect of early nutritional intake on long-term growth and bone mineralization of former very low birth weight infants.

PubMed

Christmann, V; van der Putten, M E; Rodwell, L; Steiner, K; Gotthardt, M; van Goudoever, J B; van Heijst, A F J

2018-03-01

Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period. To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants during the first 14days after birth was associated with improvement in length and bone development until 9-10years of age. Observational follow-up study of VLBW infants (birth weight<1500g or gestational age<32weeks) born in two consecutive years (eligible infants: 2004 n: 63 and 2005: n: 66). Cohort 2005 received higher intake of calcium, phosphate and protein with parenteral nutrition compared to Cohort 2004. Anthropometric data were collected during standard follow-up visits until five years, and additionally at 9-10years of age including measurements of bone mineral content, bone mineral density of the whole body and lumbar spine determined by dual-energy X-ray absorptiometry. Long-term growth trajectories of both cohorts were evaluated separately for participants born appropriate (AGA) and small for gestational age (SGA), stratified by gender. Multivariate linear regression was used to examine the effect of nutritional intake and clinical covariates on length and bone mineralization. Both cohorts achieved a catch-up in length to SDS within the normal range by 6months (length SDS: estimated mean (95% confidence interval (CI): 6months: Cohort 2004: -0.7 (-1.1, -0.3) Cohort 2005: -0.5 (-0.8, -0.2)). Bone mineral content and density were within the normal range and not different between the cohorts. SGA children achieved a catch-up in length at 5years with bone mineralization comparable to AGA children. Only for girls birth weight was significantly associated with length SDS (per gram: β 0.001; 95% CI (0.000, 0.003); p=0.03) There was no evidence of an association between early nutritional intake and bone mineralization. Children born as appropriate or small for

Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase.

PubMed

Armour, K E; Armour, K J; Gallagher, M E; Gödecke, A; Helfrich, M H; Reid, D M; Ralston, S H

2001-02-01

Nitric oxide (NO) is a pleiotropic signaling molecule that is produced by bone cells constitutively and in response to diverse stimuli such as proinflammatory cytokines, mechanical strain, and sex hormones. Endothelial nitric oxide synthase (eNOS) is the predominant NOS isoform expressed in bone, but its physiological role in regulating bone metabolism remains unclear. Here we studied various aspects of bone metabolism in female mice with targeted disruption of the eNOS gene. Mice with eNOS deficiency (eNOS KO) had reduced bone mineral density, and cortical thinning when compared with WT controls and histomorphometric analysis of bone revealed profound abnormalities of bone formation, with reduced osteoblast numbers, surfaces and mineral apposition rate. Studies in vitro showed that osteoblasts derived from eNOS KO mice had reduced rates of growth when compared with WT and were less well differentiated as reflected by lower levels of alkaline phosphatase activity. Mice with eNOS deficiency lost bone normally following ovariectomy but exhibited a significantly blunted anabolic response to high dose exogenous estrogen. We conclude that the eNOS pathway plays an essential role in regulating bone mass and bone turnover by modulating osteoblast function.

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

Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain

NASA Technical Reports Server (NTRS)

Owan, I.; Burr, D. B.; Turner, C. H.; Qiu, J.; Tu, Y.; Onyia, J. E.; Duncan, R. L.

1997-01-01

Mechanical force applied to bone produces two localized mechanical signals on the cell: deformation of the extracellular matrix (substrate strain) and extracellular fluid flow. To study the effects of these stimuli on osteoblasts, MC3T3-E1 cells were grown on type I collagen-coated plastic plates and subjected to four-point bending. This technique produces uniform levels of physiological strain and fluid forces on the cells. Each of these parameters can be varied independently. Osteopontin (OPN) mRNA expression was used to assess the anabolic response of MC3T3-E1 cells. When fluid forces were low, neither strain magnitude nor strain rate was correlated with OPN expression. However, higher-magnitude fluid forces significantly increased OPN message levels independently of the strain magnitude or rate. These data indicate that fluid forces, and not mechanical stretch, influence OPN expression in osteoblasts and suggest that fluid forces induced by extracellular fluid flow within the bone matrix may play an important role in bone formation in response to mechanical loading.

In vivo measurement of mechanical properties of human long bone by using sonic sound

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

Hossain, M. Jayed, E-mail: zed.hossain06@gmail.com; Rahman, M. Moshiur, E-mail: razib-121@yahoo.com; Alam, Morshed

Vibration analysis has evaluated as non-invasive techniques for the in vivo assessment of bone mechanical properties. The relation between the resonant frequencies, long bone geometry and mechanical properties can be obtained by vibration analysis. In vivo measurements were performed on human ulna as a simple beam model with an experimental technique and associated apparatus. The resonant frequency of the ulna was obtained by Fast Fourier Transformation (FFT) analysis of the vibration response of piezoelectric accelerometer. Both elastic modulus and speed of the sound were inferred from the resonant frequency. Measurement error in the improved experimental setup was comparable with themore » previous work. The in vivo determination of bone elastic response has potential value in screening programs for metabolic bone disease, early detection of osteoporosis and evaluation of skeletal effects of various therapeutic modalities.« less

Bone tissue reactions to biomimetic ion-substituted apatite surfaces on titanium implants.

PubMed

Ballo, Ahmed M; Xia, Wei; Palmquist, Anders; Lindahl, Carl; Emanuelsson, Lena; Lausmaa, Jukka; Engqvist, Håkan; Thomsen, Peter

2012-07-07

The aim of this study was to evaluate the bone tissue response to strontium- and silicon-substituted apatite (Sr-HA and Si-HA) modified titanium (Ti) implants. Sr-HA, Si-HA and HA were grown on thermally oxidized Ti implants by a biomimetic process. Oxidized implants were used as controls. Surface properties, i.e. chemical composition, surface thickness, morphology/pore characteristics, crystal structure and roughness, were characterized with various analytical techniques. The implants were inserted in rat tibiae and block biopsies were prepared for histology, histomorphometry and scanning electron microscopy analysis. Histologically, new bone formed on all implant surfaces. The bone was deposited directly onto the Sr-HA and Si-HA implants without any intervening soft tissue. The statistical analysis showed significant higher amount of bone-implant contact (BIC) for the Si-doped HA modification (P = 0.030), whereas significant higher bone area (BA) for the Sr-doped HA modification (P = 0.034), when compared with the non-doped HA modification. The differences were most pronounced at the early time point. The healing time had a significant impact for both BA and BIC (P < 0.001). The present results show that biomimetically prepared Si-HA and Sr-HA on Ti implants provided bioactivity and promoted early bone formation.

Early experience and results of bone graft enriched with autologous platelet gel for recalcitrant nonunions of lower extremity.

PubMed

Chiang, Chao-Ching; Su, Chen-Yao; Huang, Ching-Kuei; Chen, Wei-Ming; Chen, Tain-Hsiung; Tzeng, Yun-Hsuan

2007-09-01

Refractory nonunions of the tibia or femur are physically and mentally devastating conditions for the patients, and the treatment is challenging for orthopedic surgeons. The goal of this study was to assess the feasibility and outcome of surgical treatment in recalcitrant nonunions of a lower extremity with bone graft enriched with autologous platelet gel (APG). Twelve patients with four femoral and eight tibial atrophic nonunions after multiple prior procedures were included. All of them were treated with the bone grafting procedures with autograft complex enriched with APG. They were evaluated with radiographs, bone mineral density for bony healing process, and the Short-Form 36 Health Survey for functional outcome. Of the 12 patients, 11 healed at an average of 19.7 weeks after the first attempt and 1 healed after the second attempt at 21 weeks. The bone mineral density continued to increase steadily from early healing to the remodeling phase. Functional status was greatly improved at an average follow-up of 32.4 months. The results of this preliminary study implied the possible potential of bone graft enriched with APG in the treatment of recalcitrant nonunions of the lower extremity. More research is necessary to clarify its role in augmentation of bone graft to enhance healing of nonunion.

Early Onset of Laying and Bumblefoot Favor Keel Bone Fractures

PubMed Central

Gebhardt-Henrich, Sabine G.; Fröhlich, Ernst K. F.

2015-01-01

Simple Summary Numerous studies have documented a high prevalence of keel bone fractures in laying hens. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored. About 62% of the hens had broken keel bones at depopulation. More new fractures occurred during the time when laying rates were highest. Hens with broken keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. All birds with bumblefoot on both feet had a fracture at depopulation. Abstract Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID) from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely. PMID:26633520

The Lichfield bone study: the skeletal response to exercise in healthy young men

PubMed Central

Eleftheriou, Kyriacos I.; Kehoe, Anthony; James, Laurence E.; Payne, John R.; Skipworth, James R.; Puthucheary, Zudin A.; Drenos, Fotios; Pennell, Dudley J.; Loosemore, Mike; World, Michael; Humphries, Steve E.; Haddad, Fares S.; Montgomery, Hugh E.

2012-01-01

The skeletal response to short-term exercise training remains poorly described. We thus studied the lower limb skeletal response of 723 Caucasian male army recruits to a 12-wk training regime. Femoral bone volume was assessed using magnetic resonance imaging, bone ultrastructure by quantitative ultrasound (QUS), and bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) of the hip. Left hip BMD increased with training (mean ± SD: 0.85 ± 3.24, 2.93 ± 4.85, and 1.89 ± 2.85% for femoral neck, Ward's area, and total hip, respectively; all P < 0.001). Left calcaneal broadband ultrasound attenuation rose 3.57 ± 0.5% (P < 0.001), and left and right femoral cortical volume by 1.09 ± 4.05 and 0.71 ± 4.05%, respectively (P = 0.0001 and 0.003), largely through the rise in periosteal volume (0.78 ± 3.14 and 0.59 ± 2.58% for right and left, respectively, P < 0.001) with endosteal volumes unchanged. Before training, DXA and QUS measures were independent of limb dominance. However, the dominant femur had higher periosteal (25,991.49 vs. 2,5572 mm3, P < 0.001), endosteal (6,063.33 vs. 5,983.12 mm3, P = 0.001), and cortical volumes (19,928 vs. 19,589.56 mm3, P = 0.001). Changes in DXA, QUS, and magnetic resonance imaging measures were independent of limb dominance. We show, for the first time, that short-term exercise training in young men is associated not only with a rise in human femoral BMD, but also in femoral bone volume, the latter largely through a periosteal response. PMID:22114178

Early experience of placing image-guided minimally invasive pedicle screws without K-wires or bone-anchored trackers.

PubMed

Malham, Gregory M; Parker, Rhiannon M

2018-04-01

OBJECTIVE Image guidance for spine surgery has been reported to improve the accuracy of pedicle screw placement and reduce revision rates and radiation exposure. Current navigation and robot-assisted techniques for percutaneous screws rely on bone-anchored trackers and Kirchner wires (K-wires). There is a paucity of published data regarding the placement of image-guided percutaneous screws without K-wires. A new skin-adhesive stereotactic patient tracker (SpineMask) eliminates both an invasive bone-anchored tracker and K-wires for pedicle screw placement. This study reports the authors' early experience with the use of SpineMask for "K-wireless" placement of minimally invasive pedicle screws and makes recommendations for its potential applications in lumbar fusion. METHODS Forty-five consecutive patients (involving 204 screws inserted) underwent K-wireless lumbar pedicle screw fixation with SpineMask and intraoperative neuromonitoring. Screws were inserted by percutaneous stab or Wiltse incisions. If required, decompression with or without interbody fusion was performed using mini-open midline incisions. Multimodality intraoperative neuromonitoring assessing motor and sensory responses with triggered electromyography (tEMG) was performed. Computed tomography scans were obtained 2 days postoperatively to assess screw placement and any cortical breaches. A breach was defined as any violation of a pedicle screw involving the cortical bone of the pedicle. RESULTS Fourteen screws (7%) required intraoperative revision. Screws were removed and repositioned due to a tEMG response < 13 mA, tactile feedback, and 3D fluoroscopic assessment. All screws were revised using the SpineMask with the same screw placement technique. The highest proportion of revisions occurred with Wiltse incisions (4/12, 33%) as this caused the greatest degree of SpineMask deformation, followed by a mini midline incision (3/26, 12%). Percutaneous screws via a single stab incision resulted in the

Methoxsalen supplementation attenuates bone loss and inflammatory response in ovariectomized mice.

PubMed

Ham, Ju Ri; Choi, Ra-Yeong; Yee, Sung-Tae; Hwang, Yun-Ho; Kim, Myung-Joo; Lee, Mi-Kyung

2017-12-25

Methoxsalen (MTS) is a natural bioactive compound found in a variety of plants that has many known biofunctions; however, its effects on osteoporosis and related mechanisms are not clear. This study examined whether MTS exhibited preventive effects against postmenopausal osteoporosis. Female C3H/HeN mice were divided into four groups: Sham, ovariectomy (OVX), OVX with MTS (0.02% in diet), and OVX with estradiol (0.03 μg/day, s.c). After 6 weeks, MTS supplementation significantly increased femur bone mineral density and bone surface along with bone surface/total volume. MTS significantly elevated the levels of serum formation markers (estradiol, osteocalcin and bone-alkaline phosphatase) such as estradiol in OVX mice. Tartrate resistant acid phosphatase staining revealed that MTS suppressed osteoclast numbers and formation in femur tissues compared with the OVX group. Supplementation of MTS slightly up-regulated osteoblastogenesis-related genes (Runx-2, osterix, osteocalcin, and Alp) expression, whereas it significantly down-regulated inflammatory genes (Nfκb and Il6) expression in femur tissue compared with the OVX group. These results indicate that MTS supplementation effectively prevented OVX-induced osteoporosis via enhancement of bone formation and suppression of inflammatory response in OVX mice. Our study provides valid scientific information regarding the development and application of MTS as a food ingredient, a food supplement or an alternative agent for preventing postmenopausal osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Bone density and young athletic women. An update.

PubMed

Nichols, David L; Sanborn, Charlotte F; Essery, Eve V

2007-01-01

High-school girls and collegiate women have tremendous opportunities to participate in athletic teams. Young girls are also playing in club and select teams at an early age and often, year-round. There are many benefits for participating in sport and physical activity on both the physical and mental health of girls and women. Decreased risk for heart disease and diabetes mellitus, along with improved self-esteem and body-image, were among the first reported benefits of regular physical activity. In addition, sport participation and physical activity is also associated with bone health. Athletes have a greater bone mineral density compared with non-active and physically active females. The increase in bone mass should reduce the risk of fragility fractures in later life. There appears to be a window of opportunity during the development of peak bone mass in which the bone is especially responsive to weight-bearing physical activity. Impact loading sports such as gymnastics, rugby or volleyball tend to produce a better overall osteogenic response than sports without impact loading such as cycling, rowing and swimming. Relatively little is known about the impact of retiring from athletics on bone density. It appears that former athletes continue to have a higher bone density than non-athletes; however, the rate of bone loss appears to be similar in the femoral neck. The positive impact of sports participation on bone mass can be tempered by nutritional and hormonal status. It is not known whether female athletes need additional calcium compared with the general female population. Due to the increased energy expenditure of exercise and/or the pressure to obtain an optimal training bodyweight, some female athletes may develop low energy availability or an eating disorder and subsequently amenorrhoea and a loss of bone mineral density. The three inter-related clinical disorders are referred to as the 'female athlete triad'. This article presents a review of the

[Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Necessity of bone biopsy].

PubMed

Ito, Akemi; Yajima, Aiji

2011-09-01

Histological analysis of undecalcified bone biopsy specimens is a valuable clinical and research tool for studying the etiology, pathogenesis and treatment of metabolic bone diseases. In case of osteoporosis, bone biopsy is not usually required for the diagnosis ; however, bone histomorphometry may be useful in rare cases with unusual skeletal fragility. Bone histomorphometry also provides valuable information on the mechanism of action, safety and efficacy of new anti-osteoporosis drugs. Bone histomorphometry is useful for the diagnosis and the assessment of treatment response in rickets/osteomalacia and in CKD-MBD (chronic kidney disease-mineral and bone disorders) . In Japan, bone biopsy is often performed to establish the diagnosis of Paget's disease of bone, especially to differentiate it from metastatic bone disease.

Collagen Membrane and Immune Response in Guided Bone Regeneration: Recent Progress and Perspectives.

PubMed

Chu, Chenyu; Deng, Jia; Sun, Xianchang; Qu, Yili; Man, Yi

2017-10-01

Collagen is one of the important components of collagen membranes as well as the extracellular matrix (ECM). Most previous studies have focused on combining collagen membranes with various cross-linking agents, grafting materials, and cytokines to enhance their mechanical properties and bioactivities. Moreover, collagen membranes are often designed to minimize foreign body reactions involving macrophages. However, macrophages were recently found to play a pivotal role during bone regeneration based on their polarization into both proinflammatory and anti-inflammatory phenotypes. Because of the abilities to modulate macrophage polarization and mediate the balance of proinflammatory and anti-inflammatory microenvironments, immune-responsive collagen membranes may be an innovative strategy for promoting bone regeneration. Herein, following a brief review of collagen membranes and the background of macrophages, recent modulations and studies of immune-responsive collagen are described to express the potential of collagen interacting with macrophages and the necessity of further studies in the field of immune-responsive collagen membranes.

Early consumption of blueberry diet protects against sex steroid deficiency-induced bone loss in adult female rats

USDA-ARS?s Scientific Manuscript database

We studied the effects of blueberry consumption in early development on bone loss in ovariectomized (OVX) female rats later in life. Weanling female rats were fed AIN-93G semi-purified diets supplemented with 10% whole blueberry powder from PND 21 to PND34 (short-term group), or PND21 to PND81 (chro...

Miniscrew design and bone response: defining a correlation.

PubMed

Bhalla, Karan; Kalha, Anmol S

2013-01-01

This prospective clinical trial aims at correlating miniscrew implant (MSI) micro/macro architecture, the method of placement, and biologic markers in peri-MSI crevicular fluid (PMICF) as indicators of bone response. A comparative evaluation of surface morphology of the MSIs before placement and after retrieval defines a correlation between the architecture of the MSIs and the bone- implant contact ratio. Two types of MSIs (hybrid and cylindric) were placed in ten patients using a split-mouth technique with the aid of a restricted random number table. Each of the MSIs was placed in the intraradicular area between the second premolar and first molar in the attached gingiva, 4 mm from the cementoenamel junction. The MSIs were immediately loaded, and PMICF was collected on days 0, 7, 14, 21, 28, and 42 and evaluated using a standard laboratory protocol. Surface morphology before placement and after retrieval of the MSI was observed using scanning electron microscopy (SEM) at a magnification of ×11, ×40, and ×1,000. Alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels observed were lower in the hybrid MSI in comparison to the cylindric MSI. For both MSIs, ALP and AST levels showed a trend of significant increase at days 0, 7, and 14 and then a significant decrease on days 21, 28, and 42. Observations from SEM showed an oxide layer over the entire surface of the bone-expanding hybrid MSI; this layer was observed only at the tip of the cylindric MSI. Levels of both the diagnostic tissue destruction biologic markers ALP and AST are significantly higher in cylindric MSIs compared with hybrid MSIs, indicating a correlation to the type and method of placement of the MSI. The inflammatory markers show a definitive trend, with an elevation until day 14 and a decline after that, indicating an active inflammatory process until day 14 that could be correlated to tissue trauma. Observations from the SEM show a greater oxide layer formation in the hybrid MSI

Differential response of bone and kidney to ACEI in db/db mice: A potential effect of captopril on accelerating bone loss.

PubMed

Zhang, Yan; Li, Xiao-Li; Sha, Nan-Nan; Shu, Bing; Zhao, Yong-Jian; Wang, Xin-Luan; Xiao, Hui-Hui; Shi, Qi; Wong, Man-Sau; Wang, Yong-Jun

2017-04-01

The components of renin-angiotensin system (RAS) are expressed in the kidney and bone. Kidney disease and bone injury are common complications associated with diabetes. This study aimed to investigate the effects of an angiotensin-converting enzyme inhibitor, captopril, on the kidney and bone of db/db mice. The db/db mice were orally administered by gavage with captopril for 8weeks with db/+ mice as the non-diabetic control. Serum and urine biochemistries were determined by standard colorimetric methods or ELISA. Histological measurements were performed on the kidney by periodic acid-schiff staining and on the tibial proximal metaphysis by safranin O and masson-trichrome staining. Trabecular bone mass and bone quality were analyzed by microcomputed tomography. Quantitative polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. Captopril significantly improved albuminuria and glomerulosclerosis in db/db mice, and these effects might be attributed to the down-regulation of angiotensin II expression and the expression of its down-stream profibrotic factors in the kidney, like connective tissue growth factor and vascular endothelial growth factor. Urinary excretion of calcium and phosphorus markedly increased in db/db mice in response to captopril. Treatment with captopril induced a decrease in bone mineral density and deterioration of trabecular bone at proximal metaphysis of tibia in db/db mice, as shown in the histological and reconstructed 3-dimensional images. Even though captopril effectively reversed the diabetes-induced changes in calcium-binding protein 28-k and vitamin D receptor expression in the kidney as well as the expression of RAS components and bradykinin receptor-2 in bone tissue, treatment with captopril increased the osteoclast-covered bone surface, reduced the osteoblast-covered bone surface, down-regulated the expression of type 1 collagen and transcription factor runt-related transcription

Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

NASA Technical Reports Server (NTRS)

Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

2015-01-01

Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats.

PubMed

van der Stok, Johan; Lozano, Daniel; Chai, Yoke Chin; Amin Yavari, Saber; Bastidas Coral, Angela P; Verhaar, Jan A N; Gómez-Barrena, Enrique; Schrooten, Jan; Jahr, Holger; Zadpoor, Amir A; Esbrit, Pedro; Weinans, Harrie

2015-05-01

A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous titanium is improved with a coating of osteostatin, an osteoinductive peptide that consists of the 107-111 domain of the parathyroid hormone (PTH)-related protein (PTHrP), and the effects of this osteostatin coating on bone regeneration were evaluated in vitro and in vivo. SLM-produced porous titanium received an alkali-acid-heat treatment and was coated with osteostatin through soaking in a 100 nM solution for 24 h or left uncoated. Osteostatin-coated scaffolds contained ∼0.1 μg peptide/g titanium, and in vitro 81% was released within 24 h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin-coated scaffolds did not induce significant changes in osteogenic (alkaline phosphatase [ALP], collagen type 1 [Col1], osteocalcin [OCN], runt-related transcription factor 2 [Runx2]), or angiogenic (vascular endothelial growth factor [VEGF]) gene expression; however, it resulted in an upregulation of osteoprotegerin (OPG) gene expression after 24 h and a lower receptor activator of nuclear factor kappa-B ligand (RankL):OPG mRNA ratio. In vivo, osteostatin-coated, porous titanium implants increased bone regeneration in critical-sized cortical bone defects (p=0.005). Bone regeneration proceeded until 12 weeks, and femurs grafted with osteostatin-coated implants and uncoated implants recovered, respectively, 66% and 53% of the original femur torque strength (97±31 and 77±53 N·mm, not significant). In conclusion, the osteostatin coating improved bone regeneration of porous titanium. This effect was initiated after a short burst release and might be related to the observed in vitro upregulation of OPG gene expression by osteostatin in osteoprogenitor

Th1 biased response to a novel Porphyromonas gingivalis protein aggravates bone resorption caused by this oral pathogen

PubMed Central

Leshem, Onir; Kashino, Suely S.; Gonçalves, Reginaldo B.; Suzuki, Noriyuki; Onodera, Masao; Fujimura, Akira; Sasaki, Hajime; Stashenko, Philip; Campos-Neto, Antonio

2013-01-01

In previous studies we showed that biasing the immune response to Porphyromonas gingivalis antigens to the Th1 phenotype increases inflammatory bone resorption caused by this organism. Using a T cell screening strategy we identified eight P. gingivalis genes coding for proteins that appear to be involved in T-helper cell responses. In the present study we characterized the protein, encoded by PG_1841 gene and evaluated its relevance in the in bone resorption caused by P. gingivalis because subcutaneous infection of mice with this organism resulted in the induction of Th1 biased response to the recombinant PG1841 antigen molecule. Using an immunization regime that strongly biases toward the Th1 phenotype followed by challenge with P. gingivalis in dental pulp tissue, we demonstrate that mice pre-immunized with rPG1841 developed severe bone loss compared with control immunized mice. Pre-immunization of mice with the antigen using a Th2 biasing regime resulted in no exacerbation of the disease. These results support the notion that selected antigens of P. gingivalis are involved in a biased Th1 host response that leads to the severe bone loss caused by this oral pathogen. PMID:18457976

Impact of ¹⁸F-fluoride PET-CT on implementing early treatment of painful bone metastases with Sm-153 EDTMP.

PubMed

Storto, Giovanni; Gallicchio, Rosj; Pellegrino, Teresa; Nardelli, Anna; De Luca, Serena; Capacchione, Daniela; Sirignano, Cesare; Pace, Leonardo

2013-05-01

This study evaluated the diagnostic impact of using skeletal (18)F-fluoride PET/CT on patients with painful bone metastases to schedule an early palliative radionuclide treatment. The skeletal involvement from prostate cancer metastases was assessed by both (99m)Tc-diphosphonate bone scan (BS) and (18)F-fluoride PET/CT within four weeks in 24 patients (67.7 ± 5.1 years) suffering from a borderline degree of bone pain for which radionuclide palliation was not shortly planned for administration. The BS and (18)F-fluoride PET/CT results were compared, assessing the number and extension of the skeletal sites involved. Afterward, the patients were randomly assigned either to the study group (N=12) receiving radionuclide therapy (Samarium-153 EDTMP) or to the control group (N=12) not receiving radionuclide therapy. The short-term results from the radionuclide palliation group (evaluated with a visual analogue scale) were compared with the controls. Overall, at BS, 7.6 ± 1.4 sites were considered metastatic, involving at least 5 ± 1 body regions. At (18)F-fluoride PET/CT, 116 ± 19 sites presented metastatic involvement with 12/12 body regions concerned. No differences were found in regards to either the number of metastatic sites or regions at both BS and (18)F-fluoride PET/CT between the study group and controls (p=ns). At CT, 88 blastic metastases were identified, whereas 110 were mainly lytic. Most of mainly lytic lesions were not detectable at BS. The reduction in total discomfort and bone pain in the study group was significantly greater than in the controls (p<0.0001). Sm-153 EDTMP therapy should be considered for patients with early bone pain from prostate cancer even if their BS only indicates a few metastases before the initiation of a severe pain syndrome. (18)F-fluoride PET/CT may be helpful in deciding if the implementation of bone pain palliation using bone-seeking radionuclides at pain onset is necessary. Copyright © 2013 Elsevier Inc. All rights

Effects of exemestane, anastrozole and tamoxifen on bone mineral density and bone turnover markers in postmenopausal early breast cancer patients: results of N-SAS BC 04, the TEAM Japan substudy.

PubMed

Aihara, T; Suemasu, K; Takei, H; Hozumi, Y; Takehara, M; Saito, T; Ohsumi, S; Masuda, N; Ohashi, Y

2010-01-01

Use of aromatase inhibitors in women with postmenopausal breast cancer accompanies risks of bone loss. We evaluated changes in bone mineral density (BMD) and bone turnover markers in patients treated with exemestane, anastrozole or tamoxifen for hormone-sensitive postmenopausal early breast cancer. Sixty-eight patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational Japan bone substudy were randomly assigned to receive tamoxifen, exemestane or anastrozole. During a 2-year study period, lumbar spine BMD was measured using dual-energy X-ray absorptiometry, and urinary type I collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP) were also measured. BMD at 2 years of treatment was higher in tamoxifen patients compared with exemestane and anastrozole patients; however, the intergroup difference was not significant (p = 0.2521 and p = 0.0753, respectively). BMD was higher in exemestane patients compared with anastrozole patients; however, the intergroup difference was not significant (p = 0.7059 and p = 0.8134, respectively). NTX and BAP were significantly lower in tamoxifen patients compared with exemestane and anastrozole patients at 1 and 2 years of treatment (p < 0.05). Tamoxifen may provide better bone protection compared with exemestane or anastrozole. The effect of exemestane and anastrozole on bone loss may be comparable in Japanese postmenopausal women. Copyright © 2011 S. Karger AG, Basel.

Experiment K305: Quantitative analysis of selected bone parameters. Supplement 2: Bone elongation rate and bone mass in metaphysis of long bones

NASA Technical Reports Server (NTRS)

Jee, W. S. S.; Kimmel, D. B.; Smith, C.; Dell, R. B.

1981-01-01

The proximal humeral metaphysis of rats from time periods recovery plus zero days (R+0), recovery plus six days (R+6), and recovery plus twenty nine days (R+29) was analyzed. The volume of calcified cartilage and bone in flight and synchronous controls was reduced in groups R+0 and R+6, but was normal in group R+29. The number of functional bone cells (osteoblasts and osteoclasts) was decreased in proportion to the amount of bone in the early groups, and was normal in the last group. The fatty marrow volume was increased only in flight animals of groups R+0 and R+6, but was normal in the R+29 group. Accumulation of excess fatty marrow was seen only in flight animals. The decreased amount of bone and calcified cartilage is believed to be the result of a temporarily slowed or arrested production of calcified cartilage as a substrate for bone formation. This would have resulted from slowed bone elongation during flight and synchronous control conditions. Bone elongation returned to normal by twenty nine days after return.

Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition

PubMed Central

2013-01-01

Background In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. Methods Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. Conclusions Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair. PMID:23324433

A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength

PubMed Central

Baud’huin, Marc; Solban, Nicolas; Cornwall-Brady, Milton; Sako, Dianne; Kawamoto, Yoshimi; Liharska, Katia; Lath, Darren; Bouxsein, Mary L.; Underwood, Kathryn W.; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Seehra, Jasbir; Canalis, Ernesto; Pearsall, R. Scott; Croucher, Peter I.

2012-01-01

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. Ablation of the BMPR1A receptor in osteoblasts increases bone mass, suggesting that inhibition of BMPR1A signaling may have therapeutic benefit. The aim of this study was to determine the skeletal effects of systemic administration of a soluble BMPR1A fusion protein (mBMPR1A–mFc) in vivo. mBMPR1A–mFc was shown to bind BMP2/4 specifically and with high affinity and prevent downstream signaling. mBMPR1A–mFc treatment of immature and mature mice increased bone mineral density, cortical thickness, trabecular bone volume, thickness and number, and decreased trabecular separation. The increase in bone mass was due to an early increase in osteoblast number and bone formation rate, mediated by a suppression of Dickkopf-1 expression. This was followed by a decrease in osteoclast number and eroded surface, which was associated with a decrease in receptor activator of NF-κB ligand (RANKL) production, an increase in osteoprotegerin expression, and a decrease in serum tartrate-resistant acid phosphatase (TRAP5b) concentration. mBMPR1A treatment also increased bone mass and strength in mice with bone loss due to estrogen deficiency. In conclusion, mBMPR1A–mFc stimulates osteoblastic bone formation and decreases bone resorption, which leads to an increase in bone mass, and offers a promising unique alternative for the treatment of bone-related disorders. PMID:22761317

Linear undisplaced fracture of temporoparietal bone acting as spontaneous early decompressive craniotomy in a neonate

PubMed Central

Vankipuram, Siddharth; Balasubramanium, Srikant; Tyagi, Devendra K.; Savant, H. V.

2015-01-01

Decompressive craniotomy (DC) is used to treat intracranial hypertension associated with traumatic brain injury. Early DC is associated with better outcomes. We present a neonate with a history of fall with computed tomography scan showing a large frontoparietal contusion and associated parietal and temporal bone fracture. This acted as a spontaneous DC causing bony segment to separate due to which the edematous brain could be accommodated. Despite the presence of a large contusion, the child was neurologically intact and medically managed. The neonate presented with a posttraumatic leptomeningeal cyst 2 months later, which had to be repaired surgically. We discuss how a linear undisplaced fracture acts as spontaneous DC and the role of early DC in improving outcomes. PMID:26557171

Src Homology 2–containing 5-Inositol Phosphatase (SHIP) Suppresses an Early Stage of Lymphoid Cell Development through Elevated Interleukin-6 Production by Myeloid Cells in Bone Marrow

PubMed Central

Nakamura, Koji; Kouro, Taku; Kincade, Paul W.; Malykhin, Alexander; Maeda, Kazuhiko; Coggeshall, K. Mark

2004-01-01

The Src homology (SH)2–containing inositol 5-phosphatase (SHIP) negatively regulates a variety of immune responses through inhibitory immune receptors. In SHIP−/− animals, we found that the number of early lymphoid progenitors in the bone marrow was significantly reduced and accompanied by expansion of myeloid cells. We exploited an in vitro system using hematopoietic progenitors that reproduced the in vivo phenotype of SHIP−/− mice. Lineage-negative marrow (Lin−) cells isolated from wild-type mice failed to differentiate into B cells when cocultured with those of SHIP−/− mice. Furthermore, culture supernatants of SHIP−/− Lin− cells suppressed the B lineage expansion of wild-type lineage-negative cells, suggesting the presence of a suppressive cytokine. SHIP−/− Lin− cells contained more IL-6 transcripts than wild-type Lin− cells, and neutralizing anti–IL-6 antibody rescued the B lineage expansion suppressed by the supernatants of SHIP−/− Lin− cells. Finally, we found that addition of recombinant IL-6 to cultures of wild-type Lin− bone marrow cells reproduced the phenotype of SHIP−/− bone marrow cultures: suppression of B cell development and expansion of myeloid cells. The results identify IL-6 as an important regulatory cytokine that can suppress B lineage differentiation and drive excessive myeloid development in bone marrow. PMID:14718513

Bone Morphogenetic Protein 15 (BMP15) Acts as a BMP and Wnt Inhibitor during Early Embryogenesis*

PubMed Central

Di Pasquale, Elisa; Brivanlou, Ali H.

2009-01-01

Bone morphogenetic protein 15 (BMP15) belongs to an unusual subgroup of the transforming growth factor β (TGFβ) superfamily of signaling ligands as it lacks a key cysteine residue in the mature region required for proper intermolecular dimerization. Naturally occurring BMP15 mutation leads to early ovarian failure in humans, and BMP15 has been shown to activate the Smad1/5/8 pathway in that context. Despite its important role in germ cell specification, the embryological function of BMP15 remains unknown. Surprisingly, we find that during early Xenopus embryogenesis BMP15 acts solely as an inhibitor of the Smad1/5/8 pathway and the Wnt pathway. BMP15 gain-of-function leads to embryos with secondary ectopic heads and to direct neural induction in intact explants. BMP15 inhibits BMP4-mediated epidermal induction in dissociated explants. BMP15 strongly inhibits BRE response induced by BMP4 and blocks phosphorylation and activation of Smad1/5/8 MH2-domain. Mechanistically, BMP15 protein specifically interacts with BMP4 protein, suggesting inhibition upstream of receptor binding. Loss-of-function experiments using morpholinos or a naturally occurring human BMP15 dominant-negative mutant (BMP15-Y235C) leads to embryos lacking head. BMP15-Y235C also eliminates the inhibitory activity of BMP15 on BRE (BMP-responsive element). Finally, we show that BMP15 inhibits the canonical branch of the Wnt pathway, upstream of β-catenin. We, thus, demonstrate that BMP15 is necessary and sufficient for the specification of dorso-anterior structures and highlight novel mechanisms of BMP15 function that strongly suggest a reinterpretation of its function in ovaries specially for ovarian failure. PMID:19553676

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas

DOE PAGES

Benz, Matthias R.; Czernin, Johannes; Tap, William D.; ...

2010-01-01

Purpose . Tmore » he aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods . Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results . Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders ( 64 ± 19 % versus 29 ± 30 %, resp.; P = .03 ). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion . These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.« less

Early Onset of Laying and Bumblefoot Favor Keel Bone Fractures.

PubMed

Gebhardt-Henrich, Sabine G; Fröhlich, Ernst K F

2015-11-27

Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID) from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely.

Flexoelectricity in Bones.

PubMed

Vasquez-Sancho, Fabian; Abdollahi, Amir; Damjanovic, Dragan; Catalan, Gustau

2018-03-01

Bones generate electricity under pressure, and this electromechanical behavior is thought to be essential for bone's self-repair and remodeling properties. The origin of this response is attributed to the piezoelectricity of collagen, which is the main structural protein of bones. In theory, however, any material can also generate voltages in response to strain gradients, thanks to the property known as flexoelectricity. In this work, the flexoelectricity of bone and pure bone mineral (hydroxyapatite) are measured and found to be of the same order of magnitude; the quantitative similarity suggests that hydroxyapatite flexoelectricity is the main source of bending-induced polarization in cortical bone. In addition, the measured flexoelectric coefficients are used to calculate the (flexo)electric fields generated by cracks in bone mineral. The results indicate that crack-generated flexoelectricity is theoretically large enough to induce osteocyte apoptosis and thus initiate the crack-healing process, suggesting a central role of flexoelectricity in bone repair and remodeling. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones.

PubMed

Kaiplavil, Sreekumar; Mandelis, Andreas; Wang, Xueding; Feng, Ting

2014-08-01

Salient features of a new non-ionizing bone diagnostics technique, truncated-correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established. Selective imaging of regions of a specific mineral density range has been demonstrated in a mouse femur. The method is maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a depth range of ~3.8 mm has been achieved, which can be increased through instrumental and modulation waveform optimization. Furthermore, photoacoustic microscopy, a comparable modality with TC-PCT, has been used to resolve the trabecular structure and for comparison with the photothermal tomography.

Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones

PubMed Central

Kaiplavil, Sreekumar; Mandelis, Andreas; Wang, Xueding; Feng, Ting

2014-01-01

Salient features of a new non-ionizing bone diagnostics technique, truncated-correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established. Selective imaging of regions of a specific mineral density range has been demonstrated in a mouse femur. The method is maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a depth range of ~3.8 mm has been achieved, which can be increased through instrumental and modulation waveform optimization. Furthermore, photoacoustic microscopy, a comparable modality with TC-PCT, has been used to resolve the trabecular structure and for comparison with the photothermal tomography. PMID:25136480

Inter-species investigation of the mechano-regulation of bone healing: comparison of secondary bone healing in sheep and rat.

PubMed

Checa, Sara; Prendergast, Patrick J; Duda, Georg N

2011-04-29

Inter-species differences in regeneration exist in various levels. One aspect is the dynamics of bone regeneration and healing, e.g. small animals show a faster healing response when compared to large animals. Mechanical as well as biological factors are known to play a key role in the process. However, it remains so far unknown whether different animals follow at all comparable mechano-biological rules during tissue regeneration, and in particular during bone healing. In this study, we investigated whether differences observed in vivo in the dynamics of bone healing between rat and sheep are only due to differences in the animal size or whether these animals have a different mechano-biological response during the healing process. Histological sections from in vivo experiments were compared to in silico predictions of a mechano-biological computer model for the simulation of bone healing. Investigations showed that the healing processes in both animal models occur under significantly different levels of mechanical stimuli within the callus region, which could explain histological observations of early intramembranous ossification at the endosteal side. A species-specific adaptation of a mechano-biological model allowed a qualitative match of model predictions with histological observations. Specifically, when keeping cell activity processes at the same rate, the amount of tissue straining defining favorable mechanical conditions for the formation of bone had to be increased in the large animal model, with respect to the small animal, to achieve a qualitative agreement of model predictions with histological data. These findings illustrate that geometrical (size) differences alone cannot explain the distinctions seen in the histological appearance of secondary bone healing in sheep and rat. It can be stated that significant differences in the mechano-biological regulation of the healing process exist between these species. Future investigations should aim towards

Marginal Bone Loss Around Early-Loaded SLA and SLActive Implants: Radiological Follow-Up Evaluation Up to 6.5 Years.

PubMed

Şener-Yamaner, Işil Damla; Yamaner, Gökhan; Sertgöz, Atilla; Çanakçi, Cenk Fatih; Özcan, Mutlu

2017-08-01

The aim of this study was to compare marginal bone loss around early-loaded SLA and SLActive tissue-level implants (Straumann Dental Implants; Institut Straumann AG, Basel, Switzerland) after a mean of 81-month follow-up period. One hundred seven SLA and 68 SLActive implants were placed in 55 patients and loaded with final restoration after 8 and 3 weeks of healing time, respectively. Marginal bone loss around implants was determined radiographically at initial and after a mean observation time ranging between 20 and 81 months. The effect of location (mandible vs maxilla), smoking habit, sex, implant length and diameter, and the type of prosthesis on the marginal bone loss was evaluated. The overall cumulative survival rate was 98.2% being 99% for SLA implants and 97% for SLActive implants. After 20-month follow-up period, mean marginal bone loss values for the SLA and SLActive implants were 0.24 and 0.17 mm, respectively. After 81 months, mean marginal bone loss for the SLA and SLActive implants reached 0.71 and 0.53 mm, respectively. Marginal bone loss was affected by the length and type of implant and patients' smoking habit after a mean observation time of 20 months. However, none of the parameters had any significant effect on the marginal bone loss after a follow-up period of 81 months. With both SLA and SLActive implants, successful clinical results could be achieved up to 6.5 years of follow-up period.

Bone response to collagenized xenografts of porcine origin (mp3(®) ) and a bovine bone mineral grafting (4BONE(™) XBM) grafts in tibia defects: experimental study in rabbits.

PubMed

Calvo-Guirado, José Luis; Aguilar-Salvatierra, Antonio; Ramírez-Fernández, Maria P; Maté Sánchez de Val, José E; Delgado-Ruiz, Rafael Arcesio; Gómez-Moreno, Gerardo

2016-08-01

This study aimed to carry out the evaluation of bone response of new bone formation to two different xenografts (bovine and porcine) biomaterials inserted in rabbit tibiae. The study used a total of 20 male New Zealand albino rabbits. They received a total of 40 grafts in the proximal metaphyseal areas of both tibiae. Two biomaterials were evaluated: 20 porcine xenografts, as a bone granulate (OsteoBiol(®) MP3(®) ; Tecnoss srl, Giaveno, Italy), were placed in the proximal metaphyseal area of the right tibia, 20 anorganic bovine bone mineral grafting (4BONE(™) XBM, MIS Implants Inc., BARLEV, Israel) were placed in the left tibia. Following graft insertion, the animals were sacrificed in two groups of 10 animals, after 1 and 4 months, respectively. For each group, biomaterials were analyzed: newly formed bone, residual graft materials and the connective tissue. Histomorphometric, EDX analysis and element mapping were performed at 1 and 4 months after graft insertion. At 4 months after treatment, the bone defects displayed radiological images that showed complete repair of osseous defects. Histomorphometric evaluation showed that for the porcine xenograft, the study averages for newly formed bone represented 84.23 ± 2.9%, while bovine matrix was 79.34 ± 2.1%. For residual graft material, the porcine biomaterial had 11.23 ± 1.7% and the bovine graft 31.56 ± 2.3%. Finally, the connective tissue for MP3 was 10.33 ± 1.8%, while for the 4BONE(™) XBM we obtained 14.34 ± 2.9%. Element analysis revealed higher percentages of Ca (54 ± 9%) and P (35 ± 6%) in the group B than group A and control group (P < 0.05). Defects of a critical size in a rabbit tibia model can be sealed using a bovine porous biphasic calcium phosphate and MP3 material; this supports new bone formation, creates a bridge between borders, and facilitates bone ingrowth in both biomaterials. Furthermore, this study observed partial dissolution of the mineral phase of four

Bone response to a novel Ti-Ta-Nb-Zr alloy.

PubMed

Stenlund, Patrik; Omar, Omar; Brohede, Ulrika; Norgren, Susanne; Norlindh, Birgitta; Johansson, Anna; Lausmaa, Jukka; Thomsen, Peter; Palmquist, Anders

2015-07-01

Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al-4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis.

PubMed

Fang, Hang; Huang, Lisi; Welch, Ian; Norley, Chris; Holdsworth, David W; Beier, Frank; Cai, Daozhang

2018-02-12

To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.

BIOCHEMICAL ANALYSIS AND BONE REMODELING IN RESPONSE TO OOPHORECTOMY AND AQUATIC TRAINING

PubMed Central

SOUZA, HELENA RIBEIRO; GIROL, ANA PAULA; SCHIAVETO, ADRIANA PAULA SANCHEZ; GEROMEL, MAIRTO ROBERIS; IYOMASA, MELINA MIZUSAKI; ARRUDA, MAURÍCIO FERRAZ DE

2016-01-01

ABSTRACT Objective: To investigate whether swimming could prevent bone loss and could be indicated to assist in treatment of osteoporosis. Methods: Female rats were divided into 4 groups (n=6), two of them were oophorectomized. Animals from two groups, one oophorectomized and another not oophorectomized, underwent aquatic training for eight weeks. After training, the animals were sacrificed and their blood was collected for calcium and alkaline phosphatase serum dosage; the femur was removed and subjected to radiological and histological densitometry analysis to assess bone loss and osteoclast counting on femoral head and neck. Results: Increase in serum calcium was not observed. There was an increasing activity of alkaline phosphatase in the oophorectomized groups. The radiographs suggest that there was a greater bone mass density in the trained groups. Concerning histology, the trained groups had better tissue structural organization than the sedentary groups. In the oophorectomized and sedentary group, higher presence of osteoclasts was observed a. Conclusion: Exercise and oophorectomy did not promote changes in serum calcium levels. The decrease of sex steroids caused by oophorectomy was responsible for severe bone loss, but swimming exercise was able to reduce this loss. Oophorectomy promoted the proliferation of osteoclasts and the exercise proved to be able to diminish it. Level of Evidence I, Experimental Study. PMID:28149187

Serum markers of bone metabolism show bone loss in hibernating bears

USGS Publications Warehouse

Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

2003-01-01

Disuse osteopenia was studied in hibernating black bears (Ursus americanus) using serum markers of bone metabolism. Blood samples were collected from male and female, wild black bears during winter denning and active summer periods. Radioimmunoassays were done to determine serum concentrations of cortisol, the carboxy-terminal cross-linked telopeptide, and the carboxy-terminal propeptide of Type I procollagen, which are markers of hone resorption and formation, respectively. The bone resorption marker was significantly higher during winter hibernation than it was in the active summer months, but the bone formation marker was unchanged, suggesting an imbalance in bone remodeling and a net bone loss during disuse. Serum cortisol was significantly correlated with the bone resorption marker, but not with the bone formation marker. The bone formation marker was four- to fivefold higher in an adolescent and a 17-year-old bear early in the remobilization period compared with the later summer months. These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining osteoblastic function and have a more efficient compensatory mechanism for recovering immobilization-induced bone loss than that of humans or other animals.

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

Multiscale Analyses of the Bone-implant Interface

PubMed Central

Cha, J.Y.; Pereira, M.D.; Smith, A.A.; Houschyar, K.S.; Yin, X.; Mouraret, S.; Brunski, J.B.

2015-01-01

Implants placed with high insertion torque (IT) typically exhibit primary stability, which enables early loading. Whether high IT has a negative impact on peri-implant bone health, however, remains to be determined. The purpose of this study was to ascertain how peri-implant bone responds to strains and stresses created when implants are placed with low and high IT. Titanium micro-implants were inserted into murine femurs with low and high IT using torque values that were scaled to approximate those used to place clinically sized implants. Torque created in peri-implant tissues a distribution and magnitude of strains, which were calculated through finite element modeling. Stiffness tests quantified primary and secondary implant stability. At multiple time points, molecular, cellular, and histomorphometric analyses were performed to quantitatively determine the effect of high and low strains on apoptosis, mineralization, resorption, and collagen matrix deposition in peri-implant bone. Preparation of an osteotomy results in a narrow zone of dead and dying osteocytes in peri-implant bone that is not significantly enlarged in response to implants placed with low IT. Placing implants with high IT more than doubles this zone of dead and dying osteocytes. As a result, peri-implant bone develops micro-fractures, bone resorption is increased, and bone formation is decreased. Using high IT to place an implant creates high interfacial stress and strain that are associated with damage to peri-implant bone and therefore should be avoided to best preserve the viability of this tissue. PMID:25628271

The bones of the insane

PubMed Central

2013-01-01

This article examines alienist explanations for fracture among British asylum patients in the late nineteenth to early twentieth centuries. A series of deaths in asylums came to light in the 1870s which, in placing the blame for such incidents on asylum staff, called for a response from the psychiatric profession. This response drew upon other medical fields and employed novel pathological techniques to explain why fractures occurred among the insane, in many cases aligning bone fragility with particular forms of insanity (namely, General Paralysis of the Insane). Although such research aimed to provide a medical explanation for the ‘fracture death’, it also called into question the value of pathological research and the utility of quantitative measurement in understanding mental disease. PMID:24573259

Parathyroid hormone regulation of the human bone sialoprotein gene transcription is mediated through two cAMP response elements.

PubMed

Araki, Shouta; Mezawa, Masaru; Sasaki, Yoko; Yang, Li; Li, Zhengyang; Takai, Hideki; Nakayama, Youhei; Ogata, Yorimasa

2009-03-01

Parathyroid hormone (PTH) regulates serum calcium and inorganic phosphate levels through its actions on kidney and bone. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation and bone metabolism. We here report that two cAMP response elements (CRE) in the human BSP gene promoter are target of PTH. In human osteoblast-like Saos2 cells, PTH (human 1-34 PTH, 10 nM) increased BSP mRNA and protein levels at 3 h. From transient transfection assays, 2- to 2.5-fold increase in transcription by PTH was observed at 3 and 6 h in -184, -211, -428, -868, and -927 luciferase constructs that included the human BSP gene promoter. Effect of PTH was abrogated by 2 bp mutations in either the CRE1 (-79 to -72) or CRE2 (-674 to -667). Luciferase activities induced by PTH were blocked by protein kinase A inhibitor H89 and tyrosine kinase inhibitor herbimycin A. Gel shift analyses showed that PTH increased binding of nuclear proteins to the CRE1 and CRE2 elements. The CRE1-protein and CRE2-protein complexes were disrupted by CRE binding protein 1 (CREB1) antibodies and supershifted by phospho-CREB1 antibody. ChIP assays detected binding of CREB1 and phospho-CREB1 to a chromatin fragment containing CRE1 and CRE2, and increased binding of phospho-CREB1 to the both sites. These studies demonstrate that PTH stimulates human BSP gene transcription by targeting the two CREs in the promoter of the human BSP gene.

Paget's disease of jaw bones as primary manifestation: A case report of a proper diagnosis made by general dentist.

PubMed

Campolongo, Martin G; Cabras, Marco; Bava, Luca; Arduino, Paolo G; Carbone, Mario

2018-06-01

To present a case of early diagnosis mandibular Paget's disease of bone (PDB), recognised by a general dentist. PDB is responsible of rapid bone resorption and disorganised bone formation. The patient was a 72-year-old female patient complaining of dental malposition and blatant prognathism. Clinicians should consider PDB in differential diagnosis for an elderly patient undergoing unexplained alteration in face profile and occlusion. © 2018 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Early Loading of Fluoridated Implants Placed in Fresh Extraction Sockets and Healed Bone: A 3- to 5-Year Clinical and Radiographic Follow-Up Study of 39 Consecutive Patients.

PubMed

Oxby, Gert; Oxby, Fredrik; Oxby, Johan; Saltvik, Tomas; Nilsson, Peter

2015-10-01

Immediate placement of implants in extraction sockets for early loading is an attractive treatment modality due to reduced treatment time. However, the outcome of fluoridated implants in this situation with regard to bone levels and health of soft tissues is not well documented. To evaluate the outcome of early loading of OsseoSpeed(™) dental implants placed into fresh extraction sockets and healed bone in consecutive patients treated in a private clinic. A total of 182 OsseoSpeed(™) implants (Astra Tech Implant System, DENTSPLY Implants, Mölndal, Sweden), 72 in immediate extraction sockets and 110 in healed sites, were placed in 39 consecutive patients. The implants were loaded with permanent restorations within 60 days (average 31 days). Clinical and radiographic follow-up examinations were performed annually for at least 3 years (mean 55 months). An aesthetic index was used to evaluate the soft tissues adjacent to the prosthetic restorations. No implant was lost during the observation period, giving a survival rate of 100%. Bone level changes during the observation period were minimal, with a mean marginal bone loss of 0.3 ± 0.9 mm around the delayed implants and a mean marginal bone gain of 0.3 ± 1.4 mm around the immediate implants (p = .0036). The frequency distribution of bone level revealed that 85% of implants placed in fresh extraction sockets and 84% of implants in healed bone did not show any loss of bone level during follow-up (p = NS). Soft tissue complications were observed at two immediate implant sites in one patient. The remaining 180 implants received the highest aesthetic score. Moreover, no signs of peri-implant purulent infection or aggressive bone loss were found during the follow-up period. Early loading of fluoridated implants with permanent constructions appears to be a viable therapy for implants placed immediately in extraction sites and in healed bone. © 2014 Wiley Periodicals, Inc.

Butyric acid stimulates bone sialoprotein gene transcription.

PubMed

Yang, Li; Li, Zhengyang; Li, Xinyue; Wang, Zhitao; Wang, Shuang; Sasaki, Yoko; Takai, Hideki; Ogata, Yorimasa

2010-06-01

Butyric acid (sodium butyrate; BA) is an extracellular metabolite secreted from periodontopathic bacteria present in subgingival plaque. BA induces apoptosis of T and B cells, and acts as a potent inhibitor of histone deacetylases. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone, and may be crucial for osteoblast differentiation, bone matrix mineralization and tumor metastasis. In the present study we investigated the regulation of BSP transcription by BA in rat osteoblast-like ROS17/2.8 cells. At 12 h, BA (10(-4) M) increased the level of BSP mRNA, and enhanced the luciferase activity of the construct pLUC3, which includes the promoter sequence between nucleotides -116 and +60. Transcriptional stimulation by BA was abrogated in the pLUC3 construct which containing a 2-bp mutation in the fibroblast growth factor 2 response element (FRE). Gel shift analyses showed that BA increased the binding of nuclear protein to FRE. These data suggest that BA increases the transcription of the BSP gene mediated through FRE in the rat BSP gene promoter, and induces osteoblast activity in the early stage of bone formation.

In vivo response of bioactive PMMA-based bone cement modified with alkoxysilane and calcium acetate.

PubMed

Sugino, Atsushi; Ohtsuki, Chikara; Miyazaki, Toshiki

2008-11-01

The use of polymethylmethacrylate (PMMA)-based bone cement is popular in orthopedics for the fixation of artificial joints with bone. However, it has a major problem with prostheses loosening because of coverage by fibrous tissue after long-term implantation. Recently, a bioactive bone cement has been developed that shows direct bonding to living bone through modification of PMMA resin with gamma-methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. The cement is designed to exhibit bioactivity, through incorporation of silanol groups and calcium ions. Thus, it has the potential to form a layer of bone-like hydroxyapatite, which is essential for achieving direct bonding to living bone. This type of modification allows the cement to show spontaneous hydroxyapatite formation on its surface in a simulated body fluid after one day, and there is evidence of osteoconduction of the cement in rabbit tibia for periods of more than three weeks. However, the influence of the dissolved ions from the modified cement has not yet been clarified. Thus, the authors focused on the dissolution of the modified PMMA-based bone cement and its tissue response in muscle and bone by comparison with the behavior of non-modified PMMA-based bone cement. One week after implantation in the latissimus dorsi of a rabbit, the modified PMMA-based bone cement showed more inflammatory width than the commercial cement. However, four weeks after implantation, the inflammatory width of both cements was essentially the same. The osteoconductivity around the modified cement was higher than that for the conventional cement after four weeks implantation. These results indicate that the initial dissolution of calcium acetate from the modified cement to form the hydroxyapatite induced the acute inflammation around tissue, but also developed the osteoconductivity. It is suggested that the initial inflammation can be effective for inducing osteoconduction through a bone healing reaction when the

Bone Analyzer

NASA Technical Reports Server (NTRS)

1985-01-01

The danger of disuse osteoporosis under weightless condition in space led to extensive research into measurements of bone stiffness and mass by the Biomedical Research Division of Ames and Stanford University. Through its Technology Utilization Program, NASA funded an advanced SOBSA, a microprocessor-controlled bone probe system. SOBSA determines bone stiffness by measuring responses to an electromagnetic shaker. With this information, a physician can identify bone disease, measure deterioration and prescribe necessary therapy. The system is now undergoing further testing.

The Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans

PubMed Central

2013-01-01

Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized. PMID:23689830

Novel Radiomitigator for Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

2016-01-01

Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

Modulation of bone remodeling via mechanically activated ion channels

NASA Technical Reports Server (NTRS)

Duncan, Randall L. (Principal Investigator)

1996-01-01

A critical factor in the maintenance of bone mass is the physical forces imposed upon the skeleton. Removal of these forces, such as in a weightless environment, results in a rapid loss of bone, whereas application of exogenous mechanical strain has been shown to increase bone formation. Numerous flight and ground-based experiments indicate that the osteoblast is the key bone cell influenced by mechanical stimulation. Aside from early transient fluctuations in response to unloading, osteoclast number and activity seem unaffected by removal of strain. However, bone formation is drastically reduced in weightlessness and osteoblasts respond to mechanical strain with an increase in the activity of a number of second messenger pathways resulting in increased anabolic activity. Unfortunately, the mechanism by which the osteoblast converts physical stimuli into a biochemical message, a process we have termed biochemical coupling, remains elusive. Prior to the application of this grant, we had characterized a mechanosensitive, cation nonselective channel (SA-cat) in osteoblast-like osteosarcoma cells that we proposed is the initial signalling mechanism for mechanotransduction. During the execution of this grant, we have made considerable progress to further characterize this channel as well as to determine its role in the osteoblastic response to mechanical strain. To achieve these goals, we combined electrophysiologic techniques with cellular and molecular biology methods to examine the role of these channels in the normal function of the osteoblast in vitro.

Effect of alendronate on early bone loss of renal transplant recipients.

PubMed

Abediazar, S; Nakhjavani, M R

2011-03-01

Renal transplant recipients (RTRs) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy, hypophosphatemia, and immunosuppression. This process occurs more frequently in the first year after renal transplantation (RTX), resulting in eventual bone loss and fractures. The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX. We prospectively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16±11.73 years, mean body mass index of 23.6±3.73, and mean dialysis duration of 25.73±17.67 months. We matched them based on age and sex: the alendronate-treated group received vitamin D (Vit D) during the study plus 30 mg alendronate weekly from 1 month after RTX. The control group only received Vit D. We measured serum calcium, phosphate, alkaline phosphatase, blood urea, creatinine, and intact parathyroid hormone (iPTH) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine, femur, and radius pretransplant baseline versus 3 and 6 months after RTX. At 6 month after RTX, the lumbar BMD in the alendronate group increased significantly from 0.819±0.11 to 0.863±0.14 (P<.01), while it decreased in the control group from 0.897±0.17 to 0.817±0.16 (P<.001). There was also a significant increase in radius BMD (P<.001) and a nonsignificant increase in femoral BMD in the alendronate versus a significant decrease of femoral and radius BMD (P<.001) in the control group at 6 months. Upon multivariate analysis, there was a significant correlation between alendronate and spine BMD (r=.45, P<.001) but no linear regression between age, sex, BMI, dialysis duration of or iPTH with femoral, spine, or radius BMD changes at month 6. Low-dose alendronate was significantly useful to mitigate fast bone loss and increase BMD immediately after RTX. Copyright © 2011. Published by Elsevier Inc.

Free form fabricated features on CoCr implants with and without hydroxyapatite coating in vivo: a comparative study of bone contact and bone growth induction.

PubMed

Grandfield, Kathryn; Palmquist, Anders; Gonçalves, Stéphane; Taylor, Andy; Taylor, Mark; Emanuelsson, Lena; Thomsen, Peter; Engqvist, Håkan

2011-04-01

The current study evaluates the in vivo response to free form fabricated cobalt chromium (CoCr) implants with and without hydroxyapatite (HA) plasma sprayed coatings. The free form fabrication method allowed for integration of complicated pyramidal surface structures on the cylindrical implant. Implants were press fit into the tibial metaphysis of nine New Zealand white rabbits. Animals were sacrificed and implants were removed and embedded. Histological analysis, histomorphometry and electron microscopy studies were performed. Focused ion beam was used to prepare thin sections for high-resolution transmission electron microscopy examination. The fabricated features allowed for effective bone in-growth and firm fixation after 6 weeks. Transmission electron microscopy investigations revealed intimate bone-implant integration at the nanometre scale for the HA coated samples. In addition, histomorphometry revealed a significantly higher bone contact on HA coated implants compared to native CoCr implants. It is concluded that free form fabrication in combination with HA coating improves the early fixation in bone under experimental conditions.

Trabecular bone microarchitecture analysis, a way for an early detection of genetic dwarfism? Case study of a dwarf mother's offspring.

PubMed

Colombo, Antony; Hoogland, Menno; Coqueugniot, Hélène; Dutour, Olivier; Waters-Rist, Andrea

2018-03-01

A 66 year-old woman with a disproportionate dwarfism and who bore seven children was discovered at the Middenbeemster archaeological site (The Netherlands). Three are perinates and show no macroscopic or radiological evidence for a FGFR3 mutation causing hypo-or achondroplasia. This mutation induces dysfunction of the growth cartilage, leading to abnormalities in the development of trabecular bone. Because the mutation is autosomal dominant, these perinates have a 50% risk of having been affected. This study determines whether trabecular bone microarchitecture (TBMA) analysis is useful for detecting genetic dwarfism. Proximal metaphyses of humeri were μCT-scanned with a resolution of 7-12 μm. Three volumes of interest were segmented from each bone with TIVMI© software. The TBMA was quantified in BoneJ© using six parameters on which a multivariate analysis was then performed. Two of the Middenbeemster perinates show a quantitatively different TBMA organization. These results and the family's medical history suggest a diagnosis of genetic dwarfism for this two perinates. This study provides evidence to support the efficacy of μCT for diagnosing early-stage bone disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Metastatic Bone Pain Palliation using (177)Lu-Ethylenediaminetetramethylene Phosphonic Acid.

PubMed

Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R; Bahrami-Samani, Ali

2015-01-01

(177)Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using (177)Lu-EDTMP for MBP palliation. (177)Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. (177)Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. (177)Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for

Metastatic Bone Pain Palliation using 177Lu-Ethylenediaminetetramethylene Phosphonic Acid

PubMed Central

Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R.; Bahrami-Samani, Ali

2015-01-01

177Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177Lu-EDTMP for MBP palliation. 177Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients

Early Alterations in Bone Characteristics of Type I Diabetic Rat Femur: A Fourier Transform Infrared (FT-IR) Imaging Study.

PubMed

Bozkurt, Ozlem; Bilgin, Mehmet Dincer; Evis, Zafer; Pleshko, Nancy; Severcan, Feride

2016-12-01

Alterations in microstructure and mineral features can affect the mechanical and chemical properties of bones and their capacity to resist mechanical forces. Controversial results on diabetic bone mineral content have been reported and little is known about the structural alterations in collagen, maturation of apatite crystals, and carbonate content in diabetic bone. This current study is the first to report the mineral and organic properties of cortical, trabecular, and growth plate regions of diabetic rat femurs using Fourier transform infrared (FT-IR) microspectroscopy and the Vickers microhardness test. Femurs of type I diabetic rats were embedded into polymethylmethacrylate blocks, which were used for FT-IR imaging and microhardness studies. A lower mineral content and microhardness, a higher carbonate content especially labile type carbonate content, and an increase in size and maturation of hydroxyapatite crystals were observed in diabetic femurs, which indicate that diabetes has detrimental effects on bone just like osteoporosis. There was a decrease in the level of collagen maturity in diabetic femurs, implying a decrease in bone collagen quality that may contribute to the decrease in tensile strength and bone fragility. Taken together, the findings revealed alterations in structure and composition of mineral and matrix components, and an altered quality and mechanical strength of rat femurs in an early stage of type I diabetes. The results contribute to the knowledge of structure-function relationship of mineral and matrix components in diabetic bone disorder and can further be used for diagnostic or therapeutic purposes. © The Author(s) 2016.

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.

Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri-implant bone responses in osteoporotic rats.

PubMed

Alghamdi, Hamdan S; Bosco, Ruggero; Both, Sanne K; Iafisco, Michele; Leeuwenburgh, Sander C G; Jansen, John A; van den Beucken, Jeroen J J P

2014-07-01

The prevalence of osteoporosis will increase within the next decades due to the aging world population, which can affect the bone healing response to dental and orthopedic implants. Consequently, local drug targeting of peri-implant bone has been proposed as a strategy for the enhancement of bone-implant integration in osteoporotic conditions. In the present study, an established in-vivo femoral condyle implantation model in osteoporotic and healthy bone is used to analyze the osteogenic capacity of titanium implants coated with bisphosphonate (BP)-loaded calcium phosphate nanoparticles (nCaP) under compromised medical conditions. After 4 weeks of implantation, peri-implant bone volume (%BV; by μCT) and bone area (%BA; by histomorphometry) were significantly increased within a distance of 500 μm from implant surfaces functionalized with BP compared to control implants in osteoporotic and healthy conditions. Interestingly, the deposition of nCaP/BP coatings onto implant surfaces increased both peri-implant bone contact (%BIC) and volume (%BV) compared to the deposition of nCaP or BP coatings individually, in osteoporotic and healthy conditions. The results of real-time PCR revealed similar osteogenic gene expression levels to all implant surfaces at 4-weeks post-implantation. In conclusion, simultaneous targeting of bone formation (by nCaP) and bone resorption (by BP) using nCaP/BP surface coatings represents an effective strategy for synergistically improvement of bone-implant integration, especially in osteoporotic conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bone grafts, bone substitutes and orthobiologics

PubMed Central

Roberts, Timothy T.; Rosenbaum, Andrew J.

2012-01-01

The biology of fracture healing is better understood than ever before, with advancements such as the locking screw leading to more predictable and less eventful osseous healing. However, at times one’s intrinsic biological response, and even concurrent surgical stabilization, is inadequate. In hopes of facilitating osseous union, bone grafts, bone substitutes and orthobiologics are being relied on more than ever before. The osteoinductive, osteoconductive and osteogenic properties of these substrates have been elucidated in the basic science literature and validated in clinical orthopaedic practice. Furthermore, an industry built around these items is more successful and in demand than ever before. This review provides a comprehensive overview of the basic science, clinical utility and economics of bone grafts, bone substitutes and orthobiologics. PMID:23247591

Can physical activity improve peak bone mass?

PubMed

Specker, Bonny; Minett, Maggie

2013-09-01

The pediatric origin of osteoporosis has led many investigators to focus on determining factors that influence bone gain during growth and methods for optimizing this gain. Bone responds to bone loading activities by increasing mass or size. Overall, pediatric studies have found a positive effect of bone loading on bone size and accrual, but the types of loads necessary for a bone response have only recently been investigated in human studies. Findings indicate that responses vary by sex, maturational status, and are site-specific. Estrogen status, body composition, and nutritional status also may influence the bone response to loading. Despite the complex interrelationships among these various factors, it is prudent to conclude that increased physical activity throughout life is likely to optimize bone health.

Impregnation of bone chips with alendronate and cefazolin, combined with demineralized bone matrix: a bone chamber study in goats

PubMed Central

2012-01-01

Background Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. Methods 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 μg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. Results Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. Conclusions A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling. PMID:22443362

Studies of Intercellular Communication and Intracellular Metabolic Responses by Bone Cells to Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Doty, Stephen B.

1997-01-01

Spaceflight affects the weight bearing skeletal tissues by reducing the rate of new bone formation. This effect on the long bones of flown rats has been quantitated but the effect at the cellular level and the mechanism(s) involved are not understood. We are applying electron microscopy, coupled with histochemistry and immunocytochemistry to determine the cellular functions most affected by spaceflight. The emphasis for study of these samples from SLS-1, a 9-day mission, is on the histochemical and structural changes of the endosteal and perivascular osteoblasts found in diaphyseal bone of femur and tibia. Work is still in progress but some findings are described: (1) An expected decrease in alkaline phosphatase activity in osteoblasts from flight animals, but an increase in enzyme activity in the stromal stem cells adjacent to the osteoblast. (2) An increase in osteoclastic TRAP activity in the trabecular bone region in response to spaceflight. (3) A large increase in procollagen containing secretory granules in osteoblasts in the recovery group, and a significant decrease in granule numbers in the flight group.

Methods and application of bone densitometry in clinical diagnosis

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

Wahner, H.W.; Riggs, B.L.

1986-01-01

With the awareness of osteoporosis as a major health problem for an aging population, there is great interest in early recognition and treatment of abnormal bone loss. Effective prevention of bone loss has to occur prior to the occurrence of irreparable damage. Standard radiographic procedures are not sensitive enough for the task. Therefore, a number of alternative procedures to estimate bone loss have been developed over the years, ranging from efforts to quantitate information obtained from radiographic images to sophisticated procedures such as neutron activation analysis or procedures based on the Compton scatter phenomenon. Only two procedures, photon absorptiometry andmore » computed tomography (CT), have emerged as applicable for routine clinical use. In photon absorptiometry the entire bone mineral (cortical and trabecular bone) of a specific skeletal site is measured. CT allows measuring of bone mineral of trabecular or cortical bone alone. Normally, bone mass reaches a maximum in the third decade and then continuously declines. This age-related bone loss is greater in women in whom an accelerated rate of loss occurs at the menopause. When bone density reaches a critical fracture threshold, skeletal fractures occur (spine, hip, and distal long bones). The age at which this critical fracture threshold is reached depends on the maximal bone mass achieved in early adulthood and the rate of loss with increasing age. With the exception of NaF, present-day therapeutic efforts only retard or prevent bone loss but do not significantly add bone mineral to the skeleton. Recognition of high-risk groups and early treatment are therefore required. 79 references.« less

Histomorphometry and bone mechanical property evolution around different implant systems at early healing stages: an experimental study in dogs.

PubMed

Jimbo, Ryo; Anchieta, Rodolfo; Baldassarri, Marta; Granato, Rodrigo; Marin, Charles; Teixeira, Hellen S; Tovar, Nick; Vandeweghe, Stefan; Janal, Malvin N; Coelho, Paulo G

2013-12-01

Commercial implants differ at macro-, micro-, and nanolevels, which makes it difficult to distinguish their effect on osseointegration. The aim of this study was to evaluate the early integration of 5 commercially available implants (Astra OsseoSpeed, Straumann SLA, Intra-Lock Blossom Ossean, Nobel Active, and OsseoFix) by histomorphometry and nanoindentation. Implants were installed in the tibiae of 18 beagle dogs. Samples were retrieved at 1, 3, and 6 weeks (n = 6 for each time point) and were histologically and nanomechanically evaluated. The results presented that both time (P < 0.01) and implant system and time interaction (P < 0.02) significantly affected the bone-to-implant contact (BIC). At 1 week, the different groups presented statistically different outcomes. No significant changes in BIC were noted thereafter. There were no significant differences in rank elastic modulus (E) or in rank hardness (H) for time (E: P > 0.80; H: P > 0.75) or implant system (E: P > 0.90; H: P > 0.85). The effect of different implant designs on osseointegration was evident especially at early stages of bone healing.

Elastic intramedullary nailing and DBM-Bone marrow injection for the treatment of simple bone cysts

PubMed Central

Kanellopoulos, Anastasios D; Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Soucacos, Panayotis N

2007-01-01

Background Simple or unicameral bone cysts are common benign fluid-filled lesions usually located at the long bones of children before skeletal maturity. Methods We performed demineralized bone matrix and iliac crest bone marrow injection combined with elastic intramedullary nailing for the treatment of simple bone cysts in long bones of 9 children with a mean age of 12.6 years (range, 4 to 15 years). Results Two of the 9 patients presented with a pathological fracture. Three patients had been referred after the failure of previous treatments. Four patients had large lesions with impending pathological fractures that interfered with daily living activities. We employed a ratio to ascertain the severity of the lesion. The extent of the lesion on the longitudinal axis was divided with the normal expected diameter of the long bone at the site of the lesion. The mean follow-up was 77 months (range, 5 to 8 years). All patients were pain free and had full range of motion of the adjacent joints at 6 weeks postoperatively. Review radiographs showed that all 7 cysts had consolidated completely (Neer stage I) and 2 cysts had consolidated partially (Neer stage II). Until the latest examination there was no evidence of fracture or re-fracture. Conclusion Elastic intramedullary nailing has the twofold benefits of continuous cyst decompression, and early immediate stability to the involved bone segment, which permits early mobilization and return to the normal activities of the pre-teen patients. PMID:17916249

Purinergic signalling in bone

PubMed Central

Rumney, Robin M. H.; Wang, Ning; Agrawal, Ankita; Gartland, Alison

2012-01-01

Purinergic signaling in bone was first proposed in the early 1990s with the observation that extracellular ATP could modulate events crucial to the normal functioning of bone cells. Since then the expression of nearly all the P2Y and P2X receptors by osteoblasts and osteoclasts has been reported, mediating multiple processes including cell proliferation, differentiation, function, and death. This review will highlight the most recent developments in the field of purinergic signaling in bone, with a special emphasis on recent work resulting from the European Framework 7 funded collaboration ATPBone, as well as Arthritis Research UK and Bone Research Society supported projects. PMID:23049524

Surface modification of implants in long bone.

PubMed

Förster, Yvonne; Rentsch, Claudia; Schneiders, Wolfgang; Bernhardt, Ricardo; Simon, Jan C; Worch, Hartmut; Rammelt, Stefan

2012-01-01

Coatings of orthopedic implants are investigated to improve the osteoinductive and osteoconductive properties of the implant surfaces and thus to enhance periimplant bone formation. By applying coatings that mimic the extracellular matrix a favorable environment for osteoblasts, osteoclasts and their progenitor cells is provided to promote early and strong fixation of implants. It is known that the early bone ongrowth increases primary implant fixation and reduces the risk of implant failure. This review presents an overview of coating titanium and hydroxyapatite implants with components of the extracellular matrix like collagen type I, chondroitin sulfate and RGD peptide in different small and large animal models. The influence of these components on cells, the inflammation process, new bone formation and bone/implant contact is summarized.

Surface modification of implants in long bone

PubMed Central

Förster, Yvonne; Rentsch, Claudia; Schneiders, Wolfgang; Bernhardt, Ricardo; Simon, Jan C.; Worch, Hartmut; Rammelt, Stefan

2012-01-01

Coatings of orthopedic implants are investigated to improve the osteoinductive and osteoconductive properties of the implant surfaces and thus to enhance periimplant bone formation. By applying coatings that mimic the extracellular matrix a favorable environment for osteoblasts, osteoclasts and their progenitor cells is provided to promote early and strong fixation of implants. It is known that the early bone ongrowth increases primary implant fixation and reduces the risk of implant failure. This review presents an overview of coating titanium and hydroxyapatite implants with components of the extracellular matrix like collagen type I, chondroitin sulfate and RGD peptide in different small and large animal models. The influence of these components on cells, the inflammation process, new bone formation and bone/implant contact is summarized. PMID:23507866

The association between mammographic breast density and bone mineral density in the study of women's health across the nation.

PubMed

Crandall, Carolyn J; Zheng, Yan; Karlamangla, Arun; Sternfeld, Barbara; Habel, Laurel A; Oestreicher, Nina; Johnston, Janet; Cauley, Jane A; Greendale, Gail A

2007-08-01

Bone mineral density and mammographic breast density are each associated with markers of lifetime estrogen exposure. The association between mammographic breast density and bone mineral density in early perimenopausal women is unknown. We analyzed data from a cohort (n = 501) of premenopausal (no change in menstrual regularity) and early perimenopausal (decreased menstrual regularity in past 3 months) participants of African-American, Caucasian, Chinese, and Japanese ethnicity in the Study of Women's Health Across the Nation. Using multivariable linear regression, we examined the cross-sectional association between percent mammographic density and bone mineral density (BMD). Percent mammographic density was statistically significantly inversely associated with hip BMD and lumbar spine BMD after adjustment (body mass index, ethnicity, age, study site, parity, alcohol intake, cigarette smoking, physical activity, age at first childbirth) in early perimenopausal, but not premenopausal, women. In early perimenopausal women, every 0.1g/cm(2) greater hip BMD predicted a 2% lower percent mammographic density (95% confidence interval -37.0 to -0.6%, p = 0.04). Mammographic breast density is inversely associated with BMD in the perimenopausal participants of this community-based cohort. The biological underpinnings of these findings may reflect differential responsiveness of breast and bone mineral density to the steroid milieu.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

PubMed

Förster, Yvonne; Schmidt, Johannes R; Wissenbach, Dirk K; Pfeiffer, Susanne E M; Baumann, Sven; Hofbauer, Lorenz C; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles

PubMed Central

Wissenbach, Dirk K.; Pfeiffer, Susanne E. M.; Baumann, Sven; Hofbauer, Lorenz C.; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis. PMID:27441377

Investigating the mechanical response of paediatric bone under bending and torsion using finite element analysis.

PubMed

Altai, Zainab; Viceconti, Marco; Offiah, Amaka C; Li, Xinshan

2018-03-10

Fractures of bone account 25% of all paediatric injuries (Cooper et al. in J Bone Miner Res 19:1976-1981, 2004. https://doi.org/10.1359/JBMR.040902 ). These can be broadly categorised into accidental or inflicted injuries. The current clinical approach to distinguish between these two is based on the clinician's judgment, which can be subjective. Furthermore, there is a lack of studies on paediatric bone to provide evidence-based information on bone strength, mainly due to the difficulties of obtaining paediatric bone samples. There is a need to investigate the behaviour of children's bones under external loading. Such data will critically enhance our understanding of injury tolerance of paediatric bones under various loading conditions, related to injuries, such as bending and torsional loads. The aim of this study is therefore to investigate the response of paediatric femora under two types of loading conditions, bending and torsion, using a CT-based finite element approach, and to determine a relationship between bone strength and age/body mass of the child. Thirty post-mortem CT scans of children aged between 0 and 3 years old were used in this study. Two different boundary conditions were defined to represent four-point bending and pure torsional loads. The principal strain criterion was used to estimate the failure moment for both loading conditions. The results showed that failure moment of the bone increases with the age and mass of the child. The predicted failure moment for bending, external and internal torsions were 0.8-27.9, 1.0-31.4 and 1.0-30.7 Nm, respectively. To the authors' knowledge, this is the first report on infant bone strength in relation to age/mass using models developed from modern medical images. This technology may in future help advance the design of child, car restrain system, and more accurate computer models of children.

Assessment of bone marrow lymphocytic status during tyrosine kinase inhibitor therapy and its relation to therapy response in chronic myeloid leukaemia.

PubMed

El Missiry, Mohamed; Adnan Awad, Shady; Rajala, Hanna L; Al-Samadi, Ahmed; Ekblom, Marja; Markevän, Berit; Åstrand-Grundström, Ingbritt; Wold, Maren; Svedahl, Ellen Rabben; Juhl, Birgitte Ravn; Bjerrum, Ole Weis; Haulin, Inger; Porkka, Kimmo; Olsson-Strömberg, Ulla; Hjorth-Hansen, Henrik; Mustjoki, Satu

2016-05-01

Tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukaemia have been reported to induce immunomodulatory effects. We aimed to assess peripheral blood (PB) and bone marrow (BM) lymphocyte status at the diagnosis and during different TKI therapies and correlate it with treatment responses. BM and PB samples were acquired from 105 first-line TKI-treated patients. Relative number of BM lymphocytes was evaluated from MGG-stained BM aspirates, and immunophenotypic analyses were performed with multicolour flow cytometry. Early 3-month expansion of BM lymphocytes was found during all different TKIs (imatinib n = 71, 20 %; dasatinib n = 25, 21 %; nilotinib n = 9, 22 %; healthy controls n = 14, 12 %, p < 0.0001). Increased PB lymphocyte count was only observed during dasatinib therapy. The BM lymphocyte expansion was associated with early molecular response; patients with 3-month BCR-ABL1 <10 % showed higher lymphocyte counts than patients with BCR-ABL1 >10 % (23 vs. 17 %, p < 0.05). Detailed phenotypic analysis showed that BM lymphocyte expansion consisted of various lymphocyte subclasses, but especially the proportion of CD19+ B cells and CD3negCD16/56+ NK cells increased from diagnostic values. During dasatinib treatment, the lymphocyte balance in both BM and PB was shifted more to cytotoxic direction (increased CD8+CD57+ and CD8+HLA-DR+ cells, and low T regulatory cells), whereas no major immunophenotypic differences were observed between imatinib and nilotinib patients. Early BM lymphocytosis occurs with all current first-line TKIs and is associated with better treatment responses. PB and BM immunoprofile during dasatinib treatment markedly differs from both imatinib- and nilotinib-treated patients.

Analysis of multiple bone responses to graded strains above functional levels, and to disuse, in mice in vivo show that the human Lrp5 G171V High Bone Mass mutation increases the osteogenic response to loading but that lack of Lrp5 activity reduces it

PubMed Central

Saxon, Leanne K.; Jackson, Brendan F.; Sugiyama, Toshihiro; Lanyon, Lance E.; Price, Joanna S.

2011-01-01

Introduction To investigate the role of the low-density lipoprotein receptor-related protein 5 (Lrp5) in bones' responses to loading, we analysed changes in multiple measures of bone architecture in tibias subjected to loading or disuse in male and female mice with the Lrp5 loss of function mutation (Lrp5−/−) or heterozygous for the Lrp5 G171V High Bone Mass (HBM) mutation (Lrp5HBM+). Materials and methods The right tibias of these 17 week old male and female mice and their Wild Type (WT) littermates were subjected to short periods of loading three days a week for two weeks. Each tibia was loaded for 40 cycles, to produce peak strains at the midshaft within the low, medium or high physiological range (~ 1500, 2400 and 3000 microstrain, respectively). In similar groups of mice the right sciatic nerve was severed causing disuse of the right tibia for 3 weeks. Data from microCT of loaded, neurectomised and contra-lateral control tibias were analysed to quantify changes in the cortical and cancellous regions of the bone in the absence of functional strains and in response to graded strains in addition to those derived from function. Results and conclusion Male WT+/+ controls showed significant strain:response curves for cortical area and trabecular thickness, but Lrp5−/− mice showed no detectable strain:response in those same outcomes. Female mice of either WT+/+ or Lrp5−/− genotype did not show significant strain:response curves for cortical or trabecular parameters, the one exception being Tb.Th in Lrp5−/− mice. Since female WT+/+ mice did not respond to loading in a significant dose:responsive manner, the similar lack of responsiveness of the Lrp5−/− females could not be ascribed to their Lrp5 status. Cortical bone loss associated with disuse showed no differences between Lrp5−/− mice and WT+/+ controls, but in cancellous bone of both male and females of these mice, there was a greater loss than in WT+/+ controls. In contrast, the tibias

Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

1994-01-01

The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate, (the distal tibial metaphysis (DTM), to ovariectomy (OVX) and OVX plus a prostaglandin E(2) treatment, and compare the site's response to previous findings reported for another site, the proximal tibial metaphysis (PTM). Thirty five 3-month old female Sprague-Dawley rats were divided into five groups; basal, sham OVX, and OVX+0, +1, or +6 mg PGE(2)/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20 micrometer thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months POST OVX there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE(2)/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE(2)/kd/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation, without altering bone resportion. Futhermore, After PGE(2) admimnistration, the DTM, a cancellous bone site with a closed growth plate, increased bone formation more than did the cancellous bone in the PTM.

Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

1994-01-01

The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate (the distal tibial metaphysis, DTM) to ovariectomy (OVX) and OVX plus a prostaglandin E2 (PGE2) treatment, and compare the site's response to previous findings reported for another site (the proximal tibial metaphysis, PTM). Thirty-five 3-month old female Sprague-Dawley rats were divided into five groups: basal, sham-OVX, and OVX+0, +1, or +6 mg PGE2/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20-micron-thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months post-OVX; there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE2/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE2/kg/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation without altering bone resorption. Furthermore, after PGE2 administration, the DTM, a cancellous bone site with a closed growth plate, inereased bone formation more than did the cancellous bone in the PTM.

Cellular and molecular mechanisms for the bone response to mechanical loading

NASA Technical Reports Server (NTRS)

Bloomfield, S. A.

2001-01-01

To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

Blood gene expression profiling of an early acetaminophen response.

PubMed

Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

2017-06-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

Blood Gene Expression Profiling of an Early Acetaminophen Response

PubMed Central

Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

2018-01-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

Bone marrow transplantation alters lung antigen presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection

PubMed Central

Zhou, Xiaofeng; Loomis-King, Hillary; Gurczynski, Stephen J.; Wilke, Carol A.; Konopka, Kristine E.; Ptaschinski, Catherine; Coomes, Stephanie M; Iwakura, Yoichiro; van Dyk, Linda F.; Lukacs, Nicholas W.; Moore, Bethany B.

2015-01-01

Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplant (BMT) followed by infection with murine gamma herpesvirus (γHV-68) that results in pneumonitis and fibrosis and mimics human “non-infectious” HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection (dpi). CD4 T cells in BMT mice are skewed towards IL-17A rather than IFN-γ production. Transplantation of bone marrow from Il-17a−/− donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more TGF-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest “non-infectious” HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

Psychosocial predictors of immune response following bone marrow transplantation.

PubMed

Pulgar, Ángeles; Garrido, Sergio; Alcalá, Antonio; Reyes del Paso, Gustavo A

2012-01-01

This study analyzed the relationship between some psychosocial variables (depression, anxiety, stress, coping strategies, social support, optimism, rationality, and need for harmony) and clinical parameters indicative of immunological response after bone marrow transplantation (BMT; day of engraftment, number of infections and hemoglobin level) while controlling for demographic variables (age, educative level, civil state, and time from cancer diagnosis). Thirty-one post BMT hematological cancer patients were evaluated. Results show that higher educative levels are associated to lower number of infections, while age is associated with a delay in the time of engraftment; coping strategies, specially redefinition of the situation, relaxation, stoicism and passivity, are positively associated with the three clinical indices; depression is positively associated to number of infections during the hospitalization period; and rationality is associated with lower hemoglobin levels. These results suggest that psychosocial variables, especially coping strategies, play an important role in determining the immunological response after BMT.

Sprint Interval Training Induces A Sexual Dimorphism but does not Improve Peak Bone Mass in Young and Healthy Mice

PubMed Central

Koenen, Kathrin; Knepper, Isabell; Klodt, Madlen; Osterberg, Anja; Stratos, Ioannis; Mittlmeier, Thomas; Histing, Tina; Menger, Michael D.; Vollmar, Brigitte; Bruhn, Sven; Müller-Hilke, Brigitte

2017-01-01

Elevated peak bone mass in early adulthood reduces the risk for osteoporotic fractures at old age. As sports participation has been correlated with elevated peak bone masses, we aimed to establish a training program that would efficiently stimulate bone accrual in healthy young mice. We combined voluntary treadmill running with sprint interval training modalities that were tailored to the individual performance limits and were of either high or intermediate intensity. Adolescent male and female STR/ort mice underwent 8 weeks of training before the hind legs were analyzed for cortical and trabecular bone parameters and biomechanical strength. Sprint interval training led to increased running speeds, confirming an efficient training. However, males and females responded differently. The males improved their running speeds in response to intermediate intensities only and accrued cortical bone at the expense of mechanical strength. High training intensities induced a significant loss of trabecular bone. The female bones showed neither adverse nor beneficial effects in response to either training intensities. Speculations about the failure to improve geometric alongside mechanical bone properties include the possibility that our training lacked sufficient axial loading, that high cardio-vascular strains adversely affect bone growth and that there are physiological limits to bone accrual. PMID:28303909

Early lens ablation causes dramatic long-term effects on the shape of bones in the craniofacial skeleton of Astyanax mexicanus.

PubMed

Dufton, Megan; Hall, Brian K; Franz-Odendaal, Tamara A

2012-01-01

The Mexican tetra, Astyanax mexicanus, exists as two morphs of a single species, a sighted surface morph and a blind cavefish. In addition to eye regression, cavefish have an increased number of taste buds, maxillary teeth and have an altered craniofacial skeleton compared to the sighted morph. We investigated the effect the lens has on the development of the surrounding skeleton, by ablating the lens at different time points during ontogeny. This unique long-term study sheds light on how early embryonic manipulations on the eye can affect the shape of the adult skull more than a year later, and the developmental window during which time these effects occur. The effects of lens ablation were analyzed by whole-mount bone staining, immunohistochemisty and landmark based morphometric analyzes. Our results indicate that lens ablation has the greatest impact on the skeleton when it is ablated at one day post fertilisation (dpf) compared to at four dpf. Morphometric analyzes indicate that there is a statistically significant difference in the shape of the supraorbital bone and suborbital bones four through six. These bones expand into the eye orbit exhibiting plasticity in their shape. Interestingly, the number of caudal teeth on the lower jaw is also affected by lens ablation. In contrast, the shape of the calvariae, the length of the mandible, and the number of mandibular taste buds are unaltered by lens removal. We demonstrate the plasticity of some craniofacial elements and the stability of others in the skull. Furthermore, this study highlights interactions present between sensory systems during early development and sheds light on the cavefish phenotype.

[Subchondral bone in osteoarthritis: a review].

PubMed

Pang, Jian; Cao, Yue-long; Shi, Yin-yu

2011-08-01

Osteoarthritis (OA) is the most prevalent of joint diseases,and its pathology is characterized by the degeneration of cartilage, sclerosis of subchondral bone, and osteophyte formation. Localization of the early lesions of OA has not been clarified, but many researchers have focused on cartilage and have considered that changes in subchondral bone occur subsequently to the degeneration of cartilage. However, a low bone mineral density, particularly in the knee joint with OA, high bone turnover, and efficacy of bone resorption inhibitors for OA have recently been reported, suggesting that subchondral bone plays an important role in the pathogenesis of OA. This review aims to make a conclusion about advancement in research of subchondral bone in osteoarthritis.

Early response to psychological trauma--what GPs can do.

PubMed

Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

2013-09-01

There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

In vivo analysis of biocompatibility and vascularization of the synthetic bone grafting substitute NanoBone.

PubMed

Abshagen, K; Schrodi, I; Gerber, T; Vollmar, B

2009-11-01

One of the major challenges in the application of bone substitutes is adequate vascularization and biocompatibility of the implant. Thus, the temporal course of neovascularization and the microvascular inflammatory response of implants of NanoBone (fully synthetic nanocrystalline bone grafting material) were studied in vivo by using the mouse dorsal skinfold chamber model. Angiogenesis, microhemodynamics, and leukocyte-endothelial cell interaction were analyzed repetitively after implantation in the center and in the border zone of the implant up to 15 days. Both NanoBone granules and plates exhibited high biocompatibility comparable to that of cancellous bone, as indicated by a lack of venular leukocyte activation after implantation. In both synthetic NanoBone groups, signs of angiogenesis could be observed even at day 5 after implantation, whereas granules showed higher functional vessel density compared with NanoBone plates. The angiogenic response of the cancellous bone was markedly accelerated in the center of the implant tissue. Histologically, implant tissue showed an ingrowth of vascularized fibrous tissue into the material combined with an increased number of foreign-body giant cells. In conclusion, NanoBone, particularly in granular form, showed high biocompatibility and high angiogenic response, thus improving the healing of bone defects. Our results underline that, beside the composition and nanostructure, the macrostructure is also of importance for the incorporation of the biomaterial by the host tissue. (c) 2008 Wiley Periodicals, Inc.

Voluntary exercise in pregnant rats improves post-lactation maternal bone parameters but does not affect offspring outcomes in early life.

PubMed

Rosa, B V; Blair, H T; Vickers, M H; Morel, P C; Cockrem, J F; Firth, E C

2012-12-01

The objectives of this study were to examine the effects of voluntary exercise during pregnancy on maternal post-lactation bone parameters and offspring growth. Pregnant Wistar rats were housed in conventional cages (control), or were housed in raised cages requiring them to rise to an erect, bipedal stance to obtain food/water, throughout pregnancy. Dual energy X-ray absorptiometry and peripheral quantitative computed tomography scans were performed pre-mating and post-weaning. Maternal stress was assessed by fecal corticosterone measurement. Offspring weights were assessed at postnatal days 1 and 25 (weaning). Changes in bone mineral over the pregnancy/lactation period were site-specific. Exercise did not affect loss of bone mineral from the lumbar spine, but did attenuate the loss of trabecular bone mineral from the tibial metaphysis and enhance the strength strain index and cross-sectional moment of inertia at the tibial diaphysis (P≤0.05) in dams in the exercised group. Fecal corticosterone did not differ between dam groups. There were no significant differences in offspring weight between the exercised and control group at either time point. Voluntary exercise in the pregnant rat can improve some post-lactation bone parameters and does not adversely affect early postnatal outcomes of the offspring.

Are levels of bone turnover related to lower bone mass of adolescents previously fed a macrobiotic diet?

PubMed

Parsons, T J; van Dusseldorp, M; Seibel, M J; van Staveren, W A

2001-01-01

Dutch adolescents who consumed a macrobiotic (vegan-type) diet in early life, demonstrate a lower relative bone mass than their omnivorous counterparts. We investigated whether subjects from the macrobiotic group showed signs of catching up with controls in terms of relative bone mass, reflected by higher levels of serum osteocalcin and alkaline phosphatase and lower levels of urinary cross-links. Group differences in calciotropic hormones and mineral excretion were also investigated. Bone measurements, blood, and urine samples were obtained from 69 macrobiotic (34 girls, 35 boys) and 99 control (57 girls, 42 boys) subjects, aged 9-15. Bone turnover markers and 1,25(OH)2D reached maximal levels at pubertal stages 3-4, and decreased thereafter. After adjusting for puberty, age, and lean body mass, no group differences were found in markers of bone turnover, 1,25(OH)2D, PTH, or calcium excretion, but phosphate excretion was 23% lower in macrobiotic girls. After adjustment for puberty, 1,25(OH)2D was positively related to osteocalcin. In summary, we found no evidence for group differences in bone turnover, or catch up in relative bone mass, which might be due to the fact that 60% of subjects were still in early stages of puberty.

The Efficacy of Transverse Fixation and Early Exercise in the Treatment of Fourth Metacarpal Bone Fractures

PubMed Central

Moon, Suk-Ho; Kim, Hak-Soo; Jung, Sung-No

2016-01-01

Background Several techniques have been designed to treat fifth metacarpal fractures reported to be effective. However, these methods cannot be easily applied to the fourth metacarpal due to its central anatomical position. In this study, we sought to analyze the functional outcomes of patients who underwent transverse pinning for a fourth metacarpal bone fracture. Methods A total of 21 patients were selected and their charts were retrospectively reviewed. After fracture reduction, two transverse Kirchner wires were first inserted from the fifth metacarpal to the third metacarpal transversely at the distal part of the fractured bone, and then another two wires were inserted at the proximal part of the fractured bone. The splint was removed approximately one week postoperatively and the Kirchner wires were removed four to five weeks postoperatively. Patients started active and passive exercise one week after the operation. Pain visual analog scores, total active and passive motion, and the active and passive range of motion of the metacarpophalangeal joint and grip strength were evaluated. Results Dorsal angulation improved from a preoperative value of 44.2° to a postoperative value of 5.9°. Six weeks after surgery, functional recovery parameters, such as range of motion and grip strength, had improved to 98% of the function of the normal side. No major complication was observed. Conclusions We suggest that the transverse pinning of fourth metacarpal bone fractures is an effective treatment option that is less invasive than other procedures, easy to perform, requires no secondary surgery, minimizes joint and soft tissue injury, and allows early mobilization. PMID:27019812

The use of bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.

PubMed

Kagami, Hideaki; Agata, Hideki; Inoue, Minoru; Asahina, Izumi; Tojo, Arinobu; Yamashita, Naohide; Imai, Kohzoh

2014-06-01

Bone tissue engineering is a promising field of regenerative medicine in which cultured cells, scaffolds, and osteogenic inductive signals are used to regenerate bone. Human bone marrow stromal cells (BMSCs) are the most commonly used cell source for bone tissue engineering. Although it is known that cell culture and induction protocols significantly affect the in vivo bone forming ability of BMSCs, the responsible factors of clinical outcome are poorly understood. The results from recent studies using human BMSCs have shown that factors such as passage number and length of osteogenic induction significantly affect ectopic bone formation, although such differences hardly affected the alkaline phosphatase activity or gene expression of osteogenic markers. Application of basic fibroblast growth factor helped to maintain the in vivo osteogenic ability of BMSCs. Importantly, responsiveness of those factors should be tested under clinical circumstances to improve the bone tissue engineering further. In this review, clinical application of bone tissue engineering was reviewed with putative underlying mechanisms.

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.

Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

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

Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl; Graeff, Alexander de; Monninkhof, Evelyn M.

Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within the Dutch Bone Metastasis Study were used. These patients, irradiated for painful bone metastases, rated pain, QoL, and overall health at baseline and weekly afterward for 12 weeks. Using generalized estimating equations analysis, the course of QoL was studied, adjusted for primary tumor. To identify predictive variables, proportional hazard analyses were performed, taking into account death asmore » a competing risk, and C-statistics were calculated for discriminative value. Results: In total, 722 patients (76%) responded to radiation therapy. During follow-up, responders had a better QoL in all domains compared with nonresponders. Patients with breast or prostate cancer had a better QoL than patients with lung cancer. In multivariate analysis, baseline predictors for a pain response were breast or prostate cancer as primary tumor, younger age, good performance status, absence of visceral metastases, and using opioids. The discriminative ability of the model was low (C-statistic: 0.56). Conclusions: Responding patients show a better QoL after radiation therapy for painful bone metastases than nonresponders. Our model did not have enough discriminative power to predict which patients are likely to respond to radiation therapy. Therefore, radiation therapy should be offered to all patients with painful bone metastases, aiming to decrease pain and improve QoL.« less

Effect of bone mesenchymal stem cells transplantation on the micro-environment of early osteonecrosis of the femoral head.

PubMed

Song, Huanjin; Tao, Li; Wang, Fang; Wang, Weizhuo; Wei, Yongchang; Shen, Wenjun; Zhou, Fuling

2015-01-01

Autologous implantation of bone mesenchymal stem cells (BMSCs) has achieved promising clinical efficacy for the treatment of early-stage osteonecrosis of the femoral head (ONFH). However, the underlying mechanisms are not completely elucidated. Here, we investigated the effect of BMSCs on the early ONFH in vitro and in vivo. In co-cultured system, primary BMSCs enhanced the activity and inhibited the apoptosis of primary OB. The concentrations of VEGF and BMP-2 in the co-cultured medium were significantly higher than those without co-culture. Importantly, BMSCs implantation increased OB, capillaries and VEGF and BMP-2 expressions of the necrotic areas of femoral head in the ONFH rabbits. In conclusion, our results indicated that BMSCs treated the early ONFH possibly through increasing OB and capillaries, as well as VEGF and BMP-2 expression in the femoral head. These results provided possible mechanisms for the treatment of early-stage ONFH with BMSCs transplantation.

Coating of VEGF-releasing scaffolds with bioactive glass for angiogenesis and bone regeneration.

PubMed

Leach, J Kent; Kaigler, Darnell; Wang, Zhuo; Krebsbach, Paul H; Mooney, David J

2006-06-01

Bioactive glasses are potentially useful as bone defect fillers, and vascular endothelial growth factor (VEGF) has demonstrated benefit in bone regeneration as well. We hypothesized that the specific combination of prolonged localized VEGF presentation from a matrix coated with a bioactive glass may enhance bone regeneration. To test this hypothesis, the capacity of VEGF-releasing polymeric scaffolds with a bioactive glass coating was examined in vitro and in vivo using a rat critical-sized defect model. In the presence of a bioactive glass coating, we did not detect pronounced differences in the differentiation of human mesenchymal stem cells in vitro. However, we observed significantly enhanced mitogenic stimulation of endothelial cells in the presence of the bioactive glass coating, with an additive effect with VEGF release. This trend was maintained in vivo, where coated VEGF-releasing scaffolds demonstrated significant improvements in blood vessel density at 2 weeks versus coated control scaffolds. At 12 weeks, bone mineral density was significantly increased in coated VEGF-releasing scaffolds versus coated controls, while only a slight increase in bone volume fraction was observed. The results of this study suggest that a bioactive glass coating on a polymeric substrate participates in bone healing through indirect processes which enhance angiogenesis and bone maturation and not directly on osteoprogenitor differentiation and bone formation. The mass of bioactive glass used in this study provides a comparable and potentially additive, response to localized VEGF delivery over early time points. These studies demonstrate a materials approach to achieve an angiogenic response formerly limited to the delivery of inductive growth factors.

Abnormal subchondral bone microstructure following steroid administration is involved in the early pathogenesis of steroid-induced osteonecrosis.

PubMed

Wang, L; Zhang, L; Pan, H; Peng, S; Zhao, X; Lu, W W

2016-01-01

Loss of bone microstructure integrity is thought to be related to osteonecrosis. But the relationship between the time when bone microstructure integrity loss appears and the onset of osteonecrosis has not yet been determined. Our study demonstrated abnormal changes of subchondral bone microstructure involved in the early pathogenesis of osteonecrosis. Using a rabbit model, we investigated the changes of subchondral bone microstructure following steroid administration to identify the onset of abnormal bone microstructure development in steroid-induced osteonecrosis. Fifty-five adult female Japanese White rabbits (mean body weight 3.5 kg; mean age 24 months) were used and randomly divided among three time points (3, 7, and 14 days) consisting of 15 rabbits each, received a single intramuscular injection of methylprednisolone acetate (MP; Pfizer Manufacturing Belgium NV) at a dose of 4 mg/kg, and a control group consisting of 10 rabbits was fed and housed under identical conditions but were not given steroid injections. A micro-CT scanner was applied to detect changes in the trabecular region of subchondral bone of excised femoral head samples. Parameters including bone volume fraction (BV/TV), bone surface (BS), trabecular bone pattern factor (Tb.Pf), trabecular thickness/number/separation (Tb.Th, Tb.N, and Tb.Sp), and structure model index (SMI) were evaluated using the software CTAn (SkyScan). After micro-CT scans, bilateral femoral heads were cut in the coronal plane at a thickness of 4 μm. The sections were then stained with haematoxylin-eosin and used for the diagnosis of osteonecrosis and the rate of development of osteonecrosis. The BV/TV, BS, Tb.Th and Tb.N demonstrated a time-dependent decline from 3, 7, and 14 days compared with the control group, while the Tb.Pf, Tb.Sp and SMI demonstrated an increase at 3, 7, and 14 days compared with the control group. For the histopathology portion, osteonecrosis was not seen 3 days after steroid treatment, but was

Modulation of bone resorption by phosphorylation state of bone sialoprotein.

PubMed

Curtin, Paul; McHugh, Kevin P; Zhou, Hai-Yan; Flückiger, Rudolf; Goldhaber, Paul; Oppenheim, Frank G; Salih, Erdjan

2009-07-28

We have determined transmembrane protein tyrosine phosphorylation (outside-in signaling) in cultured osteoclasts and macrophages in response to added native purified bone sialoprotein (nBSP) and its dephosphorylated form (dBSP). There were selective/differential and potent inhibitory effects by dBSP and minimal effect by nBSP on intracellular tyrosine phosphorylation in macrophages and osteoclasts. Further studies on the downstream gene expression effects led to identification of a large number of differentially expressed genes in response to nBSP relative to dBSP in both macrophages and osteoclasts. These studies were extended to a bone resorption model using live mouse neonatal calvarial bone organ cultures stimulated by parathyroid hormone (PTH) to undergo bone resorption. Inclusion of nBSP in such cultures showed no effect on type I collagen telopeptide fragment release, hence overall bone resorption, whereas addition of dBSP abolished the PTH-induced bone resorption. The inhibition of bone resorption by dBSP was shown to be unique since in complementary experiments use of integrin receptor binding ligand, GRGDS peptide, offered only partial reduction on overall bone resorption. Quantitative RANKL analysis indicated that mechanistically the PTH-induced bone resorption was inhibited by dBSP via down-regulation of the osteoblastic RANKL production. This conclusion was supported by the RANKL analysis in cultured MC3T3-E1 osteoblast cells. Overall, these studies provided direct evidence for the involvement of covalently bound phosphates on BSP in receptor mediated "outside-in" signaling via transmembrane tyrosine phosphorylation with concurrent effects on downstream gene expressions. The use of a live bone organ culture system augmented these results with further evidence that links the observed in vivo variable state of phosphorylation with bone remodeling.

Anterior total hip arthroplasty using a metaphyseal bone-sparing stem: component alignment and early complications.

PubMed

Ahmed, Mohammed M; Otto, Thomas J; Moed, Berton R

2016-04-22

Limited-incision total hip arthroplasty (THA) preserves hip abductors, posterior capsule, and external rotators potentially diminishing dislocation risk. However, potential complications also exist, such as component malposition. Specific implants have been manufactured that enhance compatibility with this technique, while preserving metaphyseal bone; however, little data exists documenting early complications and component position. The purpose was to evaluate primary THA using a curved, bone-sparing stem inserted through the anterior approach with respect to component alignment and early complications. In a retrospective analysis of 108 cases, the surgical technique was outlined and the occurrence of intraoperative fractures, postoperative dislocations, infection, and limb length inequality was determined. Femoral stem and acetabular cup alignment was quantified using the initial postoperative radiographs. Patient follow-up averaged 12.9 (range 2 to 36) months. There were eight (7.4 %) complications requiring revision surgery in three (2.8 %) patients with three (2.8 %) infections and three (2.8 %) dislocations. Intraoperative complications included one calcar fracture above the lesser trochanter. Leg length inequality >5 mm was present in three (2.8 %) patients. Radiographic analysis showed that femoral neutral alignment was achieved in 95 hips (88.0 %). All femoral stems demonstrated satisfactory fit and fill and no evidence of subsidence, osteolysis, or loosening. An average abduction angle of 44.8° (± 5.3) and average cup anteversion of 16.2° (± 4.2) were also noted. Although the technique with this implant and approach is promising, it does not appear to offer important advantages over standard techniques. However, the findings merit further, long-term study.

Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I.

PubMed

Pievani, Alice; Azario, Isabella; Antolini, Laura; Shimada, Tsutomu; Patel, Pravin; Remoli, Cristina; Rambaldi, Benedetta; Valsecchi, Maria Grazia; Riminucci, Mara; Biondi, Andrea; Tomatsu, Shunji; Serafini, Marta

2015-03-05

Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in mucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-l-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPS IH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring α-l-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear. © 2015 by The American Society of Hematology.

A New Regulator of Osteoclastogenesis: Estrogen Response Element–Binding Protein in Bone

PubMed Central

Chen, Hong; Gilbert, Linda C; Lu, X; Liu, Zhaofan; You, Shaojin; Weitzmann, M Neale; Nanes, Mark S; Adams, John

2012-01-01

The heterogeneous nuclear ribonucleoprotein (hnRNP)–like estrogen response element–binding protein (ERE-BP) competes with estrogen receptor α (ERα) for occupancy of estrogen response elements (EREs). Here we report that ERE-BP potently stimulates osteoclastogenesis. ERE-BP mRNA and protein were found to be expressed ubiquitously in bone. Overexpression of ERE-BP in cultured osteoblasts stimulated expression of the receptor activator of NF-κB ligand (RANKL) and decreased osteoprotegerin (OPG). The effect of ERE-BP on RANKL was shown to be transcriptional in transient transfection assay and competed with via the ER. Constitutive expression of ERE-BP increased the sensitivity of cells toward 1,25-dihydroxyvitamin D3 stimulation of RANKL expression. In contrast, knockdown of ERE-BP in stromal ST-2 cells decreased basal RANKL promoter activity. Cocultures of ERE-BP lentivirus–transduced ST-2 cells with spleen monocytes induced formation of multinucleated osteoclasts (OCs) characterized by tartrate-resistant acid phosphatase, calcitonin receptors, and functional calcium resorption from bone slices. Although ERα competed with ERE-BP for an ERE in a dose-dependent manner, ERE-BP was an independent and potent regulator of RANKL and osteoclastogenesis. In preosteoclastic RAW cells, overexpression of ERE-BP increased RANK, upregulated NF-κB signaling, and enhanced differentiation toward a mature OC phenotype independent of RANKL. These results identify ERE-BP as a potent modulator of osteoclastogenesis. We hypothesize that ERE-BP may play a critical role in the regulation of bone homeostasis as a modulator of estrogen sensitivity as well as by direct action on the transcription of critical osteoclastogenic genes. PMID:21773989

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.

Health responsibility and workplace health promotion among women: early detection of cancer.

PubMed

Kushnir, T; Rabinowitz, S; Melamed, S; Weisberg, E; Ribak, J

1995-01-01

The importance of health responsibility as one aspect of a health-promoting lifestyle has been emphasized repeatedly. Yet there are only a few empirical studies of its role in preventive behavior. We examined the relationship between health responsibility and early-detection practices for breast and cervical cancer. A group of 253 women employees of a large industrial company participated in a cancer screening program subsidized by the employer. They completed questionnaires assessing health responsibility and reported early-detection practices: frequency of breast self-examination and physician breast examinations, frequency of Pap tests, and time lapsed since last Pap test and breast examinations. Health responsibility was a significant independent predictor of breast examination indicators but not of Pap tests. Education level was an important predictor for Pap tests, and age predicted most early-detection practices. The findings lend some support to the role of health responsibility in initiating breast examinations. Better prediction of early-detection practices could be achieved by adding cognitive and emotional components to the existing responsibility scale and by distinguishing between retrospective and prospective responsibility.

Demonstration of early functional compromise of bone marrow derived hematopoietic progenitor cells during bovine neonatal pancytopenia through in vitro culture of bone marrow biopsies.

PubMed

Laming, Eleanor; Melzi, Eleonora; Scholes, Sandra F E; Connelly, Maira; Bell, Charlotte R; Ballingall, Keith T; Dagleish, Mark P; Rocchi, Mara S; Willoughby, Kim

2012-10-30

Bovine neonatal pancytopenia (BNP) is a syndrome characterised by thrombocytopenia associated with marked bone marrow destruction in calves, widely reported since 2007 in several European countries and since 2011 in New Zealand. The disease is epidemiologically associated with the use of an inactivated bovine virus diarrhoea (BVD) vaccine and is currently considered to be caused by absorption of colostral antibody produced by some vaccinated cows ("BNP dams"). Alloantibodies capable of binding to the leukocyte surface have been detected in BNP dams and antibodies recognising bovine MHC class I and β-2-microglobulin have been detected in vaccinated cattle. In this study, calves were challenged with pooled colostrum collected from BNP dams or from non-BNP dams and their bone marrow hematopoietic progenitor cells (HPC) cultured in vitro from sternal biopsies taken at 24 hours and 6 days post-challenge. Clonogenic assay demonstrated that CFU-GEMM (colony forming unit-granulocyte/erythroid/macrophage/megakaryocyte; pluripotential progenitor cell) colony development was compromised from HPCs harvested as early as 24 hour post-challenge. By 6 days post challenge, HPCs harvested from challenged calves failed to develop CFU-E (erythroid) colonies and the development of both CFU-GEMM and CFU-GM (granulocyte/macrophage) was markedly reduced. This study suggests that the bone marrow pathology and clinical signs associated with BNP are related to an insult which compromises the pluripotential progenitor cell within the first 24 hours of life but that this does not initially include all cell types.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

Changes in bone microstructure and toughness during the healing process of long bones

NASA Astrophysics Data System (ADS)

Ishimoto, T.; Nakano, T.; Umakoshi, Y.; Tabata, Y.

2009-05-01

It is of great importance to understand how bone defects regain the microstructure and mechanical function of bone and how the microstructure affects the mechanical function during the bone healing process. In the present study on long bone defects, we investigated the relationship between the recovery process of fracture toughness and biological apatite (BAp)/collagen (Col) alignment as an index of the bone microstructure to clarify the bone toughening mechanisms. A 5-mm defect introduced in the rabbit ulna was allowed to heal naturally and a three-point bending test was conducted on the regenerated site to assess bone toughness. The bone toughness was quite low at the early stage of bone regeneration but increased during the postoperative period. The change in toughness agreed well with the characteristics of the fracture surface morphology, which reflected the history of the crack propagation. SEM and microbeam X-ray diffraction analyses indicated that the toughness was dominated by the degree and orientation of the preferred BAp/Col alignment, i.e. bundles aligned perpendicular to the crack propagation clearly contributed to the bone toughening owing to extra energy consumption for resistance to crack propagation. In conclusion, regenerated bone improves fracture toughness by reconstructing the preferred BAp/Col alignment along the bone longitudinal axis during the healing process of long bones.

Bone diseases in rabbits with hyperparathyroidism: computed tomography, magnetic resonance imaging and histopathology.

PubMed

Bai, Rong-jie; Cong, De-gang; Shen, Bao-zhong; Han, Ming-jun; Wu, Zhen-hua

2006-08-05

Hyperparathyroidism (HPT) occurs at an early age and has a high disability rate. Unfortunately, confirmed diagnosis in most patients is done at a very late stage, when the patients have shown typical symptoms and signs, and when treatment does not produce any desirable effect. It has become urgent to find a method that would detect early bone diseases in HPT to obtain time for the ideal treatment. This study evaluated the accuracy of high field magnetic resonance imaging (MRI) combined with spiral computed tomography (SCT) scan in detecting early bone diseases in HPT, through imaging techniques and histopathological examinations on an animal model of HPT. Eighty adult rabbits were randomly divided into two groups with forty in each. The control group was fed normal diet (Ca:P = 1:0.7); the experimental group was fed high phosphate diet (Ca:P = 1:7) for 3, 4, 5, or 6-month intervals to establish the animal model of HPT. The staging and imaging findings of the early bone diseases in HPT were determined by high field MRI and SCT scan at the 3rd, 4th, 5th and 6th month. Each rabbit was sacrificed after high field MRI and SCT scan, and the parathyroid and bones were removed for pathological examination to evaluate the accuracy of imaging diagnosis. Parathyroid histopathological studies revealed hyperplasia, osteoporosis and early cortical bone resorption. The bone diseases in HPT displayed different levels of low signal intensity on T(1)WI and low to intermediate signal intensity on T(2)WI in bone of stage 0, I, II or III, but showed correspondingly absent, probable, osteoporotic and subperiosteal cortical resorption on SCT scan. High field MRI combined with SCT scan not only detects early bone diseases in HPT, but also indicates staging, and might be a reliable method of studying early bone diseases in HPT.

Correlations Between Bone Mechanical Properties and Bone Composition Parameters in Mouse Models of Dominant and Recessive Osteogenesis Imperfecta and the Response to Anti-TGF-β Treatment.

PubMed

Bi, Xiaohong; Grafe, Ingo; Ding, Hao; Flores, Rene; Munivez, Elda; Jiang, Ming Ming; Dawson, Brian; Lee, Brendan; Ambrose, Catherine G

2017-02-01

Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by brittle bones that are prone to fracture. Although previous studies in animal models investigated the mechanical properties and material composition of OI bone, little work has been conducted to statistically correlate these parameters to identify key compositional contributors to the impaired bone mechanical behaviors in OI. Further, although increased TGF-β signaling has been demonstrated as a contributing mechanism to the bone pathology in OI models, the relationship between mechanical properties and bone composition after anti-TGF-β treatment in OI has not been studied. Here, we performed follow-up analyses of femurs collected in an earlier study from OI mice with and without anti-TGF-β treatment from both recessive (Crtap -/- ) and dominant (Col1a2 +/P.G610C ) OI mouse models and WT mice. Mechanical properties were determined using three-point bending tests and evaluated for statistical correlation with molecular composition in bone tissue assessed by Raman spectroscopy. Statistical regression analysis was conducted to determine significant compositional determinants of mechanical integrity. Interestingly, we found differences in the relationships between bone composition and mechanical properties and in the response to anti-TGF-β treatment. Femurs of both OI models exhibited increased brittleness, which was associated with reduced collagen content and carbonate substitution. In the Col1a2 +/P.G610C femurs, reduced hydroxyapatite crystallinity was also found to be associated with increased brittleness, and increased mineral-to-collagen ratio was correlated with increased ultimate strength, elastic modulus, and bone brittleness. In both models of OI, regression analysis demonstrated that collagen content was an important predictor of the increased brittleness. In summary, this work provides new insights into the relationships between bone composition and material properties in

Parameters affecting mechanical and thermal responses in bone drilling: A review.

PubMed

Lee, JuEun; Chavez, Craig L; Park, Joorok

2018-04-11

Surgical bone drilling is performed variously to correct bone fractures, install prosthetics, or for therapeutic treatment. The primary concern in bone drilling is to extract donor bone sections and create receiving holes without damaging the bone tissue either mechanically or thermally. We review current results from experimental and theoretical studies to investigate the parameters related to such effects. This leads to a comprehensive understanding of the mechanical and thermal aspects of bone drilling to reduce their unwanted complications. This review examines the important bone-drilling parameters of bone structure, drill-bit geometry, operating conditions, and material evacuation, and considers the current techniques used in bone drilling. We then analyze the associated mechanical and thermal effects and their contributions to bone-drilling performance. In this review, we identify a favorable range for each parameter to reduce unwanted complications due to mechanical or thermal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Non-elite gymnastics participation is associated with greater bone strength, muscle size, and function in pre- and early pubertal girls.

PubMed

Burt, L A; Naughton, G A; Greene, D A; Courteix, D; Ducher, G

2012-04-01

Recent reports indicate an increase in forearm fractures in children. Bone geometric properties are an important determinant of bone strength and therefore fracture risk. Participation in non-elite gymnastics appears to contribute to improving young girls' musculoskeletal health, more specifically in the upper body. The primary aim of this study was to determine the association between non-elite gymnastics participation and upper limb bone mass, geometry, and strength in addition to muscle size and function in young girls. Eighty-eight pre- and early pubertal girls (30 high-training gymnasts [HGYM, 6-16 hr/ wk], 29 low-training gymnasts [LGYM, 1-5 h r/wk] and 29 non-gymnasts [NONGYM]), aged 6-11 years were recruited. Upper limb lean mass, BMD and BMC were derived from a whole body DXA scan. Forearm volumetric BMD, bone geometry, estimated strength, and muscle CSA were determined using peripheral QCT. Upper body muscle function was investigated with muscle strength, explosive power, and muscle endurance tasks. HGYM showed greater forearm bone strength compared with NGYM, as well as greater arm lean mass, BMC, and muscle function (+5% to +103%, p < 0.05). LGYM displayed greater arm lean mass, BMC, muscle power, and endurance than NGYM (+4% to +46%, p < 0.05); however, the difference in bone strength did not reach significance. Estimated fracture risk at the distal radius, which accounted for body weight, was lower in both groups of gymnasts. Compared with NONGYM, HGYM tended to show larger skeletal differences than LGYM; yet, the two groups of gymnasts only differed for arm lean mass and muscle CSA. Non-elite gymnastics participation was associated with musculoskeletal benefits in upper limb bone geometry, strength and muscle function. Differences between the two gymnastic groups emerged for arm lean mass and muscle CSA, but not for bone strength.

"Ruffled border" formation on a CaP-free substrate: A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over.

PubMed

Merolli, Antonio; Fung, Stephanie; Murthy, N Sanjeeva; Pashuck, E Thomas; Mao, Yong; Wu, Xiaohuan; Steele, Joseph A M; Martin, Daniel; Moghe, Prabhas V; Bromage, Timothy; Kohn, Joachim

2018-03-21

Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiological bone turnover (BTO), which is the continuous cycle of bone resorption (by osteoclasts) followed by new bone formation (by osteoblasts). Osteoclasts secrete chemotactic signals to recruit cells for regeneration of vasculature and bone. We hypothesize that a biomaterial that attracts osteoclasts and re-establishes BTO will induce a better healing response than currently used bone graft materials. While the majority of bone regeneration efforts have focused on maximizing bone deposition, the novelty in this approach is the focus on stimulating osteoclastic resorption as the starter for BTO and its concurrent new vascularized bone formation. A biodegradable tyrosine-derived polycarbonate, E1001(1k), was chosen as the polymer base due to its ability to support bone regeneration in vivo. The polymer was functionalized with a RGD peptide or collagen I, or blended with β-tricalcium phosphate. Osteoclast attachment and early stages of active resorption were observed on all substrates. The transparency of E1001(1k) in combination with high resolution confocal imaging enabled visualization of morphological features of osteoclast activation such as the formation of the "actin ring" and the "ruffled border", which previously required destructive forms of imaging such as transmission electron microscopy. The significance of these results is twofold: (1) E1001(1k) is suitable for osteoclast attachment and supports osteoclast maturation, making it a base polymer that can be further modified to optimize stimulation of BTO and (2) the transparency of this polymer makes it a suitable analytical tool for studying osteoclast behavior.

Tissue-engineered bone with 3-dimensionally printed β-tricalcium phosphate and polycaprolactone scaffolds and early implantation: an in vivo pilot study in a porcine mandible model.

PubMed

Konopnicki, Sandra; Sharaf, Basel; Resnick, Cory; Patenaude, Adam; Pogal-Sussman, Tracy; Hwang, Kyung-Gyun; Abukawa, Harutsugi; Troulis, Maria J

2015-05-01

Deep bone penetration into implanted scaffolds remains a challenge in tissue engineering. The purpose of this study was to evaluate bone penetration depth within 3-dimensionally (3D) printed β-tricalcium phosphate (β-TCP) and polycaprolactone (PCL) scaffolds, seeded with porcine bone marrow progenitor cells (pBMPCs), and implanted early in vivo. Scaffolds were 3D printed with 50% β-TCP and 50% PCL. The pBMPCs were harvested, isolated, expanded, and differentiated into osteoblasts. Cells were seeded into the scaffolds and constructs were incubated in a rotational oxygen-permeable bioreactor system for 14 days. Six 2- × 2-cm defects were created in each mandible (N = 2 minipigs). In total, 6 constructs were placed within defects and 6 defects were used as controls (unseeded scaffolds, n = 3; empty defects, n = 3). Eight weeks after surgery, specimens were harvested and analyzed by hematoxylin and eosin (H&E), 4',6-diamidino-2-phenylindole (DAPI), and CD31 staining. Analysis included cell counts, bone penetration, and angiogenesis at the center of the specimens. All specimens (N = 12) showed bone formation similar to native bone at the periphery. Of 6 constructs, 4 exhibited bone formation in the center. Histomorphometric analysis of the H&E-stained sections showed an average of 22.1% of bone in the center of the constructs group compared with 1.87% in the unseeded scaffolds (P < .05). The 2 remaining constructs, which did not display areas of mature bone in the center, showed massive cell penetration depth by DAPI staining, with an average of 2,109 cells/0.57 mm(2) in the center compared with 1,114 cells/0.57 mm(2) in the controls (P < .05). CD31 expression was greater in the center of the constructs compared with the unseeded scaffolds (P < .05). 3D printed β-TCP and PCL scaffolds seeded with pBMPCs and implanted early into porcine mandibular defects display good bone penetration depth. Further study with a larger sample and larger bone defects should be

Bone vs. fat: Embryonic origin of progenitors determines response to androgen in adipocytes and osteoblasts

PubMed Central

Wiren, Kristine M.; Hashimoto, Joel G.; Semirale, Anthony A.; Zhang, Xiao-Wei

2011-01-01

Although androgen is considered an anabolic hormone, the consequences of androgen receptor (AR) overexpression in skeletally-targeted AR-transgenic lines highlight the detrimental effect of enhanced androgen sensitivity on cortical bone quality. A compartment-specific anabolic response is observed only in male but not female AR3.6-transgenic (tg) mice, with increased periosteal bone formation and calvarial thickening. To identify anabolic signaling cascades that have the potential to increase bone formation, qPCR array analysis was employed to define expression differences between AR3.6-tg and wild-type (WT) periosteal tissue. Notably, categories that were significantly different between the two genotypes included axonal guidance, CNS development and negative regulation of Wnt signaling with a node centered on stem cell pathways. Further, fine mapping of AR3.6-tg calvaria revealed that anabolic thickening in vivo is not uniform across the calvaria, occurring only in frontal but not parietal bones. Multipotent fraction 1 progenitor populations from both genotypes were cultured separately as frontal bone neural crest stem-like cells (fNCSC) and parietal bone mesenchymal stem-like cells (pMSC). Both osteoblastic and adipogenic differentiation in these progenitor populations was influenced by embryonic lineage and by genotype. Adipogenesis was enhanced in WT fNCSC compared to pMSC, but transgenic cultures showed strong suppression of lipid accumulation only in fNCSC cells. Osteoblastogenesis was significantly increased in transgenic fNCSC cultures compared to WT, with elevated alkaline phosphatase (ALP) activity and induction of mineralization and nodule formation assessed by alizarin red and von Kossa staining. Osteocalcin (OC) and ALP mRNA levels were also increased in fNCSC cultures from AR3.6-tg vs. WT, but in pMSC cultures ALP mRNA levels, mineralization and nodule formation were decreased in AR3.6-tg cells. Expression differences identified by array in long bone

Acute bone response to whole body vibration in healthy pre-pubertal boys

PubMed Central

Harrison, R.; Ward, K.; Lee, E.; Razaghi, H.; Horne, C.; Bishop, N.J.

2015-01-01

The skeleton responds to mechanical stimulation. We wished to ascertain the magnitude and speed of the growing skeleton’s response to a standardised form of mechanical stimulation, vibration. 36 prepubertal boys stood for 10 minutes in total on one of two vibrating platforms (high (>2 g) or low (<1 g) magnitude vibration) on either 1, 3 or 5 successive days (n=12 for each duration); 15 control subjects stood on an inactive platform. Blood samples were taken at intervals before and after vibration to measure bone formation (P1NP, osteocalcin) and resorption (CTx) markers as well as osteoprotegerin and sclerostin. There were no significant differences between platform and control groups in bone turnover markers immediately after vibration on days 1, 3 and 5. Combining platform groups, at day 8 P1NP increased by 25.1% (CI 12.3 to 38.0; paired t-test p=0.005) and bone resorption increased by 10.9% (CI 3.6 to 18.2; paired t-test p=0.009) compared to baseline. Osteocalcin, osteoprotogerin and sclerostin did not change significantly. The growing skeleton can respond quickly to vibration of either high or low magnitude. Further work is needed to determine the utility of such “stimulation-testing” in clinical practice. PMID:26032203

Synergistic effect of nanotopography and bioactive ions on peri-implant bone response

PubMed Central

Su, Yingmin; Komasa, Satoshi; Li, Peiqi; Nishizaki, Mariko; Chen, Luyuan; Terada, Chisato; Yoshimine, Shigeki; Nishizaki, Hiroshi; Okazaki, Joji

2017-01-01

Both bioactive ion chemistry and nanoscale surface modifications are beneficial for enhanced osseointegration of endosseous implants. In this study, a facile synthesis approach to the incorporation of bioactive Ca2+ ions into the interlayers of nanoporous structures (Ca-nano) formed on a Ti6Al4V alloy surface was developed by sequential chemical and heat treatments. Samples with a machined surface and an Na+ ion-incorporated nanoporous surface (Na-nano) fabricated by concentrated alkali and heat treatment were used in parallel for comparison. The bone response was investigated by microcomputed tomography assessment, sequential fluorescent labeling analysis, and histological and histomorphometric evaluation after 8 weeks of implantation in rat femurs. No significant differences were found in the nanotopography, surface roughness, or crystalline properties of the Ca-nano and Na-nano surfaces. Bone–implant contact was better in the Ca-nano and Na-nano implants than in the machined implant. The Ca-nano implant was superior to the Na-nano implant in terms of enhancing the volume of new bone formation. The bone formation activity consistently increased for the Ca-nano implant but ceased for the Na-nano implant in the late healing stage. These results suggest that Ca-nano implants have promising potential for application in dentistry and orthopedics. PMID:28184162

Acute bone response to whole body vibration in healthy pre-pubertal boys.

PubMed

Harrison, R; Ward, K; Lee, E; Razaghi, H; Horne, C; Bishop, N J

2015-06-01

The skeleton responds to mechanical stimulation. We wished to ascertain the magnitude and speed of the growing skeleton's response to a standardised form of mechanical stimulation, vibration. 36 prepubertal boys stood for 10 minutes in total on one of two vibrating platforms (high (>2 g) or low (<1 g) magnitude vibration) on either 1, 3 or 5 successive days (n=12 for each duration); 15 control subjects stood on an inactive platform. Blood samples were taken at intervals before and after vibration to measure bone formation (P1NP, osteocalcin) and resorption (CTx) markers as well as osteoprotegerin and sclerostin. There were no significant differences between platform and control groups in bone turnover markers immediately after vibration on days 1, 3 and 5. Combining platform groups, at day 8 P1NP increased by 25.1% (CI 12.3 to 38.0; paired t-test p=0.005) and bone resorption increased by 10.9% (CI 3.6 to 18.2; paired t-test p=0.009) compared to baseline. Osteocalcin, osteoprotogerin and sclerostin did not change significantly. The growing skeleton can respond quickly to vibration of either high or low magnitude. Further work is needed to determine the utility of such "stimulation-testing" in clinical practice.

Early relapse of Burkitt lymphoma heralded by a bone marrow necrosis and numb chin syndrome successfully treated with allogeneic stem cell transplantation.

PubMed

Cerny, Jan; Devitt, Katherine; Yu, Hongbo; Ramanathan, Muthalagu; Woda, Bruce; Nath, Rajneesh

2014-01-01

The optimal salvage therapy for patients with relapsed Burkitt lymphoma is unknown. Bone marrow necrosis is an underreported (<1% of bone marrow failures). Numb chin syndrome is another rare syndrome associated with aggressive malignancies. Survival of these syndromes is dictated by the underlying disease and is usually dismal. Our 35-year-old patient experienced an early relapse of Burkitt lymphoma accompanied by syndromes, achieved second complete remission and underwent allogeneic stem cell transplantation. He remains alive and well >2 years after the transplant. To our knowledge, this is the longest reported survival of the two syndromes in the setting of BL relapse.

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

In vivo loss of function study reveals the short stature homeobox-containing (shox) gene plays indispensable roles in early embryonic growth and bone formation in zebrafish.

PubMed

Sawada, Rie; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shimizu, Toshiaki

2015-02-01

Congenital loss of the SHOX gene is considered to be a genetic cause of short stature phenotype in Turner syndrome and Leri-Weill dyschondrosteosis patients. Though SHOX expression initiates during early fetal development, little is known about the embryonic roles of SHOX. The evolutionary conservation of the zebrafish shox gene and the convenience of the early developmental stages for analyses make zebrafish a preferred model. Here, we characterized structure, expression, and developmental roles of zebrafish shox through a loss-of-function approach. We found a previously undiscovered Shox protein that has both a homeodomain and an OAR-domain in zebrafish. The shox transcript emerged during the segmentation period and it increased in later stages. The predominant domains of shox expression were mandibular arch, pectoral fin, anterior notochord, rhombencephalon, and mesencephalon, suggesting that Shox is involved in bone and neural development. Translational blockade of Shox mRNA by an antisense morpholino oligo delayed embryonic growth, which was restored by the co-overexpression of morpholino-resistant Shox mRNA. At later stages, impaired Shox expression markedly delayed the calcification process in the anterior vertebral column and craniofacial bones. Our data demonstrate evolutionarily conserved Shox plays roles in early embryonic growth and in later bone formation. © 2014 Wiley Periodicals, Inc.

Weight-bearing exercise and bone mineral accrual in children and adolescents: a review of controlled trials.

PubMed

Hind, K; Burrows, M

2007-01-01

Osteoporosis is a serious skeletal disease and as there is currently no cure, there is a large emphasis on its prevention, including the optimisation of peak bone mass. There is increasing evidence that regular weight-bearing exercise is an effective strategy for enhancing bone status during growth. This systematic review evaluates randomised and non-randomised controlled trials to date, on the effects of exercise on bone mineral accrual in children and adolescents. An online search of Medline and the Cochrane database enabled the identification of studies. Those that met the inclusion criteria were included in the review and graded according to risk for bias. Twenty-two trials were reviewed. Nine were conducted in prepubertal children (Tanner I), 8 in early pubertal (Tanner II-III) and 5 in pubertal (Tanner IV-V). Sample sizes ranged from n=10 to 65 per group. Exercise interventions included games, dance, resistance training and jumping exercises, ranging in duration from 3 to 48 months. Approximately half of the trials (n=10) included ground reaction force (GRF) data (2 to 9 times body weight). All trials in early pubertal children, 6 in pre pubertal and 2 in pubertal children, reported positive effects of exercise on bone (P<0.05). Mean increases in bone parameters over 6 months were 0.9-4.9% in prepubertal, 1.1-5.5% in early pubertal and 0.3-1.9% in pubertal exercisers compared to controls (P<0.05). Although weight-bearing exercise appears to enhance bone mineral accrual in children, particularly during early puberty; it remains unclear as to what constitutes the optimal exercise programme. Many studies to date have a high risk for bias and only a few have a low risk. Major limitations concerned selection procedures, compliance rates and control of variables. More well designed and controlled investigations are needed. Furthermore, the specific exercise intervention that will provide the optimal stimulus for peak bone mineral accretion is unclear. Future

Kaempferol stimulates bone sialoprotein gene transcription and new bone formation.

PubMed

Yang, Li; Takai, Hideki; Utsunomiya, Tadahiko; Li, Xinyue; Li, Zhengyang; Wang, Zhitao; Wang, Shuang; Sasaki, Yoko; Yamamoto, Hirotsugu; Ogata, Yorimasa

2010-08-15

Kaempferol is a typical flavonol-type flavonoid that is present in a variety of vegetables and fruits, and has a protective effect on postmenopausal bone loss. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone and could be crucial for osteoblast differentiation, bone matrix mineralization and tumor metastasis. In the present study we investigated the regulation of BSP transcription by kaempferol in rat osteoblast-like UMR106 cells, and the effect of kaempferol on new bone formation. Kaempferol (5 microM) increased BSP and Osterix mRNA levels at 12 h and up-regulated Runx2 mRNA expression at 6 h. Kaempferol increased luciferase activity of the construct pLUC3, which including the promoter sequence between nucleotides -116 to +60. Transcriptional stimulation by kaempferol abrogated in constructs included 2 bp mutations in the inverted CCAAT, CRE, and FRE elements. Gel shift analyses showed that kaempferol increased nuclear protein binding to CRE and FRE elements, whereas the CCAAT-protein complex did not change after kaempferol stimulation. Twelve daily injections of 5 microM kaempferol directly into the periosteum of parietal bones of newborn rats increased new bone formation. These data suggest that kaempferol increased BSP gene transcription mediated through inverted CCAAT, CRE, and FRE elements in the rat BSP gene promoter, and could induce osteoblast activities in the early stage of bone formation. (c) 2010 Wiley-Liss, Inc.

Biological aspects of early osteoarthritis.

PubMed

Madry, Henning; Luyten, Frank P; Facchini, Andrea

2012-03-01

Early OA primarily affects articular cartilage and involves the entire joint, including the subchondral bone, synovial membrane, menisci and periarticular structures. The aim of this review is to highlight the molecular basis and histopathological features of early OA. Selective review of literature. Risk factors for developing early OA include, but are not limited to, a genetic predisposition, mechanical factors such as axial malalignment, and aging. In early OA, the articular cartilage surface is progressively becoming discontinuous, showing fibrillation and vertical fissures that extend not deeper than into the mid-zone of the articular cartilage, reflective of OARSI grades 1.0-3.0. Early changes in the subchondral bone comprise a progressive increase in subchondral plate and subarticular spongiosa thickness. Early OA affects not only the articular cartilage and the subchondral bone but also other structures of the joint, such as the menisci, the synovial membrane, the joint capsule, ligaments, muscles and the infrapatellar fat pad. Genetic markers or marker combinations may become useful in the future to identify early OA and patients at risk. The high socioeconomic impact of OA suggests that a better insight into the mechanisms of early OA may be a key to develop more targeted reconstructive therapies at this first stage of the disease. Systematic review, Level II.

Determination of in vivo mechanical properties of long bones from their impedance response curves

NASA Technical Reports Server (NTRS)

Borders, S. G.

1981-01-01

A mathematical model consisting of a uniform, linear, visco-elastic, Euler-Bernoulli beam to represent the ulna or tibia of the vibrating forearm or leg system is developed. The skin and tissue compressed between the probe and bone is represented by a spring in series with the beam. The remaining skin and tissue surrounding the bone is represented by a visco-elastic foundation with mass. An extensive parametric study is carried out to determine the effect of each parameter of the mathematical model on its impedance response. A system identification algorithm is developed and programmed on a digital computer to determine the parametric values of the model which best simulate the data obtained from an impedance test.

The Digital Astronaut Project Bone Remodeling Model

NASA Technical Reports Server (NTRS)

Pennline, J. A.; Mulugeta, L.; Lewandowski, B. E.; Thompson, W. K.; Sibonga, J. D.

2013-01-01

One of the main objectives is to provide a tool to help HHC address Bone Gap Osteo 4: We don't know the contribution of each risk factor on bone loss and recovery of bone strength and which factors are the best targets for countermeasure application; and Osteo7: We need to identify options for mitigation of early onset osteoporosis before, during, and after spaceflight.

Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes

PubMed Central

Morgan, Jennifer L. L.; Skulan, Joseph L.; Gordon, Gwyneth W.; Romaniello, Stephen J.; Smith, Scott M.; Anbar, Ariel D.

2012-01-01

The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible. PMID:22652567

Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

DTIC Science & Technology

2013-01-01

Praetorius, F. Guided tissue regeneration using de- gradable and nondegradable membranes in rabbit tibia. Clin Oral Implants Res 4, 172, 1993. 8. Queiroz... Regeneration of periodontal tissues : combinations of barrier membranes and grafting materials–biological foundation and preclinical evi- dence: a...structural graft provides benefits for bone tissue regeneration in terms of early interfacial integration. Introduction The treatment of large-bone defects

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.

Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

PubMed Central

Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

2016-01-01

Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

Noninvasive Determination of Bone Mechanical Properties using Vibration Response: A Refined Model and Validation in vivo

NASA Technical Reports Server (NTRS)

Roberts, S. G.; Hutchinson, T. M.; Arnaud, S. B.; Steele, C. R.; Kiratli, B. J.; Martin, R. B.

1996-01-01

Accurate non-invasive mechanical measurement of long bones is made difficult by the masking effect of surrounding soft tissues. Mechanical Response Tissue Analysis (MRTA) offers a method for separating the effects of the soft tissue and bone; however, a direct validation has been lacking. A theoretical analysis of wave propagation through the compressed tissue revealed a strong mass effect dependent on the relative accelerations of the probe and bone. The previous mathematical model of the bone and overlying tissue system was reconfigured to incorporate the theoretical finding. This newer model (six-parameter) was used to interpret results using MRTA to determine bone cross-sectional bending stiffness, EI(sub MRTA). The relationship between EI(MRTA) and theoretical EI values for padded aluminum rods was R(exp 2) = 0.999. A biological validation followed using monkey tibias. Each bone was tested in vivo with the MRTA instrument. Postmortem, the same tibias were excised and tested to failure in three-point bending to determine EI(sub 3-PT) and maximum load. Diaphyseal Bone Mineral Density (BMD) measurements were also made. The relationship between E(sub 3-PT) and in vivo EI(sub MRTA) using the six-parameter model is strong (R(exp 2) = 0.947) and better than that using the older model (R(exp 2) = 0.645). EI(MRTA) and BMD are also highly correlated (R(exp 2) = 0.853). MRTA measurements in vivo and BMD ex vivo are both good predictors of scaled maximum strength (R(exp 2) = 0.915 and R(exp 2) = 0.894, respectively). This is the first biological validation of a non-invasive mechanical measurement of bone by comparison to actual values. The MRTA technique has potential clinical value for assessing long-bone mechanical properties.

Noninvasive Determination of Bone Mechanical Properties Using Vibration Response: A Refined Model and Validation in vivo

NASA Technical Reports Server (NTRS)

Roberts, S. G.; Hutchinson, T. M.; Arnaud, S. B.; Kiratli, B. J; Steele, C. R.

1996-01-01

Accurate non-invasive mechanical measurement of long bones is made difficult by the masking effect of surrounding soft tissues. Mechanical response tissue analysis (MRTA) offers a method for separating the effects of the soft tissue and bone; however, a direct validation has been lacking. A theoretical analysis of wave propagation through the compressed tissue revealed a strong mass effect dependent on the relative accelerations of the probe and bone. The previous mathematical model of the bone and overlying tissue system was reconfigured to incorporate the theoretical finding. This newer model (six-parameter) was used to interpret results using MRTA to determine bone cross-sectional bending stiffness, EI(sub MRTA). The relationship between EI(sub MRTA) and theoretical EI values for padded aluminum rods was R(sup 2) = 0.999. A biological validation followed using monkey tibias. Each bone was tested in vivo with the MRTA instrument. Postmortem, the same tibias were excised and tested to failure in three-point bending to determine EI(sub 3-PT) and maximum load. Diaphyseal bone mineral density (BMD) measurements were also made. The relationship between EI(sub 3-PT) and in vivo EI(sub MRTA) using the six-parameter model is strong (R(sup 2) = 0.947) and better than that using the older model (R(sup 2) = 0.645). EI(sub MRTA) and BMD are also highly correlated (R(sup 2) = 0.853). MRTA measurements in vivo and BMD ex vivo are both good predictors of scaled maximum strength (R(sup 2) = 0.915 and R(sup 2) = 0.894, respectively). This is the first biological validation of a non- invasive mechanical measurement of bone by comparison to actual values. The MRTA technique has potential clinical value for assessing long-bone mechanical properties.

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.

Bone healing response in cyclically loaded implants: Comparing zero, one, and two loading sessions per day.

PubMed

de Barros E Lima Bueno, Renan; Dias, Ana Paula; Ponce, Katia J; Wazen, Rima; Brunski, John B; Nanci, Antonio

2018-05-31

When bone implants are loaded, they are inevitably subjected to displacement relative to bone. Such micromotion generates stress/strain states at the interface that can cause beneficial or detrimental sequels. The objective of this study is to better understand the mechanobiology of bone healing at the tissue-implant interface during repeated loading. Machined screw shaped Ti implants were placed in rat tibiae in a hole slightly bigger than the implant diameter. Implants were held stable by a specially-designed bone plate that permits controlled loading. Three loading regimens were applied, (a) zero loading, (b) one daily loading session of 60 cycles with an axial force of 1.5 N/cycle for 7 days, and (c) two such daily sessions with the same axial force also for 7 days. Finite element analysis was used to characterize the mechanobiological conditions produced by the loading sessions. After 7 days, the implants with surrounding interfacial tissue were harvested and processed for histological, histomorphometric and DNA microarray analyses. Histomorphometric analyses revealed that the group subjected to repeated loading sessions exhibited a significant decrease in bone-implant contact and increase in bone-implant distance, as compared to unloaded implants and those subjected to only one loading session. Gene expression profiles differed during osseointegration between all groups mainly with respect to inflammatory and unidentified gene categories. The results indicate that increasing the daily cyclic loading of implants induces deleterious changes in the bone healing response, most likely due to the accumulation of tissue damage and associated inflammatory reaction at the bone-implant interface. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Early-life inflammation, immune response and ageing.

PubMed

Khan, Imroze; Agashe, Deepa; Rolff, Jens

2017-03-15

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

Early-life inflammation, immune response and ageing

PubMed Central

2017-01-01

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. PMID:28275145

Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults.

PubMed

Cobb, Kensi M; Stuart, Andrew

2016-08-01

The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level (nHL). The lowest stimulus intensity level at which a wave V was identifiable and replicable was considered the ABR threshold. ABR thresholds to air-conducted CE-Chirps were 9.8 dB nHL for neonates and adults. ABR thresholds to bone-conducted CE-Chirps were 3.8 and 13.8 dB nHL for neonates and adults, respectively. The difference in ABR thresholds to bone-conducted CE-Chirps was significantly different (p < .0001, ηp2 = .45). Adults had significantly larger wave V amplitudes to air- (p < .0001, ηp2 = .50) and bone-conducted (p = .013, ηp2 = .15) CE-Chirps at a stimulus intensity of 30 dB nHL. At the same intensity, adults evidenced significantly shorter wave V latencies (p < .0001, ηp2 = .49) only with air-conducted CE-chirps. The difference in ABR thresholds and wave V latencies to air- and bone-conducted CE-Chirps between neonates and adults may be attributed to a disparity in effective signal delivery to the cochlea.

Micro-mechanical modeling of the cement-bone interface: the effect of friction, morphology and material properties on the micromechanical response.

PubMed

Janssen, Dennis; Mann, Kenneth A; Verdonschot, Nico

2008-11-14

In order to gain insight into the micro-mechanical behavior of the cement-bone interface, the effect of parametric variations of frictional, morphological and material properties on the mechanical response of the cement-bone interface were analyzed using a finite element approach. Finite element models of a cement-bone interface specimen were created from micro-computed tomography data of a physical specimen that was sectioned from an in vitro cemented total hip arthroplasty. In five models the friction coefficient was varied (mu=0.0; 0.3; 0.7; 1.0 and 3.0), while in one model an ideally bonded interface was assumed. In two models cement interface gaps and an optimal cement penetration were simulated. Finally, the effect of bone cement stiffness variations was simulated (2.0 and 2.5 GPa, relative to the default 3.0 GPa). All models were loaded for a cycle of fully reversible tension-compression. From the simulated stress-displacement curves the interface deformation, stiffness and hysteresis were calculated. The results indicate that in the current model the mechanical properties of the cement-bone interface were caused by frictional phenomena at the shape-closed interlock rather than by adhesive properties of the cement. Our findings furthermore show that in our model maximizing cement penetration improved the micromechanical response of the cement-bone interface stiffness, while interface gaps had a detrimental effect. Relative to the frictional and morphological variations, variations in the cement stiffness had only a modest effect on the micro-mechanical behavior of the cement-bone interface. The current study provides information that may help to better understand the load-transfer mechanisms taking place at the cement-bone interface.

Evaluation of bone tissue response to a sealer containing mineral trioxide aggregate.

PubMed

Assmann, Eloísa; Böttcher, Daiana Elisabeth; Hoppe, Carolina Bender; Grecca, Fabiana Soares; Kopper, Patrícia Maria Poli

2015-01-01

This study analyzed bone tissue reactions to MTA Fillapex (Ângelus Industria de Produtos Odontológicos Ltda, Londrina, Brazil) compared with an epoxy resin-based material in the femur of Wistar rats. Bone tissue reactions were evaluated in 15 animals after 7, 30, and 90 days (n = 5 per period). Three surgical cavities were prepared on the femur and filled with 0.2 mL MTA Fillapex, AH Plus (Dentsply DeTrey GmbH, Konstanz, Germany), or no sealer (negative control). By the end of each experimental period, 5 animals were randomly euthanized. The samples were histologically processed and analyzed using a light microscope. The presence of inflammatory cells, fibers, and hard tissue barrier formation was evaluated. Differences among the groups and between the 3 experimental periods were evaluated by using 2-way analysis of variance followed by the Bonferroni post hoc test (P ≤ .05). MTA Fillapex scored significantly higher for neutrophils at 7 days than at 90. At 7 days, the same occurred when comparing MTA Fillapex with AH Plus. The presence of lymphocytes/plasmocytes significantly decreased over time in all groups. Macrophages, giant cells, eosinophils, and fiber condensation presented no differences among groups and periods. Within 90 days, all groups presented complete hard tissue barrier formation. The presence of mineral trioxide aggregate in MTA Fillapex composition did not improve the bone tissue repair. The presence of sealers provided the re-establishment of the original bone tissue structure and the inflammatory response decreased over time, so they can be considered biocompatible. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Bone strain magnitude is correlated with bone strain rate in tetrapods: implications for models of mechanotransduction

PubMed Central

Aiello, B. R.; Iriarte-Diaz, J.; Blob, R. W.; Butcher, M. T.; Carrano, M. T.; Espinoza, N. R.; Main, R. P.; Ross, C. F.

2015-01-01

Hypotheses suggest that structural integrity of vertebrate bones is maintained by controlling bone strain magnitude via adaptive modelling in response to mechanical stimuli. Increased tissue-level strain magnitude and rate have both been identified as potent stimuli leading to increased bone formation. Mechanotransduction models hypothesize that osteocytes sense bone deformation by detecting fluid flow-induced drag in the bone's lacunar–canalicular porosity. This model suggests that the osteocyte's intracellular response depends on fluid-flow rate, a product of bone strain rate and gradient, but does not provide a mechanism for detection of strain magnitude. Such a mechanism is necessary for bone modelling to adapt to loads, because strain magnitude is an important determinant of skeletal fracture. Using strain gauge data from the limb bones of amphibians, reptiles, birds and mammals, we identified strong correlations between strain rate and magnitude across clades employing diverse locomotor styles and degrees of rhythmicity. The breadth of our sample suggests that this pattern is likely to be a common feature of tetrapod bone loading. Moreover, finding that bone strain magnitude is encoded in strain rate at the tissue level is consistent with the hypothesis that it might be encoded in fluid-flow rate at the cellular level, facilitating bone adaptation via mechanotransduction. PMID:26063842

Postradiation atrophy of mature bone

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

Erguen, H.; Howland, W.J.

1980-01-01

The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographicmore » evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecting demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.« less

Postradiation atrophy of mature bone

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

Ergun, H.; Howland, W.J.

1980-01-01

The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographicmore » evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecing demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.« less

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.

Gender differences in bone turnover in 2-year-old Thoroughbreds.

PubMed

Jackson, B F; Lonnell, C; Verheyen, K; Wood, J L N; Pfeiffert, D U; Price, J S

2003-11-01

Injuries to the skeleton are a major cause of morbidity and mortality in racehorses and age, gender and season have all been shown to influence risk of injury. To use biochemical markers of bone cell activity to establish to whether cellular processes in bone underlie these described effects. Blood samples were collected monthly from 2-year-old horses in race training between November 1998 and September 1999. Mean age at the start of the study was 20 months (range 18-23 months), with no significant difference in average age between colts (n = 84) and fillies (n = 63). Three markers were measured; osteocalcin (OC, bone formation), the carboxyterminal cross-linked telopeptide of type I collagen (ICTP, bone resorption) and the carboxyterminal propeptide of type I collagen (PICP), which is less 'bone-specific' than the other 2 markers. Colts had, on average, 3.62 ng/ml higher OC concentrations (P = 0.044) and 0.68 mg/l higher ICTP concentrations (P = 0.01) than fillies. The effect of gender was not statistically significant for PICP. However, in May, PICP concentrations were on average 157 mg/l higher in fillies than colts. There was no effect of age or season on marker concentrations. This study has shown that there are gender differences in bone turnover markers in 2-year-old Thoroughbreds; however, age, within the limited range studied, did not have a significant effect on bone cell activity. Lower bone marker concentrations may reflect smaller bone size and/or earlier skeletal maturation in fillies. An increase in concentrations of PICP in fillies in spring and early summer may relect an influence of sex hormones on collagen turnover. Gender differences in bone cell activity in 2-year-old colts and fillies may influence bone's adaptive responses to training and risk of injury.

IGF-1 REGULATES VERTEBRAL BONE AGING THROUGH SEX-SPECIFIC AND TIME-DEPENDENT MECHANISMS

PubMed Central

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L.; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-01-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, while others report that loss of IGF-1 is beneficial as it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igff/f mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan- early in postnatal development (crossing albumin-Cre mice with Igff/f mice), or early adulthood, and late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using microCT and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NFkB-ligand levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2 fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be

Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients.

PubMed

Harries, M; Taylor, A; Holmberg, L; Agbaje, O; Garmo, H; Kabilan, S; Purushotham, A

2014-08-01

Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976-2006 and followed until end 2010, we determined incidence of and survival after bone metastases. We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan-Meier methodology. Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥ four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with <1 year in women with visceral and bone metastases. There was a trend for decreased survival for patients who developed visceral metastases early, and proportionately fewer patients in this group. Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Prefabrication of bone transplants].

PubMed

Jagodzinski, M; Kokemüller, H; Jehn, P; Vogt, P; Gellrich, N-C; Krettek, C

2015-03-01

Prefabrication of bone transplants is a promising option for large defects of the long bones, especially if there is compromised vascularization of the defect. This is especially true for postinfection bone defects and other types of atrophic nonunion. The generation of a foreign body membrane (Masquelet's technique) has been investigated in order to ameliorate the response of the host tissue surrounding the defect. In an experimental animal study, a blood vessel within a bone construct could be used to generate customized, vascularized osteogenic constructs that can be used to treat large bone defects in the future.

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

PubMed

Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

2015-03-01

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

[Research advances of fluid bio-mechanics in bone].

PubMed

Chen, Zebin; Huo, Bo

2017-04-01

It has been found for more than one century that when experiencing mechanical loading, the structure of bone will adapt to the changing mechanical environment, which is called bone remodeling. Bone remodeling is charaterized as two processes of bone formation and bone resorption. A large number of studies have confirmed that the shear stress is resulted from interstitial fluid flow within bone cavities under mechanical loading and it is the key factor of stimulating the biological responses of bone cells. This review summarizes the major research progress during the past years, including the biological response of bone cells under fluid flow, the pressure within bone cavities, the theoretical modeling, numerical simulation and experiments about fluid flow within bone, and finally analyzes and predicts the possible tendency in this field in the future.

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

Early relapse of Burkitt lymphoma heralded by a bone marrow necrosis and numb chin syndrome successfully treated with allogeneic stem cell transplantation

PubMed Central

Cerny, Jan; Devitt, Katherine; Yu, Hongbo; Ramanathan, Muthalagu; Woda, Bruce; Nath, Rajneesh

2014-01-01

The optimal salvage therapy for patients with relapsed Burkitt lymphoma is unknown. Bone marrow necrosis is an underreported (<1% of bone marrow failures). Numb chin syndrome is another rare syndrome associated with aggressive malignancies. Survival of these syndromes is dictated by the underlying disease and is usually dismal. Our 35-year-old patient experienced an early relapse of Burkitt lymphoma accompanied by syndromes, achieved second complete remission and underwent allogeneic stem cell transplantation. He remains alive and well >2 years after the transplant. To our knowledge, this is the longest reported survival of the two syndromes in the setting of BL relapse. PMID:25068102

VDR deficiency affects alveolar bone and cementum apposition in mice.

PubMed

Zhang, Xueming; Rahemtulla, Firoz; Zhang, Ping; Thomas, Huw F

2011-07-01

To compare the mineralisation density (MD), morphology and histology of alveolar bone and cementum amongst VDR +/+, VDR -/-, and VDR -/- groups supplemented with a diet TD 96348, containing 20% lactose, 2.0% calcium and 1.25% phosphorous. Four groups of mice (6 mice/group) were identified by genotyping: VDR +/+ mice (VDR wild type), VDR -/- mice (VDR deficient), VDR -/- offsprings derived from VDR -/- parents receiving a supplemental diet (early rescued), and VDR -/- mice fed with a supplemental diet beginning at age one month (late rescued). All mice were sacrificed at age 70.5 days. Micro-CT was used to compare MD and morphology of alveolar bone and cementum. H-E and Toluidine blue staining was used to examine the ultrastructure of the alveolar bone and cementum at matched locations. In VDR -/- group, alveolar bone and cementum failed to mineralise normally. Early rescue increased MD of alveolar bone in VDR -/- mice with excessive alveolar bone formation, but which not observed in late rescue group. MD and morphology of cementum-dentine complex in both early and late rescue groups were comparable with VDR +/+ group when feeding with high-calcium rescue diet. VDR affects alveolar bone mineralisation and formation systemically and locally. However, cementum apposition and mineralisation is mainly regulated by calcium concentrations in serum. Copyright © 2010 Elsevier Ltd. All rights reserved.

Bone mineralization in childhood and adolescence.

PubMed

Bachrach, L K

1993-08-01

Prevention of osteoporosis depends on establishing adequate peak bone mass in the first two decades of life. Achievement of this goal requires an understanding of factors that promote skeletal health. Genetic factors are important determinants of adult bone mass, but nonheritable variables, including body mass, calcium nutriture, sex steroids, and activity can strongly influence whether maximal bone mineral is achieved. Acquisition of bone mineral continues throughout childhood and adolescence, reaching a lifetime maximum in early adulthood. Adolescence is a particularly critical time for bone mineral accretion as more than half of the bone calcium is normally laid down during the teen years. Chronic illness, malnutrition, or endocrine deficiencies at this age may result in profound deficits in bone mass, which may not be fully reversible. These risk factors contribute to the osteopenia associated with anorexia nervosa, exercise-induced amenorrhea, delayed puberty, Turner's syndrome, and growth hormone deficiency.

Early prophylactic autogenous bone grafting in type III open tibial fractures.

PubMed

Kesemenli, Cumhur C; Kapukaya, Ahmet; Subaşi, Mehmet; Arslan, Huseyin; Necmioğlu, Serdar; Kayikçi, Cuma

2004-08-01

The authors report the results achieved in patients with type III open tibial fractures who underwent primary autogenous bone grafting at the time of debridement and skeletal stabilisation. Twenty patients with a mean age of 35.8 years (range, 24-55) were treated between 1996 and 1999. Eight fractures were type IIIA, 11 were type IIIB, and 1 was type IIIC. At the index procedure, wound debridement, external fixation and autogenous bone grafting with bone coverage were achieved. The mean follow-up period was 46 months (range, 34-55). The mean time to fixator removal was 21 weeks (range, 14-35), and the mean time to union was 28 weeks (range, 19-45). Skin coverage was achieved by a myocutaneous flap in 2 patients, late primary closure in 4, and split skin grafting in 14. One (5%) of the patients experienced delayed union, and 1 (5%) developed infection. In tibial type III open fractures, skin coverage may be delayed, using the surrounding soft tissue to cover any exposed bone after thorough débridement and wound cleansing. Primary prophylactic bone grafting performed at the same time reduces the rate of delayed union, shortens the time to union, and does not increase the infection rate.

Palaeobiological implications of the bone histology of Pterodaustro guinazui.

PubMed

Chinsamy, Anusuya; Codorniú, Laura; Chiappe, Luis

2009-09-01

This study provides a comprehensive investigation of the bone microstructure of multiple bones of the Early Cretaceous filter-feeder, Pterodaustro guinazui, from the Largacito Formation of Central Argentina. We provide information regarding the bone histology of multiple elements from single skeletons, as well as a variety of bones from different individuals. In addition, we analysed changes in bone microstructure through ontogeny in growth series of several long bones of the taxon. Our investigation of skeletal and ontogenetic variation in Pterodaustro gives insights into the developmental growth dynamics of this unusual ctenochasmatid pterodactyloid from early ontogeny through to adulthood and also provides information pertaining to histological variability within and between bones of individuals. This study also documents the presence of what appears to be medullary bone tissue within the medullary cavity of a large femur of Pterodaustro. This suggests that, like birds, reproductively active female pterosaurs may have deposited a special bone tissue (medullary bone) to cope with the demand of calcium during eggshelling. Our study supports the hypothesis that small Jurassic pterodactyloids took several years to reach adult body size. More specifically, we provide data that suggests that Pterodaustro attained sexual maturity at about 2 years of age, and continued to grow for a further 3-4 years doubling in size before attaining skeletal maturity. (c) 2009 Wiley-Liss, Inc.

"Bounce at the Bell": a novel program of short bouts of exercise improves proximal femur bone mass in early pubertal children

PubMed Central

McKay, H; MacLean, L; Petit, M; MacKelvie-O'Brien, K; Janssen, P; Beck, T; Khan, K

2005-01-01

Objectives: To examine the effects of a simple and inexpensive physical activity intervention on change in bone mass and structure in school aged children. Methods: Fifty one children (n = 23 boys and 28 girls; mean age 10.1 years) participated in "Bounce at the Bell" which consisted of 10 counter-movement jumps 3x per day (total ∼3 min/day). Controls were 71 matched children who followed usual school practice. We assessed dietary calcium, physical activity, physical performance, and anthropometry in September and after 8 months of intervention (June). We measured bone mineral content (BMC) and bone area at the lumbar spine, total body, and proximal femur. Proximal femur scans were also analysed for bone geometry and structural strength using the hip structural analysis program. Lean and fat mass (g) were also calculated. Results: Groups were similar at baseline and did not differ in weight, height, total body, lumbar spine, proximal femur, or femoral neck BMC. Control children had a greater increase in adjusted total body BMC (1.4%). Intervention children gained significantly more BMC at the total proximal femur (2%) and the intertrochanteric region (27%). Change in bone structural parameters did not differ between groups. Conclusions: This novel, easily implemented exercise program, took only a few minutes each day and enhanced bone mass at the weight bearing proximal femur in early pubertal children. A large, randomised study of boys and girls should be undertaken powered to test the effectiveness of Bounce at the Bell in children at different stages of maturity, and in boys and girls independently. PMID:16046335

Istanbul Earthquake Early Warning and Rapid Response System

NASA Astrophysics Data System (ADS)

Erdik, M. O.; Fahjan, Y.; Ozel, O.; Alcik, H.; Aydin, M.; Gul, M.

2003-12-01

As part of the preparations for the future earthquake in Istanbul a Rapid Response and Early Warning system in the metropolitan area is in operation. For the Early Warning system ten strong motion stations were installed as close as possible to the fault zone. Continuous on-line data from these stations via digital radio modem provide early warning for potentially disastrous earthquakes. Considering the complexity of fault rupture and the short fault distances involved, a simple and robust Early Warning algorithm, based on the exceedance of specified threshold time domain amplitude levels is implemented. The band-pass filtered accelerations and the cumulative absolute velocity (CAV) are compared with specified threshold levels. When any acceleration or CAV (on any channel) in a given station exceeds specific threshold values it is considered a vote. Whenever we have 2 station votes within selectable time interval, after the first vote, the first alarm is declared. In order to specify the appropriate threshold levels a data set of near field strong ground motions records form Turkey and the world has been analyzed. Correlations among these thresholds in terms of the epicenter distance the magnitude of the earthquake have been studied. The encrypted early warning signals will be communicated to the respective end users by UHF systems through a "service provider" company. The users of the early warning signal will be power and gas companies, nuclear research facilities, critical chemical factories, subway system and several high-rise buildings. Depending on the location of the earthquake (initiation of fault rupture) and the recipient facility the alarm time can be as high as about 8s. For the rapid response system one hundred 18 bit-resolution strong motion accelerometers were placed in quasi-free field locations (basement of small buildings) in the populated areas of the city, within an area of approximately 50x30km, to constitute a network that will enable early

Mesenchymal stem cells induce dermal fibroblast responses to injury

PubMed Central

Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

2009-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury. PMID:19666021

Mesenchymal stem cells induce dermal fibroblast responses to injury

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

Smith, Andria N., E-mail: snosmith@u.washington.edu; Willis, Elise, E-mail: elise.willis@gmail.com; Chan, Vincent T.

2010-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. Whenmore » co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.« less

Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein.

PubMed

Gerard, David A; Carlson, Eric R; Gotcher, Jack E; Pickett, David O

2014-01-01

This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA. Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically. A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced. A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The

A quantification strategy for missing bone mass in case of osteolytic bone lesions

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

Fränzle, Andrea, E-mail: a.fraenzle@dkfz.de; Giske, Kristina; Bretschi, Maren

Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approachmore » is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way

Bone conduction responses of middle ear structures in Thiel embalmed heads

NASA Astrophysics Data System (ADS)

Arnold, Andreas; Stieger, Christof; Caversaccio, Marco; Kompis, Martin; Guignard, Jérémie

2015-12-01

Thiel-embalmed human whole-head specimens offer a promising alternative model for bone conduction (BC) studies of middle ear structures. In this work we present the Thiel model's linearity and stability over time as well as its possible use in the study of a fixed ossicle chain. Using laser Doppler vibrometry (LDV), the motion of the retroauricular skull, the promontory, the stapes footplate and the round window (RW) were measured. A bone-anchored hearing aid stimulated the ears with step sinus tones logarithmically spread between 0.1 and 10 kHz. Linearity of the model was verified using input levels in steps of 10 dBV. The stability of the Thiel model over time was examined with measurements repeated after hours and weeks. The influence of a cement-fixed stapes was assessed. The middle ear elements measured responded linearly in amplitude for the applied input levels (100, 32.6, and 10 mV). The variability of measurements for both short- (2 h) and long-term (4-16 weeks) repetitions in the same ear was lower than the interindividual difference. The fixation of the stapes induced a lowered RW displacement for frequencies near 750 Hz (-4 dB) and an increased displacement for frequencies above 1 kHz (max. +3.7 dB at 4 kHz). LDV assessment of BC-induced middle ear motion in Thiel heads can be performed with stable results. The vibratory RW response is affected by the fixation of the stapes, indicating a measurable effect of ossicle chain inertia on BC response in Thiel embalmed heads.

IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

PubMed

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-02-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data

Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

PubMed

Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

2015-09-01

Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry. © 2015 Poultry Science Association Inc.

Effects of Ionizing Radiation on Murine Gene Expression in Skin and Bone

NASA Technical Reports Server (NTRS)

Terada, Masahiro; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Alwood, Joshua; Tahimic, Candice; Sowa, Marianne B.; Globus, Ruth K.

2017-01-01

Long duration spaceflight causes a negative calcium balance and reduces bone density in astronauts. The potential for exposure to space radiation to contribute to lasting decrements in bone mass is not yet understood. Sustained changes to bone mass have a relatively long latency for development, however skin is a radiation sensitive organ and changes in skin gene expression may serve as an early radiation biomarker of exposures and may correlate with adverse effects on skeletal tissue. Previous studies have shown that FGF18 gene expression levels of hair follicles collected from astronauts on the ISS rose over time. In the hair follicle, FGF18 signaling mediates radioresistance in the telogen by arresting the cell cycle, and FGF18 has the potential to function as a radioprotector. In bone, FGF18 appears to regulate cell proliferation and differentiation positively during osteogenesis and negatively during chondrogenesis. Cellular defense responses to radiation are shared by a variety of organs, hence in this study, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We have examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (TBI). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and TBI (0.5 Gy Fe-56 600 MeV/n and 0.5 Gy H-1 150 MeV/n). Animals were euthanized one and 11 days post-IR. Statistical analysis was performed via a Student's ttest. In skin samples one day after IR, skin expression of FGF18 was significantly greater (3.8X) than sham-irradiated controls (3.8X), but did not differ 11 days post TBI. Expression levels of other radiation related genes (Nfe2l2, Trp53, Cdkn1a, FoxO3

[New methods for the evaluation of bone quality. Bone anabolic agents and bone quality.

PubMed

Yamamoto, Norio; Tsuchiya, Hiroyuki

Teriparatide(TPTD)products that can be used clinically in Japan include a daily subcutaneous injection form produced by genetic engineering and a weekly subcutaneous injectable TPTD acetate form produced by chemical synthesis. Published reports indicate that both forms exhibit excellent antifracture efficacy, and as the only anabolic agents that promote osteogenesis, TPTD products now occupy a prominent position. However, the two forms differ considerably, not only in frequency of administration, but also in mechanism of action. The daily form stimulates osteogenesis and accompanying resorption through more radical high bone turnover, and early in the course of treatment, intracortical porosity and apatite crystallization decrease, while immature collagen crosslinking increases. However, because daily formulations also produce an increase in cortical surface area or cortical thickness, the effects are counterbalanced, and bone strength is maintained. In contrast, the weekly form prioritizes osteogenesis, and by concurrently lowering turnover below pretreatment levels, improves trabecular bone mass and structure, and enhances strength without leading to cortical porosity and other undesirable phenomena. Abaloparatide, a PTHrP(1-34)analog that is homologous with the biologically active site of PTH drugs, is currently under development, and we eagerly anticipate further clarification of the mechanism of action of each formulation on bone.

Early Conversion of External Fixation to Interlocked Nailing in Open Fractures of Both Bone Leg Assisted with Vacuum Closure (VAC) - Final Outcome

PubMed Central

Raj, Manish; Kumar, Sunil; Singh, Pulkesh; Kumar, Dinesh; Singh, Jasveer; Deep, Akash

2016-01-01

Introduction Management of compound grade III fractures of both bone leg includes external stabilization for long period, followed by various soft tissue coverage procedures. Primary interlocking of tibia had been also done with variable results. External fixation for long time without any bone loss often leads to infected nonunion, loss of reduction, pin tract infection and failure of fixation, primary interlocking in compound grade III fractures had shown high medullary infection rate. We managed all cases of compound grade III A/B fractures with primary external fixation, simultaneous wound management using vacuum assisted closure (VAC) followed by early conversion to interlocking within 2 weeks of fixator application. Aim To determine the effectiveness of vacuum assisted closure (VAC) for the early conversion of external fixator to definitive interlocking in open fractures of the both bone leg. Materials and Methods In current study we selected 84 cases of compound grade IIIA/B diaphyseal fractures of both bone leg during period of May 2010 to September 2013. We managed these cases by immediate debridement and application of external fixation followed by repeated debridement, application of vacuum assisted closure (VAC) and conversion to interlocking within two weeks. Results Out of 84 cases union was achieved in 80(95%) of cases with definitive tibial interlocking. Excellent to good result were obtained in 77(91.8%) of cases and fair to poor result seen in rest of 7(8.2%) of cases according to modified Ketenjian’s criteria. 5 out of these 7 poor result group cases were from Compound Grade III B group to start with. Deep infection rate in our series were 7% i.e. total 6 cases and 4 out of these were from compound Grade III B group to start with. Conclusion Vacuum assisted closure (VAC) give a good help for rapid closure of the wound and help in early conversion to definitive intramedullary nailing. Reamed nail could well be used in compound grade IIIA

Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

PubMed

Subbiah, Vivek; Chuang, Hubert H; Gambhire, Dhiraj; Kairemo, Kalevi

2017-02-15

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

Influence of exercise mode and osteogenic index on bone biomarker responses during short-term physical training.

PubMed

Lester, Mark E; Urso, Maria L; Evans, Rachel K; Pierce, Joseph R; Spiering, Barry A; Maresh, Carl M; Hatfield, Disa L; Kraemer, William J; Nindl, Bradley C

2009-10-01

Prescribing exercise based on intensity, frequency, and duration of loading may maximize osteogenic responses in bone, but a model of the osteogenic potential of exercise has not been established in humans. In rodents, an osteogenic index (OI) has been used to predict the osteogenic potential of exercise. The current study sought to determine whether aerobic, resistance, or combined aerobic and resistance exercise programs conducted over eight weeks and compared to a control group could produce changes in biochemical markers of bone turnover indicative of bone formation. We further sought to determine whether an OI could be calculated for each of these programs that would reflect observed biochemical changes. We collected serum biomarkers [bone-specific alkaline phosphatase (BAP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide fragment of type I collagen (CTx), deoxypyridinoline (DPD), 25-hydroxy vitamin D (25(OH)D), and parathyroid hormone (PTH)] in 56 women (20.3+/-1.8 years) before, during and after eight weeks of training. We also measured bone mineral density (BMD) at regional areas of interest using DXA and pQCT. Biomarkers of bone formation (BAP and osteocalcin) increased in the Resistance and Combined groups (p<0.05), while biomarkers of bone resorption (TRAP and DPD) decreased and increased, respectively, after training (p<0.05) in all groups. Small changes in volumetric and areal BMD (p<0.05) were observed in the distal tibia in the Aerobic and Combined groups, respectively. Mean weekly OIs were 16.0+/-1.9, 20.6+/-2.2, and 36.9+/-5.2 for the Resistance, Aerobic, and Combined groups, respectively. The calculated osteogenic potential of our programs did not correlate with the observed changes in biomarkers of bone turnover. The results of the present study demonstrate that participation in an eight week physical training program that incorporates a resistance component by previously inactive young women results in