Bone involvement at diagnosis as a predictive factor in children with acute lymphoblastic leukemia.

PubMed

Tragiannidis, A; Vasileiou, E; Papageorgiou, M; Damianidou, L; Hatzipantelis, E; Gombakis, N; Giannopoulos, A

2016-01-01

Bone involvement represents a common symptom at diagnosis in children with acute lymphoblastic leukemia, and its prognostic value is not entirely clarified. The aim of this study was to evaluate bone involvement at diagnosis in children with acute lymphoblastic leukemia as a predictive factor and to correlate its presence with other demographic, clinical, and laboratory findings. We retrospectively reviewed the medical records of 97 children with acute lymphoblastic leukemia diagnosed from January 2005 to December 2014. The mean age of patients was 5.7 years, and 83 (85.6 %) of them were diagnosed with B-acute lymphoblastic leukemia. Among the 97 children, 46 (47.4 %) reported bone involvement at the time of diagnosis. Among children with B-acute lymphoblastic leukemia 43/83 (51.8 %) reported bone involvement, while among children with T-acute lymphoblastic leukemia only 3/14 (21.4 %) (p =0.04). Bone involvement was registered more frequently among males (30/59; 50.8 %) in comparison to females (16/38; 42.2 %) (p =0.414). The mean white blood cell count at diagnosis was lower among children with bone involvement (109,800/mm 3 vs. 184,700/mm 3 ) (p =0.092). The mean age of patients with bone involvement was four years, which differs significantly from those without bone involvement (p =0.029). Moreover, children with bone involvement at diagnosis were prednisone "good responders" (79.5 %) when compared with those without bone involvement (58.8 %) (p =0.046). Additionally, mean serum phosphate values were higher at diagnosis among children with bone involvement (5.3 mg/dl vs. 4.8 mg/dl, p =0.035). The presence of bone involvement at diagnosis is related with immunophenotype of B-acute lymphoblastic leukemia, lower mean age, lower mean white blood cell count and good prednisone response. According to presented data, we conclude that the presence of bone involvement at diagnosis represents a positive predictive factor for outcome/survival. Hippokratia 2016, 20(3): 227-230.

Bone involvement at diagnosis as a predictive factor in children with acute lymphoblastic leukemia

PubMed Central

Tragiannidis, A; Vasileiou, E; Papageorgiou, M; Damianidou, L; Hatzipantelis, E; Gombakis, N; Giannopoulos, A

2016-01-01

Background: Bone involvement represents a common symptom at diagnosis in children with acute lymphoblastic leukemia, and its prognostic value is not entirely clarified. The aim of this study was to evaluate bone involvement at diagnosis in children with acute lymphoblastic leukemia as a predictive factor and to correlate its presence with other demographic, clinical, and laboratory findings. Methods: We retrospectively reviewed the medical records of 97 children with acute lymphoblastic leukemia diagnosed from January 2005 to December 2014. The mean age of patients was 5.7 years, and 83 (85.6 %) of them were diagnosed with B-acute lymphoblastic leukemia. Results: Among the 97 children, 46 (47.4 %) reported bone involvement at the time of diagnosis. Among children with B-acute lymphoblastic leukemia 43/83 (51.8 %) reported bone involvement, while among children with T-acute lymphoblastic leukemia only 3/14 (21.4 %) (p =0.04). Bone involvement was registered more frequently among males (30/59; 50.8 %) in comparison to females (16/38; 42.2 %) (p =0.414). The mean white blood cell count at diagnosis was lower among children with bone involvement (109,800/mm3 vs. 184,700/mm3) (p =0.092). The mean age of patients with bone involvement was four years, which differs significantly from those without bone involvement (p =0.029). Moreover, children with bone involvement at diagnosis were prednisone “good responders” (79.5 %) when compared with those without bone involvement (58.8 %) (p =0.046). Additionally, mean serum phosphate values were higher at diagnosis among children with bone involvement (5.3 mg/dl vs. 4.8 mg/dl, p =0.035). Conclusions: The presence of bone involvement at diagnosis is related with immunophenotype of B-acute lymphoblastic leukemia, lower mean age, lower mean white blood cell count and good prednisone response. According to presented data, we conclude that the presence of bone involvement at diagnosis represents a positive predictive factor for

76 FR 36993 - Medical Devices; Neurological Devices; Clarification of Classification for Human Dura Mater...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

...; Clarification of Classification for Human Dura Mater; Technical Amendment AGENCY: Food and Drug Administration... amending the device regulations to clarify the applicability of the device classification for human dura..., human dura mater is now defined under 21 CFR 1271.3(d) as a HCT/P. As such, it is regulated under...

Effect of electrical polarization of hydroxyapatite ceramics on new bone formation.

PubMed

Itoh, S; Nakamura, S; Kobayashi, T; Shinomiya, K; Yamashita, K; Itoh, S

2006-03-01

Large surface charges can be induced on hydroxyapatite (HAp) ceramics by proton transport polarization, but this does not affect beta-tricalcium phosphate (TCP) because of its low polarizability. We wished to examine differences in osteogenic cell activity and new bone growth between positively or negatively surface-charged HAp and HAp/TCP plates using a calvarial bone defect model. In the first group of rats, test pieces were placed with their positively charged surfaces face down on the dura mater. In the second group, test pieces were placed with their negatively charged surfaces face down on the dura mater. A third group received noncharged test pieces. Histological examination, including enzymatic staining for osteoblasts and osteoclasts, was carried out. While no bone formation was observed at the pericranium, direct bone formation on the cranial bone debris and new bone growth expanded from the margins of the sites of injury to bridge across both the positively and negatively charged surfaces of HAp and HAp/TCP plates occurred. Electrical polarization of implanted plates, including positive charge, led to enhanced osteoblast activity, though decreased osteoclast activity was seen on the positively charged plate surface. Thus, polarization of HAp ceramics may modulate new bone formation and resorption.

Bone marrow involvement is rare in superficial gastric mucosa-associated lymphoid tissue lymphoma.

PubMed

Park, Jae Yong; Kim, Sang Gyun; Kim, Joo Sung; Jung, Hyun Chae

2016-01-01

The initial staging work-up of gastric mucosa-associated lymphoid tissue (MALT) lymphoma includes bone marrow examination. Since gastric MALT lymphoma is mostly detected in early stages with the national cancer screening programme in Korea, bone marrow is rarely involved. To investigate the incidence of bone marrow involvement in gastric MALT lymphomas and the role of bone marrow examination for an initial staging work-up. Patients diagnosed with gastric MALT lymphoma at Seoul National University Hospital from January 2005 to July 2014 were enrolled. Clinical databases of the patients were retrospectively reviewed. Out of 105 patients, 91 (86.7%) were classified as stage IE1. Among these patients, 78 patients with Helicobacter pylori infection underwent eradication therapy, and complete remission was achieved in 74 cases (94.9%). Twelve out of 13 patients (92.3%) without H. pylori infection underwent radiotherapy or surgery and all achieved complete remission. Bone marrow involvement was proven in only one patient (1.0%). Bone marrow involvement was rare in patients with only superficial gastric MALT lymphoma without extragastric invasion. Further studies are warranted to identify the risk factors of bone marrow involvement in gastric MALT lymphoma. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Visualizing the root-PDL-bone interface using high-resolution microtomography

NASA Astrophysics Data System (ADS)

Dalstra, Michel; Cattaneo, Paolo M.; Herzen, Julia; Beckmann, Felix

2008-08-01

The root/periodontal ligament/bone (RPB) interface is important for a correct understanding of the load transfer mechanism of masticatory forces and orthodontic loads. It is the aim of this study to assess the three-dimensional structure of the RPB interface using high-resolution microtomography. A human posterior jaw segment, obtained at autopsy from a 22-year old male donor was first scanned using a tomograph at the HASYLAB/DESY synchrotron facility (Hamburg, Germany) at 31μm resolution. Afterwards the first molar and its surrounding bone were removed with a 10mm hollow core drill. From this cylindrical sample smaller samples were drilled out in the buccolingual direction with a 1.5mm hollow core drill. These samples were scanned at 4μm resolution. The scans of the entire segment showed alveolar bone with a thin lamina dura, supported by an intricate trabecular network. Although featuring numerous openings between the PDL and the bone marrow on the other side to allow blood vessels to transverse, the lamina dura seems smooth at this resolution. First at high resolution, however, it becomes evident that it is irregular with bony spiculae and pitted surfaces. Therefore the stresses in the bone during physiological or orthodontic loading are much higher than expected from a smooth continuous alveolus.

Collagen fibril organization within rat vertebral bone modified with metastatic involvement.

PubMed

Burke, Mikhail; Golaraei, Ahmad; Atkins, Ayelet; Akens, Margarete; Barzda, Virginijus; Whyne, Cari

2017-08-01

Metastatic involvement diminishes the mechanical integrity of vertebral bone, however its specific impact on the structural characteristics of a primary constituent of bone tissue, the collagen-I fibril matrix, has not been adequately characterized. Female athymic rats were inoculated with HeLa or Ace-1 cancer cells lines producing osteolytic or mixed (osteolytic & osteoblastic) metastases respectively. A maximum of 21days was allowed between inoculation and rat sacrifice for vertebrae extraction. Linear polarization-in, polarization-out (PIPO) second harmonic generation (SHG) and transmission electron microscopy (TEM) imaging was utilized to assess the impact of metastatic involvement on collagen fibril organization. Increased observations of deviations in the typical plywood motif or a parallel packing structure and an increased average measured susceptibility ratio (related to relative degree of in-plane vs. out-plane fibrils in the analyzed tissue area) in bone adjacent to metastatic involvement was indicative of change in fibrilar organization compared to healthy controls. In particular, collagen-I fibrils in tumour-induced osteoblastic bone growth showed no adherence to the plywood motif or parallel packing structure seen in healthy lamellar bone, exhibiting a much higher susceptibility ratio and degree of fibril disorder. Negative correlations were established between measured susceptibility ratios and the hardness and modulus of metastatic bone tissue assessed in a previous study. Characterizing modifications in tissue level properties is key in defining bone quality in the presence of metastatic disease and their potential impact on material behaviour. Copyright © 2017 Elsevier Inc. All rights reserved.

ON LOVE AND MELANCHOLIA IN MARGUERITE DURAS'S AUTOFICTION.

PubMed

Simoglou, Vassiliki N

2015-07-01

In the Durassian melancholic atmosphere, past and present, fantasy and reality come together as one. This paper addresses the themes of love and destruction in Marguerite Duras's life that pervade her oeuvre, allowing us to discern a melancholic structure within her autofiction. Writing down her melancholia--the impossible mourning of a loved object--Duras captures nothingness and loss--in order not to die of love. In a constant exchange with her readers, she searches for herself and delivers herself to her readers. This renewable creative process of writing enables her to engage in an ongoing experience of identity reconstruction, in a way similar to the patient in psychoanalysis re-creating his/her life's fiction. © 2015 The Psychoanalytic Quarterly, Inc.

Immunohistochemical profile of neurotrophins in human cranial dura mater and meningiomas.

PubMed

Artico, Marco; Bronzetti, Elena; Pompili, Elena; Ionta, Brunella; Alicino, Valentina; D'Ambrosio, Anna; Santoro, Antonio; Pastore, Francesco S; Elenkov, Ilia; Fumagalli, Lorenzo

2009-06-01

The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as from the area in which the meningioma had its dural attachment. Immunohistochemical characterization and distribution of neurotrophins, with their receptors, were analyzed. The concrete role played by these neurotrophic factors in general regulation, vascular permeability, algic responsivity and release of locally active substances in the human dura mater is still controversial. Our study revealed a general structural alteration of dural tissue due to the invasivity of meningiomatous lesions, together with an improved expression of brain derived neurotrophic factor (BDNF) in highly proliferating neoplastic cells and an evident production of nerve growth factor (NGF) in inflammatory cells, suggesting that BDNF has a role in supporting the proliferation rate of neoplastic cells, while NGF is involved in the activation of a chronic inflammatory response in neoplastic areas.

Effect of quercetin on plasma extravasation in rat CNS and dura mater by ACE and NEP inhibition.

PubMed

Cyrino, Luiz A R; Cardoso, Ronie C F; Hackl, Luciane P N; Nicolau, Mauro

2002-09-01

The effects of quercetin on substance P-induced plasma protein extravasation (PE) in the rat dura mater, cerebellum, olfactory bulb and cortex and also its modulation by endopeptidases, angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) were studied. PE was assessed by photometric measurement of extravasated Evans blue. Substance P (SP) and NEP or ACE inhibitors increased the PE in dura mater. Pretreatment with captopril or phosphoramidon potentiated PE induced by SP in the dura mater and cerebellum, respectively. Quercetin increased the PE in the dura mater, cerebellum and cortex. Further results suggested that the PE induced by SP in the dura mater was enhanced by pretreatment with quercetin, similar to that observed with selective peptidase inhibitors. Quercetin-stimulated extravasation in all tissues was abolished by NK-1 receptor blockade. These results suggest that quercetin increases PE in the dura mater and CNS tissues by inhibiting NEP and/or ACE, showing that the effect induced in the dura mater, cerebellum and cortex occurs through endogenous SP accumulation. Copyright 2002 John Wiley & Sons, Ltd.

A Bone-Thickness Map as a Guide for Bone-Anchored Port Implantation Surgery in the Temporal Bone

PubMed Central

Guignard, Jérémie; Arnold, Andreas; Weisstanner, Christian; Caversaccio, Marco; Stieger, Christof

2013-01-01

The bone-anchored port (BAP) is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implant’s location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map (n = 10) with conventional surgery without assistance (n = 5) in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be used as a low-complexity method to improve patient’s safety during BAP surgery in the temporal bone. PMID:28788390

A Bone-Thickness Map as a Guide for Bone-Anchored Port Implantation Surgery in the Temporal Bone.

PubMed

Guignard, Jérémie; Arnold, Andreas; Weisstanner, Christian; Caversaccio, Marco; Stieger, Christof

2013-11-19

The bone-anchored port (BAP) is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implant's location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map ( n = 10) with conventional surgery without assistance ( n = 5) in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be used as a low-complexity method to improve patient's safety during BAP surgery in the temporal bone.

Evidence for CGRP re-uptake in rat dura mater encephali

PubMed Central

Gupta, Saurabh; Amrutkar, Dipak Vasantrao; Mataji, Aydin; Salmasi, Hassan; Hay-Schmidt, Anders; Sheykhzade, Majid; Messlinger, Karl; Olesen, Jes; Jansen-Olesen, Inger

2010-01-01

BACKGROUND AND PURPOSE Calcitonin gene-related peptide (CGRP) is widely distributed in the trigeminovascular system and released from sensory fibres of the cranial dura mater upon noxious stimulation. Such release may be a mechanism underlying migraine headache. Based on data from guinea pig basilar artery preparations, we have here studied CGRP release and uptake in an organ preparation of the hemisected rat skull. EXPERIMENTAL APPROACH CGRP release from the cranial dura was quantified by a commercial enzyme-linked immunoassay. CGRP was depleted using repetitive challenges of capsaicin. After incubating the tissue with CGRP for 20 min and extensive washing, another capsaicin challenge was performed. Immunohistochemistry was used to visualize CGRP immunofluorescence in dural nerve fibres. KEY RESULTS Capsaicin-induced CGRP release was attenuated by the transient receptor potential vanilloid receptor type I antagonist capsazepine or by Ca2+-free solutions. After the CGRP-depleted preparation had been exposed to exogenous CGRP, capsaicin-induced CGRP release was increased compared to the challenge just prior to incubation. CGRP uptake was not influenced by Ca2+-free solutions. Olcegepant and CGRP8–37 (CGRP receptor antagonists) did not affect uptake of CGRP. However, a monoclonal CGRP-binding antibody decreased CGRP uptake significantly. Release of CGRP after incubation was attenuated by Ca2+-free solutions and by capsazepine. Immunohistochemical assays indicated a weak trend towards CGRP uptake in rat dura mater. CONCLUSION AND IMPLICATIONS We have presented evidence for CGRP uptake in nerves and its re-release in rat dura mater. This may have implications for the pathophysiology and treatment of migraine. PMID:20804493

Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain

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

Markowitz, S.; Saito, K.; Moskowitz, M.A.

Utilizing /sup 125/I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated /sup 125/I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and /supmore » 125/I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of /sup 125/I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs.« less

A Defining Time for Physical Education Futures? Exploring the Legacy of Fritz Duras

ERIC Educational Resources Information Center

Kirk, David

2014-01-01

This paper explores the legacy of Dr Fritz Duras in order to address the issue of whether the implementation of a new curriculum for health and physical education in Australia represents a defining time for the subject. Dr Duras was Director of the first physical education teacher education course at the University of Melbourne during an earlier…

Fibrin Sealants in Dura Sealing: A Systematic Literature Review

PubMed Central

2016-01-01

Background Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. Methods A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. Results A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or

Fibrin Sealants in Dura Sealing: A Systematic Literature Review.

PubMed

Esposito, Felice; Angileri, Filippo Flavio; Kruse, Peter; Cavallo, Luigi Maria; Solari, Domenico; Esposito, Vincenzo; Tomasello, Francesco; Cappabianca, Paolo

2016-01-01

Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a

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

PubMed

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

2015-07-01

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

ADRA2A is involved in neuro-endocrine regulation of bone resorption

PubMed Central

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

2015-01-01

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

Variability and performance evaluation of introgressed Nigerian dura x Deli dura oil palm progenies.

PubMed

Noh, A; Rafii, M Y; Mohd Din, A; Kushairi, A; Norziha, A; Rajanaidu, N; Latif, M A; Malek, M A

2014-04-03

Twelve introgressed oil palm (Elaeis guineensis) progenies of Nigerian dura x Deli dura were evaluated for bunch yield, yield attributes, bunch quality components and vegetative characters at the Malaysian Palm Oil Board Research Station, in Keratong, Pahang, Malaysia. Analysis of variance revealed significant to highly significant genotypic differences, indicating sufficient genetic variability among the progenies for bunch yield and its attributes, vegetative characters and bunch quality components, except fruit to bunch ratio. Fresh fruit bunch yield ranged from 167 kg·palm(-1)·year(-1) in PK1330 to 212 kg·palm(-1)·year(-1) in PK1351, with a mean yield of 192 kg·palm(-1)·year(-1). Among the progeny, PK1313 had the highest oil to bunch ratio (19.36%), due to its high mesocarp to fruit ratio, fruit to bunch ratio and low shell to fruit ratio. Among the progenies, PK1313 produced the highest oil yield of 31.4 kg·palm(-1)·year(-1), due to a high mesocarp to fruit ratio (61.2%) and a low shell to fruit ratio (30.7%), coupled with high fruit to bunch ratio (65.6%). PK1330 was found promising for selection, as it had desirable vegetative characters, including smaller petiole cross section (27.15 cm2), short rachis length (4.83 m), short palm height (1.85 m), and the lowest leaf number (164.6), as these vegetative characters are prerequisites for selecting palms for high density planting and high yield per hectare. The genetic variability among the progenies was found to be high, indicating ample scope for further breeding, followed by selection.

Autophagy in osteoblasts is involved in mineralization and bone homeostasis

PubMed Central

Nollet, Marie; Santucci-Darmanin, Sabine; Breuil, Véronique; Al-Sahlanee, Rasha; Cros, Chantal; Topi, Majlinda; Momier, David; Samson, Michel; Pagnotta, Sophie; Cailleteau, Laurence; Battaglia, Séverine; Farlay, Delphine; Dacquin, Romain; Barois, Nicolas; Jurdic, Pierre; Boivin, Georges; Heymann, Dominique; Lafont, Frank; Lu, Shi Shou; Dempster, David W; Carle, Georges F; Pierrefite-Carle, Valérie

2014-01-01

Bone remodeling is a tightly controlled mechanism in which osteoblasts (OB), the cells responsible for bone formation, osteoclasts (OC), the cells specialized for bone resorption, and osteocytes, the multifunctional mechanosensing cells embedded in the bone matrix, are the main actors. Increased oxidative stress in OB, the cells producing and mineralizing bone matrix, has been associated with osteoporosis development but the role of autophagy in OB has not yet been addressed. This is the goal of the present study. We first show that the autophagic process is induced in OB during mineralization. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralization capacity. Moreover, our data suggest that autophagic vacuoles could be used as vehicles in OB to secrete apatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and secretion of the receptor activator of NFKB1 (TNFSF11/RANKL), favoring generation of OC, the cells specialized in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralization process and in bone homeostasis. These findings are of importance for mineralized tissues which extend from corals to vertebrates and uncover new therapeutic targets for calcified tissue-related metabolic pathologies. PMID:25484092

T cell numbers relate to bone involvement in Gaucher disease.

PubMed

Lacerda, L; Arosa, F A; Lacerda, R; Cabeda, J; Porto, G; Amaral, O; Fortuna, A; Pinto, R; Oliveira, P; McLaren, C E; Sá Miranda, C; de Sousa, M

1999-04-01

The major elements of bone pathology in Gaucher disease are a failure of osteoclast and osteoblast function, resulting in osteopenia and also osteonecrosis. T lymphocytes have recently been found to be involved in the regulation of osteoblast/osteoclast activity in vitro. In the present report the peripheral blood T major lymphocyte subsets were investigated in a group of genotyped type 1 Gaucher disease patients. A total of 31 patients were studied: 21 non-splenectomized (5 N370S homozygotes) and 10 splenectomized (of whom 1 was a N370S homozygote). The results show that non-splenectomized patients present a decrease in absolute numbers of peripheral blood T lymphocytes, specially the CD4+ T subset. However, when patients were analyzed with respect to the presence of bone disease, the number of CD8+ T lymphocytes was found to be statistically significantly lower in patients presenting bone involvement. Furthermore, lower numbers of CD8+ T lymphocytes were significantly correlated with higher levels of plasma tartrate resistant acid phosphatase (TRAP) activity, a putative marker of osteoclast cell activity. These in vivo findings are in agreement with the results reached in vitro by others. They provide an additional marker of disease severity in Gaucher disease. In the group of genotyped Gaucher disease patients, the majority of the N370S homozygous patients presented a clinically milder phenotype, including the absence of bone involvement, confirming earlier reports predicting that a number of these patients may remain undiagnosed. Collectively the homozygosity for the N370S mutation and normal T cell numbers may provide additional markers for the clinical heterogeneity of Gaucher disease.

Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.

PubMed

Raspanti, M; Marchini, M; Della Pasqua, V; Strocchi, R; Ruggeri, A

1992-10-01

The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened.

CO(2) Laser Fascia to Dura Soldering for Pig Dural Defect Reconstruction.

PubMed

Forer, Boaz; Vasileyev, Tamar; Gil, Ziv; Brosh, Tamar; Kariv, Naam; Katzir, Abraham; Fliss, Dan M

2007-02-01

The purposes of this study were to demonstrate that laser soldering is safe and effective for tissue bonding in dural reconstruction and to compare this new reconstruction technique to an established one. A temperature-controlled fiberoptic CO(2) laser system or fibrin glue were used for in vitro dural defect reconstruction in two groups of pigs. The CO(2) laser technique was also used for dural reconstruction in live pigs. The burst pressure of the reconstructed dura by the laser system was significantly higher than that of fibrin glue (mean pressure 258.5 +/- 117.3 cm H(2)O and 76.8 +/- 47.2 cm H(2)O, respectively). There were no postoperative complications and no signs of thermal damage to the dura, fascia, or underlying tissue on histological analysis following the in vivo CO(2) laser experiments. Temperature-controlled laser soldering is an effective technique for dural repair. It creates a strong tissue bonding with no thermal damage to the tissue. The burst pressure of the reconstructed dura done with laser soldering is significantly higher than that of fibrin glue.

Methyl Jasmonate-Induced Lipidomic and Biochemical Alterations in the Intertidal Macroalga Gracilaria dura (Gracilariaceae, Rhodophyta)

PubMed Central

Kumari, Puja; Reddy, C.R.K.; Jha, Bhavanath

2015-01-01

The role of exogenously added methyl jasmonate (MeJA), a lipid-derived signaling compound, in inducing oxidative stress in the marine red macroalga Gracilaria dura was investigated. MeJA at a concentration of 1–100 µM was a strong stimulant of reactive oxygen species (H2O2, HO· and O2·−) (P < 0.05) causing considerable oxidative stress in G. dura. This further led to lipid peroxidation and degradation of the pigments Chl a and phycocyanin, with a concomitant increase in phycoerythrin. The MeJA-induced oxidative burst also led to the induction of a fatty acid oxidation cascade, resulting in the synthesis of hydroxy-oxylipins and the up-regulation of the 13-lipoxygenase pathway. Electrospray ionization-mass spectrometry-based shotgun lipidomic analysis revealed that monogalactosyldiacylglycerol (a chloroplastic glycerolipid) and phosphatidylcholine (extrachloroplastidic phopholipid) were the most affected lipid classes. The degradation of 18:3-fatty acid-containing monogalactosyldiacylglycerol inferred that it provided fatty acyl chains for the biosynthesis of 13-hydroperoxylinolenic acid, which was further directed towards either the jasmonate pathway or other alternative pathways of the fatty acid oxidation cascade, analogous to higher plants. Also, G. dura modulated the lipid acyl chains in such a way that no significant change was observed in the fatty acid profile of the treated thalli as compared with those of the control, except for C16:0, C16:1 (n-9), C20:3 (n-6) and C20:4 (n-6) (P < 0.05). Furthermore, MeJA caused the accumulation of phenolic compounds and the up-regulation of enzymes involved in secondary metabolism such as polyphenol oxidase, shikimate dehydrogenase and phenylalanine ammonia-lyase, indicating a shift towards secondary metabolism as a defense strategy to combat the induced oxidative stress. PMID:26276825

Involvement of Cot/Tp12 in bone loss during periodontitis.

PubMed

Ohnishi, T; Okamoto, A; Kakimoto, K; Bandow, K; Chiba, N; Matsuguchi, T

2010-02-01

Periodontitis causes resorption of alveolar bone, in which RANKL induces osteoclastogenesis. The binding of lipopolysaccharide to Toll-like receptors causes phosphorylation of Cot/Tp12 to activate the MAPK cascade. Previous in vitro studies showed that Cot/Tp12 was essential for the induction of RANKL expression by lipopolysaccharide. In this study, we examined whether Cot/Tp12 deficiency reduced the progression of alveolar bone loss and osteoclastogenesis during experimental periodontitis. We found that the extent of alveolar bone loss and osteoclastogenesis induced by ligature-induced periodontitis was decreased in Cot/Tp12-deficient mice. In addition, reduction of RANKL expression was observed in periodontal tissues of Cot/Tp12-deficient mice with experimental periodontitis. Furthermore, we found that Cot/Tp12 was involved in the induction of TNF-alpha mRNA expression in gingiva of mice with experimental periodontitis. Our observations suggested that Cot/Tp12 is essential for the progression of alveolar bone loss and osteoclastogenesis in periodontal tissue during experimental periodontitis mediated through increased RANKL expression.

Modified three-dimensional skull base model with artificial dura mater, cranial nerves, and venous sinuses for training in skull base surgery: technical note.

PubMed

Mori, Kentaro; Yamamoto, Takuji; Oyama, Kazutaka; Ueno, Hideaki; Nakao, Yasuaki; Honma, Keiichirou

2008-12-01

Experience with dissection of the cavernous sinus and the temporal bone is essential for training in skull base surgery, but the opportunities for cadaver dissection are very limited. A modification of a commercially available prototype three-dimensional (3D) skull base model, made by a selective laser sintering method and incorporating surface details and inner bony structures such as the inner ear structures and air cells, is proposed to include artificial dura mater, cranial nerves, venous sinuses, and the internal carotid artery for such surgical training. The transpetrosal approach and epidural cavernous sinus surgery (Dolenc's technique) were performed on this modified model using a high speed drill or ultrasonic bone curette under an operating microscope. The model could be dissected in almost the same way as a real cadaver. The modified 3D skull base model provides a good educational tool for training in skull base surgery.

Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.

PubMed Central

Raspanti, M; Marchini, M; Della Pasqua, V; Strocchi, R; Ruggeri, A

1992-01-01

The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:1295858

Repair of pig dura in vivo using temperature controlled CO(2) laser soldering.

PubMed

Forer, Boaz; Vasilyev, Tamar; Brosh, Tamar; Kariv, Noam; Gil, Ziv; Fliss, Dan M; Katzir, Abraham

2005-10-01

The purpose of this study was to demonstrate that laser soldering might be successfully used for closing holes or cuts in the dura layer, which encapsulates the brain. A temperature controlled fiberoptic CO(2) laser system and albumin solder were used for spot soldering of fascia patches to holes in the dura of farm pigs, in vitro and in vivo. The mean burst pressure of the soldered patches in the in vitro experiments was 190 +/- 88 mm Hg-significantly higher than typical maximum CSF pressure of 15 mm Hg. In the in vivo experiments the pigs showed no postoperative complications. Histopathological studies exhibited an accepted level of inflammatory reaction and showed no thermal damage to the underlying brain tissue. It has been clearly demonstrated that temperature controlled laser soldering is a very useful technique for the repair of the dura. It provides significant advantages over standard closure techniques: it is easy to apply, the bond is strong and watertight and the procedure is likely to be much faster than suturing. This research work will lead to clinical trials.

Full-Scale Evaluation of DuraDeck (registered trademark) and MegaDeck (trademark) Matting Systems

DTIC Science & Technology

2013-07-01

plates studded with threaded bolts were placed ERDC/GSL TR-13-27 10 underneath two pre-drilled corners of the panel. The plates were positioned so...metal plates studded with threaded ERDC/GSL TR-13-27 4 Figure 1. DuraDeck® mat panel, top surface. Figure 2. DuraDeck® mat panel, bottom surface...ERDC/GSL TR-13-27 5 bolts , as shown in Figure 3, underneath the mat corners and then installing special connector nuts from the top surface

Functional adaptation of long bone extremities involves the localized ``tuning'' of the cortical bone composition; evidence from Raman spectroscopy

NASA Astrophysics Data System (ADS)

Buckley, Kevin; Kerns, Jemma G.; Birch, Helen L.; Gikas, Panagiotis D.; Parker, Anthony W.; Matousek, Pavel; Goodship, Allen E.

2014-11-01

In long bones, the functional adaptation of shape and structure occurs along the whole length of the organ. This study explores the hypothesis that adaptation of bone composition is also site-specific and that the mineral-to-collagen ratio of bone (and, thus, its mechanical properties) varies along the organ's length. Raman spectroscopy was used to map the chemical composition of long bones along their entire length in fine spatial resolution (1 mm), and then biochemical analysis was used to measure the mineral, collagen, water, and sulfated glycosaminoglycan content where site-specific differences were seen. The results show that the mineral-to-collagen ratio of the bone material in human tibiae varies by <5% along the mid-shaft but decreases by >10% toward the flared extremities of the bone. Comparisons with long bones from other large animals (horses, sheep, and deer) gave similar results with bone material composition changing across tens of centimeters. The composition of the bone apatite also varied with the phosphate-to-carbonate ratio decreasing toward the ends of the tibia. The data highlight the complexity of adaptive changes and raise interesting questions about the biochemical control mechanisms involved. In addition to their biological interest, the data provide timely information to researchers developing Raman spectroscopy as a noninvasive tool for measuring bone composition in vivo (particularly with regard to sampling and measurement protocol).

Functional adaptation of long bone extremities involves the localized "tuning" of the cortical bone composition; evidence from Raman spectroscopy.

PubMed

Buckley, Kevin; Kerns, Jemma G; Birch, Helen L; Gikas, Panagiotis D; Parker, Anthony W; Matousek, Pavel; Goodship, Allen E

2014-01-01

In long bones, the functional adaptation of shape and structure occurs along the whole length of the organ. This study explores the hypothesis that adaptation of bone composition is also site-specific and that the mineral-to-collagen ratio of bone (and, thus, its mechanical properties) varies along the organ's length. Raman spectroscopy was used to map the chemical composition of long bones along their entire length in fine spatial resolution (1 mm), and then biochemical analysis was used to measure the mineral, collagen, water, and sulfated glycosaminoglycan content where site-specific differences were seen. The results show that the mineral-to-collagen ratio of the bone material in human tibiae varies by <5% along the mid-shaft but decreases by >10% toward the flared extremities of the bone. Comparisons with long bones from other large animals (horses, sheep, and deer) gave similar results with bone material composition changing across tens of centimeters. The composition of the bone apatite also varied with the phosphate-to-carbonate ratio decreasing toward the ends of the tibia. The data highlight the complexity of adaptive changes and raise interesting questions about the biochemical control mechanisms involved. In addition to their biological interest, the data provide timely information to researchers developing Raman spectroscopy as a noninvasive tool for measuring bone composition in vivo (particularly with regard to sampling and measurement protocol).

Low complication rate of sellar reconstruction by artificial dura mater during endoscopic endonasal transsphenoidal surgery.

PubMed

Ye, Yuanliang; Wang, Fuyu; Zhou, Tao; Luo, Yi

2017-12-01

To evaluate effect of sellar reconstruction during pituitary adenoma resection surgery by the endoscopic endonasal transsphenoidal approach using artificial cerebral dura mater patch.This was a retrospective study of 1281 patients who underwent endoscopic transsphenoidal resection for the treatment of pituitary adenomas between December 2006 and May 2014 at the Neurosurgery Department of the People's Liberation Army General Hospital. The patients were classified into 4 grades according to intraoperative cerebrospinal fluid (CSF) leakage site. All patients were followed up for 3 months by telephone and outpatient visits.One thousand seventy three (83.7%) patients underwent sellar reconstruction using artificial dura matter patched outside the sellar region (method A), 106 (8.3%) using artificial dura matter patched inside the sellar region (method B), and 102 (8.0%) using artificial dura matter and a mucosal flap (method C). Method A was used for grade 0-1 leakage, method B for grade 1 to 2 leakage, and method C for grade 2 to 3 leakage. During the 3-month follow-up, postoperative CSF leakage was observed in 7 patients (0.6%): 2 among patients who underwent method B (1.9%) and 5 among those who underwent method C (4.9%). Meningitis was diagnosed in 13 patients (1.0%): 2 among patients who underwent method A (0.2%), 4 among those who underwent method B (3.8%), and 7 among those who underwent method C (6.7%).Compared with other reconstruction methods, sellar reconstruction surgery that only use artificial dura mater as repair material had a low rate of complications. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

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

The use of a reconstituted collagen foil dura mater substitute in paediatric neurosurgical procedures--experience in 47 patients.

PubMed

Pettorini, Benedetta Ludovica; Tamburrini, Gianpiero; Massimi, Luca; Paternoster, Giovanna; Caldarelli, Massimo; Di Rocco, Concezio

2010-02-01

CSF leakage is a common complication of neurosurgical procedures, with defective dural suture thought to be the most frequent cause. We report our experience with a new collagen foil (TissuDura, Baxter Healthcare SA, Switzerland) utilized as dural substitute in paediatric neurosurgical procedures. TissuDura was used in children consecutively operated on at the department of paediatric neurosurgery, Catholic University, Rome, from March 2004 to August 2007. Children underwent surgical procedures in supratentorial, infratentorial and spinal compartments. In supratentorial and spinal procedures, the dural graft was used according to the overlay technique. In the posterior fossa procedures, the underlay technique was used. Forty-seven patients received TissuDura during surgery. Thirty-one patients underwent surgery for the removal of posterior fossa tumours, nine for supratentorial tumours and seven for spinal dysraphisms. No CSF leakage was observed following the use of TissuDura in supratentorial procedures. Two post-operative CSF leaks occurred in patients who had undergone spinal surgery. No post-operative hydrocephalus was noted in these two surgery groups. Three cases of CSF leakage occurred in patients who had undergone posterior cranial fossa surgery. All 3 cases had an associated supratentorial ventricular dilation present prior to the removal of the tumour (one case) or occurring after the tumour excision (two cases). No clinically evident adverse reactions directly related to TissuDura were observed. The main advantages of TissuDura were its apparent ability to prevent CSF leakage when utilized in a specific subset of patients, and the absence of reactions or postoperative infections.

Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

PubMed

Eller-Vainicher, C; Bassotti, A; Imeraj, A; Cairoli, E; Ulivieri, F M; Cortini, F; Dubini, M; Marinelli, B; Spada, A; Chiodini, I

2016-08-01

The Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients. The Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients. Fifty consecutive Caucasian patients, aged 30-50 years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects' calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed. Patients showed reduced BMD (Z-scores LS -0.45 ± 1.00, FN -0.56 ± 1.01, FT -0.58 ± 0.92) and TBS (1.299 ± 0.111) and increased prevalence of morphometric VFx (32 %) than controls (Z-scores LS 0.09 ± 1.22, FN 0.01 ± 0.97, FT 0.08 ± 0.89; TBS 1.382 ± 0.176; VFx 8 %, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.245 ± 0.138 vs 1.325 ± 0.086, p < 0.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency. EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.

The spinal cord dura mater reaction to nitinol and titanium alloy particles: a 1-year study in rabbits

PubMed Central

Rhalmi, Souad; Charette, Sylvie; Assad, Michel; Coillard, Christine

2007-01-01

This investigation was undertaken to simulate in an animal model the particles released from a porous nitinol interbody fusion device and to evaluate its consequences on the dura mater, spinal cord and nerve roots, lymph nodes (abdominal para-aortic), and organs (kidneys, spleen, pancreas, liver, and lungs). Our objective was to evaluate the compatibility of the nitinol particles with the dura mater in comparison with titanium alloy. In spite of the great use of metallic devices in spine surgery, the proximity of the spinal cord to the devices raised concerns about the effect of the metal debris that might be released onto the neural tissue. Forty-five New Zealand white female rabbits were divided into three groups: nitinol (treated: N = 4 per implantation period), titanium (treated: N = 4 per implantation period), and sham rabbits (control: N = 1 per observation period). The nitinol and titanium alloy particles were implanted in the spinal canal on the dura mater at the lumbar level L2–L3. The rabbits were sacrificed at 1, 4, 12, 26, and 52 weeks. Histologic sections from the regional lymph nodes, organs, from remote and implantation sites, were analyzed for any abnormalities and inflammation. Regardless of the implantation time, both nitinol and titanium particles remained at the implantation site and clung to the spinal cord lining soft tissue of the dura mater. The inflammation was limited to the epidural space around the particles and then reduced from acute to mild chronic during the follow-up. The dura mater, sub-dural space, nerve roots, and the spinal cord were free of reaction. No particles or abnormalities were found either in the lymph nodes or in the organs. In contact with the dura, the nitinol elicits an inflammatory response similar to that of titanium. The tolerance of nitinol by a sensitive tissue such as the dura mater during the span of 1 year of implantation demonstrated the safety of nitinol and its potential use as an intervertebral

Systemic sarcoidosis with bone marrow involvement responding to therapy with adalimumab: a case report.

PubMed

Patel, Supen R

2009-07-29

Sarcoidosis is an inflammatory disorder characterized by the presence of non-caseating granulomas in affected organs. The presence of CD4-positive T lymphocytes and macrophages in affected organs suggests an ongoing immune response. Systemic corticosteroids remain the mainstay of treatment, but therapy is often limited by adverse effects. This is the first report of the use of adalimumab (HUMIRA((R)), Abbott Laboratories, North Chicago, IL, USA), an anti-tumor necrosis factor monoclonal antibody, in a patient with systemic sarcoidosis with bone marrow involvement. A 42-year-old African-American man with a medical history significant for hypertension and diabetes mellitus presented with anemia and thrombocytopenia of two months duration. The patient underwent physical examination, bone marrow aspiration and biopsy, chest X-ray, acid-fast bacilli stain, computed tomography with contrast, and additional laboratory tests. He was diagnosed with systemic sarcoidosis with splenomegaly and bone marrow involvement. Drug therapy included prednisone, which had to be discontinued owing to adverse effects, and adalimumab. This is the first report describing the use of adalimumab in a patient with systemic sarcoidosis with bone marrow involvement. Tumor necrosis factor antagonism with adalimumab was efficacious and well-tolerated in this patient and may be considered as a treatment option for similar cases.

Sclerosteosis involving the temporal bone: histopathologic aspects.

PubMed

Nager, G T; Hamersma, H

1986-01-01

Sclerosteosis is a rare, potentially lethal, autosomal recessive, progressive craniotubular sclerosing bone dysplasia with characteristic facial and skeletal features. The temporal bone changes include a marked increase in overall size, extensive sclerosis, narrowing of the external auditory canal, and severe constriction of the internal auditory meatus, fallopian canal, eustachian tube, and middle ear cleft. Attenuation of the bony canals of the 9th, 10th, and 11th cranial nerves, reduction in size of the internal carotid artery, and severe obliteration of the sigmoid sinus and jugular bulb also occur. Loss of hearing, generally bilateral, is a frequent symptom. It often manifests in early childhood and initially is expressed as sound conduction impairment. Later, a sensorineural hearing loss and loss of vestibular nerve function often develop. Impairment of facial nerve function is another feature occasionally present at birth. In the beginning, a unilateral intermittent facial weakness may occur which eventually progresses to a bilateral permanent facial paresis. The histologic examination of the temporal bones from a patient with sclerosteosis explains the mechanisms involved in the progressive impairment of sound conduction and loss of cochlear, vestibular, and facial nerve function. There is a decrease of the arterial blood supply to the brain and an obstruction of the venous drainage from it. The histopathology reveals the obstacles to decompression of the middle ear cleft, ossicular chain, internal auditory and facial canals, and the risks, and in many instances the contraindications, to such procedures. On the other hand, decompression of the sigmoid sinus and jugular bulb should be considered as an additional life-saving procedure in conjunction with the prophylactic craniotomy recommended in all adult patients.

Mechanical suitability of glycerol-preserved human dura mater for construction of prosthetic cardiac valves.

PubMed

McGarvey, K A; Lee, J M; Boughner, D R

1984-03-01

We have examined the tensile viscoelastic properties of fresh and glycerol-preserved human dura mater, and correlated the results with structural information from the scanning electron microscope. The interwoven laminar structure of dura produces rather high flexural stiffness, while the crossed-fibrillar laminae produce planar mechanical isotropy. Glycerol storage shifts the stress-strain curve to lower strain, reduces stress relaxation and creep, and lowers the ultimate tensile strength and strain at fracture. These changes may be due to glyceraldehyde crosslinking, or to increased interfibrillar friction. The latter hypothesis suggests that glycerol storage may reduce the fatigue lifetime of the tissue.

Prevalence and Implications of Bone Marrow Involvement in Patients with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

PubMed Central

Choi, Sang Il; Kook, Myeong-Cherl; Hwang, Sanghyun; Kim, Young-Il; Lee, Jong Yeul; Kim, Chan Gyoo; Choi, Il Ju; Lee, Hyewon; Eom, Hyeon Seok

2018-01-01

Background/Aims Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. Methods In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. Results Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. Conclusions Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall. PMID:29409307

The effects of tumour necrosis factor-α on bone cells involved in periodontal alveolar bone loss; osteoclasts, osteoblasts and osteocytes.

PubMed

Algate, K; Haynes, D R; Bartold, P M; Crotti, T N; Cantley, M D

2016-10-01

Periodontitis is the most common bone loss pathology in adults and if left untreated is responsible for premature tooth loss. Cytokines, such as tumour necrosis factor-α (TNFα), involved in the chronic inflammatory response within the periodontal gingiva, significantly influence the normal bone remodelling processes. In this review, the effects of TNFα on bone metabolism in periodontitis are evaluated in relation to its direct and indirect actions on bone cells including osteoclasts, osteoblasts and osteocytes. Evidence published to date suggests a potent catabolic role for TNFα through the stimulation of osteoclastic bone resorption as well as the suppression of osteoblastic bone formation and osteocytic survival. However, the extent and timing of TNFα exposure in vitro and in vivo greatly influences its effect on skeletal cells, with contradictory anabolic activity observed with TNFα in a number of studies. None the less, it is evident that managing the chronic inflammatory response in addition to the deregulated bone metabolism is required to improve periodontal and inflammatory bone loss treatments‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synchrotron Ultraviolet Microspectroscopy on Rat Cortical Bone: Involvement of Tyrosine and Tryptophan in the Osteocyte and Its Environment

PubMed Central

Pallu, Stéphane; Rochefort, Gael Y.; Jaffre, Christelle; Refregiers, Matthieu; Maurel, Delphine B.; Benaitreau, Delphine; Lespessailles, Eric; Jamme, Frédéric; Chappard, Christine; Benhamou, Claude-Laurent

2012-01-01

Alcohol induced osteoporosis is characterized by a bone mass decrease and microarchitecture alterations. Having observed an excess in osteocyte apoptosis, we aimed to assess the bone tissue biochemistry, particularly in the osteocyte and its environment. For this purpose, we used a model of alcohol induced osteoporosis in rats. Bone sections of cortical bone were investigated using synchrotron UV-microspectrofluorescence at subcellular resolution. We show that bone present three fluorescence peaks at 305, 333 and 385 nm, respectively corresponding to tyrosine, tryptophan and collagen. We have determined that tyrosine/collagen and tryptophan/collagen ratios were higher in the strong alcohol consumption group. Tryptophan is related to the serotonin metabolism involved in bone formation, while tyrosine is involved in the activity of tyrosine kinases and phosphatases in osteocytes. Our experiment represents the first combined synchrotron UV microspectroscopy analysis of bone tissue with a quantitative biochemical characterization in the osteocyte and surrounding matrix performed separately. PMID:22937127

Interaction of micron and nano-sized particles with cells of the dura mater.

PubMed

Papageorgiou, Iraklis; Marsh, Rainy; Tipper, Joanne L; Hall, Richard M; Fisher, John; Ingham, Eileen

2014-10-01

Intervertebral total disc replacements (TDR) are used in the treatment of degenerative spinal disc disease. There are, however, concerns that they may be subject to long-term failure due to wear. The adverse effects of TDR wear have the potential to manifest in the dura mater and surrounding tissues. The aim of this study was to investigate the physiological structure of the dura mater, isolate the resident dural epithelial and stromal cells and analyse the capacity of these cells to internalise model polymer particles. The porcine dura mater was a collagen-rich structure encompassing regularly arranged fibroblastic cells within an outermost epithelial cell layer. The isolated dural epithelial cells had endothelial cell characteristics (positive for von Willebrand factor, CD31, E-cadherin and desmoplakin) and barrier functionality whereas the fibroblastic cells were positive for collagen I and III, tenascin and actin. The capacity of the dural cells to take up model particles was dependent on particle size. Nanometer sized particles readily penetrated both types of cells. However, dural fibroblasts engulfed micron-sized particles at a much higher rate than dural epithelial cells. The study suggested that dural epithelial cells may offer some barrier to the penetration of micron-sized particles but not nanometer sized particles. © 2014 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.

Evaluation of cranial bone transport distraction with and without adipose grafting.

PubMed

Koch, Felix P; Yuhasz, Mikell M; Travieso, Rob; Wong, Kenneth; Clune, James; Zhuang, Zhen W; Van Houten, Joshua; Steinbacher, Derek M

2014-05-01

Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration.

[A case of cavernous angioma at the convexity in the dura mater: characteristics of images in the literature].

PubMed

Yonezawa, Ushio; Ikawa, Fusao; Hamasaki, Osamu; Hidaka, Toshikazu; Kurokawa, Yasuharu; Onuma, Hideyuki

2014-08-01

We describe a rare case of cavernous angioma in the dura mater and discuss published MRI findings on similar cases. The patient was a 78-year-old woman who was referred to Shimane Prefectural Central Hospital with complaints of headaches. We were subsequently able to identify a tumor at the convexity in the dura mater. The tumor showed a high intensity on T2-weighted images and was heterogeneously enhanced on contrast-enhanced T1-weighted images. The maximum size of the tumor was 35 mm. Moreover, preoperative angiography showed a slight vascularity in the tumor. We performed surgery with the expectation of finding a meningioma, metastatic brain tumor, or another mesenchymal tumor. The tumor was dark and red, attached to the dura mater, and adhered to the arachnoid. However, we were able to peel the tumor away from the meninges and achieved a total removal of the mass, successfully cutting a fine feeding cortical artery. The patient was discharged without neurological defects 9 days after surgery;the pathological diagnosis was cavernous angioma. In conclusion, it is difficult to discern between meningioma and cavernous angioma in the dura mater. However, the specificity of high intensity on T2-weighted images is relatively high, and preoperative diagnosis can be determined by MRI and angiography findings.

PV Module Reliability Experts Gather for DuraMAT Workshop | News | NREL

Science.gov Websites

DuraMAT Workshop June 20, 2017 On May 22 and 23, 2017, the Bay Area Photovoltaic Consortium (BAPVC) and with the photovoltaic and supply-chain industries to discover, develop, de-risk, and enable the commercialization of new materials and designs for photovoltaic modules-with the potential for a levelized cost of

Interaction of micron and nano-sized particles with cells of the dura mater

PubMed Central

Papageorgiou, Iraklis; Marsh, Rainy; Tipper, Joanne L; Hall, Richard M; Fisher, John; Ingham, Eileen

2014-01-01

Intervertebral total disc replacements (TDR) are used in the treatment of degenerative spinal disc disease. There are, however, concerns that they may be subject to long-term failure due to wear. The adverse effects of TDR wear have the potential to manifest in the dura mater and surrounding tissues. The aim of this study was to investigate the physiological structure of the dura mater, isolate the resident dural epithelial and stromal cells and analyse the capacity of these cells to internalise model polymer particles. The porcine dura mater was a collagen-rich structure encompassing regularly arranged fibroblastic cells within an outermost epithelial cell layer. The isolated dural epithelial cells had endothelial cell characteristics (positive for von Willebrand factor, CD31, E-cadherin and desmoplakin) and barrier functionality whereas the fibroblastic cells were positive for collagen I and III, tenascin and actin. The capacity of the dural cells to take up model particles was dependent on particle size. Nanometer sized particles readily penetrated both types of cells. However, dural fibroblasts engulfed micron-sized particles at a much higher rate than dural epithelial cells. The study suggested that dural epithelial cells may offer some barrier to the penetration of micron-sized particles but not nanometer sized particles. © 2014 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1496–1505, 2014. PMID:24604838

Retrospective study of sonographic findings in bone involvement associated with rotator cuff calcific tendinopathy: preliminary results of a case series.

PubMed

Nogueira-Barbosa, Marcello H; Gregio-Junior, Everaldo; Lorenzato, Mario Muller

2015-01-01

The present study was aimed at investigating bone involvement secondary to rotator cuff calcific tendonitis at ultrasonography. Retrospective study of a case series. The authors reviewed shoulder ultrasonography reports of 141 patients diagnosed with rotator cuff calcific tendonitis, collected from the computer-based data records of their institution over a four-year period. Imaging findings were retrospectively and consensually analyzed by two experienced musculoskeletal radiologists looking for bone involvement associated with calcific tendonitis. Only the cases confirmed by computed tomography were considered for descriptive analysis. Sonographic findings of calcific tendinopathy with bone involvement were observed in 7/141 (~ 5%) patients (mean age, 50.9 years; age range, 42-58 years; 42% female). Cortical bone erosion adjacent to tendon calcification was the most common finding, observed in 7/7 cases. Signs of intraosseous migration were found in 3/7 cases, and subcortical cysts in 2/7 cases. The findings were confirmed by computed tomography. Calcifications associated with bone abnormalities showed no acoustic shadowing at ultrasonography, favoring the hypothesis of resorption phase of the disease. Preliminary results of the present study suggest that ultrasonography can identify bone abnormalities secondary to rotator cuff calcific tendinopathy, particularly the presence of cortical bone erosion.

Diagnosis and Treatment of Bone Disease in Multiple Myeloma: Spotlight on Spinal Involvement

PubMed Central

Tosi, Patrizia

2013-01-01

Bone disease is observed in almost 80% of newly diagnosed symptomatic multiple myeloma patients, and spine is the bone site that is more frequently affected by myeloma-induced osteoporosis, osteolyses, or compression fractures. In almost 20% of the cases, spinal cord compression may occur; diagnosis and treatment must be carried out rapidly in order to avoid a permanent sensitive or motor defect. Although whole body skeletal X-ray is considered mandatory for multiple myeloma staging, magnetic resonance imaging is presently considered the most appropriate diagnostic technique for the evaluation of vertebral alterations, as it allows to detect not only the exact morphology of the lesions, but also the pattern of bone marrow infiltration by the disease. Multiple treatment modalities can be used to manage multiple myeloma-related vertebral lesions. Surgery or radiotherapy is mainly employed in case of spinal cord compression, impending fractures, or intractable pain. Percutaneous vertebroplasty or balloon kyphoplasty can reduce local pain in a significant fraction of treated patients, without interfering with subsequent therapeutic programs. Systemic antimyeloma therapy with conventional chemotherapy or, more appropriately, with combinations of conventional chemotherapy and compounds acting on both neoplastic plasma cells and bone marrow microenvironment must be soon initiated in order to reduce bone resorption and, possibly, promote bone formation. Bisphosphonates should also be used in combination with antimyeloma therapy as they reduce bone resorption and prolong patients survival. A multidisciplinary approach is thus needed in order to properly manage spinal involvement in multiple myeloma. PMID:24381787

Intravital Imaging of a Massive Lymphocyte Response in the Cortical Dura of Mice after Peripheral Infection by Trypanosomes

PubMed Central

Coles, Jonathan A.; Myburgh, Elmarie; Ritchie, Ryan; Hamilton, Alana; Rodgers, Jean; Mottram, Jeremy C.; Barrett, Michael P.; Brewer, James M.

2015-01-01

Peripheral infection by Trypanosoma brucei, the protozoan responsible for sleeping sickness, activates lymphocytes, and, at later stages, causes meningoencephalitis. We have videoed the cortical meninges and superficial parenchyma of C56BL/6 reporter mice infected with T.b.brucei. By use of a two-photon microscope to image through the thinned skull, the integrity of the tissues was maintained. We observed a 47-fold increase in CD2+ T cells in the meninges by 12 days post infection (dpi). CD11c+ dendritic cells also increased, and extravascular trypanosomes, made visible either by expression of a fluorescent protein, or by intravenous injection of furamidine, appeared. The likelihood that invasion will spread from the meninges to the parenchyma will depend strongly on whether the trypanosomes are below the arachnoid membrane, or above it, in the dura. Making use of optical signals from the skull bone, blood vessels and dural cells, we conclude that up to 40 dpi, the extravascular trypanosomes were essentially confined to the dura, as were the great majority of the T cells. Inhibition of T cell activation by intraperitoneal injection of abatacept reduced the numbers of meningeal T cells at 12 dpi and their mean speed fell from 11.64 ± 0.34 μm/min (mean ± SEM) to 5.2 ± 1.2 μm/min (p = 0.007). The T cells occasionally made contact lasting tens of minutes with dendritic cells, indicative of antigen presentation. The population and motility of the trypanosomes tended to decline after about 30 dpi. We suggest that the lymphocyte infiltration of the meninges may later contribute to encephalitis, but have no evidence that the dural trypanosomes invade the parenchyma. PMID:25881126

Involvement of CD147 in alveolar bone remodeling and soft tissue degradation in experimental periodontitis.

PubMed

Yang, D; Liu, R; Liu, L; Liao, H; Wang, C; Cao, Z

2017-08-01

The objective of this study was to investigate the possible roles of clusters of differentiation 147 (CD147) in bone resorption and mineralization through the bone markers of bone sialoprotein, osteocalcin, osteopontin and alkaline phosphatase (ALP), trabecular structure of alveolar bone and number of osteoclasts. We also investigated the effects of CD147 on inflammation and collagen breakdown. Twenty-eight male Wistar rats were randomly divided into four groups of seven animals each: healthy group, periodontitis group, periodontitis + saline group and periodontitis + anti-CD147 groups. Hematoxylin and eosin staining were used for histological assessment. Alveolar bone loss and trabecula microstructure were evaluated using micro-computed tomography. Collagen fiber breakdown was assessed via picrosirius red staining. Tartrate-resistant acid phosphatase staining was conducted for osteoclast analysis. The expressions of ALP, bone sialoprotein, osteocalcin and osteopontin were evaluated using immunohistochemistry. Anti-CD147 treatment significantly inhibited alveolar bone loss and osteoclastogenesis, and improved the bone volume/tissue volume, and the trabecular thickness of alveolar bone. Histological staining revealed that anti-CD147 significantly reduced the infiltration of inflammation and limited the fractions of degraded areas in collagen fibers. The expression of bone markers (ALP, bone sialoprotein, osteocalcin and osteopontin) was enhanced by anti-CD147 treatment. The results of the anti-CD147 treatment indicate that CD147 was involved in alveolar bone mineralization, osteoclastogenesis and trabecular microstructure. The inhibition of CD147 could increase the expression level of osteogenic markers, alveolar bone crest height and suppressed collagen fiber degradation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sex-, stress-, and sympathetic post-ganglionic-dependent changes in identity and proportions of immune cells in the dura.

PubMed

McIlvried, Lisa A; Cruz, J Agustin; Borghesi, Lisa A; Gold, Michael S

2017-01-01

Aim of investigation Due to compelling evidence in support of links between sex, stress, sympathetic post-ganglionic innervation, dural immune cells, and migraine, our aim was to characterize the impacts of these factors on the type and proportion of immune cells in the dura. Methods Dural immune cells were obtained from naïve or stressed adult male and female Sprague Dawley rats for flow cytometry. Rats with surgical denervation of sympathetic post-ganglionic neurons of the dura were also studied. Results Immune cells comprise ∼17% of all cells in the dura. These included: macrophages/granulocytes ("Macs"; 63.2% of immune cells), dendritic cells (0.88%), T-cells (4.51%), natural killer T-cells (0.51%), natural killer cells (3.08%), and B-cells (20.0%). There were significantly more Macs and fewer B- and natural killer T-cells in the dura of females compared with males. Macs and dendritic cells were significantly increased by stress in males, but not females. In contrast, T-cells were significantly increased in females with a 24-hour delay following stress. Lastly, Macs, dendritic cells, and T-cells were significantly higher in sympathectomized-naïve males, but not females. Conclusions It may not only be possible, but necessary to use different strategies for the most effective treatment of migraine in men and women.

Retrospective study of sonographic findings in bone involvement associated with rotator cuff calcific tendinopathy: preliminary results of a case series*

PubMed Central

Nogueira-Barbosa, Marcello H.; Gregio-Junior, Everaldo; Lorenzato, Mario Muller

2015-01-01

Objective The present study was aimed at investigating bone involvement secondary to rotator cuff calcific tendonitis at ultrasonography. Materials and Methods Retrospective study of a case series. The authors reviewed shoulder ultrasonography reports of 141 patients diagnosed with rotator cuff calcific tendonitis, collected from the computer-based data records of their institution over a four-year period. Imaging findings were retrospectively and consensually analyzed by two experienced musculoskeletal radiologists looking for bone involvement associated with calcific tendonitis. Only the cases confirmed by computed tomography were considered for descriptive analysis. Results Sonographic findings of calcific tendinopathy with bone involvement were observed in 7/141 (~ 5%) patients (mean age, 50.9 years; age range, 42-58 years; 42% female). Cortical bone erosion adjacent to tendon calcification was the most common finding, observed in 7/7 cases. Signs of intraosseous migration were found in 3/7 cases, and subcortical cysts in 2/7 cases. The findings were confirmed by computed tomography. Calcifications associated with bone abnormalities showed no acoustic shadowing at ultrasonography, favoring the hypothesis of resorption phase of the disease. Conclusion Preliminary results of the present study suggest that ultrasonography can identify bone abnormalities secondary to rotator cuff calcific tendinopathy, particularly the presence of cortical bone erosion. PMID:26811551

Novel characterization of monocyte-derived cell populations in the meninges and choroid plexus and their rates of replenishment in bone marrow chimeric mice.

PubMed

Chinnery, Holly R; Ruitenberg, Marc J; McMenamin, Paul G

2010-09-01

The mouse dura mater, pia mater, and choroid plexus contain resident macrophages and dendritic cells (DCs). These cells participate in immune surveillance, phagocytosis of cellular debris, uptake of antigens from the surrounding cerebrospinal fluid and immune regulation in many pathologic processes. We used Cx3cr1 knock-in, CD11c-eYFP transgenic and bone marrow chimeric mice to characterize the phenotype, density and replenishment rate of monocyte-derived cells in the meninges and choroid plexus and to assess the role of the chemokine receptor CX3CR1 on their number and tissue distribution. Iba-1 major histocompatibility complex (MHC) Class II CD169 CD68 macrophages and CD11c putative DCs were identified in meningeal and choroid plexus whole mounts. Comparison of homozygous and heterozygous Cx3cr1 mice did not reveal CX3CR1-dependancy on density, distribution or phenotype of monocyte-derived cells. In turnover studies, wild type lethally irradiated mice were reconstituted with Cx3cr1/-positive bone marrow and were analyzed at 3 days, 1, 2, 4 and 8 weeks after transplantation. There was a rapid replenishment of CX3CR1-positive cells in the dura mater (at 4 weeks) and the choroid plexus was fully reconstituted by 8 weeks. These data provide the foundation for future studies on the role of resident macrophages and DCs in conditions such as meningitis, autoimmune inflammatory disease and in therapies involving irradiation and hematopoietic or stem cell transplantation.

[Local fixation of antibiotics by fibrin spray : In bone defects with soft tissue involvement].

PubMed

Janko, Maren; Nau, Christoph; Marzi, Ingo; Frank, Johannes

2017-02-01

In acute and chronic bone infections with concomitant soft tissue involvement the current gold standard is radical surgical debridement including explantation of the infected prosthetic devices. This is followed by initiation of systemic antibiotic therapy appropriate for the antibiogram. Several revision operations are often necessary to achieve complete healing. Additional treatment with local antibiotics or antibiotic-containing substances is routinely used in bone surgery. Apart from the typical procedures with commercially available products, we have conducted a study with 21 patients by application of local antibiotic treatment in combination with the fibrin glue spray technique and evaluated the results. Out of nine wounds of the lower extremities with bone involvement, total healing could be achieved in eight cases. We were also successful in two out of three very complex pelvic wounds; however, as expected the implant infections were complicated. Out of the seven desolate cases we were only able to achieve complete long-term healing in two cases. In the meantime we routinely use the described method in such special disastrous infection situations; however, this is carried out only in combination with established surgical procedures in sepsis surgery and anti-infection management.

A new collagen biomatrix of equine origin versus a cadaveric dura graft for the repair of dural defects--a comparative animal experimental study.

PubMed

Knopp, U; Christmann, F; Reusche, E; Sepehrnia, A

2005-08-01

Numerous types of materials have been evaluated over the past decades in the quest for the ideal dural replacement, but no product fully meets all the applicable criteria. This paper presents the long-term results of an animal trial of a collagen biomatrix (TISSUDURA, Baxter AG, Vienna/Austria) for the repair and regeneration of dural defects. This product provides a matrix with a special layer structure and consists of pure naturally cross-linked collagen of equine origin. The comparable material is Tutoplast Dura, a human cadaveric-derived dural graft preserved in a multiple stage chemical process. Bihemispheric parietotoccipital dural defects of a defined size were induced in 25 sheep and subsequently closed with the collagen graft or Tutoplast Dura, respectively. Postoperative neurological abnormalities did not occur in any animal. There were no signs of graft rejection or formation of cerebrospinal fluid fistulae. The collagen graft site displayed histological signs as early as 2 weeks postoperatively consistent with a moderate Iymphocytic inflammatory response and infiltration with fibroblasts and macrophages. The graft subsequently developed a neodura-like connective tissue architecture. The Tutoplast Dura showed only minimal cellular infiltration, and again the surrounding structures displayed a mild inflammatory response. 24 weeks postoperatively, the dura and neomembrane were barely distinguishable at the collagen biomatrix site, but the Tutoplast Dura displayed inadequate fusion with the dural border and was encapsulated in a connective tissue layer. The outcomes demonstrate that the collagen graft can be used for dura reconstruction as a temporary dural replacement and at the same time as a biomatrix for dural regeneration.

IL-20 bone diseases involvement and therapeutic target potential.

PubMed

Wang, Hsiao-Hsuan; Hsu, Yu-Hsiang; Chang, Ming-Shi

2018-04-24

Millions of people around the world suffer from bone disorders, likes osteoporosis, rheumatoid arthritis (RA), and cancer-induced osteolysis. In general, the bone remodeling balance is determined by osteoclasts and osteoblasts, respectively responsible for bone resorption and bone formation. Excessive inflammation disturbs the activities of these two kinds of cells, typically resulting in the bone loss. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory disorders likes psoriasis, atherosclerosis, cancer, liver fibrosis, and RA. IL-20 has an important role in the regulation of osteoclastogenesis and osteoblastogenesis and is upregulated in several bone-related diseases. The anti-IL-20 monoclonal antibody treatment has a therapeutic potential in several experimental disease models including ovariectomy-induced osteoporosis, cancer-induced osteolysis, and bone fracture. This review article provides an overview describing the IL-20's biological functions in the common bone disorders and thus providing a novel therapeutic strategy in the future.

Predictive value of bone scintigraphy for the detection of joint involvement in Behçet's disease: Dermatologists' perspectives.

PubMed

Seo, Jimyung; Lee, Minseok; Choi, Min Ju; Zheng, Zhenlong; Cho, Arthur; Bang, Dongsik; Kim, Do Young

2015-01-01

Behçet's disease (BD) is a multisystemic inflammatory disease with articular involvement. Non-specific arthralgia without objective signs of arthritis, such as swelling or effusion, is common in such patients. Thus, an accurate diagnosis of joint involvement may be challenging for dermatologists. To evaluate the validity of (99m)Tc-methylene diphosphonate (Tc-99m-MDP) bone scintigraphy for joint involvement assessment in patients with BD. In 211 patients with BD who had scintigraphic evaluations due to joint symptoms, agreement between bone scintigraphy findings and clinically evaluated joint complaints was retrospectively assessed using Cohen's kappa (κ) statistic. A patient subset (n = 104) showing agreement between joint complaints and scintigraphy results was re-evaluated by a rheumatologist to determine the level of diagnostic specificity attained by combining bone scintigraphy with clinical examinations of dermatologists. The total kappa value (211 patients) was 0.604, indicating fair agreement between joint complaints and scintigraphy results. Individual analysis of eleven joint categories revealed statistically significant correlations for wrist (κ = 0.677), shoulder (κ = 0.661), and foot joints (κ = 0.618). Of the 104 referrals to a rheumatologist, 95 (91.34%) were confirmed as having BD-associated articular involvement. Joint acral areas (e.g., foot, hand, wrist and shoulder) that had the highest kappa value correlations also ranked highest in diagnostic specificity. Bone scintigraphy presents a simple and useful option for dermatologists to assess joint involvement in BD patients, especially for specific anatomic sites.

CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

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

Oue, Erika; Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Global Center of Excellence

Highlights: Black-Right-Pointing-Pointer Oral cancer cells synthesize CXCL2. Black-Right-Pointing-Pointer CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. Black-Right-Pointing-Pointer CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. Black-Right-Pointing-Pointer We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cellmore » lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is

Successful conservative management of symptomatic bilateral dorsal patellar defects presenting with cartilage involvement and bone marrow edema: MRI findings.

PubMed

Kwee, Thomas C; Sonneveld, Heleen; Nix, Maarten

2016-05-01

The dorsal patellar defect is a relatively rare entity that involves the superolateral quadrant of the patella. It is usually considered to represent a delayed ossification process, although its exact origin remains unclear. Because of its usually innocuous nature and clinical course, invasive interventions are generally deemed unnecessary, although curretage has been successfully performed on symptomatic cases. This case report presents a rather unusual case of symptomatic bilateral dorsal patellar defects with cartilage involvement and widespread surrounding bone marrow edema as demonstrated by magnetic resonance imaging (MRI). Both cartilage involvement and bone marrow edema should be considered part of the spectrum of associated MRI findings that can be encountered in this entity. Furthermore, the presented case shows that symptomatic dorsal patellar defects can be treated conservatively with success and that (decrease of) pain symptoms are likely related to (decrease of) bone marrow edema.

Current and emerging basic science concepts in bone biology: implications in craniofacial surgery.

PubMed

Oppenheimer, Adam J; Mesa, John; Buchman, Steven R

2012-01-01

Ongoing research in bone biology has brought cutting-edge technologies into everyday use in craniofacial surgery. Nonetheless, when osseous defects of the craniomaxillofacial skeleton are encountered, autogenous bone grafting remains the criterion standard for reconstruction. Accordingly, the core principles of bone graft physiology continue to be of paramount importance. Bone grafts, however, are not a panacea; donor site morbidity and operative risk are among the limitations of autologous bone graft harvest. Bone graft survival is impaired when irradiation, contamination, and impaired vascularity are encountered. Although the dura can induce calvarial ossification in children younger than 2 years, the repair of critical-size defects in the pediatric population may be hindered by inadequate bone graft donor volume. The novel and emerging field of bone tissue engineering holds great promise as a limitless source of autogenous bone. Three core constituents of bone tissue engineering have been established: scaffolds, signals, and cells. Blood supply is the sine qua non of these components, which are used both individually and concertedly in regenerative craniofacial surgery. The discerning craniofacial surgeon must determine the proper use for these bone graft alternatives, while understanding their concomitant risks. This article presents a review of contemporary and emerging concepts in bone biology and their implications in craniofacial surgery. Current practices, areas of controversy, and near-term future applications are emphasized.

Dura-arachnoid lesions produced by 22 gauge Quincke spinal needles during a lumbar puncture.

PubMed

Reina, M A; López, A; Badorrey, V; De Andrés, J A; Martín, S

2004-06-01

The dural and arachnoid hole caused by lumbar puncture needles is a determining factor in triggering headaches. The aim of this study is to assess the dimensions and morphological features of the dura mater and arachnoids when they are punctured by a 22 gauge Quincke needle having its bevel either in the parallel or in the transverse position. Fifty punctures were made with 22 gauge Quincke needles in the dural sac of four fresh cadavers using an "in vitro" model especially designed for this purpose. The punctures were performed by needles with bevels parallel or perpendicular to the spinal axis and studied under scanning electron microscopy. Thirty five of the 50 punctures done by Quincke needles (19 in the external surface and 16 in the internal) were used for evaluation. When the needle was inserted with its bevel parallel to the axis of the dural sac (17 of 35), the size of the dura-arachnoid lesion was 0.032 mm(2) in the epidural surface and 0.037 mm(2) in the subarachnoid surface of the dural sac. When the needle's bevel was perpendicular to the axis (18 of 35) the measurement of the lesion size was 0.042 mm(2) for the external surface and 0.033 mm(2) for the internal. There were no statistical significant differences between these results. It is believed that the reported lower frequency of postdural puncture headache when the needle is inserted parallel to the cord axis should be explained by some other factors besides the size of the dura-arachnoid injury.

Ultrastructural characteristics of the cranial dura mater-arachnoid interface layer.

PubMed

Angelov, D N

1990-01-01

The ultrastructural features of the encephalic dura mater-arachnoid borderline (interface) layer (zone) of rats, rabbits, cats and humans were studied. The rat's interface zone included the electron-lucent epithelium-like arranged fibroblasts of the inner dural layer, the rich in filaments cells of the dural neurothelium, a 20 nm wide intercellular cleft filled with electron-dense material and the dark mitochondria-rich cells of the outer arachnoidal layer; in rabbits and cats, this laminar distinction was less prominent, while in man, it was almost absent.

FLOCK cluster analysis of plasma cell flow cytometry data predicts bone marrow involvement by plasma cell neoplasia.

PubMed

Dorfman, David M; LaPlante, Charlotte D; Li, Betty

2016-09-01

We analyzed plasma cell populations in bone marrow samples from 353 patients with possible bone marrow involvement by a plasma cell neoplasm, using FLOCK (FLOw Clustering without K), an unbiased, automated, computational approach to identify cell subsets in multidimensional flow cytometry data. FLOCK identified discrete plasma cell populations in the majority of bone marrow specimens found by standard histologic and immunophenotypic criteria to be involved by a plasma cell neoplasm (202/208 cases; 97%), including 34 cases that were negative by standard flow cytometric analysis that included clonality assessment. FLOCK identified discrete plasma cell populations in only a minority of cases negative for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria (38/145 cases; 26%). Interestingly, 55% of the cases negative by standard analysis, but containing a FLOCK-identified discrete plasma cell population, were positive for monoclonal gammopathy by serum protein electrophoresis and immunofixation. FLOCK-identified and quantitated plasma cell populations accounted for 3.05% of total cells on average in cases positive for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria, and 0.27% of total cells on average in cases negative for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria (p<0.0001; area under the curve by ROC analysis=0.96). The presence of a FLOCK-identified discrete plasma cell population was predictive of the presence of plasma cell neoplasia with a sensitivity of 97%, compared with only 81% for standard flow cytometric analysis, and had specificity of 74%, PPV of 84% and NPV of 95%. FLOCK analysis, which has been shown to provide useful diagnostic information for evaluating patients with suspected systemic mastocytosis, is able to identify neoplastic plasma cell populations analyzed by flow cytometry, and may be helpful in the diagnostic

Solid variant of aneurysmal bone cyst of the left parietal bone without preceding trauma.

PubMed

Nestler, Ulf; Wagner, Hans-Joachim; Schaenzer, Anne; Preuss, Matthias

2013-12-01

We report the case of a 17-year-old girl with an indolent, smooth swelling of the left cranial vault that had been developing for 2 months. Complete surgical excision was performed and the defect was closed using artificial bone cement. The integrity of the dura mater was conserved and the patient recovered without neurological deficit. Magnetic resonance imaging (MRI) controls 6 and 18 months after the operation did not find signs of recurrence. The lesion consisted of an elastic bone shell containing bony trabeculae with soft brown-greyish tissue and posthemorrhagic dark fluid. Histological assessment found CD68 positive multinucleated giant cells in a highly cellular fibroblastic matrix surrounding bony lamellar structures, without signs of inflammation or malignancy. Hyperparathyroidism was ruled out by normal serum values for parathyroid hormone, calcium, phosphate, and alkaline phosphatase. Histologically, first diagnosis was giant cell reparative granuloma and reference pathology disclosed aneurysmal bone cyst. The solid variant of aneurysmal bone cyst and the giant cell reparative granuloma can be histologically indistinguishable. Both lesions are only rarely encountered in cranial bones and most published cases affected the cranial base or the jaw, mainly in children or young adults. From a clinical point of view, classification into "outward" lesions (osteolysis of external parts of the vault with preservation of internal tabula) and "inward" lesions (intracranial multicystic lesions with raise of intracranial pressure) has been proposed. Three phases of development can be identified, and spontaneous involution has been described. Both entities are benign, but because in several cases an underlying malignant disease has been found, complete resection and regular follow-up by MRI are recommended. Georg Thieme Verlag KG Stuttgart · New York.

Consecutive assessment of FA and ADC values of normal lumbar nerve roots from the junction of the dura mater.

PubMed

Miyagi, Ryo; Sakai, Toshinori; Yamabe, Eiko; Yoshioka, Hiroshi

2015-06-27

Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are widely used in the evaluation of the central nervous system and recently have been reported as a potential tool for diagnosis of the peripheral nerve or the lumbar nerve entrapment. The purpose of this study was to evaluate consecutive changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of normal lumbar nerve roots from the junction of the dura mater. The lumbar spinal nerves were examined in 6 male healthy volunteers (mean age, 35 years) with no experiences of sciatica, with a 3.0-T MR unit using a five-element phased-array surface coil. DTI was performed with the following imaging parameters: 11084.6/73.7 ms for TR/TE; b-value, 800 s/mm2; MPG, 33 directions; slice thickness, 1.5 mm; and total scan time, 7 min 35 s. ADC and FA values at all consecutive points along the L4, L5 and S1 nerves were quantified on every 1.5 mm slice from the junction of the dura mater using short fiber tracking. ADC values of all L4, 5, and S1 nerve roots decreased linearly up to 15 mm from the dura junction and was constant distally afterward. ADC values in the proximal portion demonstrated S1 > L5 > L4 (p < 0.05). On the other hand, FA values increased linearly up to 15 mm from the dura junction, and was constant distally afterward. FA values in the proximal portion showed L4 > L5 > S1 (p < 0.05). Our study demonstrated that ADC and FA values of each L4, 5, and S1 at the proximal portion from the junction of the dura matter changed linearly. It would be useful to know the normal profile of DTI values by location of each nerve root so that we can detect subtle abnormalities in each nerve root.

Effect of quorum sensing signals produced by seaweed-associated bacteria on carpospore liberation from Gracilaria dura

PubMed Central

Singh, Ravindra Pal; Baghel, Ravi S.; Reddy, C. R. K.; Jha, Bhavanath

2015-01-01

Epiphytic and endophytic bacteria associated with green macroalgae Ulva (U. fasciata and U. lactuca) and red macroalgae Gracilaria (G. corticata and G. dura) have been identified from three different seasons to evaluate the effect of quorum sensing (QS) molecules on carpospores liberation from Gracilaria dura. The bacterial isolates belonging to the orders Bacillales, Pseudomonadales, Alteromonadales, and Vibrionales were present in all seasons, whereas Actinomycetales and Enterobacteriales were confined to pre-monsoon and post-monsoon seasons, respectively. Among all the Gram-negative bacteria, seven isolates were found to produce different types of N-acyl homoserine lactones (AHLs). Interestingly, Shewanella algae produced five types of AHL: C4-HSL, HC4-HSL, C6-HSL, 3-oxo-C6-HSL, and 3-oxo-C12-HSL. Subsequently, the AHLs producing bacterial isolates were screened for carpospore liberation from G. dura and these isolates were found to positively induce carpospore liberation over the control. Also, observed that carpospore liberation increased significantly in C4- and C6-HSL treated cystocarps. Sodium dodecyl sulfate and native polyacrylamide gel electrophoresis of the total protein of the C4- and C6-HSL treated cystocarps showed two specific peptide bands of different molecular weights (50 kDa and 60 kDa) as compared to the control, confirming their indirect effect on carpospore liberation. PMID:25788899

Dura-arachnoid lesions produced by 22 gauge Quincke spinal needles during a lumbar puncture

PubMed Central

Reina, M; Lopez, A; Badorrey, V; De Andres, J A; Martin, S

2004-01-01

Aims: The dural and arachnoid hole caused by lumbar puncture needles is a determining factor in triggering headaches. The aim of this study is to assess the dimensions and morphological features of the dura mater and arachnoids when they are punctured by a 22 gauge Quincke needle having its bevel either in the parallel or in the transverse position. Methods: Fifty punctures were made with 22 gauge Quincke needles in the dural sac of four fresh cadavers using an "in vitro" model especially designed for this purpose. The punctures were performed by needles with bevels parallel or perpendicular to the spinal axis and studied under scanning electron microscopy. Results: Thirty five of the 50 punctures done by Quincke needles (19 in the external surface and 16 in the internal) were used for evaluation. When the needle was inserted with its bevel parallel to the axis of the dural sac (17 of 35), the size of the dura-arachnoid lesion was 0.032 mm2 in the epidural surface and 0.037 mm2 in the subarachnoid surface of the dural sac. When the needle's bevel was perpendicular to the axis (18 of 35) the measurement of the lesion size was 0.042 mm2 for the external surface and 0.033 mm2 for the internal. There were no statistical significant differences between these results. Conclusions: It is believed that the reported lower frequency of postdural puncture headache when the needle is inserted parallel to the cord axis should be explained by some other factors besides the size of the dura-arachnoid injury. PMID:15146008

A comparison between "sandwich" and conventional methods of repairing spinal dura rupture.

PubMed

Wang, Hui-ren; Cao, Sheng-sheng; Jiang, Yun-qi; Li, Jun-ning; Li, Xi-lei; Fu, Yun-gen; Zhao, Ming-dong; Dong, Jian

2012-11-01

To study the therapeutic efficacy of the "sandwich" method (medical glue + gelatin sponge + medical glue) of spinal dural repair for preventing cerebrospinal fluid (CSF) leaks during treatment of subdural tumors. Fifty-four patients with spinal subdural tumors treated between April 2007 and June 2011 were retrospectively investigated. The patients were divided into two groups: a conventional group (group A) and a "sandwich" group (group B). The group A patients included 16 males and 7 females with an average tumor course of 11 months (range, 2-34 months). Four of their 23 tumors were in the cervical spine, eight thoracic, and eleven lumbar. The group B patients included 19 males and 12 females with an average tumor course of 12 months (range, 3-36 months). Five of their 31 tumors were in the cervical spines, 10 thoracic, and 16 lumbar. In group A, the dural repairs were performed with interlocking sutures and a gelatin sponge covering the dura; whereas in group B, they were performed with interlocking sutures, painting of medical glue around the dural incision, covering this with a gelatin sponge, and finally covering of the gelatin sponge with medical glue. The total volume of drainage after operation, incidence of CSF leaks, healing of the incision, and recovery of clinical performance were recorded. Compared to group A patients, group B patients had a significantly smaller total volume of drainage (P < 0.05) on the day of surgery, and the first, second, and third postoperative days. The incidence of CSF leakage in group B was also significantly less than in group A (P < 0.05). Before discharge, three patients in group A developd hydrops, which was successfully treated by aspiration, continuous pressure from sandbags, and the prone position. During the first 3 months of follow-up, five patients developed deep hydrops under their incisions but required no treatment. There were no obvious abnormalities in group B. After removal of subdural spinal tumors by

Use of Subdural Evacuating Port System Following Open Craniotomy with Excision of Native Dura and Membranes for Management of Chronic Subdural Hematoma.

PubMed

Cage, Tene; Bach, Ashley; McDermott, Michael W

2017-04-26

An 86-year-old woman was admitted to the intensive care unit with a chronic subdural hematoma (CSDH) and rapid onset of worsening neurological symptoms. She was taken to the operating room for a mini-craniotomy for evacuation of the CSDH including excision of the dura and CSDH membrane. Postoperatively, a subdural evacuation port system (SEPS) was integrated into the craniotomy site and left in place rather than a traditional subdural catheter drain to evacuate the subdural space postoperatively. The patient had a good recovery and improvement of symptoms after evacuation and remained clinically well after the SEPS was removed. We offer the technique of dura and CSDH membrane excision plus SEPS drain as an effective postoperative alternative to the standard craniotomy leaving the native dura intact with traditional subdural drain that overlies the cortical surface of the brain in treating patients with CSDH.

Use of Subdural Evacuating Port System Following Open Craniotomy with Excision of Native Dura and Membranes for Management of Chronic Subdural Hematoma

PubMed Central

Bach, Ashley; McDermott, Michael W.

2017-01-01

An 86-year-old woman was admitted to the intensive care unit with a chronic subdural hematoma (CSDH) and rapid onset of worsening neurological symptoms. She was taken to the operating room for a mini-craniotomy for evacuation of the CSDH including excision of the dura and CSDH membrane. Postoperatively, a subdural evacuation port system (SEPS) was integrated into the craniotomy site and left in place rather than a traditional subdural catheter drain to evacuate the subdural space postoperatively. The patient had a good recovery and improvement of symptoms after evacuation and remained clinically well after the SEPS was removed. We offer the technique of dura and CSDH membrane excision plus SEPS drain as an effective postoperative alternative to the standard craniotomy leaving the native dura intact with traditional subdural drain that overlies the cortical surface of the brain in treating patients with CSDH. PMID:28560123

Borrelia burgdorferi adhere to blood vessels in the dura mater and are associated with increased meningeal T cells during murine disseminated borreliosis

PubMed Central

Divan, Ali; Casselli, Timothy; Narayanan, S. Anand; Mukherjee, Sanjib; Zawieja, David C.; Watt, John A.

2018-01-01

Borrelia burgdorferi, the causative agent of Lyme disease, is a vector-borne bacterial infection that is transmitted through the bite of an infected tick. If not treated with antibiotics during the early stages of infection, disseminated infection can spread to the central nervous system (CNS). In non-human primates (NHPs) it has been demonstrated that the leptomeninges are among the tissues colonized by B. burgdorferi spirochetes. Although the NHP model parallels aspects of human borreliosis, a small rodent model would be ideal to study the trafficking of spirochetes and immune cells into the CNS. Here we show that during early and late disseminated infection, B. burgdorferi infects the meninges of intradermally infected mice, and is associated with concurrent increases in meningeal T cells. We found that the dura mater was consistently culture positive for spirochetes in transcardially perfused mice, independent of the strain of B. burgdorferi used. Within the dura mater, spirochetes were preferentially located in vascular regions, but were also present in perivascular, and extravascular regions, as late as 75 days post-infection. At the same end-point, we observed significant increases in the number of CD3+ T cells within the pia and dura mater, as compared to controls. Flow cytometric analysis of leukocytes isolated from the dura mater revealed that CD3+ cell populations were comprised of both CD4 and CD8 T cells. Overall, our data demonstrate that similarly to infection in peripheral tissues, spirochetes adhere to the dura mater during disseminated infection, and are associated with increases in the number of meningeal T cells. Collectively, our results demonstrate that there are aspects of B. burgdorferi meningeal infection that can be modelled in laboratory mice, suggesting that mice may be useful for elucidating mechanisms of meningeal pathogenesis by B. burgdorferi. PMID:29723263

SEM corrosion-casts study of the microcirculation of the flat bones in the rat.

PubMed

Pannarale, L; Morini, S; D'Ubaldo, E; Gaudio, E; Marinozzi, G

1997-04-01

Little is known about the organization of microcirculation in flat bones in comparison with long bones. This study, therefore, helps us to determine the design of this vascular system in flat bones in relation to their structure and function. The organization of microvasculature in parietal, scapula, and ileum bones of 15 young sexually mature rats, aged 6-7 weeks, was studied by light and scanning electron microscopy (SEM) from vascular corrosion cast (vcc), a resin-cast obtained material. Our observations show that the pattern of the microcirculation in flat bones is different in the thick and thin parts of such bones. Where the bone is thinner than 0.4 mm, only periosteal and dural network exist. Larger vessels which do not form a real network connect the two tables of the bones in these regions. In thicker areas, the organization of the microvasculature is similar to that in long bones, with distinct periosteal, cortical and bone marrow networks. Moreover, in different bones, outer networks show slightly different characteristics according to the different adjacent structures (dura mater, muscles etc.). Different types of vessels were recognized by comparing their different diameter, course and endothelial imprints. The microvascular patterns of the flat bones are strongly influenced by the bone thickness. The different microvascular systems can interact both with the bone modelling and remodeling and with the variable metabolic needs, modifying the microvascular pattern and the blood flow. This is even more important in view of the reciprocal influence of the different networks within the same bone.

Polybrominated diphenyl ethers from the marine organisms Lendenfeldia dendyi and Sinularia dura with anti-MRSa activity

USDA-ARS?s Scientific Manuscript database

Bioassay-guided fractionation of the marine sponge Lendenfeldia dendyi and the soft coral Sinularia dura resulted in the isolation of five polybrominated diphenyl ethers (1-5). The structures of the isolated compounds were determined using spectroscopic methods(lD and 2D NMR) and HRMS analyses. The ...

76 FR 6839 - ActiveCore Technologies, Inc., Battery Technologies, Inc., China Media1 Corp., Dura Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-08

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] ActiveCore Technologies, Inc., Battery Technologies, Inc., China Media1 Corp., Dura Products International, Inc. (n/k/a Dexx Corp.), Global Mainframe... Battery Technologies, Inc. because it has not filed any periodic reports since the period ended December...

Effect of six weeks of dura disc and mini-trampoline balance training on postural sway in athletes with functional ankle instability.

PubMed

Kidgell, Dawson J; Horvath, Deanna M; Jackson, Brendan M; Seymour, Philip J

2007-05-01

Lateral ankle sprain (LAS) is one of the most common injuries incurred during sporting activities, and effective rehabilitation programs for this condition are challenging to develop. The purpose of this research was to compare the effect of 6 weeks of balance training on either a mini-trampoline or a dura disc on postural sway and to determine if the mini-trampoline or the dura disc is more effective in improving postural sway. Twenty subjects (11 men, 9 women) with a mean age of 25.4 +/- 4.2 years were randomly allocated into a control group, a dura disc training (DT) group, or a mini-trampoline (MT) group. Subjects completed 6 weeks of balance training. Postural sway was measured by subjects performing a single limb stance on a force plate. The disbursement of the center of pressure was obtained from the force plate in the medial-lateral and the anterior-posterior sway path and was subsequently used for pretest and posttest analysis. After the 6-week training intervention, there was a significant (p < 0.05) difference in postural sway between pre- and posttesting for both the MT (pretest = 56.8 +/- 20.5 mm, posttest = 33.3 +/- 8.5 mm) and DT (pretest = 41.3 +/- 2.6 mm, posttest = 27.2 +/- 4.8 mm) groups. There was no significant (p > 0.05) difference detected for improvements between the MT and DT groups. These results indicate that not only is the mini-trampoline an effective tool for improving balance after LAS, but it is equally as effective as the dura disc.

[Pathological diagnosis of pediatric Burkitt lymphoma involving bone marrow].

PubMed

Sun, Qi; Chen, Zhenping; Liu, Enbin; Li, Zhanqi; Yang, Qingying; Sun, Fujun; Ma, Yue; Zhang, Hongju; Zhang, Peihong; Ru, Kun

2015-02-01

To investigate pathologic and differential diagnostic features of pediatric Burkitt lymphoma (BL). A total of 20 cases of pediatric BL were retrospectively reviewed for their clinical and pathologic profiles. Bone marrow aspiration specimens were available in all cases and bone marrow biopsies were available for immunohistochemical study in 18 cases. Flow cytometry study was available in 16 cases. MYC translocation by FISH method was performed in 11 cases. Atypical lymphocytes with cytoplasmic vacuoles were found in bone marrow smears in all 20 cases and peripheral blood films in all 19 available cases. The bone marrow biopsies showed infiltration by uniform medium-sized atypical lymphocytes with multiple small nucleoli but without the starry-sky pattern in all 18 cases. Immunohistochemistry showed the following results in all 18 cases: positive for CD20, PAX-5, CD10, CD34 and TdT, but negative for bcl-2 and CD3 with Ki-67 > 95%.Flow cytometry showed CD19+CD20+CD10+FMC7+CD22+TdT-CD3- in 16 cases, including κ+ in 8 cases, λ+ in 7 cases, and κ-λ- in 1 case. MYC gene rearrangement by FISH was observed in 10 of the 11 cases. The histopathology of BL is distinct, including atypical lymphocytes with cytoplasmic vacuoles in bone marrow aspirate, lack of starry-sky patternin bone marrow biopsy. Generally, the diagnosis should be made with a combined immunophenotype and FISH approach. Pediatric BL must be distinguished from DLBCL and B-cell lymphoma, unclassifiable, which has intermediate features between DLBCL and Burkitt lymphoma.

Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study

PubMed Central

Papageorgiou, Iraklis; Abberton, Thomas; Fuller, Martin; Tipper, Joanne L.; Fisher, John; Ingham, Eileen

2014-01-01

Medical interventions for the treatment of spinal disc degeneration include total disc replacement and fusion devices. There are, however, concerns regarding the generation of wear particles by these devices, the majority of which are in the nanometre sized range with the potential to cause adverse biological effects in the surrounding tissues. The aims of this study were to develop an organ culture model of the porcine dura mater and to investigate the biological effects of CoCr nanoparticles in this model. A range of histological techniques were used to analyse the structure of the tissue in the organ culture. The biological effects of the CoCr wear particles and the subsequent structural changes were assessed using tissue viability assays, cytokine assays, histology, immunohistochemistry, and TEM imaging. The physiological structure of the dura mater remained unchanged during the seven days of in vitro culture. There was no significant loss of cell viability. After exposure of the organ culture to CoCr nanoparticles, there was significant loosening of the epithelial layer, as well as the underlying collagen matrix. TEM imaging confirmed these structural alterations. These structural alterations were attributed to the production of MMP-1, -3, -9, -13, and TIMP-1. ELISA analysis revealed that there was significant release of cytokines including IL-8, IL-6, TNF-α, ECP and also the matrix protein, tenascin-C. This study suggested that CoCr nanoparticles did not cause cytotoxicity in the dura mater but they caused significant alterations to its structural integrity that could lead to significant secondary effects due to nanoparticle penetration, such as inflammation to the local neural tissue. PMID:28344233

Roles of leptin in bone metabolism and bone diseases.

PubMed

Chen, Xu Xu; Yang, Tianfu

2015-09-01

Adipose tissue has been more accepted as an active contributor to whole body homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was discovered as the product of the obese gene in 1994. With more and more studies conducted on this hormone, it has been shown that there is a close relationship between adipose tissue and bone, which have important effects on each other. Bone is the source of many hormones, such as osteocalcin, that can affect energy metabolism and then the anabolism or catabolism of fat tissue. In contrast, the adipose tissue synthesizes and releases a series of adipokines, which are involved in bone metabolism through direct or indirect effects on bone formation and resorption. Interestingly, leptin, one of the most important cytokines derived from fat tissue, seems to account for the largest part of effects on bone, through direct or indirect involvement in bone remodeling and by playing a significant role in many bone diseases, such as osteoporosis, osteoarthritis, rheumatic arthritis, bone tumors and even fractures. In this review, we will discuss the progress in leptin research, particularly focusing on the roles of leptin in bone diseases.

Bone-Immune Cell Crosstalk: Bone Diseases

PubMed Central

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma. PMID:26000310

Bone-immune cell crosstalk: bone diseases.

PubMed

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma.

Reconstruction of the mandible bone by treatment of resected bone with pasteurization.

PubMed

Uehara, Masataka; Inokuchi, Tsugio; Sano, Kazuo; Sumita, Yoshinori; Tominaga, Kazuhiro; Asahina, Izumi

2012-11-01

The results of long-term follow-up for reimplantation of the mandibular bone treated with pasteurization are reported. Mandibulectomy was performed for mandibular malignancy in 3 cases. The resected bones were subsequently reimplanted after treatment with pasteurization in 3 cases to eradicate tumor cells involved in the resected bone. Although postoperative infection was observed in 2 of 3 cases, reimplantation of the resected mandibular bone treated by pasteurization was finally successful. Ten to 22 years of follow-up was carried out. Pasteurization was able to devitalize tumor cells involved in the resected bone and to preserve bone-inductive activity. Reimplantation of pasteurization could be a useful strategy for reconstruction of the mandible in patients with mandibular malignancy.

Enhancement of bone consolidation in mandibular distraction osteogenesis: a contemporary review of experimental studies involving adjuvant therapies.

PubMed

Hong, Paul; Boyd, Daniel; Beyea, Steven D; Bezuhly, Michael

2013-07-01

One of the major disadvantages of mandibular distraction osteogenesis (MDO) is the prolonged time required for consolidation of the regenerate bone. The objective of the present study is to perform a contemporary review of various adjuvant therapies to enhance bone consolidation in MDO. A PubMed search for articles related to MDO, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to enhance bone consolidation. A total of 1414 titles and abstracts were initially reviewed; 61 studies were included for full review. Many studies involved growth factors, hormones, pharmacological agents, gene therapy, and stem cells. Other adjuvant therapies included mechanical stimulation, laser therapy, and hyperbaric oxygen. Majority of the studies demonstrated positive bone healing effects and thus adjuvant therapies remain a viable strategy to enhance and hasten the consolidation period. Although most studies have demonstrated promising results, many questions still remain, such as optimal amount, timing, and delivery methods required to stimulate the most favorable bone regeneration. As well, further studies comparing various adjuvant therapies and documentation of long-term adverse effects are required prior to clinical application. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Laser bonding with ICG-infused chitosan patches: preliminary experiences in suine dura mater and vocal folds

NASA Astrophysics Data System (ADS)

Rossi, Francesca; Matteini, Paolo; Ratto, Fulvio; Pini, Roberto; Iacoangeli, Maurizio; Giannoni, Luca; Fortuna, Damiano; Di Cicco, Emiliano; Corbara, Sylwia; Dallari, Stefano

2014-05-01

Laser bonding is a promising minimally invasive approach, emerging as a valid alternative to conventional suturing techniques. It shows widely demonstrated advantages in wound treatment: immediate closuring effect, minimal inflammatory response and scar formation, reduced healing time. This laser based technique can overcome the difficulties in working through narrow surgical corridors (e.g. the modern "key-hole" surgery as well as the endoscopy setting) or in thin tissues that are impossible to treat with staples and/or stitches. We recently proposed the use of chitosan matrices, stained with conventional chromophores, to be used in laser bonding of vascular tissue. In this work we propose the same procedure to perform laser bonding of vocal folds and dura mater repair. Laser bonding of vocal folds is proposed to avoid the development of adhesions (synechiae), after conventional or CO2 laser surgery. Laser bonding application in neurosurgery is proposed for the treatment of dural defects being the Cerebro Spinal Fluid leaks still a major issue. Vocal folds and dura mater were harvested from 9-months old porks and used in the experimental sessions within 4 hours after sacrifice. In vocal folds treatment, an IdocyanineGreen-infused chitosan patch was applied onto the anterior commissure, while the dura mater was previously incised and then bonded. A diode laser emitting at 810 nm, equipped with a 600 μm diameter optical fiber was used to weld the patch onto the tissue, by delivering single laser spots to induce local patch/tissue adhesion. The result is an immediate adhesion of the patch to the tissue. Standard histology was performed, in order to study the induced photothermal effect at the bonding sites. This preliminary experimental activity shows the advantages of the proposed technique in respect to standard surgery: simplification of the procedure; decreased foreign-body reaction; reduced inflammatory response; reduced operating times and better handling in

Dura mater graft-associated Creutzfeldt-Jakob disease with 30-year incubation period.

PubMed

Shijo, Masahiro; Honda, Hiroyuki; Koyama, Sachiko; Ishitsuka, Koji; Maeda, Koichiro; Kuroda, Junya; Tanii, Mitsugu; Kitazono, Takanari; Iwaki, Toru

2017-06-01

Over 60% of all patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been diagnosed in Japan. The incubation period has ranged from 1 to 30 years and the age at onset from 15 to 80 years. Here, we report a 77-year-old male Japanese autopsied dCJD case with the longest incubation period so far in Japan. He received a cadaveric dural graft at the right cranial convexity following a craniotomy for meningioma at the age of 46. At 30 years post-dural graft placement, disorientation was observed as an initial symptom of dCJD. He rapidly began to present with inconsistent speech, cognitive impairment and tremor of the left upper extremity. Occasional myoclonic jerks were predominantly observed on the left side. Brain MRI presented hyperintense signals on diffusion-weighted and T2-weighted images, at the right cerebral cortex. The most hyperintense lesion was located at the right parietal lobe, where the dura mater graft had been transplanted. Single-photon emission CT scan showed markedly decreased cerebral blood flow at the right parietal lobe. EEG revealed diffuse and slow activities with periodic sharp-wave complex discharges seen in the right parietal, temporal and occipital lobes. He died of pneumonia 9 months after onset. Brain pathology revealed non-plaque-type dCJD. Laterality of neuropathological changes, including spongiform change, neuronal loss, gliosis or PrP deposits, was not evident. Western blot analysis showed type 1 PrP CJD . Alzheimer-type pathology and PSP-like pathology were also observed. © 2016 Japanese Society of Neuropathology.

Impact of holmium fibre laser radiation (λ = 2.1 μm) on the spinal cord dura mater and adipose tissue

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

Filatova, S A; Kamynin, V A; Ryabova, A V

The impact of holmium fibre laser radiation on the samples of biologic tissues (dura mater of spinal cord and adipose tissue with interlayers of muscle) is studied. The experimental results are evaluated by the size of carbonisation and coagulation necrosis zones. The experiment shows that in the case of irradiation of the spinal cord dura mater samples the size of carbonisation and coagulation necrosis zones is insignificant. In the adipose tissue the carbonisation zone is also insignificant, but the region of cellular structure disturbance is large. In the muscle tissue the situation is opposite. The cw laser operation provides clinicallymore » acceptable degree of destruction in tissue samples with a minimal carbonisation zone. (laser applications in medicine)« less

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.

Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

PubMed Central

Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

2013-01-01

Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival soft tissue and alveolar bone following tooth extraction. For target identification and validation, hard and soft tissue were extracted from mini-pigs at the indicated times after tooth extraction. From triplicate experiments, 56 proteins in soft tissue and 27 proteins in alveolar bone were found to be differentially expressed before and after tooth extraction. The expression of 21 of those proteins was altered in both soft tissue and bone. Comparison of the activated networks in soft tissue and alveolar bone highlighted their distinct responsibilities in bone and tissue healing. Moreover, we found that there is crosstalk between identified proteins in soft tissue and alveolar bone with respect to cellular assembly, organization, and communication. Among these proteins, we examined in detail the expression patterns and associated networks of ATP5B and fibronectin 1. ATP5B is involved in nucleic acid metabolism, small molecule biochemistry, and neurological disease, and fibronectin 1 is involved in cellular assembly, organization, and maintenance. Collectively, our findings indicate that bone regeneration is accompanied by a profound interaction among networks regulating cellular resources, and they provide novel insight into the molecular mechanisms involved in the healing of periodontal tissue after tooth extraction. PMID:23824910

Development, identification and validation of CAPS marker for SHELL trait which governs dura, pisifera and tenera fruit forms in oil palm (Elaeis guineensis Jacq.)

PubMed Central

Babu, B. Kalyana; Mathur, R. K.; Kumar, P. Naveen; Ramajayam, D.; Ravichandran, G.; Venu, M. V. B.; Babu, S. Sparjan

2017-01-01

The oil palm fruit forms (dura, pisifera and tenera) governed by the shell thickness gene (Sh) plays a major role in identification of fruit type and also influences palm oil yield. Identification of desired fruit type is a major asset to the breeders and oil palm workers for applications in breeding, seed certification and to reduce time, space and money spent on identification of fruit form. In the present study, we developed Sh gene specific primer pairs and bulk segregant analysis was done using 300 genomic and 8 genic SSR markers. We identified one cleaved amplified polymorphic site (CAPS) marker for differentiation of oil palm fruit type which produced two alleles (280 and 250bp) in dura genotypes, three alleles in tenera genotypes (550, 280, and 250bp) and one allele in pisifera genotypes (550bp). The shell allele sequencing results showed that two SNPs were present, of which SNP2 contributed for variation of fruit forms. The nucleotide ‘A’ was present in only dura genotypes, where as ‘T’ was present only in pisifera genotypes, which in turn led to the change of amino acid lysine to aspargine. The identified CAPS marker was validated on 300 dura, 25 pisifera and 80 tenera genotypes, 80 dura/ pisifera cross progenies and 60 lines of tenera/ tenera cross progeny. Association mapping of marker data with phenotypic data of eight oil yield related traits resulted in identification of seven significant QTLs by GLM approach, four by MLM approach at a significant threshold (P) level of 0.001. Significant QTLs were identified for fruit to bunch and oil to bunch traits, which explained R2 of 12.9% and 11.5% respectively. The CAPS marker used in the present study facilitate selection and timely distribution of desirable high yielding tenera sprouts to the farmers instead of waiting for 4–5 years. This saves a lot of land, time and money which will be a major breakthrough to the oil palm community. PMID:28192462

Supraorbital keyhole surgery for optic nerve decompression and dura repair.

PubMed

Chen, Yuan-Hao; Lin, Shinn-Zong; Chiang, Yung-Hsiao; Ju, Da-Tong; Liu, Ming-Ying; Chen, Guann-Juh

2004-07-01

Supraorbital keyhole surgery is a limited surgical procedure with reduced traumatic manipulation of tissue and entailing little time in the opening and closing of wounds. We utilized the approach to treat head injury patients complicated with optic nerve compression and cerebrospinal fluid leakage (CSF). Eleven cases of basal skull fracture complicated with either optic nerve compression and/or CSF leakage were surgically treated at our department from February 1995 to June 1999. Six cases had primary optic nerve compression, four had CSF leakage and one case involved both injuries. Supraorbital craniotomy was carried out using a keyhole-sized burr hole plus a small craniotomy. The size of craniotomy approximated 2 x 3 cm2. The optic nerve was decompressed via removal of the optic canal roof and anterior clinoid process with high-speed drills. The defect of dura was repaired with two pieces of tensa fascia lata that were attached on both sides of the torn dural defect with tissue glue. Seven cases with optic nerve injury included five cases of total blindness and two cases of light perception before operation. Vision improved in four cases. The CSF leakage was stopped successfully in all four cases without complication. As optic nerve compression and CSF leakage are skull base lesions, the supraorbital keyhole surgery constitutes a suitable approach. The supraorbital keyhole surgery allows for an anterior approach to the skull base. This approach also allows the treatment of both CSF leakage and optic nerve compression. Our results indicate that supraorbital keyhole operation is a safe and effective method for preserving or improving vision and attenuating CSF leakage following injury.

Epithelioid Hemangioma Involving Three Contiguous Bones: a Case Report with a Review of the Literature

PubMed Central

Jinawath, Arthit; Jaovisidha, Suphaneewan

2010-01-01

An epithelioid hemangioma involving three contiguous bones in continuity has, to the best of our knowledge, not been reported in the literature. A case of a 48-year-old man presented with radiating pain to the lower thoracic region for two years. A radiograph and CT scan revealed both permeative osteolytic and multiple trabeculated lesions involving the left posterior part of the 10th rib as well as the 9th and 10th vertebral bodies in continuity and was misled as a malignant or infectious lesion. The histopathology and immuno-histochemistry of the lesion confirmed the diagnosis of an epithelioid hemangioma. The lesion was still stable as of three years after surgery. PMID:21076597

Next-generation sequencing identifies equine cartilage and subchondral bone miRNAs and suggests their involvement in osteochondrosis physiopathology.

PubMed

Desjardin, Clémence; Vaiman, Anne; Mata, Xavier; Legendre, Rachel; Laubier, Johan; Kennedy, Sean P; Laloe, Denis; Barrey, Eric; Jacques, Claire; Cribiu, Edmond P; Schibler, Laurent

2014-09-17

MicroRNAs (miRNAs) are an abundant class of small single-stranded non-coding RNA molecules ranging from 18 to 24 nucleotides. They negatively regulate gene expression at the post-transcriptional level and play key roles in many biological processes, including skeletal development and cartilage maturation. In addition, miRNAs involvement in osteoarticular diseases has been proved and some of them were identified as suitable biomarkers for pathological conditions. Equine osteochondrosis (OC) is one of the most prevalent juvenile osteoarticular disorders in horses and represents a major concern for animal welfare and economic reasons. Its etiology and pathology remain controversial and biological pathways as well as molecular mechanisms involved in the physiopathology are still unclear. This study aims to investigate the potential role of miRNAs in equine osteochondrosis (OC) physiopathology.Short-read NGS technology (SOLID™, Life Technologies) was used to establish a comprehensive repertoire of miRNA expressed in either equine cartilage or subchondral bone. Undamaged cartilage and subchondral bone samples from healthy (healthy samples) and OC-affected (predisposed samples) 10-month Anglo-Arabian foals were analysed. Samples were also subjected or not to an experimental mechanical loading to evaluate the role of miRNAs in the regulation of mechano-transduction pathways. Predicted targets of annotated miRNAs were identified using miRmap. Epiphyseal cartilage and subchondral bone miRNome were defined, including about 300 new miRNAs. Differentially expressed miRNAs were identified between bone and cartilage from healthy and OC foals, as well as after an experimental mechanical loading. In cartilage, functional annotation of their predicted targets suggests a role in the maintenance of cartilage integrity through the control of cell cycle and differentiation, energy production and metabolism as well as extracellular matrix structure and dynamics. In bone, mi

Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

PubMed Central

Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

2015-01-01

With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. PMID:26330833

A case of extensive hyperostosis frontalis interna in an 87-year-old female human cadaver.

PubMed

Talarico, Ernest F; Prather, Andrew D; Hardt, Kevin D

2008-04-01

Hyperostosis frontalis interna (HFI) is a condition that involves thickening of the inner surface of the frontal bone with sparing of the midline. Little is known about the etiology and clinical presentation of HFI. We report unusual findings in a woman with extensive Type D hyperostosis of the frontal bone and a large hyperostotic nodule in the parietal bone with impingement on the precentral gyrus, distinguishing this from the common form of HFI. The scalp was dissected from the cranial vault, and the calvaria and brain were removed and digitally imaged. Bone specimens were embedded in methyl methacrylate plastic, sectioned, and stained using the Von Kossa Method with MacNeal's tetrachrome. Medical records were reviewed, and additional history was obtained through interviews with the donor's family. The calvaria had extensive, bilateral thickening of the frontal bone with irregular topography and clearly demarcated borders. The dura was adherent to all hyperostotic regions. A 3.5-cm nodule was visible on the inner table of the left parietal bone. The dura and cerebrum showed compression in this region, but it was unclear if this resulted in clinical ramifications. Microscopic analysis revealed a larger proportion of cancellous bone was present in regions of macroscopic hyperostosis. Quantitative analysis of sections through areas of gross hyperostosis demonstrated a lower proportion of lamellar bone than in the control. The patient exhibited symptoms that have been correlated to HFI in previous studies. We suggest that the HFI disease process was responsible for the manifestation of these symptoms in this patient. (c) 2008 Wiley-Liss, Inc.

Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

PubMed Central

Sheikh, Zeeshan; Javaid, Mohammad Ahmad; Hamdan, Nader; Hashmi, Raheel

2015-01-01

Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs). BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration. PMID:28788032

[Simultaneous existence of unicameral bone cysts involving the femur and ischium].

PubMed

Makris, Vassilios; Papavasiliou, Kyriakos A; Bobos, Mattheos; Hytiroglou, Prodromos; Kirkos, John M; Kapetanos, George A

2009-01-01

We report a 30-year-old male patient with two unicameral bone cysts (UBC) simultaneously located in the proximal third of the right femur and ipsilateral ischium ramus, respectively. Fine needle biopsies were attempted for both lesions. Biopsy of the femoral lesion under local anesthesia was unsuccessful, so an open biopsy was performed which confirmed the diagnosis of UBC. Biopsy of the ischial lesion was not sufficient for diagnosis. Cytological examination of both specimens showed no other benign or malignant pathology. The femoral lesion was treated with intralesional (due to its large size) excision-curettage, bone grafting, and the introduction of a long gamma locking intramedullary nail to prevent the occurrence of a pathological fracture. The ischial lesion was left untreated and followed conservatively. The patient was free of any symptoms and complications three years postoperatively. This is the first report of an adult patient with UBCs simultaneously located both in a long tubular bone (femur) and a flat bone (ischium ramus).

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

Prognostic value of bone marrow involvement by clonal immunoglobulin gene rearrangements in follicular lymphoma

PubMed Central

Berget, Ellen; Helgeland, Lars; Liseth, Knut; Løkeland, Turid; Molven, Anders; Vintermyr, Olav Karsten

2014-01-01

Aims We aimed to evaluate the prognostic value of routine use of PCR amplification of immunoglobulin gene rearrangements in bone marrow (BM) staging in patients with follicular lymphoma (FL). Methods Clonal rearrangements were assessed by immunoglobulin heavy and light-chain gene rearrangement analysis in BM aspirates from 96 patients diagnosed with FL and related to morphological detection of BM involvement in biopsies. In 71 patients, results were also compared with concurrent flow cytometry analysis. Results BM involvement was detected by PCR in 34.4% (33/96) of patients. The presence of clonal rearrangements by PCR was associated with advanced clinical stage (I–III vs IV; p<0.001), high FL International Prognostic Index (FLIPI) score (0–1, 2 vs ≥3; p=0.003), and detection of BM involvement by morphology and flow cytometry analysis (p<0.001 for both). PCR-positive patients had a significantly poorer survival than PCR-negative patients (p=0.001, log-rank test). Thirteen patients positive by PCR but without morphologically detectable BM involvement, had significantly poorer survival than patients with negative morphology and negative PCR result (p=0.002). The poor survival associated with BM involvement by PCR was independent of the FLIPI score (p=0.007, Cox regression). BM involvement by morphology or flow cytometry did not show a significant impact on survival. Conclusions Our results showed that routine use of PCR-based clonality analysis significantly improved the prognostic impact of BM staging in patients with FL. BM involvement by PCR was also an independent adverse prognostic factor. PMID:25233852

Clinical experience with a novel bovine collagen dura mater substitute

PubMed Central

Costa, Bruno Silva; Cavalcanti-Mendes, George de Albuquerque; de Abreu, Marcelo Sartori; de Sousa, Atos Alves

2010-01-01

Background: Dural substitutes are used to achieve a watertight closure in situations where adequate closure is not possible .This study was conducted to evaluate the efficacy and safety of use a new collagen matrix dural substitute ( Duradry, Tecnodry, Belo Horizonte MG) in repair or expansion of cranial and spinal dura-mater. Methods: 30 patients operated on between March and September 2008, were studied. Surgical logs were reviewed for sex, age, diagnosis, location of the graft, technique and presence of fistula or infection. The patients were followed-up for at least 3 months, and the presence of complications as cerebrospinal leakage, infection, aseptic meningitis, hydrocephalus, pseudomeningocele were analysed. Results: Only one patient presented with CSF fistula. No patients presented with wound infections, hydrocephalus, pseudomeningocele, meningitis, brain abscesses or signs of toxicity related to the material. Conclusions: The new dural substitute used in this study is effective and safe, and the initial results are similar to those of other dural substitutes reported in the literature. PMID:22028756

Gut microbiome and bone.

PubMed

Ibáñez, Lidia; Rouleau, Matthieu; Wakkach, Abdelilah; Blin-Wakkach, Claudine

2018-04-11

The gut microbiome is now viewed as a tissue that interacts bidirectionally with the gastrointestinal, immune, endocrine and nervous systems, affecting the cellular responses in numerous organs. Evidence is accumulating of gut microbiome involvement in a growing number of pathophysiological processes, many of which are linked to inflammatory responses. More specifically, data acquired over the last decade point to effects of the gut microbiome on bone mass regulation and on the development of bone diseases (such as osteoporosis) and of inflammatory joint diseases characterized by bone loss. Mice lacking a gut microbiome have bone mass alteration that can be reversed by gut recolonization. Changes in the gut microbiome composition have been reported in mice with estrogen-deficiency osteoporosis and have also been found in a few studies in humans. Probiotic therapy decreases bone loss in estrogen-deficient animals. The effect of the gut microbiome on bone tissue involves complex mechanisms including modulation of CD4 + T cell activation, control of osteoclastogenic cytokine production and modifications in hormone levels. This complexity may contribute to explain the discrepancies observed betwwen some studies whose results vary depending on the age, gender, genetic background and treatment duration. Further elucidation of the mechanisms involved is needed. However, the available data hold promise that gut microbiome manipulation may prove of interest in the management of bone diseases. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Evaluation of a haptics-based virtual reality temporal bone simulator for anatomy and surgery training.

PubMed

Fang, Te-Yung; Wang, Pa-Chun; Liu, Chih-Hsien; Su, Mu-Chun; Yeh, Shih-Ching

2014-02-01

Virtual reality simulation training may improve knowledge of anatomy and surgical skills. We evaluated a 3-dimensional, haptic, virtual reality temporal bone simulator for dissection training. The subjects were 7 otolaryngology residents (3 training sessions each) and 7 medical students (1 training session each). The virtual reality temporal bone simulation station included a computer with software that was linked to a force-feedback hand stylus, and the system recorded performance and collisions with vital anatomic structures. Subjects performed virtual reality dissections and completed questionnaires after the training sessions. Residents and students had favorable responses to most questions of the technology acceptance model (TAM) questionnaire. The average TAM scores were above neutral for residents and medical students in all domains, and the average TAM score for residents was significantly higher for the usefulness domain and lower for the playful domain than students. The average satisfaction questionnaire for residents showed that residents had greater overall satisfaction with cadaver temporal bone dissection training than training with the virtual reality simulator or plastic temporal bone. For medical students, the average comprehension score was significantly increased from before to after training for all anatomic structures. Medical students had significantly more collisions with the dura than residents. The residents had similar mean performance scores after the first and third training sessions for all dissection procedures. The virtual reality temporal bone simulator provided satisfactory training for otolaryngology residents and medical students. Copyright © 2013. Published by Elsevier Ireland Ltd.

Carbon nanotubes with high bone-tissue compatibility and bone-formation acceleration effects.

PubMed

Usui, Yuki; Aoki, Kaoru; Narita, Nobuyo; Murakami, Narumichi; Nakamura, Isao; Nakamura, Koichi; Ishigaki, Norio; Yamazaki, Hiroshi; Horiuchi, Hiroshi; Kato, Hiroyuki; Taruta, Seiichi; Kim, Yoong Ahm; Endo, Morinobu; Saito, Naoto

2008-02-01

Carbon nanotubes (CNTs) have been used in various fields as composites with other substances or alone to develop highly functional materials. CNTs hold great interest with respect to biomaterials, particularly those to be positioned in contact with bone such as prostheses for arthroplasty, plates or screws for fracture fixation, drug delivery systems, and scaffolding for bone regeneration. Accordingly, bone-tissue compatibility of CNTs and CNT influence on bone formation are important issues, but the effects of CNTs on bone have not been delineated. Here, it is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2). This study provides an initial investigational basis for CNTs in biomaterials that are used adjacent to bone, including uses to promote bone regeneration. These findings should encourage development of clinical treatment modalities involving CNTs.

Macroscopic Innervation of the Dura Mater Covering the Middle Cranial Fossa in Humans Correlated to Neurovascular Headache

PubMed Central

Lee, Shin-Hyo; Hwang, Seung-Jun; Koh, Ki-Seok; Song, Wu-Chul; Han, Sang-Don

2017-01-01

The trigeminovascular system within the cranial dura mater is a possible cause of headaches. The aim of this study is to investigate macroscopically dural innervation around the middle meningeal artery (MMA) in the middle cranial fossa. Forty-four sides of the cranial dura overlying the skull base obtained from 24 human cadavers were stained using Sihler’s method. Overall, the nervus spinosus (NS) from either the maxillary or mandibular trigeminal divisions ran along the lateral wall of the middle meningeal vein rather than that of the MMA. Distinct bundles of the NS running along the course of the frontal branches of the MMA were present in 81.8% of cases (N = 36). Others did not form dominant nerve bundles, instead giving off free nerve endings along the course of the MMA or dural connective tissue. The distribution of these nerve endings was similar to that of the course of the frontal, parietal and petrosal branches of the MMA (11.4%). The others were not restricted to a perivascular plexus, crossing the dural connective tissues far from the MMA (6.8%). These findings indicate that the NS generally travels alongside the course of the frontal branches of the MMA and terminates in the vicinity of the pterion. PMID:29311855

Macroscopic Innervation of the Dura Mater Covering the Middle Cranial Fossa in Humans Correlated to Neurovascular Headache.

PubMed

Lee, Shin-Hyo; Hwang, Seung-Jun; Koh, Ki-Seok; Song, Wu-Chul; Han, Sang-Don

2017-01-01

The trigeminovascular system within the cranial dura mater is a possible cause of headaches. The aim of this study is to investigate macroscopically dural innervation around the middle meningeal artery (MMA) in the middle cranial fossa. Forty-four sides of the cranial dura overlying the skull base obtained from 24 human cadavers were stained using Sihler's method. Overall, the nervus spinosus (NS) from either the maxillary or mandibular trigeminal divisions ran along the lateral wall of the middle meningeal vein rather than that of the MMA. Distinct bundles of the NS running along the course of the frontal branches of the MMA were present in 81.8% of cases ( N = 36). Others did not form dominant nerve bundles, instead giving off free nerve endings along the course of the MMA or dural connective tissue. The distribution of these nerve endings was similar to that of the course of the frontal, parietal and petrosal branches of the MMA (11.4%). The others were not restricted to a perivascular plexus, crossing the dural connective tissues far from the MMA (6.8%). These findings indicate that the NS generally travels alongside the course of the frontal branches of the MMA and terminates in the vicinity of the pterion.

Disorders of Bone Remodeling

PubMed Central

Feng, Xu; McDonald, Jay M.

2013-01-01

The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms. PMID:20936937

Bone disease in primary hyperparathyroidism

PubMed Central

Bandeira, Francisco; Cusano, Natalie E.; Silva, Barbara C.; Cassibba, Sara; Almeida, Clarissa Beatriz; Machado, Vanessa Caroline Costa; Bilezikian, John P.

2015-01-01

Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT. PMID:25166047

Clinical Comparison of Autogenous Bone Graft with and without Plasma Rich in Growth Factors in the Treatment of Grade II Furcation Involvement of Mandibular Molars

PubMed Central

Lafzi, Ardeshir; Shirmohammadi, Adileh; Faramarzi, Masoumeh; Jabali, Sahar; Shayan, Arman

2013-01-01

Background and aims Plasma rich in growth factors (PRGF) is a concentrated suspension of growth factors, which is used to promote periodontal tissue regeneration. The aim of this randomized, controlled, clinical trial was to evaluate of the treatment of grade II mandibular molar furcation involvement using autogenous bone graft with and without PRGF. Materials and methods In this double-blind clinical trial, thirty mandibular molars with grade II furcation involvement in 30 patients were selected. The test group received bone graft combined with PRGF, while the control group was treated with bone graft only. Clinical parameters included clinical probing depth (CPD), vertical clinical attachment level (V-CAL), horizontal clinical attachment level (H-CAL), location of gingival margin (LGM), surgically exposed horizontal probing depth of bony defect (E-HPD), vertical depth of bone crest (V-DBC), vertical depth of the base of bony defect (V-DBD), and length of the intrabony defect (LID). After six months, a re-entry surgery was performed. Data were analyzed by SPSS 14, using Kolmogorov, Mann-Whitney U, and paired t-test. Results After 6 months, both treatment methods led to significant improvement in V-CAL and H-CAL and significant decreases in CPD, E-HPD, V-DBD and LID; there was no significant difference in LGM and V-DBC in any of the treated groups compared to the baseline values. Also, none of the parameters showed significant differences between the study groups. Conclusion Although autogenous bone grafts, with or without PRGF, were successful in treating grade II furcation involvement, no differences between the study groups were observed. PMID:23486928

Correlations of External Landmarks With Internal Structures of the Temporal Bone.

PubMed

Piromchai, Patorn; Wijewickrema, Sudanthi; Smeds, Henrik; Kennedy, Gregor; O'Leary, Stephen

2015-09-01

The internal anatomy of a temporal bone could be inferred from external landmarks. Mastoid surgery is an important skill that ENT surgeons need to acquire. Surgeons commonly use CT scans as a guide to understanding anatomical variations before surgery. Conversely, in cases where CT scans are not available, or in the temporal bone laboratory where residents are usually not provided with CT scans, it would be beneficial if the internal anatomy of a temporal bone could be inferred from external landmarks. We explored correlations between internal anatomical variations and metrics established to quantify the position of external landmarks that are commonly exposed in the operating room, or the temporal bone laboratory, before commencement of drilling. Mathematical models were developed to predict internal anatomy based on external structures. From an operating room view, the distances between the following external landmarks were observed to have statistically significant correlations with the internal anatomy of a temporal bone: temporal line, external auditory canal, mastoid tip, occipitomastoid suture, and Henle's spine. These structures can be used to infer a low lying dura mater (p = 0.002), an anteriorly located sigmoid sinus (p = 0.006), and a more lateral course of the facial nerve (p < 0.001). In the temporal bone laboratory view, the mastoid tegmen and sigmoid sinus were also regarded as external landmarks. The distances between these two landmarks and the operating view external structures were able to further infer the laterality of the facial nerve (p < 0.001) and a sclerotic mastoid (p < 0.001). Two nonlinear models were developed that predicted the distances between the following internal structures with a high level of accuracy: the distance from the sigmoid sinus to the posterior external auditory canal (p < 0.001) and the diameter of the round window niche (p < 0.001). The prospect of encountering some of the more technically challenging anatomical

Bone cysts: unicameral and aneurysmal bone cyst.

PubMed

Mascard, E; Gomez-Brouchet, A; Lambot, K

2015-02-01

Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Polymorphisms in Genes Involved in the NF-κB Signalling Pathway Are Associated with Bone Mineral Density, Geometry and Turnover in Men

PubMed Central

Roshandel, Delnaz; Thomson, Wendy; Pye, Stephen R.; Boonen, Steven; Borghs, Herman; Vanderschueren, Dirk; Huhtaniemi, Ilpo T.; Adams, Judith E.; Ward, Kate A.; Bartfai, Gyorgy; Casanueva, Felipe F.; Finn, Joseph D.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Kula, Krzysztof; Lean, Michael E.; Pendleton, Neil; Punab, Margus; Wu, Frederick C.

2011-01-01

Introduction In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r2≥0.8) within MAP3K14 (±10 kb) were genotyped in 2359 men aged 40–79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-κB signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health. PMID:22132199

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

PubMed

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

2011-01-01

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

Melorheostosis involving the craniofacial skeleton.

PubMed

Ethunandan, Madanagopalan; Khosla, Nalin; Tilley, Elizabeth; Webb, Andrew

2004-11-01

Melorheostosis is a rare bone disorder, usually affecting the long bones and adjacent soft tissue. It was originally described by Leri and Joanny in 1922, after its classic x-ray features of flowing hyperostosis resembling dripping candle wax. There have been fewer than 10 reported cases of craniofacial involvement, and in most instances these have also involved the appendicular skeleton. The authors report a case of melorheostosis with isolated craniofacial involvement, describe the clinical course and radiologic and histologic features, and review the pertinent literature.

Clinical characteristics of patients with bone sarcoidosis.

PubMed

Zhou, Ying; Lower, Elyse E; Li, Huiping; Farhey, Yolanda; Baughman, Robert P

2017-08-01

To assess the clinical features, diagnosis, and treatment of bone sarcoidosis in the United States. Patients with bone sarcoidosis were identified and matched to sarcoidosis patients based on race, gender, and age. Detailed characteristics were obtained by medical record review. A total of 64 patients with bone sarcoidosis were enrolled in this study. The female:male ratio was 1.46:1 and the white:black ratio was 3:1. Thirty-eight (59.4%) of 64 patients had bone symptoms. Compared to matched cases, bone sarcoidosis patients have more multi-organ involvement and higher incidence with liver, spleen, and extrathoracic lymph node involvement than controls (P < 0.05). Spine was the most commonly affected bone in 44 (68.8%) of patients, followed by pelvis (35.9%), and hands (15.6%). MRI and PET/CT scan was the common imaging technology, which performed in 36 patients and 32 patients, respectively, and with 97.2% and 93.8% positive bone uptake. Laboratory test indicated anemia was more common in bone sarcoidosis group than controls (P = 0.044). Infliximab was more commonly used in bone sarcoidosis patients than controls (P = 0.009). Bone sarcoidosis was associated with multi-organs affection, and high frequency of liver, spleen, or extrathoracic lymph node involvement. Infliximab should be considered in those patients with aggressive and refractory bone sarcoidosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Medieval times' influencing figure Rhaze's approach to head injuries in Liber Almansoris.

PubMed

Acıduman, Ahmet; Aşkit, Cağatay; Belen, Deniz

2014-12-01

To present the chapter "On wound of the head and fracture of the head bone" of Kitāb al-Manṣūrī / Liber Almansoris, which was one of the early works of Rhazes. Both Arabic (Süleymaniye Manuscript Library, Ayasofya collection, Nr. 3751 and Millet Library, Feyzullah Efendi collection, Nr. 1327) and the Latin (Basileae, 1544) texts of Kitāb al-Manṣūrī / Liber Almansoris were studied, and the 26th section of the 7th chapter, entitled "Fī al-shajja kasr al-'aẓm al-ra's / De plagis capitis et fractura cranei / On wound of the head and fracture of the head bone" was translated into English and English text created. Rhazes underlined removing bone fragments in depressed and separated fractures of cranium along with protection of the dura, but he did not describe any surgical technique in this chapter. Galen's contemplation for the care of the dura with its integrity and as well his proposal to remove the bone fragments for preventing the dura from injury were the golden standards at the time that Rhazes also followed in the treatment of skull fractures. Copyright © 2014 Elsevier Inc. All rights reserved.

Radioisotope bone scanning in a case of sarcoidosis

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

Cinti, D.C.; Hawkins, H.B.; Slavin, J.D. Jr.

1985-03-01

The application of radioisotope scanning to osseous involvement from systemic sarcoidosis has been infrequently described in the scientific literature. Most commonly, the small bones of the hands and feet are affected if sarcoidosis involves the skeleton. Nonetheless, there are also occasional manifestations of sarcoid in the skull, long bones, and vertebral bodies. This paper describes a case of sarcoid involving the lung parenchyma with multiple lesions in the skull and ribs demonstrated by bone scanning with Tc-99m MDP. Following treatment with steroids, the bone scan showed complete resolution of the rib lesions and almost complete resolution of the lesions inmore » the calvarium.« less

FDG PET/CT in bone sarcoidosis.

PubMed

Grozdic Milojevic, Isidora; Sobic-Saranovic, Dragana; Videnovic-Ivanov, Jelica; Saranovic, Djordjije; Odalovic, Strahinja; Artiko, Vera

2016-03-29

Bone sarcoidosis is rare manifestation of disease usually accompanied with pulmonary involvement. Until today, exact prevalence of bone sarcoidosis is not known, since reported prevalence varies widely depending on the studied population and the used diagnostic techniques. To determine the prevalence of bone involvement and distribution pattern in active chronic sarcoidosis by using FDG PET/CT. Between January 2010 and December 2011, 98 patients with chronic sarcoidosis and presence of prolonged symptoms or other findings suggestive of active disease were referred to FDG PET/CT examination. Active disease was found in 82 patients, and they all were screened for presence of bone sarcoidosis on FDG PET/CT. All patients also underwent MDCT and assessment of serum ACE level. Bone sarcoidosis was present in 18/82 patients with active sarcoidosis. FDG uptake in bones was focal in 8 (44.4%), diffuse in 6 (33.3%) and both diffuse and focal in 4 (22.2%) patients. CT indicated bone abnormalities only in 5% patients. Osseous involvement was present in: pelvis (61.1%), vertebrae (44.4%), ribs (27.8%) and bone marrow (16.7%). Some patients had two or more locations of disease. Follow-up FDG PET/CT showed normal findings in two patients, same localization of active disease in four patients and progression of disease in one. In patients with active chronic sarcoidosis 22% of patients had osseous abnormalities on FDG PET/CT that mostly were not detected on CT.

[The biological role of exosomes in bone remodeling and bone diseases.

PubMed

Urabe, Fumihiko; Yoshioka, Yusuke; Ochiya, Takahiro

Exosomes are about 100nm membrane vesicles, and released from almost all cell types. They carry and transfer a wide variety of molecules, such as mRNAs, microRNAs, proteins, and lipids, as modulators of intercellular communication. Various studies have shown that this exosome-mediated intercellular communication lead to proliferation, invasion and metastasis of cancer cells. In addition to that, emerging data suggest that exosomes are also involved in physiological processes of bone remodeling and bone diseases. Increasing understanding of the working mechanism of exosomes will provide us with new therapeutic and diagnostic opportunities. Here we summarize the current research on exosomes in bone remodeling and bone diseases.

Paget disease of the bone

MedlinePlus

... ency/article/000414.htm Paget disease of the bone To use the sharing features on this page, ... Paget disease is a disorder that involves abnormal bone destruction and regrowth. This results in deformity of ...

Otosclerosis: Temporal Bone Pathology.

PubMed

Quesnel, Alicia M; Ishai, Reuven; McKenna, Michael J

2018-04-01

Otosclerosis is pathologically characterized by abnormal bony remodeling, which includes bone resorption, new bone deposition, and vascular proliferation in the temporal bone. Sensorineural hearing loss in otosclerosis is associated with extension of otosclerosis to the cochlear endosteum and deposition of collagen throughout the spiral ligament. Persistent or recurrent conductive hearing loss after stapedectomy has been associated with incomplete footplate fenestration, poor incus-prosthesis connection, and incus resorption in temporal bone specimens. Human temporal bone pathology has helped to define the role of computed tomography imaging for otosclerosis, confirming that computed tomography is highly sensitive for diagnosis, yet limited in assessing cochlear endosteal involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

Involvement of skeletal renin-angiotensin system and kallikrein-kinin system in bone deteriorations of type 1 diabetic mice with estrogen deficiency.

PubMed

Zhang, Yan; Wang, Liang; Liu, Jin-Xin; Wang, Xin-Luan; Shi, Qi; Wang, Yong-Jun

This study was aimed to investigate the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) in bone deteriorations of mice in response to the combination treatment of estrogen deficiency and hyperglycemia. The female C57BL/6J mice were sham-operated or ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later, the biochemistries in serum and urine were determined by standard colorimetric methods or ELISA. The H&E and TRAP staining were performed at the tibial proximal metaphysis. The polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. The mice after treating with ovariectomy and STZ showed the decreased level of serum Ca and the increased level of serum PTH and urine Ca. The H&E staining showed trabecular bone abnormalities as demonstrated by the loss, disconnection and separation of trabecular bone network as well as the loss of chondrocytes and appearance of chondrocyte cluster at growth plate of tibia. The significant increase of matured osteoclast number was shown in group with double treatments. The combination treatment significantly up-regulated mRNA expression of AGT, ACE, renin receptor, MMP-9 and CAII, and protein expression of renin, and decreased the ratio of OPG/RANKL and the expression of bradykinin receptors in bone tissue. Ovariectomy combined with STZ induction produced more detrimental actions on bone through the activation of local bone RAS and the down-regulation of bradykinin receptors, as compared to the respective single treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular cloning and chromosomal mapping of bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth

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

Ishikawa, Jun; Kaisho, Tsuneyasu; Tomizawa, Hitoshi

1995-04-10

Bone marrow stromal cells regulate B-cell growth and development through their surface molecules and cytokines. In this study, we generated a mAb, RS38, that recognized a novel human membrane protein, BST-2, expressed on bone marrow stromal cell lines and synovial cell lines. We cloned a cDNA encoding BST-2 from a rheumatoid arthritis-derived synovial cell line. BST-2 is a 30- to 36-kDa type II transmembrane protein, consisting of 180 amino acids. The BST-2 gene (HGMW-approved symbol BST2) is located on chromosome 19p13.2. BST-2 is expressed not only on certain bone marrow stromal cell lines but also on various normal tissues, althoughmore » its expression pattern is different from that of another bone marrow stromal cell surface molecule, BST-1. BST-2 surface expression on fibroblast cell lines facilitated the stromal cell-dependent growth of a murine bone marrow-derived pre-B-cell line, DW34. The results suggest that BST-2 may be involved in pre-B-cell growth. 45 refs., 7 figs., 2 tabs.« less

Is Serum Serotonin Involved in the Bone Loss of Young Females with Anorexia Nervosa?

PubMed

Maïmoun, L; Guillaume, S; Lefebvre, P; Philibert, P; Bertet, H; Picot, M-C; Courtet, P; Mariano-Goulart, D; Renard, E; Sultan, C

2016-03-01

Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies. © Georg Thieme Verlag KG Stuttgart · New York.

Vertebral sarcoidosis: demonstration of bone involvement by computerized axial tomography

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

Dinerstein, S.L.; Kovarsky, J.

1984-08-01

A report is given of a rare case of vertebral sarcoidosis with negative conventional spinal x-ray films, yet with typical cystic lesions of the spine found incidentally during abdominal computerized axial tomography (CAT). The patient was a 28-year-old black man, who was admitted for evaluation of a 1 1/2-year history of diffuse myalgias, intermittent fever to 102 F orally, bilateral hilar adenopathy, and leukopenia. A technetium polyphosphate bone scan revealed diffuse areas of increased uptake over the sternum, entire vertebral column, and pelvis. Conventional x-ray films of the cervical, thoracic, and lumbar spine, and an AP view of the pelvismore » were all normal. Chest x-ray film revealed only bilateral hilar adenopathy. During the course of an extensive negative evaluation for infection, an abdominal CAT scan was done, showing multiple, small, sclerotic-rimmed cysts at multiple levels of the lower thoracic and lumbar spine. Bone marrow biopsy revealed only changes consistent with anemia of chronic disease. Mediastinal lymph node biopsy revealed noncaseating granulomas. A tentative diagnosis of sarcoidosis was made, and treatment with prednisone, isoniazid and rifampin was begun. Within two weeks of initiation of prednisone therapy, the patient was symptom-free. A repeat technetium polyphosphate bone scan revealed only a small residual area of mildly increased uptake over the upper thoracic vertebrae.« less

Bone nutrients for vegetarians.

PubMed

Mangels, Ann Reed

2014-07-01

The process of bone mineralization and resorption is complex and is affected by numerous factors, including dietary constituents. Although some dietary factors involved in bone health, such as calcium and vitamin D, are typically associated with dairy products, plant-based sources of these nutrients also supply other key nutrients involved in bone maintenance. Some research suggests that vegetarian diets, especially vegan diets, are associated with lower bone mineral density (BMD), but this does not appear to be clinically significant. Vegan diets are not associated with an increased fracture risk if calcium intake is adequate. Dietary factors in plant-based diets that support the development and maintenance of bone mass include calcium, vitamin D, protein, potassium, and soy isoflavones. Other factors present in plant-based diets such as oxalic acid and phytic acid can potentially interfere with absorption and retention of calcium and thereby have a negative effect on BMD. Impaired vitamin B-12 status also negatively affects BMD. The role of protein in calcium balance is multifaceted. Overall, calcium and protein intakes in accord with Dietary Reference Intakes are recommended for vegetarians, including vegans. Fortified foods are often helpful in meeting recommendations for calcium and vitamin D. Plant-based diets can provide adequate amounts of key nutrients for bone health. © 2014 American Society for Nutrition.

Bone scintigraphy in children with cat scratch disease.

PubMed

Donoso, Gilda; Paulsen, Cesar; Riquelme, Paulina; Lobo, Gabriel; Gutierrez, Daniela; Perez, Andrés; Jiménez, César

2013-12-01

The objective of this study was to evaluate the degree and incidence of bone involvement in patients with cat scratch disease. Patients admitted between 2004 and 2011 at the pediatric department for cat scratch disease and a positive serology for Bartonella henselae were identified. Only those having undergone a bone scintigraphy (BS) were included in this retrospective study. Sixteen girls and 8 boys with a mean age of 7 years were studied. Bone scintigraphy was positive in 6 (25%), but only 2 had bone pain. Axial involvement was present in all 6 patients, and appendicular lesions in 3 of them. Three patients had a BS control, with improvement or normalization after treatment with antibiotics. Bone involvement occurs infrequently in patients with cat scratch disease and is not always associated with specific signs. Cat scratch disease must be suspected in patients with fever of unknown origin presenting multifocal lesions on BS.

A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome presenting with hypertrophic pachymeningitis.

PubMed

Shiraishi, Wataru; Hayashi, Shintaro; Iwanaga, Yasutaka; Murai, Hiroyuki; Yamamoto, Akifumi; Kira, Jun-ichi

2015-02-15

A 43-year-old woman with a 3-year history of headache, fever, and swelling of the forehead, presented to our hospital. A general examination revealed palmar and plantar pustules. Blood analyses showed an elevated white blood cell count, C-reactive protein level, and erythrocyte sedimentation rate. Brain MRI revealed a partially thickened cranial bone with gadolinium enhancement, and also abnormally enhanced dura mater. Bone scintigraphy showed involvement of the cranial bone and bilateral sternoclavicular joints. Palmar skin biopsy indicated palmoplantar pustulosis. From these results, SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome with associated hypertrophic pachymeningitis was diagnosed. After corticosteroid therapy and tonsillectomy, the clinical symptoms and radiological abnormalities were improved. Clinicians should be aware of SAPHO as a potential unusual cause of hypertrophic pachymeningitis. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

Jeney, Viktória

2017-01-01

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

Microarray analysis of gene expression after electrical stimulation of the dura mater surrounding the superior sagittal sinus in conscious adult rats.

PubMed

Jiang, Lei; Dong, Zhao; Li, Fengpeng; Liu, Ruozhuo; Qiu, Enchao; Wang, Xiaolin; Yu, Shengyuan

2014-01-01

The molecular and cellular origins of migraine headache are among the most complex problems in contemporary neurology. Up to now the pathogenesis of migraine still remains unclearly defined. The objective of this study was to explore new factors that may be related to the mechanism of migraine. The present study performed a comprehensive analysis of gene expression in the trigeminal nucleus caudalis induced by electrical stimulation of dura mater surrounding the superior sagittal sinus in conscious rats using microarray analysis followed by quantitative real-time reverse-transcribed polymerase chain reaction (qRT-PCR) verification. Student's two sample t-test was employed when two groups were compared. A P value <0.05 was considered to be statistically significant. Comparing the placebo and the electrical stimulation groups, 40 genes were determined to be significantly differentially expressed. These significantly differentially expressed genes were involved in many pathways, including transporter activity, tryptophan metabolism, G protein signaling, kinase activity, actin binding, signal transducer activity, anion transport, protein folding, enzyme inhibitor activity, coenzyme metabolism, binding, ion transport, cell adhesion, metal ion transport, oxidoreductase activity, mitochondrion function, and others. Most of the genes were involved in more than 2 pathways. Of particular interest is the up-regulation of Phactr3 and Akap5 and the down-regulation of Kdr. These findings may provide important clues for a better understanding of the molecular mechanism of migraine.

The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

PubMed

Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

2013-03-01

Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

The Value of PET/CT in Detecting Bone Marrow Involvement in Patients With Follicular Lymphoma.

PubMed

Perry, Chava; Lerman, Hedva; Joffe, Erel; Sarid, Nadav; Amit, Odelia; Avivi, Irit; Kesler, Mikhail; Ben-Ezra, Jonathan; Even-Sapir, Einat; Herishanu, Yair

2016-03-01

Follicular lymphoma (FL) is the 2nd most common type of lymphoma diagnosed in the Western World. Bone marrow (BM) involvement is an adverse prognostic factor in FL, routinely assessed by an arbitrary biopsy of the iliac crest. This study was aimed to investigate the role of positron emission tomography/computed tomography (PET/CT) in identifying BM involvement by FL. In this retrospective, single-center study we reviewed the records of consecutive patients with FL at diagnosis or relapse who underwent staging/restaging workup visual assessment of BM uptake was categorized as either normal, diffusely increased, or focally increased. Quantitative BM fluorine-18-fluro-deoxyglucose (FDG) uptake was measured using mean standardized uptake value (BM-SUVmean). The diagnosis of BM involvement was based on either BM histological findings or disappearance of increased uptake at end-treatment PET/CT in patients who responded to treatment. Sixty eight cases with FL were included. Sixteen (23.5%) had BM involvement, 13 (19.1%) had a biopsy proven involvement, and 3 (4.4%) had a negative BM biopsy, but increased medullary uptake that normalized post-treatment. BM FDG uptake in these patients was diffuse in 8 (50%) and focal in 8 (50%). Focal increased uptake was indicative of BM involvement; however, diffuse uptake was associated with 17 false positive cases (32.7%). Overall, visual assessment of BM involvement had a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 48.5%. On a quantitative assessment, BM-SUVmean was significantly higher in patients with BM involvement (SUVmean of 3.7 [1.7-6] vs 1.4 [0.4-2.65], P < 0.001). On receiver operator curve (ROC) analysis, BM-SUVmean > 2.7 had a PPV of 100% for BM involvement (sensitivity of 68%), while BM-SUVmean < 1.7 had an NPV of 100% (specificity of 73%). Visual assessment of PET/CT is appropriate for ruling out BM involvement by FL. Although focal increased uptake indicates marrow

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

PubMed

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

2015-04-11

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

MiRNAs in bone diseases.

PubMed

Moore, Benjamin T; Xiao, Peng

2013-01-01

MicroRNAs (miRNAs), which mainly inhibit protein expression by targeting the 3'UTR (untranslated region) of mRNAs, are known to play various roles in the pathogenesis of many different types of diseases. Specifically, in bone diseases, recent emphasis has been placed on the involvement of miRNAs in the differentiation and proliferation of bone and cartilage cells, particularly with regards to how these mechanisms contribute to bone homeostasis. In this review, we summarize miRNAs that are important in the differentiation and proliferation of bone cells, and specific miRNAs associated with bone diseases, such as osteoporosis, osteoarthritis and rheumatoid arthritis. This review also provides the perspective that miRNA studies will identify not only new mechanisms in basic bone research, but also potential novel diagnostic biomarkers and drug targets for bone diseases.

3D-Printing Composite Polycaprolactone-Decellularized Bone Matrix Scaffolds for Bone Tissue Engineering Applications.

PubMed

Rindone, Alexandra N; Nyberg, Ethan; Grayson, Warren L

2017-05-11

Millions of patients worldwide require bone grafts for treatment of large, critically sized bone defects from conditions such as trauma, cancer, and congenital defects. Tissue engineered (TE) bone grafts have the potential to provide a more effective treatment than current bone grafts since they would restore fully functional bone tissue in large defects. Most bone TE approaches involve a combination of stem cells with porous, biodegradable scaffolds that provide mechanical support and degrade gradually as bone tissue is regenerated by stem cells. 3D-printing is a key technique in bone TE that can be used to fabricate functionalized scaffolds with patient-specific geometry. Using 3D-printing, composite polycaprolactone (PCL) and decellularized bone matrix (DCB) scaffolds can be produced to have the desired mechanical properties, geometry, and osteoinductivity needed for a TE bone graft. This book chapter will describe the protocols for fabricating and characterizing 3D-printed PCL:DCB scaffolds. Moreover, procedures for culturing adipose-derived stem cells (ASCs) in these scaffolds in vitro will be described to demonstrate the osteoinductivity of the scaffolds.

[Electron microscopy of the lesions produced in the human dura mater by Quincke beveled and Whitacre needles].

PubMed

Reina, M A; López-García, A; de Andrés-Ibáñez, J A; Dittmann, M; Cascales, M R; del Caño, M C; Daneri, J; Zambrano, O

1997-02-01

Comparisons of Quincke needles and non traumatic "pencil point" needles in recent years have reported lower rates of post dural puncture headache using the later type. Our new understanding of the morphology of the human dura mater motivated us to study dural lesions caused by the Whitacre 25 G and Quincke 26 G needles, using scanning electron microscopy with the aim of determining whether there is an anatomic basis for the different outcomes. The dura mater from three fresh cadavers of individuals aged 65, 70 and 72 years were punctured 40 times at an angle of 90 degrees each time. The Whitacre 25 G needle was used for 20 punctures and the Quincke 26 G needle was used for the other 20. Half the punctures were performed with the bevel in the parallel alignment and the other half with the bevel perpendicular to the spinal column. Fifteen min after causing the punctures, specimens were fixed in solutions of glutaraldehyde phosphate buffer and dehydrated in acetone. After critical point removal of the acetone, after the specimens were treated with carbon and metallized with gold. The lesions were examined externally and internally and expressed as the ratio of area of lesion to diameter of the needle that had caused them. Whitacre needle: each lesion consisted in the superimposition of multiple damaged layers that started to close individually. After 15 min the outermost layers were 90% closed and the innermost ones had closed entirely. Layers in the arachnoid surface of the dura mater had closed from 86 to 88%, while deeper layers in the thick part had closed 97 to 98%. Quincke needle: lesions were V-shaped or half-moon shaped, much like the opening formed by a can opener, on both the external and internal surfaces. Alignment of the bevel of the needle parallel to the spinal column did not lead to a different shape of puncture. After 15 min the lesions had closed 94 to 95% on the epidural surface and 95 to 96% on the arachnoid side, a difference attributable to the

Management of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow.

PubMed

Datta, N K; Das, K P; Alam, M S; Kaiser, M S

2014-07-01

Unicameral bone cyst is a common benign bone tumor and most frequent cause of the pathological fracture in children. We have started a prospective study for that treatment of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow in the department of Orthopaedics, Bangabandhu Sheikh Mujib Medical University (BSMMU) during May 1999 to April 2012. Aim of this study was to see Freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow a satisfactory graft material in the treatment of unicameral bone cyst as well as factors such as patients age, sex, cyst size and site of lesion influence on cyst healing. A total 35 patients of unicameral bone cyst were operated. In this study out of 35 patients, male were 22(62.86%) and female were 13(37.14). Male Female ratio 22:13(1.70:1) Age of the patients ranging from 2 years 6 month to 20 years, mean age 12.18 years more common 11 years to 20 years 29(82.86%) patients. Common bones sites involvements are proximal end of Humerus 20(57.14%), proximal end of Femur 7(20 %), proximal end of Tibia 3(8.57%), Calcanium 2(5.71%), proximal end of Ulna 1(2.86%), shaft of Radius 1(2.86%) and Phalanx 1(2.86%). Final clinical outcome of unicameral bone cyst treated by thorough curettage of cavity and tightly filled with freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow in which healed (success rate) 88.57% (31) and recurrence rate is 11.43% (4). P value is <0.001. Follow up period was 6 month to 11 years. From our study it was realized that freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow is useful graft material for healing of the lesional area as well as restoring structural integrity for the treatment of unicameral bone cyst.

Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation

PubMed Central

McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

2015-01-01

ABSTRACT Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. PMID:26157160

Physiological Challenges of Bone Repair

DTIC Science & Technology

2012-12-01

expression, in general, followed the same pattern in both groups, but significantly, lower levels of mRNA for Indian Hedgehog (ihh) and BMP-2 were detected in...the fracture calluses of the older rats. Indian Hedgehog is thought to be involved in chondrogenesis and bone repair, whereas BMP-2 stimulates bone

A Particle Model for Prediction of Cement Infiltration of Cancellous Bone in Osteoporotic Bone Augmentation.

PubMed

Basafa, Ehsan; Murphy, Ryan J; Kutzer, Michael D; Otake, Yoshito; Armand, Mehran

2013-01-01

Femoroplasty is a potential preventive treatment for osteoporotic hip fractures. It involves augmenting mechanical properties of the femur by injecting Polymethylmethacrylate (PMMA) bone cement. To reduce the risks involved and maximize the outcome, however, the procedure needs to be carefully planned and executed. An important part of the planning system is predicting infiltration of cement into the porous medium of cancellous bone. We used the method of Smoothed Particle Hydrodynamics (SPH) to model the flow of PMMA inside porous media. We modified the standard formulation of SPH to incorporate the extreme viscosities associated with bone cement. Darcy creeping flow of fluids through isotropic porous media was simulated and the results were compared with those reported in the literature. Further validation involved injecting PMMA cement inside porous foam blocks - osteoporotic cancellous bone surrogates - and simulating the injections using our proposed SPH model. Millimeter accuracy was obtained in comparing the simulated and actual cement shapes. Also, strong correlations were found between the simulated and the experimental data of spreading distance (R(2) = 0.86) and normalized pressure (R(2) = 0.90). Results suggest that the proposed model is suitable for use in an osteoporotic femoral augmentation planning framework.

Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate

PubMed Central

Pederson, Larry; Ruan, Ming; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

2008-01-01

Under most conditions, resorbed bone is nearly precisely replaced in location and amount by new bone. Thus, it has long been recognized that bone loss through osteoclast-mediated bone resorption and bone replacement through osteoblast-mediated bone formation are tightly coupled processes. Abundant data conclusively demonstrate that osteoblasts direct osteoclast differentiation. Key questions remain, however, as to how osteoblasts are recruited to the resorption site and how the amount of bone produced is so precisely controlled. We hypothesized that osteoclasts play a crucial role in the promotion of bone formation. We found that osteoclast conditioned medium stimulates human mesenchymal stem (hMS) cell migration and differentiation toward the osteoblast lineage as measured by mineralized nodule formation in vitro. We identified candidate osteoclast-derived coupling factors using the Affymetrix microarray. We observed significant induction of sphingosine kinase 1 (SPHK1), which catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (S1P), in mature multinucleated osteoclasts as compared with preosteoclasts. S1P induces osteoblast precursor recruitment and promotes mature cell survival. Wnt10b and BMP6 also were significantly increased in mature osteoclasts, whereas sclerostin levels decreased during differentiation. Stimulation of hMS cell nodule formation by osteoclast conditioned media was attenuated by the Wnt antagonist Dkk1, a BMP6-neutralizing antibody, and by a S1P antagonist. BMP6 antibodies and the S1P antagonist, but not Dkk1, reduced osteoclast conditioned media-induced hMS chemokinesis. In summary, our findings indicate that osteoclasts may recruit osteoprogenitors to the site of bone remodeling through SIP and BMP6 and stimulate bone formation through increased activation of Wnt/BMP pathways. PMID:19075223

Micro-CT evaluation of bone defects: applications to osteolytic bone metastases, bone cysts, and fracture.

PubMed

Buie, Helen R; Bosma, Nick A; Downey, Charlene M; Jirik, Frank R; Boyd, Steven K

2013-11-01

Bone defects can occur in various forms and present challenges to performing a standard micro-CT evaluation of bone quality because most measures are suited to homogeneous structures rather than ones with spatially focal abnormalities. Such defects are commonly associated with pain and fragility. Research involving bone defects requires quantitative approaches to be developed if micro-CT is to be employed. In this study, we demonstrate that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia of two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases. In these models, the cortical and trabecular bone compartments were both affected by the defect and were, therefore, evaluated as a single unit to avoid splitting the defects into multiple analysis regions. The burr-hole defect increased mean spacing (Sp) by 27.6%, spacing standard deviation (SpSD) by 113%, and maximum spacing (Spmax) by 72.8%. Regression modeling revealed SpSD (β=0.974, p<0.0001) to be a significant predictor of the defect volume (R(2)=0.949) and Spmax (β=0.712, p<0.0001) and SpSD (β=0.271, p=0.022) to be significant predictors of the defect diameter (R(2)=0.954). In the mice with osteolytic bone metastases, spacing parameters followed similar patterns of change as reflected by other imaging technologies, specifically bioluminescence data which is indicative of tumor burden. These data highlight the sensitivity of spacing measurements to bone architectural abnormalities from 3D micro-CT data and provide a tool for quantitative evaluation of defects within a bone. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Bone scanning in lymphoma. [/sup 99m/Tc tracer technique

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

Schechter, J.P.; Jones, S.E.; Woolfenden, J.M.

1976-09-01

The results of bone scanning with the newer technetium-99m complexes were correlated with clinical, laboratory, and radiographic findings in 26 patients with malignant lymphoma (10 with Hodgkin's disease and 16 with non-Hodgkin's lymphomas). Abnormalities on bone scan compatible with lymphomatous involvement of the skeleton appeared to occur more commonly in patients with diffuse lymphomas than in patients with nodular lymphomas and were generally observed in the setting of advanced disease (15 of 23 patients). Twenty-seven (73 percent) of the 37 scans obtained were abnormal. Although abnormal scans were observed with the greatest frequency in patients with bone pain (11 ofmore » 11), bone marrow involvement (11 of 12), abnormal skeletal radiographs (11 of 11), and elevated serum alkaline phosphatase levels (5 of 6), bone scanning also detected lymphomatous involvement in patients free of pain or with normal laboratory tests. Moreover, conventional radiography was entirely normal in six (35 percent) of 17 patients with abnormal scans and revealed only nonspecific osteopenia in another two patients (12 percent). Serial bone scans in nine patients reflected their response to chemotherapy. Of the 37 scans, only one was judged falsely positive and one falsely negative. Bone scanning with /sup 99m/Tc complexes is a safe, simple, and sensitive screening procedure for detecting both extensive and focal lymphomatous involvement of the skeletal system and is a useful means of following such involvement in response to treatment.« less

Hypoxia induced E-cadherin involving regulators of Hippo pathway due to HIF-1α stabilization/nuclear translocation in bone metastasis from breast carcinoma

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

Maroni, Paola; Matteucci, Emanuela; Drago, Lorenzo

The present study deals with the molecular mechanisms involved in the regulation of E-cadherin expression under hypoxia, because the adjustment of the amount of E-cadherin due to physical stimuli of the microenvironment might influence the colonization of metastasis to skeleton. We analyzed the effect of 1% oxygen tension, that is similar to that encountered in the bone marrow by metastatic cells spreading from breast carcinoma. The purpose was to evaluate the hypoxia-orchestrated control of E-cadherin transactivation via hypoxia inducible factor-1 (HIF-1) and peroxisome proliferator activated receptor-γ (PPARγ), and the involvement of Hippo pathway members, as regulators of transcription factors. Tomore » give a translational significance to the study, we took into consideration human pair-matched ductal breast carcinoma and bone metastasis: E-cadherin and Wwox were expressed in bone metastasis but not in breast carcinoma, while HIF-1α and TAZ seemed localized principally in nuclei of metastasis and were found in all cell compartments of breast carcinoma. A close examination of the regulatory mechanisms underlying E-cadherin expression in bone metastasis was done in 1833 clone derived from MDA-MB231 cells. Hypoxia induced E-cadherin only in 1833 clone, but not in parental cells, through HIF-1 and PPARγ activities, while Wwox decreased. Since Wwox was highly expressed in bone metastasis, the effect of ectopic Wwox was evaluated, and we showed E-cadherin transactivation and enhanced invasiveness in WWOX transfected 1833 cells. Also, hypoxia was additive with ectopic Wwox remarkably enhancing HIF-1α nuclear shuttle and accumulation due to the lengthening of the half-life of HIF-1α protein; under this experimental condition HIF-1α appeared as a slower migrated band compared with control, in agreement with the phosphorylation state. The in vitro data strongly supported the almost exclusive presence of HIF-1α in nuclei of human-bone metastasis. Thus, we

Osseous and meningeal involvement in secondary syphilis.

PubMed

Egan, Kendall M; Walters, Michelle C

2012-04-15

Osseous involvement, although typically described in congenital or tertiary syphilis, has rarely been reported in secondary syphilis. Spirochetes are transported to the medullary cavity or within the deep periosteal vasculature via hematological spread and may be seen in biopsies of the osseous lesions. The skull, shoulder girdle, and long bones are most commonly affected. Patients present with bone pain, which may manifest as headaches or shin splits, depending on the affected bone. This case illustrates the importance of including secondary syphilis in the differential diagnosis of a cutaneous eruption accompanied with headaches. Although the CT scan and CSF testing were negative, the MRI showed osseous and meningeal involvement.

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.

Computed tomographic features of apical infection of equine maxillary cheek teeth: a retrospective study of 49 horses.

PubMed

Bühler, M; Fürst, A; Lewis, F I; Kummer, M; Ohlerth, S

2014-07-01

Computed tomographic (CT) studies evaluating the relevance of individual CT features of apical infection in maxillary cheek teeth are lacking. To study the prevalence and relationship of single CT features in horses with and without clinical evidence of apical infection in maxillary cheek teeth. Retrospective case-control study. Multislice CT scans of the head of 49 horses were evaluated retrospectively. Changes of the infundibulum, pulp, root, lamina dura, periodontal space and alveolar bone in maxillary cheek teeth were recorded. Single CT changes were much more prevalent in the 28 horses with clinical signs. However, infundibular changes and a nondetectable lamina dura were also common in the 21 horses without clinical evidence of apical infection. Computed tomographic abnormalities of the pulp, root, periapical bone and periodontal space and the presence of a tooth fracture were significantly related. Infundibular changes were not associated with other CT signs of apical infection. Although nondetectable lamina dura was the most frequent CT change in all teeth in both studied groups, it was most commonly a solitary feature in otherwise normal teeth. Apical infections, defined as ≥3 CT changes, occurred mainly in the 108/208, 109/209 and 110/210 (Triadan numbers) and were found only in horses with clinical evidence of apical infection, except in one horse without clinical signs that had one affected root. Combined CT changes of the pulp, root, lamina dura, periapical bone and periodontal space and the presence of a tooth fracture appear to be reliable features to diagnose apical infection in maxillary cheek teeth. As a solitary feature, a nondetectable lamina dura should be interpreted cautiously and may even be considered normal due to its minor thickness and/or too low resolution of the imaging modality. © 2013 EVJ Ltd.

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

PubMed

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

2017-06-01

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

High-dose bone morphogenetic protein-induced ectopic abdomen bone growth.

PubMed

Deutsch, Harel

2010-02-01

Infuse [bone morphogenetic protein (BMP)] is increasingly used in spinal fusion surgery. The authors report a rare complication of BMP use. This is a case report. A 55-year-old male underwent a thoracic T8 to the pelvis fusion for degenerative lumbar disc disease and pseudarthrosis at another institution. The procedure involved an anterior and posterior approach with the use of multiple units of BMP. The patient presented to our institution with complaints of weight loss, pain, tenderness, and increasing solid growth in the left lower quadrant several months after his surgery. A computed tomography revealed ectopic bone growth in the retroperitoneal area and pelvis contiguous to the anterior lumbar exposure. The anterior wound was re-explored, and a large sheet of ectopic bone was removed from the retroperitoneal space. We report a rare case of extraspinal ectopic bone growth because of the use of multiple packages of BMP. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Bone marrow involvement is not associated with the clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma.

PubMed

Gong, Eun Jeong; Ahn, Ji Yong; Jung, Hwoon-Yong; Jung, Kyoungwon; Cho, Charles J; Na, Hee Kyong; Jung, Kee Wook; Kim, Do Hoon; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho; Yoon, Dok Hyun

2016-08-01

Objective Bone marrow (BM) examination is recommended as part of the initial staging work-up in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the clinical significance of BM involvement in gastric MALT lymphoma patients has not been evaluated. Materials and methods From November 1995 to September 2014, 496 subjects who were diagnosed with gastric MALT lymphoma and underwent BM examination were eligible to be included in this study. BM involvement was found in 33 patients (6.7%) by retrospective review, and after exclusions, the clinical outcomes of 28 patients with BM involvement and 412 patients without BM involvement were evaluated. Results When comparing the characteristics of patients, age (median 60 vs. 53 years, p = 0.007) and Helicobacter pylori infection rate (71.0% vs. 85.5%, p = 0.040) were different between patients with and without BM involvement, while the location, macroscopic findings, and depth of invasion were similar. The overall complete remission (CR) rate was 85.2% during a median follow-up period of 42 months (interquartile range, 23-66 months) and did not differ between the two groups (78.6 and 85.7%, p = 0.280). Eradication therapy was performed as the first-line treatment in 18 of the 28 patients (64.3%) with BM involvement, and CR was achieved in 13 patients (72.2%). Logistic regression analysis showed that age and location in the upper part of the stomach were factors related to remission failure. Conclusion Gastric MALT lymphoma has a favorable outcome, and eradication therapy can be justified in selected cases even with BM involvement, when these patients are closely monitored.

Systematic Identification, Characterization and Target Gene Analysis of microRNAs Involved in Osteoarthritis Subchondral Bone Pathogenesis.

PubMed

Prasadam, Indira; Batra, Jyotsna; Perry, Samuel; Gu, Wenyi; Crawford, Ross; Xiao, Yin

2016-07-01

This study aimed to identify the microRNAs associated with sclerotic status of subchondral bone in the pathogenesis of osteoarthritis (OA). Total RNA was extracted from non-sclerotic and sclerotic OA subchondral bone from patients undergoing knee replacement surgeries. miRCURY™ LNA miRNA chip and qRT-PCR were used to profile and validate differential microRNA expression. In addition, we further confirmed profiles of altered miRNAs in an OA rat meniscectomy animal model and their putative targets of the miRNAs were predicted using ingenuity (IPA) software. Finally, five short-listed miRNAs were reactivated by transient in vitro overexpression (miRNA mimics) in subchondral bone osteoblasts and their phenotypes were assessed. Functional screening identified 30 differentiated miRNAs in sclerotic subchondral bone compared to non-sclerotic bone of OA patients. Data integration resulted in confirmation of the eight miRNAs, with aberrant expression in independent human OA bone sample set. In silico analysis (IPA) identified 732 mRNA transcripts as putative targets of the eight altered miRNAs, of which twenty genes were validated to be differentially expressed in sclerotic compared to non-sclerotic bone samples. Out of eight dysregulated miRNA's, five of them showed consistent time-dependent downregulation in a rat OA model. Furthermore, synthetic miR-199a-3p, miR-199a-5p, miR-590-5p, and miR-211-5p mimics rescued the abnormal osteoarthritic subchondral bone osteoblast gene expression and mineralization. We have identified four novel miRNAs that play important roles in subchondral bone pathogenesis in OA. Additional studies are required to develop these miRNAs into therapeutic modalities for OA.

Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway.

PubMed

Zeng, Qi-bing; Xu, Yu-yan; Yu, Xian; Yang, Jun; Hong, Feng; Zhang, Ai-hua

2014-01-01

Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride-arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride-arsenic anomaly group (130) and the fluoride-arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity. Copyright © 2013. Published by Elsevier B.V.

Cellular Therapy to Obtain Rapid Endochondral Bone Formation

DTIC Science & Technology

2012-03-01

biological information and involves the development of a novel biomaterial that can safely house the cells expressing the bone inductive factor to... produce the new bone at which time the material is then selectively eliminated. Ultimately this system has significant applicability. Often bone graft must...hypothesis will provide a safe and efficacious material for the production of bone leading to reliable fracture healing, circumventing the need for

Inflammation, Fracture and Bone Repair

PubMed Central

Loi, Florence; Córdova, Luis A.; Pajarinen, Jukka; Lin, Tzu-hua; Yao, Zhenyu; Goodman, Stuart B.

2016-01-01

The reconstitution of lost bone is a subject that is germane to many orthopaedic conditions including fractures and non-unions, infection, inflammatory arthritis, osteoporosis, osteonecrosis, metabolic bone disease, tumors, and periprosthetic particle-associated osteolysis. In this regard, the processes of acute and chronic inflammation play an integral role. Acute inflammation is initiated by endogenous or exogenous adverse stimuli, and can become chronic in nature if not resolved by normal homeostatic mechanisms. Dysregulated inflammation leads to increased bone resorption and suppressed bone formation. Crosstalk amongst inflammatory cells (polymorphonuclear leukocytes and cells of the monocyte-macrophage-osteoclast lineage) and cells related to bone healing (cells of the mesenchymal stem cell-osteoblast lineage and vascular lineage) is essential to the formation, repair and remodeling of bone. In this review, the authors provide a comprehensive summary of the literature related to inflammation and bone repair. Special emphasis is placed on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair. PMID:26946132

Tooth dentin defects reflect genetic disorders affecting bone mineralization

PubMed Central

Vital, S. Opsahl; Gaucher, C.; Bardet, C.; Rowe, P.S.; George, A.; Linglart, A.; Chaussain, C.

2012-01-01

Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding of deciduous teeth and the extractions of premolars and third molars for orthodontic treatment. The feasibility of obtaining dentin makes this a good model to study biomineralization in physiological and pathological conditions. In this review, we focus on two genetic diseases that disrupt both bone and dentin mineralization. Hypophosphatemic rickets is related to abnormal secretory proteins involved in the ECM organization of both bone and dentin, as well as in the calcium and phosphate metabolism. Osteogenesis imperfecta affects proteins involved in the local organization of the ECM. In addition, dentin examination permits evaluation of the effects of the systemic treatment prescribed to hypophosphatemic patients during growth. In conclusion, dentin constitutes a valuable tool for better understanding of the pathological processes affecting biomineralization. PMID:22296718

The application of x-ray, computed tomography, and magnetic resonance imaging on 22 pediatric Langerhans cell histiocytosis patients with long bone involvement: A retrospective analysis.

PubMed

Zhang, Xiaojun; Zhou, Jing; Chai, Xuee; Chen, Guiling; Guo, Bin; Ni, Lei; Wu, Peng

2018-04-01

The studies focusing on x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) in pediatric Langerhans cell histiocytosis (LCH) patients were still rare. Therefore, we aimed to evaluate the application of x-ray, CT, and MRI in pediatric LCH patients with long bone involvement.Total 22 pediatric LCH patients were included in this study. The diagnosis of LCH was confirmed by pathological examination. All patients were followed up for 3 years. X-ray, CT, or MRI was performed and the results were recorded for further analyses.Among 22 pediatric patients, x-ray (n = 20), CT (n = 18), or MRI (n = 12) were used to scan the lesion on long bones affected by LCH. Femurs (n = 13, 38.24%), tibia (n = 11, 32.35%), humerus (n = 5, 14.71%), and radius (n = 4, 11.76%) were the most frequently affected anatomic sites. Ovoid or round radiolucent lesions, aggressive periosteal reaction, and swelling of surrounding soft tissues were characteristic image of long bones on x-ray, CT, and MRI in pediatric LCH.Femurs, tibia, humerus, and radius were the most commonly affected long bones of pediatric LCH. The application of x-ray, CT, and MRI on long bones could help with the diagnosis of pediatric LCH.

HIV and Bone Metabolism

PubMed Central

Ofotokun, Ighovwerha; Weitzmann, M. Neale

2013-01-01

The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone by osteoblasts. In young adult humans and animals this process is homeostatic with no net gain or loss of bone mass. With natural aging and exacerbated by numerous pathological conditions, bone removal exceeds bone formation, disrupting homeostasis and resulting in bone loss. Over time, skeletal decline reaches clinical significance with development of osteopenia and eventually osteoporosis, conditions that dramatically increase bone fragility and the risk of fracture. Bone fractures can be devastating with significant morbidity and mortality. Over the last decade, it has become clear that skeletal renewal is strongly influenced by the immune system, a consequence of deep integration and centralization of common cell types and cytokine mediators, which we have termed the “immuno-skeletal interface.” Consequently, dysregulated skeletal renewal and bone loss is a common feature of inflammatory conditions associated with immune activation. Interestingly, bone loss is also associated with conditions of immunodeficiency, including infection by the human immunodeficiency virus (HIV) that leads to acquired immunodeficiency syndrome (AIDS). Disruptions to the immuno-skeletal interface drive skeletal deterioration contributing to a high rate of bone fracture in HIV infection. This review examines current knowledge concerning the prevalence and etiology of skeletal complications in HIV infection, the effect of antiretroviral therapies (ART) on the skeleton, and how disruption of the immuno-skeletal interface may underlie bone loss in HIV infection and ART. PMID:21616037

Engineering-Scale Demonstration of DuraLith and Ceramicrete Waste Forms

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

Josephson, Gary B.; Westsik, Joseph H.; Pires, Richard P.

2011-09-23

To support the selection of a waste form for the liquid secondary wastes from the Hanford Waste Immobilization and Treatment Plant, Washington River Protection Solutions (WRPS) has initiated secondary waste form testing on four candidate waste forms. Two of the candidate waste forms have not been developed to scale as the more mature waste forms. This work describes engineering-scale demonstrations conducted on Ceramicrete and DuraLith candidate waste forms. Both candidate waste forms were successfully demonstrated at an engineering scale. A preliminary conceptual design could be prepared for full-scale production of the candidate waste forms. However, both waste forms are stillmore » too immature to support a detailed design. Formulations for each candidate waste form need to be developed so that the material has a longer working time after mixing the liquid and solid constituents together. Formulations optimized based on previous lab studies did not have sufficient working time to support large-scale testing. The engineering-scale testing was successfully completed using modified formulations. Further lab development and parametric studies are needed to optimize formulations with adequate working time and assess the effects of changes in raw materials and process parameters on the final product performance. Studies on effects of mixing intensity on the initial set time of the waste forms are also needed.« less

Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

PubMed

Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

2016-09-01

Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious

Bone Balance within a Cortical BMU: Local Controls of Bone Resorption and Formation

PubMed Central

Smith, David W.; Gardiner, Bruce S.; Dunstan, Colin

2012-01-01

Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the ‘integration of information’ occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors

Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging.

PubMed

Rahmouni, Alain; Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Belhadj, Karim; Gaulard, Philippe; Bouanane, Mohamed; Golli, Mondher; Kobeiter, Hicham

2003-12-01

To evaluate gadolinium enhancement of bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement. Dynamic contrast material-enhanced magnetic resonance (MR) imaging of the thoracolumbar spine was performed in 42 patients with histologically proved diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non-Hodgkin lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from enhancement time curves (ETCs). A three-grade system for scoring bone marrow involvement was based on the percentage of neoplastic cells in bone marrow samples. Quantitative ETC values for the 42 patients were compared with ETC values for healthy subjects and with grades of bone marrow involvement by using mean t test comparisons. Receiver operating characteristic (ROC) analysis was conducted by comparing Emax values between patients with and those without bone marrow involvement. Baseline and follow-up MR imaging findings were compared in nine patients. Significant differences in Emax (P <.001), slope (P <.001), and washout (P =.005) were found between subjects with normal bone marrow and patients with diffuse bone marrow involvement. ROC analysis results showed Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values increased with increasing bone marrow involvement grade. The mean Emax increased from 339% to 737%. Contrast enhancement decreased after treatment in all six patients who responded to treatment but not in two of three patients who did not respond to treatment. Dynamic contrast-enhanced MR images can demonstrate increased bone marrow enhancement in patients with lymphoproliferative diseases and marrow involvement.

Metastases to bones.

PubMed

Wick, Mark R

2014-01-01

Metastatic tumors involving the bones may derive from a number of visceral primary sites, and they can assume several histological appearances. In selected instances, diagnostic confusion with some primary bone tumors may eventuate, necessitating the use of adjunctive pathologic studies to reach a final interpretation. This review considers metastatic osseous neoplasms in the small-cell, large-polygonal-cell, and spindle-cell-pleomorphic microscopic categories. The use of immunohistology and molecular analysis to study such tumors is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone cell communication factors and Semaphorins

PubMed Central

Negishi-Koga, Takako; Takayanagi, Hiroshi

2012-01-01

Bone tissue is continuously renewed throughout adult life by a process called 'remodeling', which involves a dynamic interplay among bone cells including osteoclasts, osteoblasts and osteocytes. For example, a tight coupling between bone resorption and formation is essential for the homeostasis of the skeletal system. Studies on the coupling mechanism in physiological and pathological settings have revealed that osteoclasts or osteoclastic bone resorption promote bone formation through the production of diverse coupling factors. The classical coupling factors are the molecules that promote bone formation after resorption, but there may be distinct mechanisms at work in various phases of bone remodeling. A recent study revealed that the Semaphorin 4D expressed by osteoclasts inhibits bone formation, which represents a mechanism by which coupling is dissociated. Furthermore, it has been demonstrated that osteoblastic expression of Semaphorin 3A exerts an osteoprotective effect by both suppressing bone resorption and increasing bone formation. Thus, recent advances have made it increasingly clear that bone remodeling is regulated by not only classical coupling factors, but also molecules that mediate cell–cell communication among bone cells. We propose that such factors be called bone cell communication factors, which control the delicate balance of the interaction of bone cells so as to maintain bone homeostasis. PMID:24171101

Epigenetics of bone diseases.

PubMed

Michou, Laetitia

2017-12-12

Histone deacetylation, DNA methylation, and micro-RNAs (miRNAs) are the three main epigenetic mechanisms that regulate gene expression. All the physiological processes involved in bone remodeling are tightly regulated by epigenetic factors. This review discusses the main epigenetic modifications seen in tumoral and non-tumoral bone diseases, with emphasis on miRNAs. The role for epigenetic modifications of gene expression in the most common bone diseases is illustrated by drawing on the latest publications in the field. In multifactorial bone diseases such as osteoporosis, many epigenetic biomarkers, either alone or in combination, have been associated with bone mineral density or suggested to predict osteoporotic fractures. In addition, treatments designed to modulate bone remodeling by selectively targeting the function of specific miRNAs are being evaluated. Advances in the understanding of epigenetic regulation shed new light on the pathophysiology of other non-tumoral bone diseases, including genetic conditions inherited on a Mendelian basis. Finally, in the area of primary and metastatic bone tumors, the last few years have witnessed considerable progress in elucidating the epigenetic regulation of oncogenesis and its local interactions with bone tissue. These new data may allow the development of epigenetic outcome predictors, which are in very high demand, and of innovative therapeutic agents acting via miRNA modulation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Cancer-associated bone disease.

PubMed

Rizzoli, R; Body, J-J; Brandi, M-L; Cannata-Andia, J; Chappard, D; El Maghraoui, A; Glüer, C C; Kendler, D; Napoli, N; Papaioannou, A; Pierroz, D D; Rahme, M; Van Poznak, C H; de Villiers, T J; El Hajj Fuleihan, G

2013-12-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

Cancer-associated bone disease

PubMed Central

Body, J.-J.; Brandi, M.-L.; Cannata-Andia, J.; Chappard, D.; El Maghraoui, A.; Glüer, C.C.; Kendler, D.; Napoli, N.; Papaioannou, A.; Pierroz, D.D.; Rahme, M.; Van Poznak, C.H.; de Villiers, T.J.; El Hajj Fuleihan, G.

2016-01-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

Pharmacological activation of aldehyde dehydrogenase 2 promotes osteoblast differentiation via bone morphogenetic protein-2 and induces bone anabolic effect

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

Mittal, Monika; Pal, Subhashis; China, Shyamsundar

Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuatedmore » the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40 mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40 mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress. - Highlights: • Alda-1 induced osteoblast differentiation that involved upregulation of ALDH2 and BMP-2 • Alda

Gastric cancer bone metastases together with osteopoikilosis diagnosed using bone scintigraphy and 18F-FDG PET/CT.

PubMed

Prado Wohlwend, S; Sánchez Vaño, R; Sopena Novales, P; Uruburu García, E; Aparisi Rodríguez, F; Martínez Carsí, C

The coexistence of different bone diseases in the same patient involves a complex differential diagnosis. A patient is presented who was studied due to a renal mass that showed many sclerotic lesions in spine and limbs in conventional radiology and CT. These lesions were evaluated with 99m TC-HDP bone scintigraphy and 18 F-FDG PET/CT, which helped to obtain the definitive pathological diagnosis of osteopoikilosis (OP) co-existing with gastric cancer bone metastases. Of the different imaging scans performed, bone scintigraphy was particularly relevant due to its ability to discriminate between benign and metastatic bone disease. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Skeleton and Glucose Metabolism: A Bone-Pancreas Loop

PubMed Central

Luce, Vincenza; Ventura, Annamaria; Colucci, Silvia; Cavallo, Luciano; Grano, Maria

2015-01-01

Bone has been considered a structure essential for mobility, calcium homeostasis, and hematopoietic function. Recent advances in bone biology have highlighted the importance of skeleton as an endocrine organ which regulates some metabolic pathways, in particular, insulin signaling and glucose tolerance. This review will point out the role of bone as an endocrine “gland” and, specifically, of bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone remodeling, as osteoprotegerin, in the regulation of insulin function and glucose metabolism. PMID:25873957

Primary telangiectatic osteosarcoma of occipital bone: a case report and review of literature.

PubMed

Patibandla, Mohana Rao; Uppin, Shantveer G; Thotakura, Amit Kumar; Panigrahi, Manas K; Challa, Sundaram

2011-01-01

Telangiectatic osteosarcoma (TOS), an uncommon variant of osteosarcoma, involving skull bones is extremely rare. We present clinico-pathological, imageological and treatment outcome of a primary TOS of occipital bone in a 30-year-old woman and review the previously reported skull bone TOS. We suggest that TOS should be included in the differential diagnosis of destructive lytic lesions involving the skull bones. As radical surgical procedures are not applicable to skull bones, the outcome is poor even with adjuvant chemotherapy.

Bone metabolism and adipokines: are there perspectives for bone diseases drug discovery?

PubMed

Scotece, Morena; Conde, Javier; Abella, Vanessa; López, Verónica; Pino, Jesús; Lago, Francisca; Gómez-Reino, Juan J; Gualillo, Oreste

2014-08-01

Over the past 20 years, the idea that white adipose tissue (WAT) is simply an energy depot organ has been radically changed. Indeed, present understanding suggests WAT to be an endocrine organ capable of producing and secreting a wide variety of proteins termed adipokines. These adipokines appear to be relevant factors involved in a number of different functions, including metabolism, immune response, inflammation and bone metabolism. In this review, the authors focus on the effects of several adipose tissue-derived factors in bone pathophysiology. They also consider how the modification of the adipokine network could potentially lead to promising treatment options for bone diseases. There are currently substantial developments being made in the understanding of the interplay between bone metabolism and the metabolic system. These insights could potentially lead to the development of new treatment strategies and interventions with the aim of successful outcomes in many people affected by bone disorders. Specifically, future research should look into the intimate mechanisms regulating peripheral and central activity of adipokines as it has potential for novel drug discovery.

Steps in Prostate Cancer Progression that lead to Bone Metastasis

PubMed Central

Jin, Jung-Kang; Dayyani, Farshid; Gallick, Gary E.

2011-01-01

Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone remain incompletely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bi-directional interactions between the tumor and the bone microenvironment. In this review, we discuss the current understanding of the biologic processes and regulatory factors involved in the metastasis of prostate cancer cells, and their specific properties that promote growth in bone. Although many of these processes still need to be fully elucidated, a better understanding of the complex tumor/microenvironment interplay is slowly leading to more effective therapies for patients with prostate cancer bone metastases. PMID:21365645

Treated unicameral bone cysts.

PubMed

Weinman, J; Servaes, S; Anupindi, S A

2013-06-01

Unicameral bone cysts (UBCs) are a common benign entity involving the metaphysis of growing bone, occurring within the first two decades of life. Assessment of these lesions, both before and after surgery, is performed routinely utilizing radiographs. We present a review of UBCs at various stages of treatment, including both successful and incomplete healing, and describe the imaging findings throughout their postoperative course. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing.

PubMed

Monfoulet, Laurent; Malaval, Luc; Aubin, Jane E; Rittling, Susan R; Gadeau, Alain P; Fricain, Jean-Christophe; Chassande, Olivier

2010-02-01

Bone healing is a complex multi-step process, which depends on the position and size of the lesion, and on the mechanical stability of the wounded area. To address more specifically the mechanisms involved in cortical bone healing, we created drill-hole defects in the cortex of mouse femur, a lesion that triggers intramembranous repair, and compared the roles of bone sialoprotein (BSP) and osteopontin (OPN), two proteins of the extracellular matrix, in the repair process. Bone regeneration was analyzed by ex vivo microcomputerized X-ray tomography and histomorphometry of bones of BSP-deficient, OPN-deficient and wild-type mice. In all mouse strains, the cortical gap was bridged with woven bone within 2 weeks and no mineralized tissue was observed in the marrow. Within 3 weeks, lamellar cortical bone filled the gap. The amount and degree of mineralization of the woven bone was not affected by OPN deficiency, but cortical bone healing was delayed in BSP-deficient mice due to delayed mineralization. Gene expression studies showed a higher amount of BSP transcripts in the repair bone of OPN-deficient mice, suggesting a possible compensation of OPN function by BSP in OPN-null mice. Our data suggest that BSP, but not OPN, plays a role in primary bone formation and mineralization of newly formed bone during the process of cortical bone healing. (c) 2009 Elsevier Inc. All rights reserved.

Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone.

PubMed

Ma, Xinlong; Lv, Jianwei; Sun, Xiaolei; Ma, Jianxiong; Xing, Guosheng; Wang, Ying; Sun, Lei; Wang, Jianbao; Li, Fengbo; Li, Yanjun; Zhao, Zhihu

2016-04-25

Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis.

Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone

PubMed Central

Ma, Xinlong; Lv, Jianwei; Sun, Xiaolei; Ma, Jianxiong; Xing, Guosheng; Wang, Ying; Sun, Lei; Wang, Jianbao; Li, Fengbo; Li, Yanjun; Zhao, Zhihu

2016-01-01

Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis. PMID:27109829

Use of cone beam computed tomography in periodontology

PubMed Central

Acar, Buket; Kamburoğlu, Kıvanç

2014-01-01

Diagnosis of periodontal disease mainly depends on clinical signs and symptoms. However, in the case of bone destruction, radiographs are valuable diagnostic tools as an adjunct to the clinical examination. Two dimensional periapical and panoramic radiographs are routinely used for diagnosing periodontal bone levels. In two dimensional imaging, evaluation of bone craters, lamina dura and periodontal bone level is limited by projection geometry and superpositions of adjacent anatomical structures. Those limitations of 2D radiographs can be eliminated by three-dimensional imaging techniques such as computed tomography. Cone beam computed tomography (CBCT) generates 3D volumetric images and is also commonly used in dentistry. All CBCT units provide axial, coronal and sagittal multi-planar reconstructed images without magnification. Also, panoramic images without distortion and magnification can be generated with curved planar reformation. CBCT displays 3D images that are necessary for the diagnosis of intra bony defects, furcation involvements and buccal/lingual bone destructions. CBCT applications provide obvious benefits in periodontics, however; it should be used only in correct indications considering the necessity and the potential hazards of the examination. PMID:24876918

Biochemical markers of bone turnover in diagnosis of myeloma bone disease.

PubMed

Dizdar, Omer; Barista, Ibrahim; Kalyoncu, Umut; Karadag, Omer; Hascelik, Gulsen; Cila, Aysenur; Pinar, Asli; Celik, Ismail; Kars, Ayse; Tekuzman, Gulten

2007-03-01

This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were significantly correlated with beta2-microglobulin and lactate dehydrogenase levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha needs to be further investigated. Copyright (c) 2006 Wiley-Liss, Inc.

The Biology of Bone and Ligament Healing.

PubMed

Cottrell, Jessica A; Turner, Jessica Cardenas; Arinzeh, Treena Livingston; O'Connor, J Patrick

2016-12-01

This review describes the normal healing process for bone, ligaments, and tendons, including primary and secondary healing as well as bone-to-bone fusion. It depicts the important mediators and cell types involved in the inflammatory, reparative, and remodeling stages of each healing process. It also describes the main challenges for clinicians when trying to repair bone, ligaments, and tendons with a specific emphasis on Charcot neuropathy, fifth metatarsal fractures, arthrodesis, and tendon sheath and adhesions. Current treatment options and research areas are also reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Force-induced bone growth and adaptation: A system theoretical approach to understanding bone mechanotransduction

NASA Astrophysics Data System (ADS)

Maldonado, Solvey; Findeisen, Rolf

2010-06-01

The modeling, analysis, and design of treatment therapies for bone disorders based on the paradigm of force-induced bone growth and adaptation is a challenging task. Mathematical models provide, in comparison to clinical, medical and biological approaches an structured alternative framework to understand the concurrent effects of the multiple factors involved in bone remodeling. By now, there are few mathematical models describing the appearing complex interactions. However, the resulting models are complex and difficult to analyze, due to the strong nonlinearities appearing in the equations, the wide range of variability of the states, and the uncertainties in parameters. In this work, we focus on analyzing the effects of changes in model structure and parameters/inputs variations on the overall steady state behavior using systems theoretical methods. Based on an briefly reviewed existing model that describes force-induced bone adaptation, the main objective of this work is to analyze the stationary behavior and to identify plausible treatment targets for remodeling related bone disorders. Identifying plausible targets can help in the development of optimal treatments combining both physical activity and drug-medication. Such treatments help to improve/maintain/restore bone strength, which deteriorates under bone disorder conditions, such as estrogen deficiency.

Metabolic and biochemical considerations of bone.

PubMed

Lutwak, L

1975-01-01

Recognition of the dynamic aspects of bone metabolism can lead to a unified concept involving endocrine and nutritional influences. Although most hormones can influence bone metabolism directly or indirectly, the principal ones involved in skeletal metabolism are parathyroid hormone, calcitonin and 1,25-dihydroxy-vitamin D. The actions of parathyroid hormone and 1,25-dihydroxy-vitamin D result in elevations of circulating extracellular fluid calcium concentration through actions directly on bone, intestine, and kidney. Calcitonin leads to decreases in calcium concentration, primarily by action on bone and kidney. The absorption and retention of calcium by the organism is further influenced by the dietary content of calcium, phosphorus, protein, and fluoride. Chronic dietary deficiencies of calcium and excesses of phosphorus may lead to chronic nutritional secondary hyperparathyroidism with resulting skeletal demineralization. In both experimental animals and in man, the earliest manifestation of this condition may be demineralization of the jaw with resultant paradentosis. Experimental studies in animals and in man have shown that this form of demineralization may be completely reversed by increasing dietary calcium and decreasing dietary phosphrous.

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

[Bone hydatidosis. 12 cases].

PubMed

Jlidi, R; Yaakoubi, M T; Ladeb, M F; Ben Ayeche, M L; Ghannouchi, G; Moula, T

1992-01-01

The hydatic cyst is a parasitic disease caused by the development in man of the larval form of echinococcus granulosus. All parts of the body may be involved, but the liver and lungs are the main locations of the disease. The bone site is rare, accounting for 0.9 to 2% of all hydatic lesions. Between 1982 and 1988, we have compiled 12 cases of hydatic disease of bone. They were located in the skull (4 cases), the iliac bone (4 cases), the omoplate (1 case), the ribs (1 case), the femur (1 case) and the fibula (1 case). These lesions are generally considered as primary, but association with visceral locations was noted in 3 cases in our series.

Tocotrienols for bone health: a translational approach.

PubMed

Shen, Chwan-Li; Klein, Annika; Chin, Kok-Yong; Mo, Huanbiao; Tsai, Peihsuan; Yang, Rong-Sen; Chyu, Ming-Chien; Ima-Nirwana, Soelaiman

2017-08-01

Osteoporosis, a degenerative bone disease, is characterized by low bone mass and microstructural deterioration of bone tissue resulting in aggravated bone fragility and susceptibility to fractures. The trend of extended life expectancy is accompanied by a rise in the prevalence of osteoporosis and concomitant complications in the elderly population. Epidemiological evidence has shown an association between vitamin E consumption and the prevention of age-related bone loss in elderly women and men. Animal studies show that ingestion of vitamin E, especially tocotrienols, may benefit bone health in terms of maintaining higher bone mineral density and improving bone microstructure and quality. The beneficial effects of tocotrienols on bone health appear to be mediated via antioxidant/anti-inflammatory pathways and/or 3-hydroxy-3-methylglutaryl coenzyme A mechanisms. We discuss (1) an overview of the prevalence and etiology of osteoporosis, (2) types of vitamin E (tocopherols versus tocotrienols), (3) findings of tocotrienols and bone health from published in vitro and animal studies, (4) possible mechanisms involved in bone protection, and (5) challenges and future direction for research. © 2017 New York Academy of Sciences.

Interaction betwen Lead and Bone Protein to Affect Bone Calcium Level Using UV-Vis Spectroscopy

NASA Astrophysics Data System (ADS)

Noor, Z.; Azharuddin, A.; Aflanie, I.; Kania, N.; Suhartono, E.

2018-05-01

This present study aim to evaluate the interactions between lead (Pb) and with bone protein by UV-Vis approach. In addition, this prsent study also aim to investigate the effect of Pb on bone calcium (Ca) level. The present study was a true experimental study design to examine the impact of Pb exposure in bone of male rats (Rattus novergicus). The study involved 5 groups, P1 was the control group, while the other (P2-P5) were the case group with exposure of Pb in different concentration within 4 weeks. At the end of the exposure, the interaction between Pb and protein was determined using UV-Vis spectrophotometric method, and the Ca level was determined using permanganometric method. The results shows that that there is an interaction between Pb and bone protein. The result also shows that the value of the binding constant of Protein-Pb is 32.71. It means Pb have an high affinity to bind with bone protein, which promote a further reaction to induced the release of bone Ca from the bone protein. In conclusion, this present study found an obvious relationship between Pb and bone protein which promote a further reaction to increase the releasing of bone calcium.

In vivo ultrasound imaging of the bone cortex

NASA Astrophysics Data System (ADS)

Renaud, Guillaume; Kruizinga, Pieter; Cassereau, Didier; Laugier, Pascal

2018-06-01

Current clinical ultrasound scanners cannot be used to image the interior morphology of bones because these scanners fail to address the complicated physics involved for exact image reconstruction. Here, we show that if the physics is properly addressed, bone cortex can be imaged using a conventional transducer array and a programmable ultrasound scanner. We provide in vivo proof for this technique by scanning the radius and tibia of two healthy volunteers and comparing the thickness of the radius bone with high-resolution peripheral x-ray computed tomography. Our method assumes a medium that is composed of different homogeneous layers with unique elastic anisotropy and ultrasonic wave-speed values. The applicable values of these layers are found by optimizing image sharpness and intensity over a range of relevant values. In the algorithm of image reconstruction we take wave refraction between the layers into account using a ray-tracing technique. The estimated values of the ultrasonic wave-speed and anisotropy in cortical bone are in agreement with ex vivo studies reported in the literature. These parameters are of interest since they were proposed as biomarkers for cortical bone quality. In this paper we discuss the physics involved with ultrasound imaging of bone and provide an algorithm to successfully image the first segment of cortical bone.

Fat, Sugar, and Bone Health: A Complex Relationship

PubMed Central

Tian, Li; Yu, Xijie

2017-01-01

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation

Fat, Sugar, and Bone Health: A Complex Relationship.

PubMed

Tian, Li; Yu, Xijie

2017-05-17

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation

Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD.

PubMed

Ciucci, Thomas; Ibáñez, Lidia; Boucoiran, Agathe; Birgy-Barelli, Eléonore; Pène, Jérôme; Abou-Ezzi, Grazia; Arab, Nadia; Rouleau, Matthieu; Hébuterne, Xavier; Yssel, Hans; Blin-Wakkach, Claudine; Wakkach, Abdelilah

2015-07-01

Under both physiological and pathological conditions, bone volume is determined by the rate of bone formation by osteoblasts and bone resorption by osteoclasts. Excessive bone loss is a common complication of human IBD whose mechanisms are not yet completely understood. Despite the role of activated CD4(+) T cells in inflammatory bone loss, the nature of the T cell subsets involved in this process in vivo remains unknown. The aim of the present study was to identify the CD4(+) T cell subsets involved in the process of osteoclastogenesis in vivo, as well as their mechanism of action. CD4(+) T cells were studied in IL10-/- mice and Rag1-/- mice adoptively transferred with naive CD4(+)CD45RB(high) T cells, representing two well-characterised animal models of IBD and in patients with Crohn's disease. They were phenotypically and functionally characterised by flow cytometric and gene expression analysis, as well as in in vitro cocultures with osteoclast precursors. In mice, we identified bone marrow (BM) CD4(+) T cells producing interleukin (IL)-17 and tumour necrosis factor (TNF)-α as an osteoclastogenic T cell subset referred to as Th17 TNF-α(+) cells. During chronic inflammation, these cells migrate to the BM where they survive in an IL-7-dependent manner and where they promote the recruitment of inflammatory monocytes, the main osteoclast progenitors. A population equivalent to the Th17 TNF-α(+) cells was also detected in patients with Crohn's disease. Our results highlight the osteoclastogenic function of the Th17 TNF-α(+) cells that contribute to bone loss in vivo in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mice lacking the conserved transcription factor Grainyhead-like 3 (Grhl3) display increased apposition of the frontal and parietal bones during embryonic development.

PubMed

Goldie, Stephen J; Arhatari, Benedicta D; Anderson, Peter; Auden, Alana; Partridge, Darren D; Jane, Stephen M; Dworkin, Sebastian

2016-10-18

Increased apposition of the frontal and parietal bones of the skull during embryogenesis may be a risk factor for the subsequent development of premature skull fusion, or craniosynostosis. Human craniosynostosis is a prevalent, and often serious embryological and neonatal pathology. Other than known mutations in a small number of contributing genes, the aetiology of craniosynostosis is largely unknown. Therefore, the identification of novel genes which contribute to normal skull patterning, morphology and premature suture apposition is imperative, in order to fully understand the genetic regulation of cranial development. Using advanced imaging techniques and quantitative measurement, we show that genetic deletion of the highly-conserved transcription factor Grainyhead-like 3 (Grhl3) in mice (Grhl3 -/- ) leads to decreased skull size, aberrant skull morphology and premature apposition of the coronal sutures during embryogenesis. Furthermore, Grhl3 -/- mice also present with premature collagen deposition and osteoblast alignment at the sutures, and the physical interaction between the developing skull, and outermost covering of the brain (the dura mater), as well as the overlying dermis and subcutaneous tissue, appears compromised in embryos lacking Grhl3. Although Grhl3 -/- mice die at birth, we investigated skull morphology and size in adult animals lacking one Grhl3 allele (heterozygous; Grhl3 +/- ), which are viable and fertile. We found that these adult mice also present with a smaller cranial cavity, suggestive of post-natal haploinsufficiency in the context of cranial development. Our findings show that our Grhl3 mice present with increased apposition of the frontal and parietal bones, suggesting that Grhl3 may be involved in the developmental pathogenesis of craniosynostosis.

Simultaneous occurrence of ocular, disseminated mucocutaneous, and multivisceral involvement of leishmaniasis.

PubMed

Philips, Cyriac Abby; Kalal, Chetan Ramesh; Kumar, K N Chandan; Bihari, Chhagan; Sarin, Shiv Kumar

2014-01-01

Leishmaniasis is a tropical infection caused by the protozoan, belonging to the group of Leishmania which causes Old World and New World disease. These are typically divided into cutaneous, mucocutaneous, visceral, viscerotropic, and disseminated disease. Cutaneous leishmaniasis in the presence of visceral disease is a rarity. Isolated case reports have documented this occurrence, in the immunocompromised setting, and few otherwise. The concurrent presence of visceral leishmaniasis (bone marrow involvement) with solitary cutaneous and ocular disease and also solitary cutaneous and visceral disease (bone marrow involvement) has been reported before. Here, we present an immunocompetent patient who was diagnosed to have visceral leishmaniasis (liver and bone marrow involvement) along with simultaneous disseminated mucocutaneous and ocular involvement, a combination that has never been reported before.

Simultaneous Occurrence of Ocular, Disseminated Mucocutaneous, and Multivisceral Involvement of Leishmaniasis

PubMed Central

Kalal, Chetan Ramesh; Kumar, K. N. Chandan; Bihari, Chhagan; Sarin, Shiv Kumar

2014-01-01

Leishmaniasis is a tropical infection caused by the protozoan, belonging to the group of Leishmania which causes Old World and New World disease. These are typically divided into cutaneous, mucocutaneous, visceral, viscerotropic, and disseminated disease. Cutaneous leishmaniasis in the presence of visceral disease is a rarity. Isolated case reports have documented this occurrence, in the immunocompromised setting, and few otherwise. The concurrent presence of visceral leishmaniasis (bone marrow involvement) with solitary cutaneous and ocular disease and also solitary cutaneous and visceral disease (bone marrow involvement) has been reported before. Here, we present an immunocompetent patient who was diagnosed to have visceral leishmaniasis (liver and bone marrow involvement) along with simultaneous disseminated mucocutaneous and ocular involvement, a combination that has never been reported before. PMID:24707415

NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

PubMed Central

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

2013-01-01

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

76 FR 17135 - Clarifying Edits to Existing Special Controls Guidance Documents; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... Virus, 29. Endotoxin Assay, 30. Dental Sonography and Jaw Tracking Devices, 31. Human Dura Mater... for the Topical Approximation of Skin, 78. Bone Sonometers, 79. Tissue Expander, 80. Cord Blood...

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.

Clinical and radiographic features of solitary and cemento-osseous dysplasia-associated simple bone cysts.

PubMed

Chadwick, J W; Alsufyani, N A; Lam, E W N

2011-05-01

The simple bone cyst (SBC) is a pseudocyst that can occur as a solitary entity in the jaws or may occur in association with cemento-osseous dysplasia (COD). The purpose of this study was to review the clinical and radiographic features of solitary and COD-associated SBCs. Archived imaging reports from the Special Procedures Clinic in Oral and Maxillofacial Radiology at the Faculty of Dentistry at the University of Toronto between 1 January 1989 and 31 December 2009 revealed 23 COD-associated SBCs and 68 solitary SBCs. Almost all solitary and COD-associated SBCs were found in the mandible. Furthermore, 87.0% of COD-associated SBCs were found in females in their fifth decade of life (P < 0.001) while solitary SBCs were found in equal numbers in both sexes in their second decade of life (P < 0.005). COD-associated SBCs were also more likely to cause thinning of the endosteal cortex, bone expansion and scalloping of the superior border between teeth (all P < 0.001) than solitary SBCs that are classically described as having these characteristics. Finally, COD-associated SBC demonstrated a loss of lamina dura more often (P < 0.05) than solitary SBCs. Knowledge of the sporadic association between COD and SBC and their potential radiographic appearances should prevent inappropriate treatment and management of these patients.

Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

NASA Astrophysics Data System (ADS)

Ramasamy, Saravana K.; Kusumbe, Anjali P.; Wang, Lin; Adams, Ralf H.

2014-03-01

Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

Update: Dura Mater Graft-Associated Creutzfeldt-Jakob Disease - Japan, 1975-2017.

PubMed

Ae, Ryusuke; Hamaguchi, Tsuyoshi; Nakamura, Yosikazu; Yamada, Masahito; Tsukamoto, Tadashi; Mizusawa, Hidehiro; Belay, Ermias D; Schonberger, Lawrence B

2018-03-09

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder that, according to the most well accepted hypothesis (1), is caused by replicating, transmissible, abnormal forms of a host-encoded prion protein (prions). Most CJD cases occur spontaneously (sporadic CJD) or are inherited (genetic CJD). Iatrogenic CJD can occur after exposure to prion-contaminated instruments or products in medical/surgical settings. Cadaveric dura mater graft-associated CJD (dCJD) accounts for a common form of iatrogenic CJD. This report summarizes the epidemiologic features of 154 cases of dCJD identified in Japan during 1975-2017; these cases account for >60% of dCJD cases reported worldwide (1,2). The unusually high prevalence of dCJD in Japan was first reported in 1997 (3). In 2008, a single brand of graft (Lyodura [B. Braun Melsungen AG, Melsungen, Germany]), frequently used as a patch in neurosurgical procedures, was identified as the probable vehicle of transmission (4). No international recall of the implicated Lyodura occurred, the product had a relatively long shelf life, and the grafts were used frequently in Japanese patients with non-life-threatening conditions (4,5). Since 2008, additional cases have been ascertained, reflecting the identification of previously missed cases and the occurrence of new cases with longer latency periods (interval from exposure to symptom onset) for dCJD (up to 30 years), underscoring the importance of maintaining surveillance for dCJD.

Targeting mast cells in gastric cancer with special reference to bone metastases

PubMed Central

Leporini, Christian; Ammendola, Michele; Marech, Ilaria; Sammarco, Giuseppe; Sacco, Rosario; Gadaleta, Cosmo Damiano; Oakley, Caroline; Russo, Emilio; De Sarro, Giovambattista; Ranieri, Girolamo

2015-01-01

Bone metastases from gastric cancer (GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells (MCs) positive to tryptase (MCPT) in primary gastric tumor angiogenesis. Recently, we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumor-infiltrating, peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents, such as MCs tryptase inhibitors (gabexate mesylate, nafamostat mesylate) or c-KitR tyrosine kinase inhibitors (imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patients affected by bone metastases. PMID:26457010

Leukemia inhibitory factor: a novel bone-active cytokine.

PubMed

Reid, L R; Lowe, C; Cornish, J; Skinner, S J; Hilton, D J; Willson, T A; Gearing, D P; Martin, T J

1990-03-01

A number of cytokines have been found to be potent regulators of bone resorption and to share the properties originally attributed to osteoclast-activating factor. One such activity, differentiation-inducing factor (DIF, D-factor) from mouse spleen cells, shares a number of biological and biochemical properties with the recently characterized and cloned leukemia inhibitory factor (LIF). We have assessed the effects of recombinant LIF on bone resorption and other parameters in neonatal mouse calvaria. Both recombinant murine and human (h) LIFs stimulated 45Ca release from prelabeled calvaria in a dose-dependent manner. The increase in bone resorption was associated with an increase in the number of osteoclasts per mm2 bone. The osteolytic effect of hLIF were blocked by 10(-7) M indomethacin. hLIF also stimulated incorporation of [3H] thymidine into calvaria, but the dose-response relationship was distinct from that for bone resorption, and this effect was not blocked by indomethacin. Similarly, hLIF increased [3H]phenylalanine incorporation into calvaria, and this was also not inhibited by indomethacin. It is concluded that LIF stimulates bone resorption by a mechanism involving prostaglandin production, but that a distinct mechanism is responsible for its stimulation of DNA and protein synthesis. The primary structure of LIF differs from that of other fully characterized, bone-active cytokines, and it, thus, represents a novel factor which may be involved in the normal regulation of bone cell function.

Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms.

PubMed

Herroon, Mackenzie K; Rajagurubandara, Erandi; Hardaway, Aimalie L; Powell, Katelyn; Turchick, Audrey; Feldmann, Daniel; Podgorski, Izabela

2013-11-01

Incidence of skeletal metastases and death from prostate cancer greatly increases with age and obesity, conditions which increase marrow adiposity. Bone marrow adipocytes are metabolically active components of bone metastatic niche that modulate the function of neighboring cells; yet the mechanisms of their involvement in tumor behavior in bone have not been explored. In this study, using experimental models of intraosseous tumor growth and diet-induced obesity, we demonstrate the promoting effects of marrow fat on growth and progression of skeletal prostate tumors. We reveal that exposure to lipids supplied by marrow adipocytes induces expression of lipid chaperone FABP4, pro-inflammatory interleukin IL-1β, and oxidative stress protein HMOX-1 in metastatic tumor cells and stimulates their growth and invasiveness. We show that FABP4 is highly overexpressed in prostate skeletal tumors from obese mice and in bone metastasis samples from prostate cancer patients. In addition, we provide results suggestive of bi-directional interaction between FABP4 and PPARγ pathways that may be driving aggressive tumor cell behavior in bone. Together, our data provide evidence for functional relationship between bone marrow adiposity and metastatic prostate cancers and unravel the FABP4/IL-1β axis as a potential therapeutic target for this presently incurable disease.

Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms

PubMed Central

Herroon, Mackenzie K.; Rajagurubandara, Erandi; Hardaway, Aimalie L.; Powell, Katelyn; Turchick, Audrey; Feldmann, Daniel; Podgorski, Izabela

2013-01-01

Incidence of skeletal metastases and death from prostate cancer greatly increases with age and obesity, conditions which increase marrow adiposity. Bone marrow adipocytes are metabolically active components of bone metastatic niche that modulate the function of neighboring cells; yet the mechanisms of their involvement in tumor behavior in bone have not been explored. In this study, using experimental models of intraosseous tumor growth and diet-induced obesity, we demonstrate the promoting effects of marrow fat on growth and progression of skeletal prostate tumors. We reveal that exposure to lipids supplied by marrow adipocytes induces expression of lipid chaperone FABP4, pro-inflammatory interleukin IL-1β, and oxidative stress protein HMOX-1 in metastatic tumor cells and stimulates their growth and invasiveness. We show that FABP4 is highly overexpressed in prostate skeletal tumors from obese mice and in bone metastasis samples from prostate cancer patients. In addition, we provide results suggestive of bi-directional interaction between FABP4 and PPARγ pathways that may be driving aggressive tumor cell behavior in bone. Together, our data provide evidence for functional relationship between bone marrow adiposity and metastatic prostate cancers and unravel the FABP4/IL-1β axis as a potential therapeutic target for this presently incurable disease. PMID:24240026

Cat-scratch disease and bone scintigraphy.

PubMed

Ismaili-Alaoui, Nadia; Vuong, Valerie; Marcu-Marin, M; Sergent-Alaoui, Aline; Chevallier, Bertrand; de Labriolle-Vaylet, Claire

2012-08-01

Cat-scratch disease is a bacterial infection caused by Bartonella henselae. Bone involvement is rare. We describe the case of a 7-year-old boy with a systemic form of the disease. He presented with a 15-day history of fever, altered general condition, weight loss and cough, associated with back pain, and right-sided coxalgia. Bone scintigraphy with Tc-99m hydroxymethylene diphosphonate showed spinal involvement, the iliac crest, the right ankle, and the right first metatarsal. Magnetic resonance imaging confirmed these locations. He was positive for anti-Bartonella henselae. The fever regressed before treatment with rifampicin began, and he made a full recovery.

Greater Bone Fomation Induction Occurred in Aged Than Young Cancellous Bone Sites

NASA Technical Reports Server (NTRS)

Ke, H. Z.; Jee, Webster S. S.; Ito, H.; Setterberg, R. B.; Li, M.; Lin, B. Y.; Liang, X. G.; Ma, Y.F.

1993-01-01

We have determined the differences in the effects of continual prostaglandin E2 (PGE2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7 month-old Sprague-Dawley rats. The sites involved are the aged Distal Tibial Metaphysis (DTM) with a closed epiphysis and the young Proximal Tibial Metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE2/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometty of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE2/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE2 treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE2 treatment than young growing metaphysis.

Regulation of bone remodeling by vitamin K2.

PubMed

Myneni, V D; Mezey, E

2017-11-01

All living tissues require essential nutrients such as amino acids, fatty acids, carbohydrates, minerals, vitamins, and water. The skeleton requires nutrients for development, maintaining bone mass and density. If the skeletal nutritional requirements are not met, the consequences can be quite severe. In recent years, there has been growing interest in promotion of bone health and inhibition of vascular calcification by vitamin K2. This vitamin regulates bone remodeling, an important process necessary to maintain adult bone. Bone remodeling involves removal of old or damaged bone by osteoclasts and its replacement by new bone formed by osteoblasts. The remodeling process is tightly regulated, when the balance between bone resorption and bone formation shifts to a net bone loss results in the development of osteoporosis in both men and women. In this review, we focus on our current understanding of the effects of vitamin K2 on bone cells and its role in prevention and treatment of osteoporosis. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

The gut microbiota regulates bone mass in mice

PubMed Central

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

2012-01-01

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

Generalized metabolic bone disease in Neurofibromatosis type I

USDA-ARS?s Scientific Manuscript database

Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1), but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical, and pathological level the bone involvement ...

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.

Cavernous hemangioma--uncommon presentation in zygomatic bone.

PubMed

Dhupar, Vikas; Yadav, Sunil; Dhupar, Anita; Akkara, Francis

2012-03-01

Hemangiomas are benign vascular neoplasms characterized by an abnormal proliferation of blood vessels. They may occur in any vascularized tissue including skin, subcutaneous tissue, muscle, and bone. Intraosseous hemangiomas are uncommon, constituting less than 1% of all osseous tumors. The most frequent sites are the calvaria and the vertebral column. Involvement of the facial bones is rare and occurs most commonly in the maxilla, mandible, and nasal bones. In literature, only 20 cases of zygomatic involvement have been reported. We report a case of an intraosseous hemangioma of the zygoma with the history and physical findings of slowly growing, bony, hard tumor causing facial and ocular deformity. The typical clinicopathologic and radiologic findings helped to set up the correct diagnosis. Early recognition and excision are recommended to preserve facial contour. Operative blood loss is minimal, and there is no need for preoperative angiography.

[Mastocytosis and bone manifestations. Results of the survey of the bone and phosphorus-calcium metabolism section of the French Society of Rheumatology].

PubMed

Grardel, B; Hardouin, P

1992-01-01

Thirty two cases of the association of mastocytosis and bone lesions were collected in a multicentre study. Five cases involved osteocondensation forms. However, most often (27 cases), there was osteoporosis (OP). The diagnosis was made in the absence of obvious risk factors, and thus often in men (2/3 of patients), when there was the association of pigmented urticaria and an excess of mast cells in bone biopsies. Laboratory, radiological and isotope scan findings are often non-specific, being identical to those encountered in common OP. The histomorphometric profile involves an association of decreased cancellous bone volume, increased area of resorption and decreased bone formation parameters. Progression to malignant mastocytosis occurs essentially in diffuse osteocondensation forms and is rare in OP types. Emphasis must be placed on the importance of qualitative study of bone marrow, using specific stains, since the diagnosis may be missed in the absence of typical skin lesions. Conversely, since a simple increase in mast cell count is possible during common OP, a search for mast cell nodules is important in order to establish the diagnosis with certitude.

3D-Printed Atsttrin-Incorporated Alginate/Hydroxyapatite Scaffold Promotes Bone Defect Regeneration with TNF/TNFR Signaling Involvement.

PubMed

Wang, Quan; Xia, Qingqing; Wu, Yan; Zhang, Xiaolei; Wen, Feiqiu; Chen, Xiaowen; Zhang, Shufang; Heng, Boon Chin; He, Yong; Ouyang, Hong-Wei

2015-08-05

High expression levels of pro-inflammatory tumor necrosis factor (TNF)-α within bone defects can decelerate and impair bone regeneration. However, there are few available bone scaffolds with anti-inflammatory function. The progranulin (PGRN)-derived engineered protein, Atsttrin, is known to exert antagonistic effects on the TNF-α function. Hence, this study investigates whether 3D-printed Atsttrin-incorporated alginate(Alg)/hydroxyapatite(nHAp) scaffolds can facilitate bone healing through affecting the TNF/TNFR signaling. A 3D bioprinting system is used to fabricate Atsttrin-Alg/nHAp composite scaffolds, and the Atsttrin release from this scaffold is characterized, followed by evaluation of its efficacy on bone regeneration both in vitro and in vivo. The 3D-printed Atsttrin-Alg/nHAp scaffold exhibits a precisely defined structure, can sustain Atsttrin release for at least 5 days, has negligible cytotoxicity, and supports cell adhesion. Atsttrin can also attenuate the suppressive effects of TNF-α on BMP-2-induced osteoblastic differentiation in vitro. The 3D-printed Atsttrin-Alg/nHAp scaffold significantly reduces the number of TNF-α positive cells within wound sites, 7 days after post-calvarial defect surgery. Additionally, histological staining and X-ray scanning results also show that the 3D-printed Atsttrin-Alg/nHAp scaffold enhances the regeneration of mice calvarial bone defects. These findings thus demonstrate that the precise structure and anti-inflammatory properties of 3D-printed Atsttrin-Alg/nHAp scaffolds may promote bone defect repair. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Are Bones Alive?

ERIC Educational Resources Information Center

Caravita, Silvia; Falchetti, Elisabetta

2005-01-01

Many studies have investigated the classification of living things. Our study deals with a different problem: the attribution of life to one component of a living organism, specifically the bones. The task involves not only specifying what we mean by "alive", but also requires "informed thinking" leading to an understanding of…

A structural approach in the study of bones: fossil and burnt bones at nanosize scale

NASA Astrophysics Data System (ADS)

Piga, Giampaolo; Baró, Maria Dolors; Escobal, Irati Golvano; Gonçalves, David; Makhoul, Calil; Amarante, Ana; Malgosa, Assumpció; Enzo, Stefano; Garroni, Sebastiano

2016-12-01

We review the different factors affecting significantly mineral structure and composition of bones. Particularly, it is assessed that micro-nanostructural and chemical properties of skeleton bones change drastically during burning; the micro- and nanostructural changes attending those phases manifest themselves, amongst others, in observable alterations to the bones colour, morphology, microstructure, mechanical strength and crystallinity. Intense changes involving the structure and chemical composition of bones also occur during the fossilization process. Bioapatite material is contaminated by an heavy fluorination process which, on a long-time scale reduces sensibly the volume of the original unit cell, mainly the a-axis of the hexagonal P63/m space group. Moreover, the bioapatite suffers to a varying degree of extent by phase contamination from the nearby environment, to the point that rarely a fluorapatite single phase may be found in fossil bones here examined. TEM images supply precise and localized information, on apatite crystal shape and dimension, and on different processes that occur during thermal processes or fossilization of ancient bone, complementary to that given by X-ray diffraction and Attenuated Total Reflection Infrared spectroscopy. We are presenting a synthesis of XRD, ATR-IR and TEM results on the nanostructure of various modern, burned and palaeontological bones.

Feasibility of simultaneous measurement of bone formation and bone resorption markers to assess bone turnover rate in postmenopausal women: an EPOLOS study.

PubMed

Łukaszkiewicz, Jacek; Karczmarewicz, Elzbieta; Płudowski, Paweł; Jaworski, Maciej; Czerwiński, Edward; Lewiński, Andrzej; Marcinowska-Suchowierska, Ewa; Milewicz, Andrzej; Spaczyński, Marek; Lorenc, Roman S

2008-12-01

One of the most important risk factors for osteoporotic fractures in postmenopausal women is elevated bone turnover (EBT), occurring in 25-30% of this population. This study's aim was to find a correlation between bone resorption and bone formation markers to assess bone turnover rate and qualify an individual postmenopausal woman as a possible EBT subject. Three hundred twenty postmenopausal women (> or = one year after the last menstruation, < or = 70 years old) were enrolled at seven clinical sites in this cross-sectional observational study conducted within the EPOLOS. The group was a random sample of the population. The study was performed in a referral center involved in the diagnosis and treatment of osteoporosis. The exclusion criteria included pregnancy, cancer, fracture in the last year, and overweight (> 100 kg). Bone mineral density (BMD) measurements of the lumbar spine, total hip, trochanter, and femoral neck regions were performed. Bone resorption and formation rates were evaluated by serum levels of C-terminal telopeptide of type I collagen (CTX) and osteocalcin (OC), respectively. Using logistic regression to correlate the concentrations of CTX and OC it was possible not only to distinguish the EBT subgroup, but also to construct a simple nomogram for easy classification of individual patients as possible EBT subjects. EBT patients showed generally decreased BMD values and increased bone formation and resorption rates. Evaluation of both CTX and OC levels enables a more proper indication for EBT. The proposed nomogram may assist in evaluating outcome from the two markers of bone turnover.

Quantification of Bone Marrow Involvement in Treated Gaucher Disease With Proton MR Spectroscopy: Correlation With Bone Marrow MRI Scores and Clinical Status.

PubMed

Jaramillo, Diego; Bedoya, Maria A; Wang, Dah-Jyuu; Pena, Andres H; Delgado, Jorge; Jaimes, Camilo; Ho-Fung, Victor; Kaplan, Paige

2015-06-01

The objective of our study was to use proton MR spectroscopy (MRS) to quantitatively evaluate bone marrow infiltration by measuring the fat fraction (FF) and to compare the FF with semiquantitative bone marrow MRI scores and clinical status in children treated for type 1 Gaucher disease (GD). Over a 2-year period, we prospectively evaluated 10 treated GD patients (six males, four females; median age, 15.1 years) and 10 healthy age-matched control subjects (five males, five females; median age, 15.3 years) using 3-T proton MRS of L5 and the femoral neck. Water and lipid AUCs were measured to calculate the FF. Two blinded pediatric musculoskeletal radiologists performed a semiquantitative analysis of the conventional MR images using the bone marrow burden score and modified Spanish MRI score. We evaluated symptoms, spleen and liver volumes, platelet levels, hemoglobin levels, and bone complications. In the femur, the FF was higher in the control subjects (median, 0.71) than the GD patients (0.54) (p = 0.02). In L5, the difference in FF--higher FF in control subjects (0.37) than in GD patients (0.26)--was not significant (p = 0.16). In both groups and both regions, the FF increased with patient age (p < 0.02). Semiquantitative scores showed no differences between control subjects and treated GD patients (p > 0.11). Eight of 10 GD patients were asymptomatic and two had chronic bone pain. The median age of patients at symptom onset was 4.0 years, the median age of patients at the initiation of enzyme replacement therapy was 4.3 years, and the median treatment duration was 10.2 years. Hemoglobin level, platelet count, and liver volume at MRI were normal. Mean pretreatment spleen volume (15.4-fold above normal) decreased to 2.8-fold above normal at the time of MRI (p = 0.01). Proton MRS detected FF differences that were undetectable using conventional MRI; for that reason, proton MRS can be used to optimize treatment of GD patients.

The safety of bone allografts used in dentistry: a review.

PubMed

Holtzclaw, Dan; Toscano, Nicholas; Eisenlohr, Lisa; Callan, Don

2008-09-01

Recent media reports concerning "stolen body parts" have shaken the public's trust in the safety of and the use of ethical practices involving human allografts. The authors provide a comprehensive review of the safety aspects of human bone allografts. The authors reviewed U.S. government regulations, industry standards, independent industry association guidelines, company guidelines and scientific articles related to the use of human bone allografts in the practice of dentistry published in the English language. The use of human bone allografts in the practice of dentistry involves the steps of procurement, processing, use and tracking. Rigorous donor screening and aseptic proprietary processing programs have rendered the use of human bone allografts safe and effective as a treatment option. When purchasing human bone allografts for the practice of dentistry, one should choose products accredited by the American Association of Tissue Banks for meeting uniformly high safety and quality control measures. Knowledge of human bone allograft procurement, processing, use and tracking procedures may allow dental clinicians to better educate their patients and address concerns about this valuable treatment option.

Prebiotics and Bone.

PubMed

Whisner, Corrie M; Weaver, Connie M

2017-01-01

Recent advancements in food science have resulted in the extraction and synthesis of novel dietary fibers or prebiotics. Subsequently, great interest has emerged in developing strategies to improve metabolic conditions like osteoporosis by modulating the intestinal microbiome with fiber. Prebiotics have been shown to increase calcium absorption in the lower gut of both animals and humans as well as improve measures of bone mineral density and strength in rodent models. Fewer data are available in humans, but data from growing children and postmenopausal women suggest that prebiotics have both short- and long-term effects that beneficially affect bone turnover and mineral accretion in the skeleton. Currently, the exact mechanism by which these products elicit their effects on bone is poorly understood, but emerging data suggest that the gut microbiota may be involved in one or more direct and indirect pathways. The most well-accepted mechanism is through microbial fermentation of prebiotics which results in the production of short-chain fatty acids and a concomitant decrease in pH which increases the bioavailability of calcium in the colon. While other mechanisms may be eliciting a prebiotic effect on bone, the current data suggest that novel dietary fibers may be an affordable and effective method of maximizing mineral accretion in growing children and preventing bone loss in later years when osteoporosis is a greater risk. This chapter will discuss the dynamic role of prebiotics in bone health by discussing the current state of the art, addressing gaps in knowledge and their role in public health.

The role of pleiotrophin in bone repair.

PubMed

Lamprou, Margarita; Kaspiris, Angelos; Panagiotopoulos, Elias; Giannoudis, Peter V; Papadimitriou, Evangelia

2014-12-01

Bone has an enormous capacity for growth, regeneration, and remodelling, largely due to induction of osteoblasts that are recruited to the site of bone formation. Although the pathways involved have not been fully elucidated, it is well accepted that the immediate environment of the cells is likely to play a role via cell–matrix interactions, mediated by several growth factors. Formation of new blood vessels is also significant and interdependent to bone formation, suggesting that enhancement of angiogenesis could be beneficial during the process of bone repair. Pleiotrophin (PTN), also called osteoblast-specific factor 1, is a heparin-binding angiogenic growth factor, with a well-defined and significant role in both physiological and pathological angiogenesis. In this review we summarise the existing evidence on the role of PTN in bone repair.

Primary Ewing's Sarcoma of the Temporal Bone: A Rare Case Report and Literature Review.

PubMed

Gupta, Divya; Gulati, Achal; Purnima

2017-09-01

Ewing's sarcoma is a malignant, round cell tumor arising from the bones and primarily affecting children and adolescent, accounting for 3 % of all childhood malignancies. Although the long bones and the trunk are typically affected, rare cases of it involving isolated bones throughout the body have been reported. Involvement of the skull bones is rare, constituting 1-6 % of the total Ewing's sarcoma cases but those affecting the cranial bones are rarer still, constituting only 1 %. We describe an 8 months old infant having Ewing sarcoma, of the petrous and mastoid parts of temporal bone along with the occipital bone, whose clinical presentation mimicked mastoiditis with facial nerve palsy. We discuss the clinical and therapeutic course of an extensive primary Ewing sarcoma of the temporal bone, which was treated without performing surgery and review this entity's literature in detail.

[Progress of Masquelet technique to repair bone defect].

PubMed

Yin, Qudong; Sun, Zhenzhong; Gu, Sanjun

2013-10-01

To summarize the progress of Masquelet technique to repair bone defect. The recent literature concerning the application of Masquelet technique to repair bone defect was extensively reviewed and summarized. Masquelet technique involves a two-step procedure. First, bone cement is used to fill the bone defect after a thorough debridement, and an induced membrane structure surrounding the spacer formed; then the bone cement is removed after 6-8 weeks, and rich cancellous bone is implanted into the induced membrane. Massive cortical bone defect is repaired by new bone forming and consolidation. Experiments show that the induced membrane has vascular system and is also rich in vascular endothelial growth factor, transforming growth factor beta1, bone morphogenetic protein 2, and bone progenitor cells, so it has osteoinductive property; satisfactory results have been achieved in clinical application of almost all parts of defects, various types of bone defect and massive defect up to 25 cm long. Compared with other repair methods, Masquelet technique has the advantages of reliable effect, easy to operate, few complications, low requirements for recipient site, and wide application. Masquelet technique is an effective method to repair bone defect and is suitable for various types of bone defect, especially for bone defects caused by infection and tumor resection.

Exercise and bone mass in adults.

PubMed

Guadalupe-Grau, Amelia; Fuentes, Teresa; Guerra, Borja; Calbet, Jose A L

2009-01-01

There is a substantial body of evidence indicating that exercise prior to the pubertal growth spurt stimulates bone growth and skeletal muscle hypertrophy to a greater degree than observed during growth in non-physically active children. Bone mass can be increased by some exercise programmes in adults and the elderly, and attenuate the losses in bone mass associated with aging. This review provides an overview of cross-sectional and longitudinal studies performed to date involving training and bone measurements. Cross-sectional studies show in general that exercise modalities requiring high forces and/or generating high impacts have the greatest osteogenic potential. Several training methods have been used to improve bone mineral density (BMD) and content in prospective studies. Not all exercise modalities have shown positive effects on bone mass. For example, unloaded exercise such as swimming has no impact on bone mass, while walking or running has limited positive effects. It is not clear which training method is superior for bone stimulation in adults, although scientific evidence points to a combination of high-impact (i.e. jumping) and weight-lifting exercises. Exercise involving high impacts, even a relatively small amount, appears to be the most efficient for enhancing bone mass, except in postmenopausal women. Several types of resistance exercise have been tested also with positive results, especially when the intensity of the exercise is high and the speed of movement elevated. A handful of other studies have reported little or no effect on bone density. However, these results may be partially attributable to the study design, intensity and duration of the exercise protocol, and the bone density measurement techniques used. Studies performed in older adults show only mild increases, maintenance or just attenuation of BMD losses in postmenopausal women, but net changes in BMD relative to control subjects who are losing bone mass are beneficial in

Bone Densitometry (Bone Density Scan)

MedlinePlus

... News Physician Resources Professions Site Index A-Z Bone Densitometry (DEXA) Bone densitometry, also called dual-energy ... limitations of DEXA Bone Densitometry? What is a Bone Density Scan (DEXA)? Bone density scanning, also called ...

Flow cytometry in the bone marrow evaluation of follicular and diffuse large B-cell lymphomas.

PubMed

Palacio, C; Acebedo, G; Navarrete, M; Ruiz-Marcellán, C; Sanchez, C; Blanco, A; López, A

2001-09-01

Bone marrow biopsies are routinely performed in the staging of patients with lymphoma. Despite the lack of evidence for its usefulness, many institutions include flow cytometry (FC) of bone-marrow aspirates in an attempt to increase sensitivity and specificity. The aim of this study is to evaluate the usefulness of FC for the assessment of bone-marrow involvement by lymphoma in follicular (FL) and diffuse large B-cell lymphomas (DLBCL). Seventy-nine bone marrow biopsies from 65 patients diagnosed with FL or DLBCL were examined to compare histology and FC for the assessment of bone-marrow involvement by lymphoma. Bone marrow histology showed involvement (BM+) in 16 cases (20.3%), lack of infiltration (BM(-)) in 52 cases (65.8%) and undetermined or undiagnosed for involvement (BMu) in 11 cases (13.9%). FC was positive for involvement in 28 cases (35.4%) and negative in 51 cases (64.6%). 65 cases (95%) showed concordance between the results of morphology and FC (BM(+)/FC(+) or BM(-)/FC(-)). No BM(+)/FC(-) cases were observed. 3 cases showed discrepant results (BM(-)/FC(+)). In these 3 cases the molecular studies (PCR) demonstrated clonal rearrangement of the heavy immunoglobulin chain (IgH) and/or bcl2-IgH in agreement with the flow results. Among the 11 cases with BMu, all but 2 were FC(+) and concordance with the PCR results was seen in 9 cases (81.9%). We conclude that FC is just as sensitive or perhaps slightly more sensitive than histology in the detection of bone marrow involvement in FL and DLBCL. FC studies may be warranted in those cases in which the morphology is not diagnosed. The clinical relevance of the small clonal B-cell population in patients without histologic bone marrow involvement (BM(-)/FC(+) cases) remains an open question.

Cold-Induced Bone Lesions in the Domestic Feline.

DTIC Science & Technology

1980-05-01

injured and noninjured metatarsal bones demon- strated a true osteoporosis in the injured bone. Increased osteoclastic resorption, especially on the...proposed as the mediator of the unusual osteoporosis that involves primarily the periosteal envelope. ’ I I~F e ce s s i o n F or - DTIC TA9U ,,In-.1oncad...radiographically, for a maximum of 15 months post-injury. A clas- sification of bone change produced by frostbite was divided as follows:I (1) osteoporosis

Weight loss and bone mineral density.

PubMed

Hunter, Gary R; Plaisance, Eric P; Fisher, Gordon

2014-10-01

Despite evidence that energy deficit produces multiple physiological and metabolic benefits, clinicians are often reluctant to prescribe weight loss in older individuals or those with low bone mineral density (BMD), fearing BMD will be decreased. Confusion exists concerning the effects that weight loss has on bone health. Bone density is more closely associated with lean mass than total body mass and fat mass. Although rapid or large weight loss is often associated with loss of bone density, slower or smaller weight loss is much less apt to adversely affect BMD, especially when it is accompanied with high intensity resistance and/or impact loading training. Maintenance of calcium and vitamin D intake seems to positively affect BMD during weight loss. Although dual energy X-ray absorptiometry is normally used to evaluate bone density, it may overestimate BMD loss following massive weight loss. Volumetric quantitative computed tomography may be more accurate for tracking bone density changes following large weight loss. Moderate weight loss does not necessarily compromise bone health, especially when exercise training is involved. Training strategies that include heavy resistance training and high impact loading that occur with jump training may be especially productive in maintaining, or even increasing bone density with weight loss.

Histologic and morphologic evaluation of explanted bone anchors from bone-anchored hearing aids.

PubMed

Mlynski, Robert; Goldberg, Eva; Ebmeyer, Joerg; Scheich, Matthias; Gattenlöhner, Stefan; Schwager, Konrad; Hagen, Rudolf; Shehata-Dieler, Wafaa

2009-05-01

Bone-anchored hearing aids are a standard option in rehabilitation of patients with conductive or mixed hearing loss, and also CROS fitting. However, the skin-penetrating bone anchor repeatedly gives reason for discussion about the risk of infection of surrounding tissues as a major cause of malfunction. In the present study, explanted bone anchors with surrounding bone and soft tissue were examined and compared with the morphology of lost implants. The anchors originated from five patients. Two needed explantation due to deafness with the need of cochlea implantation. A third patient underwent explantation due to meningeal irritation by the bone anchor. Another patient lost the implant due to mechanical stress shortly after implantation. The last implant was lost in a child without apparent reason. All implants were clinically free of infection and had been stable for a median implantation period of 12 months. During the explantation procedure, the fixtures were recovered together with the attached soft tissue and bone. The specimens were examined by light microscopy or scanning electron microscopy (SEM). Sectioning for light microscopy was performed with a diamond-coated saw microtome. Histopathologic examination of the surrounding skin and subcutaneous soft tissue showed slight inflammation in one case only. The bone was regularly vital, presenting no signs of inflammation. The threads of the fixtures were filled with bone, with particularly strong attachment to the flank of traction. The SEM investigation exposed the ultrastructural interaction of bone with the implant surface. Filiform- and podocyte-like processes of osteocytes attach to the implant; lost implants did not reflect these features. Implant integration involves both osseointegration as well as soft tissue integration. Titanium oxide as the active implant surface promotes this integration even in unstable implants. The morphologic analysis exposed structural areas of the implant with weak bone

Nucleation of hydroxyapatite by bone sialoprotein.

PubMed Central

Hunter, G K; Goldberg, H A

1993-01-01

Bone sialoprotein (BSP) and osteopontin, the major phosphorylated proteins of mammalian bone, have been proposed to function in the initiation of mineralization. To test this hypothesis, the effects of BSP and osteopontin on hydroxyapatite crystal formation were determined by using a steady-state agarose gel system. At low calcium phosphate concentrations, no accumulation of calcium and phosphate occurred in control gels or gels containing osteopontin. Gels containing BSP at 1-5 micrograms/ml, however, exhibited a visible precipitation band and significantly elevated Ca + PO4 contents. By powder x-ray diffraction, the precipitate formed in the presence of BSP was shown to be hydroxyapatite. These findings suggest that bone sialoprotein may be involved in the nucleation of hydroxyapatite at the mineralization front of bone. Images Fig. 4 PMID:8397409

Bone biomaterials and interactions with stem cells

PubMed Central

Gao, Chengde; Peng, Shuping; Feng, Pei; Shuai, Cijun

2017-01-01

Bone biomaterials play a vital role in bone repair by providing the necessary substrate for cell adhesion, proliferation, and differentiation and by modulating cell activity and function. In past decades, extensive efforts have been devoted to developing bone biomaterials with a focus on the following issues: (1) developing ideal biomaterials with a combination of suitable biological and mechanical properties; (2) constructing a cell microenvironment with pores ranging in size from nanoscale to submicro- and microscale; and (3) inducing the oriented differentiation of stem cells for artificial-to-biological transformation. Here we present a comprehensive review of the state of the art of bone biomaterials and their interactions with stem cells. Typical bone biomaterials that have been developed, including bioactive ceramics, biodegradable polymers, and biodegradable metals, are reviewed, with an emphasis on their characteristics and applications. The necessary porous structure of bone biomaterials for the cell microenvironment is discussed, along with the corresponding fabrication methods. Additionally, the promising seed stem cells for bone repair are summarized, and their interaction mechanisms with bone biomaterials are discussed in detail. Special attention has been paid to the signaling pathways involved in the focal adhesion and osteogenic differentiation of stem cells on bone biomaterials. Finally, achievements regarding bone biomaterials are summarized, and future research directions are proposed. PMID:29285402

Open reduction and cranial bone plate fixation of fractures involving the distal aspect of the radius and ulna in miniature- and toy-breed dogs: 102 cases (2008-2015).

PubMed

De Arburn Parent, Rebecca; Benamou, Jérôme; Gatineau, Matthieu; Clerfond, Pierre; Planté, Jérôme

2017-06-15

OBJECTIVE To determine outcomes and complication rates of open reduction and cranial bone plate fixation of fractures involving the distal aspect of the radius and ulna in miniature- and toy-breed dogs. DESIGN Retrospective case series. ANIMALS 102 miniature- and toy-breed dogs (105 fractures) weighing ≤ 7 kg (15.4 lb) that had undergone open reduction and cranial bone plate fixation of a fracture involving the distal aspect of the radius and ulna from 2008 through 2015. PROCEDURES Medical records were reviewed and information extracted regarding dog and fracture characteristics, surgical variables, and follow-up examination data (including postoperative complications). Postoperative radiographs were examined for distal fragment size, implant placement, apposition, alignment, and healing stage. A long-term follow-up questionnaire was completed by telephone interview with dog owners at least 6 months after surgery. RESULTS Mean length of the distal bone fragment in all fractures was 19.2 mm, with a mean distal-to-total radial length ratio of 0.21. At last follow-up examination (typically 6 weeks after surgery), 97 (95%) dogs had no signs of lameness; minor lameness was identified in 5 (5%) dogs. Complications developed in 26 (25%) fractures (23 [22%] minor and 3 [3%] major complications). Sixty-eight of 71 (96%) owners rated the overall and long-term outcome as excellent and 3 (4%) as good; 68 of 71 (96%) dogs reportedly had no signs of residual lameness. CONCLUSIONS AND CLINICAL RELEVANCE Open reduction and cranial bone plate fixation for the treatment of radius-ulna fractures in miniature- and toy-breed dogs provided an excellent outcome with a low complication rate.

Comparative evaluation of guided tissue regeneration with use of collagen-based barrier freeze-dried dura mater allograft for mandibular class 2 furcation defects (a comparative controlled clinical study).

PubMed

Patel, Sandeep; Kubavat, Ajay; Ruparelia, Brijesh; Agarwal, Arvind; Panda, Anup

2012-01-01

The aim of periodontal surgery is complete regeneration. The present study was designed to evaluate and compare clinically soft tissue changes in form of probing pocket depth, gingival shrinkage, attachment level and hard tissue changes in form of horizontal and vertical bone level using resorbable membranes. Twelve subjects with bilateral class 2 furcation defects were selected. After initial phase one treatment, open debridement was performed in control site while freezedried dura mater allograft was used in experimental site. Soft and hard tissue parameters were registered intrasurgically. Nine months reentry ensured better understanding and evaluation of the final outcome of the study. Guided tissue regeneration is a predictable treatment modality for class 2 furcation defect. There was statistically significant reduction in pocket depth as compared to control (p < 0.01). There is statistically significant increase in periodontal attachment level within control and experimental sites showed better results (p < 0.01). For hard tissue parameter, significant defect fill resulted in experimental group, while in control group, less significant defect fill was found in horizontal direction and nonsignificant defect fill was found in vertical direction. The results showed statistically significant improvement in soft and hard tissue parameters and less gingival shrinkage in experimental sites compared to control site. The use of FDDMA in furcation defects helps us to achieve predictable results. This cross-linked collagen membrane has better handling properties and ease of procurement as well as economic viability making it a logical material to be used in regenerative surgeries.

Greater Bone Formation Induction Occurred in Aged than Young Cancellous Bone Sites

NASA Technical Reports Server (NTRS)

Ke, H. Z.; Jee, W. S. S.; Ito, H.; Setterberg, R. B.; Li, M.; Lin, B. Y.; Liang, X. G.; Ma, Y. F.

1993-01-01

We have determined the differences in the effects of continual prostaglandin E(sub 2) (PGE(sub 2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7-month-old Sprague-Dawley rats. The sites involved are the aged distal tibial metaphysis (DTM) with a closed epiphysis and the young proximal tibial metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE(sub 2)/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometry of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE(sub 2)/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE(sub 2) treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE(sub 2) treatment than young growing metaphysis.

A novel concept for smart trepanation.

PubMed

Follmann, Axel; Korff, Alexander; Fuertjes, Tobias; Kunze, Sandra C; Schmieder, Kirsten; Radermacher, Klaus

2012-01-01

Trepanation of the skull is a common procedure in craniofacial and neurosurgical interventions, allowing access to the innermost cranial structures. Despite a careful advancement, injury of the dura mater represents a frequent complication during these cranial openings. The technology of computer-assisted surgery offers different support systems such as navigated tools and surgical robots. This article presents a novel technical approach toward an image- and sensor-based synergistic control of the cutting depth of a manually guided soft-tissue-preserving saw. Feasibility studies in a laboratory setup modeling relevant skull tissue parameters demonstrate that errors due to computed tomography or magnetic resonance image segmentation and registration, optical tracking, and mechanical tolerances of up to 2.5 mm, imminent to many computer-assisted surgery systems, can be compensated for by the cutting tool characteristics without damaging the dura. In conclusion, the feasibility of a computer-controlled trepanation system providing a safer and efficient trepanation has been demonstrated. Injuries of the dura mater can be avoided, and the bone cutting gap can be reduced to 0.5 mm with potential benefits for the reintegration of the bone flap.

Phase field approaches of bone remodeling based on TIP

NASA Astrophysics Data System (ADS)

Ganghoffer, Jean-François; Rahouadj, Rachid; Boisse, Julien; Forest, Samuel

2016-01-01

The process of bone remodeling includes a cycle of repair, renewal, and optimization. This adaptation process, in response to variations in external loads and chemical driving factors, involves three main types of bone cells: osteoclasts, which remove the old pre-existing bone; osteoblasts, which form the new bone in a second phase; osteocytes, which are sensing cells embedded into the bone matrix, trigger the aforementioned sequence of events. The remodeling process involves mineralization of the bone in the diffuse interface separating the marrow, which contains all specialized cells, from the newly formed bone. The main objective advocated in this contribution is the setting up of a modeling and simulation framework relying on the phase field method to capture the evolution of the diffuse interface between the new bone and the marrow at the scale of individual trabeculae. The phase field describes the degree of mineralization of this diffuse interface; it varies continuously between the lower value (no mineral) and unity (fully mineralized phase, e.g. new bone), allowing the consideration of a diffuse moving interface. The modeling framework is the theory of continuous media, for which field equations for the mechanical, chemical, and interfacial phenomena are written, based on the thermodynamics of irreversible processes. Additional models for the cellular activity are formulated to describe the coupling of the cell activity responsible for bone production/resorption to the kinetics of the internal variables. Kinetic equations for the internal variables are obtained from a pseudo-potential of dissipation. The combination of the balance equations for the microforce associated to the phase field and the kinetic equations lead to the Ginzburg-Landau equation satisfied by the phase field with a source term accounting for the dissipative microforce. Simulations illustrating the proposed framework are performed in a one-dimensional situation showing the evolution of

Noninvasive imaging of bone microarchitecture

PubMed Central

Patsch, Janina M.; Burghardt, Andrew J.; Kazakia, Galateia; Majumdar, Sharmila

2015-01-01

The noninvasive quantification of peripheral compartment-specific bone microarchitecture is feasible with high-resolution peripheral quantitative computed tomography (HR-pQCT) and high-resolution magnetic resonance imaging (HR-MRI). In addition to classic morphometric indices, both techniques provide a suitable basis for virtual biomechanical testing using finite element (FE) analyses. Methodical limitations, morphometric parameter definition, and motion artifacts have to be considered to achieve optimal data interpretation from imaging studies. With increasing availability of in vivo high-resolution bone imaging techniques, special emphasis should be put on quality control including multicenter, cross-site validations. Importantly, conclusions from interventional studies investigating the effects of antiosteoporotic drugs on bone microarchitecture should be drawn with care, ideally involving imaging scientists, translational researchers, and clinicians. PMID:22172043

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

PubMed

Hambli, Ridha

2014-01-01

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

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

What Is Breast in the Bone?

PubMed

Shemanko, Carrie S; Cong, Yingying; Forsyth, Amanda

2016-10-22

The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%-50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural "recycling" of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle.

Drilling of bone: A comprehensive review

PubMed Central

Pandey, Rupesh Kumar; Panda, S.S.

2013-01-01

Background Bone fracture treatment usually involves restoring of the fractured parts to their initial position and immobilizing them until the healing takes place. Drilling of bone is common to produce hole for screw insertion to fix the fractured parts for immobilization. Orthopaedic drilling during surgical process causes increase in the bone temperature and forces which can cause osteonecrosis reducing the stability and strength of the fixation. Methods A comprehensive review of all the relevant investigations carried on bone drilling is conducted. The experimental method used, results obtained and the conclusions made by the various researchers are described and compared. Result Review suggests that the further improvement in the area of bone drilling is possible. The systematic review identified several consequential factors (drilling parameters and drill specifications) affecting bone drilling on which there no general agreement among investigators or are not adequately evaluated. These factors are highlighted and use of more advanced methods of drilling is accentuated. The use of more precise experimental set up which resembles the actual situation and the development of automated bone drilling system to minimize human error is addressed. Conclusion In this review, an attempt has been made to systematically organize the research investigations conducted on bone drilling. Methods of treatment of bone fracture, studies on the determination of the threshold for thermal osteonecrosis, studies on the parameters influencing bone drilling and methods of the temperature measurement used are reviewed and the future work for the further improvement of bone drilling process is highlighted. PMID:26403771

Applications of transgenics in studies of bone sialoprotein.

PubMed

Zhang, Jin; Tu, Qisheng; Chen, Jake

2009-07-01

Bone sialoprotein (BSP) is a major non-collagenous protein in mineralizing connective tissues such as dentin, cementum and calcified cartilage tissues. As a member of the Small Integrin-Binding Ligand, N-linked Glycoprotein (SIBLING) gene family of glycoproteins, BSP is involved in regulating hydroxyapatite crystal formation in bones and teeth, and has long been used as a marker gene for osteogenic differentiation. In the most recent decade, new discoveries in BSP gene expression and regulation, bone remodeling, bone metastasis, and bone tissue engineering have been achieved with the help of transgenic mice. In this review, we discuss these new discoveries obtained from the literatures and from our own laboratory, which were derived from the use of transgenic mouse mutants related to BSP gene or its promoter activity.

Development of Bone Targeting Drugs.

PubMed

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

2017-06-23

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

Development of Bone Targeting Drugs

PubMed Central

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2017-01-01

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

Bone age in cerebral palsy

PubMed Central

Miranda, Eduardo Régis de Alencar Bona; Palmieri, Maurício D'arc; de Assumpção, Rodrigo Montezuma César; Yamada, Helder Henzo; Rancan, Daniela Regina; Fucs, Patrícia Maria de Moraes Barros

2013-01-01

Objective To compare the chronological age and bone age among cerebral palsy patients in the outpatient clinic and its correlation with the type of neurological involvement, gender and functional status. Methods 401 patients with spastic cerebral palsy, and ages ranging from three months to 20 years old, submitted to radiological examination for bone age and analyzed by two independent observers according Greulich & Pyle. Results In the topographic distribution, there was a significant delay (p<0.005) in tetraparetic (17.7 months), hemiparetic (10.1 months), and diparetic patients (7.9 months). In the hemiparetic group, the mean bone age in the affected side was 96.88 months and the uncompromised side was 101.13 months (p<0.005). Regarding functional status, the ambulatory group showed a delay of 18.73 months in bone age (p<0.005). Comparing bone age between genders, it was observed a greater delay in males (13.59 months) than in females (9.63 months), but not statistically significant (p = 0.54). Conclusion There is a delay in bone age compared to chronological age influenced by the topography of spasticity, functional level and gender in patients with cerebral palsy. Level of Evidence IV, Case Series. PMID:24453693

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

PubMed

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

2015-11-01

Vitamin C is an important antioxidant and cofactor that is involved in the regulation of development, function, and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain, and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures. © 2015 American Society for Bone and Mineral Research.

Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling

PubMed Central

Accardi, Fabrizio; Toscani, Denise; Dalla Palma, Benedetta; Aversa, Franco; Giuliani, Nicola

2015-01-01

Multiple myeloma (MM) is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI) bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease. PMID:26579531

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

PubMed Central

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-01-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

PubMed

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

Why does starvation make bones fat?

PubMed Central

Devlin, Maureen J.

2011-01-01

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. Here I review the possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? To evaluate these possibilities, here I review what is known about the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance. PMID:21793093

Why does starvation make bones fat?

PubMed

Devlin, Maureen J

2011-01-01

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. This review considers several possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? These possibilities are evaluated in terms of the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance. Copyright © 2011 Wiley-Liss, Inc.

Osteosarcoma and MFH of Bone Treatment (PDQ®)—Patient Version

Cancer.gov

Osteosarcoma and malignant fibrous histiocytoma (MFH) of the bone treatment usually involves surgery to remove the tumor. Chemotherapy, radiation therapy, and/or targeted therapy may also be used. Learn more about osteosarcoma and MFH of bone in this expert-reviewed summary.

Aging and bone loss: new insights for the clinician

PubMed Central

Demontiero, Oddom; Vidal, Christopher

2012-01-01

It is well known that the underlying mechanisms of osteoporosis in older adults are different than those associated with estrogen deprivation. Age-related bone loss involves a gradual and progressive decline, which is also seen in men. Markedly increased bone resorption leads to the initial fall in bone mineral density. With increasing age, there is also a significant reduction in bone formation. This is mostly due to a shift from osteoblastogenesis to predominant adipogenesis in the bone marrow, which also has a lipotoxic effect that affects matrix formation and mineralization. We review new evidence on the pathophysiology of age-related bone loss with emphasis upon the mechanism of action of current osteoporosis treatments. New potential treatments are also considered, including therapeutic approaches to osteoporosis in the elderly that focus on the pathophysiology and potential reversal of adipogenic shift in bone. PMID:22870496

Occurrence and pattern of long bone fractures in growing dogs with normal and osteopenic bones.

PubMed

Kumar, K; Mogha, I V; Aithal, H P; Kinjavdekar, P; Singh, G R; Pawde, A M; Kushwaha, R B

2007-11-01

A retrospective study was undertaken to record the occurrence and pattern of long bone fractures, and the efficacy of Intramedullary (IM) Steinmann pin fixing in growing dogs. All the records of growing dogs during a 10-year-period were screened to record the cause of trauma, the age and sex of the animal, the bone involved, the type and location of the fracture, the status of fixation, alignment, maintenance of fixation and fracture healing. The results were analysed and comparisons were made between growing dogs with normal and osteopenic bones. Among the 310 cases of fractures recorded, the bones were osteopenic in 91 cases (29%). Minor trauma was the principal cause of fracture in dogs with osteopenia (25%), and indigenous breeds were most commonly affected (38%). Fractures in dogs with osteopenic bones were most commonly recorded in the age group of 2-4 months (53%), whereas fractures in normal dogs were almost equally distributed between 2 and 8 months of age. Male dogs were affected significantly more often in both groups. In osteopenic bones, most fractures were recorded in the femur (56%), and they were distributed equally along the length of the bone. Whereas in normal bones, fractures were almost equally distributed in radius/ulna, femur and tibia, and were more often recorded at the middle and distal third of long bones. Oblique fractures were most common in both groups; however, comminuted fractures were more frequent in normal bones, whereas incomplete fractures were more common in osteopenic bones. Ninety-nine fracture cases treated with IM pinning (66 normal, 33 osteopenic) were evaluated for the status of fracture reduction and healing. In a majority of the cases (61%) with osteopenic bones, the diameter of the pin was relatively smaller than the diameter of the medullary cavity (<70-75%), whereas in 68% of the cases in normal bones the pin diameter was optimum. The status of fracture fixing was satisfactory to good in significantly more

Extracorporeal human bone-like tissue generation

PubMed Central

Rosenberg, N.; Rosenberg, O.

2012-01-01

Objectives The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation. Methods Human osteoblast-like cells were seeded on porous granules of tricalcium phosphate and incubated in osteogenic media while exposed to mechanical stimulation by vibration in the infrasonic range of frequencies. The generated tissue was examined microscopically following haematoxylin eosin, trichrome and immunohistochemical staining. Results Following 14 days of incubation the generated tissue showed histological characteristics of bone-like material due to the characteristic eosinophilic staining, a positive staining for collagen trichrome and a positive specific staining for osteocalcin and collagen 1. Macroscopically, this tissue appeared in aggregates of between 0.5 cm and 2 cm. Conclusions We present evidence that the interaction of the cellular, inorganic and mechanical components in vitro can rapidly generate three-dimensional bone-like tissue that might be used as an autologous bone graft. PMID:23610651

Virtual temporal bone dissection system: OSU virtual temporal bone system: development and testing.

PubMed

Wiet, Gregory J; Stredney, Don; Kerwin, Thomas; Hittle, Bradley; Fernandez, Soledad A; Abdel-Rasoul, Mahmoud; Welling, D Bradley

2012-03-01

The objective of this project was to develop a virtual temporal bone dissection system that would provide an enhanced educational experience for the training of otologic surgeons. A randomized, controlled, multi-institutional, single-blinded validation study. The project encompassed four areas of emphasis: structural data acquisition, integration of the system, dissemination of the system, and validation. Structural acquisition was performed on multiple imaging platforms. Integration achieved a cost-effective system. Dissemination was achieved on different levels including casual interest, downloading of software, and full involvement in development and validation studies. A validation study was performed at eight different training institutions across the country using a two-arm randomized trial where study subjects were randomized to a 2-week practice session using either the virtual temporal bone or standard cadaveric temporal bones. Eighty subjects were enrolled and randomized to one of the two treatment arms; 65 completed the study. There was no difference between the two groups using a blinded rating tool to assess performance after training. A virtual temporal bone dissection system has been developed and compared to cadaveric temporal bones for practice using a multicenter trial. There was no statistical difference between practice on the current simulator compared to practice on human cadaveric temporal bones. Further refinements in structural acquisition and interface design have been identified, which can be implemented prior to full incorporation into training programs and used for objective skills assessment. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury.

PubMed

Wang, Lei; Liu, Linjuan; Pan, Zhanpeng; Zeng, Yanjun

2015-11-16

Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.

Italian Multicenter Study on Accuracy of 18F-FDG PET/CT in Assessing Bone Marrow Involvement in Pediatric Hodgkin Lymphoma.

PubMed

Cistaro, Angelina; Cassalia, Laura; Ferrara, Cinzia; Quartuccio, Natale; Evangelista, Laura; Bianchi, Maurizio; Fagioli, Franca; Bisi, Gianni; Baldari, Sergio; Zanella, Alessandro; Pillon, Marta; Zucchetta, Pietro; Burei, Marta; Sala, Alessandra; Guerra, Luca; Guglielmo, Priscilla; Burnelli, Roberta; Panareo, Stefano; Scalorbi, Federica; Rambaldi, Ilaria; Piccardo, Arnoldo; Garaventa, Alberto; Familiari, Demetrio; Fornito, Maria Concetta; Lopci, Egesta; Mascarin, Maurizio; Altini, Corinna; Ferrari, Cristina; Perillo, Teresa; Santoro, Nicola; Borsatti, Eugenio; Rubini, Giuseppe

2018-06-01

The present study investigated the utility of fluorine-18 ( 18 F) fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in newly diagnosed pediatric Hodgkin lymphoma (HL). A total of 224 pediatric patients with HL underwent 18 F-FDG PET/CT at staging. BMB or follow-up imaging was used as the standard of reference for the evaluation of BMI. 18 F-FDG PET/CT was negative for BMI in 193 cases. Of the 193 patients, the findings for 16 were originally reported as doubtful and later interpreted as negative for BMI, with negative findings on follow-up imaging and BMB. At BMB, 1 of the 16 patients (6.25%) had BMI. Of the 193 patients, 192 (99.48%) had negative BMB findings. Thus, the 18 F-FDG PET/CT findings were truly negative for 192 patients and falsely negative for 1 patient for BMI. 18 F-FDG PET/CT showed high diagnostic performance in the evaluation of BMI in pediatric HL. Thus, BMB should be ideally reserved for patients presenting with doubtful 18 F-FDG PET/CT findings for BMI. Copyright © 2018 Elsevier Inc. All rights reserved.

Bone marrow derived stem cells in joint and bone diseases: a concise review.

PubMed

Marmotti, Antonio; de Girolamo, Laura; Bonasia, Davide Edoardo; Bruzzone, Matteo; Mattia, Silvia; Rossi, Roberto; Montaruli, Angela; Dettoni, Federico; Castoldi, Filippo; Peretti, Giuseppe

2014-09-01

Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients' life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a "reservoir" of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called "stem cell niche" was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the

Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma.

PubMed

Holmer, Helene; Popovic, Vera; Ekman, Bertil; Follin, Cecilia; Siversson, Ann Britt; Erfurth, Eva Marie

2011-07-01

Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment. The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures. BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls. Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (P=0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels ≤-2.0 s.d. Furthermore, 75% of those with a Z-score ≤-2.0 s.d. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only. Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.

Chitosan based nanofibers in bone tissue engineering.

PubMed

Balagangadharan, K; Dhivya, S; Selvamurugan, N

2017-11-01

Bone tissue engineering involves biomaterials, cells and regulatory factors to make biosynthetic bone grafts with efficient mineralization for regeneration of fractured or damaged bones. Out of all the techniques available for scaffold preparation, electrospinning is given priority as it can fabricate nanostructures. Also, electrospun nanofibers possess unique properties such as the high surface area to volume ratio, porosity, stability, permeability and morphological similarity to that of extra cellular matrix. Chitosan (CS) has a significant edge over other materials and as a graft material, CS can be used alone or in combination with other materials in the form of nanofibers to provide the structural and biochemical cues for acceleration of bone regeneration. Hence, this review was aimed to provide a detailed study available on CS and its composites prepared as nanofibers, and their associated properties found suitable for bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Applications of Transgenics in Studies of Bone Sialoprotein

PubMed Central

Zhang, Jin; Tu, Qisheng; Chen, Jake

2010-01-01

Bone sialoprotein (BSP) is a major non-collagenous protein in mineralizing connective tissues such as dentin, cementum and calcified cartilage tissues. As a member of the SIBLING (Small Integrin-Binding Ligand, N-linked Glycoprotein) gene family of glycoproteins, BSP is involved in regulating hydroxyapatite crystal formation in bones and teeth, and has long been used as a marker gene for osteogenic differentiation. In the most recent decade, new discoveries in BSP gene expression and regulation, bone remodeling, bone metastasis, and bone tissue engineering have been achieved with the help of transgenic mice. In this review, we discuss these new discoveries obtained from the literatures and from our own laboratory, which were derived from the use of transgenic mouse mutants related to BSP gene or its promoter activity. PMID:19326395

Sarcoidosis: nail dystrophy without underlying bone changes.

PubMed

Wakelin, S H; James, M P

1995-06-01

Sarcoidosis is a chronic granulomatous disease of unknown origin that affects multiple organs and may present with a variety of skin lesions. Involvement of the nails is rare and almost invariably associated with underlying bone disease. We describe a patient with sarcoid nail dystrophy in whom this diagnosis was confirmed by a proximal nail fold biopsy. Radiologic investigation did not show evidence of an associated bone dystrophy in this case.

Whole bone mechanics and bone quality.

PubMed

Cole, Jacqueline H; van der Meulen, Marjolein C H

2011-08-01

The skeleton plays a critical structural role in bearing functional loads, and failure to do so results in fracture. As we evaluate new therapeutics and consider treatments to prevent skeletal fractures, understanding the basic mechanics underlying whole bone testing and the key principles and characteristics contributing to the structural strength of a bone is critical. We therefore asked: (1) How are whole bone mechanical tests performed and what are the key outcomes measured? (2) How do the intrinsic characteristics of bone tissue contribute to the mechanical properties of a whole bone? (3) What are the effects of extrinsic characteristics on whole bone mechanical behavior? (4) Do environmental factors affect whole bone mechanical properties? We conducted a PubMed search using specific search terms and limiting our included articles to those related to in vitro testing of whole bones. Basic solid mechanics concepts are summarized in the context of whole bone testing and the determinants of whole bone behavior. Whole bone mechanical tests measure structural stiffness and strength from load-deformation data. Whole bone stiffness and strength are a function of total bone mass and the tissue geometric distribution and material properties. Age, sex, genetics, diet, and activity contribute to bone structural performance and affect the incidence of skeletal fractures. Understanding and preventing skeletal fractures is clinically important. Laboratory tests of whole bone strength are currently the only measures for in vivo fracture prediction. In the future, combined imaging and engineering models may be able to predict whole bone strength noninvasively.

Utilization of ring-shaped bone allograft for surgical treatment of adolescent post-tubercular kyphosis

PubMed Central

Yin, Xiang; Liu, Peng; Liu, Yao-yao; Fan, Wei-Li; Liu, Bai-yi; Zhao, Jian-Hua

2017-01-01

Abstract This study aimed to investigate the mid-term outcome of ring-shaped bone allografts in the surgical treatment of adolescent post-tubercular kyphosis secondary to spinal tuberculosis. The records of adolescent patients diagnosed with spinal tuberculosis who received treatment in our department between 2009 and 2013 were retrospectively reviewed. The anterior approach was used in cases of cervical kyphosis and the posterior approach was used in cases of thoracic and lumbar kyphosis. During the surgery, the ring-shaped bone was used as a structural bone graft associated with the cancellous bone filing in the center portion of the ring shape. Cobb's angle, signs of spinal infusion on computed tomography, and complications were followed up. A total of 25 patients were included in our study. Among them, 3 involved the cervical region, 5 involved the thoracic region, 8 involved the thoracolumbar region, and 9 involved the lumbar region. The preoperative kyphosis deformity was a mean 65° Cobb's angle (40°–97°) compared to the postoperative 14° Cobb's angle (10°–21°) for an average correction of 51°. All wounds healed well without graft rejection. All patients achieved bone fusion 3 months postoperative for a 100% fusion rate. Our results show that the ring-shaped allograft bone is an effective option for the treatment of adolescent kyphosis. The ring-shaped allograft bone demonstrated satisfactory mechanical strength and vertebral fusion without mid-term metallic toxicity. PMID:28614236

Isolated juvenile xanthogranuloma in the bone marrow: report of a case and review of the literature.

PubMed

Kesserwan, Chimen; Boué, Daniel R; Kahwash, Samir B

2007-01-01

We report a case of juvenile xanthogranuloma limited to involvement of the bone marrow in a 6-week-old male infant. Evaluation of the bone marrow was a part of the workup for peripheral blood cytopenia. Examination showed hypercellular marrow with paratrabecular clusters of lipidized histiocytes positive for CD68, CD4, and factor XIII(a) and negative for S100 and CD1a. Clinical and radiological workup showed no associated skin lesions or osseous or visceral involvement. The patient was started on chemotherapy with clinical improvement and gradual decreased bone marrow involvement. The child is alive and well at 16 months of age. This case represents, to the best of our knowledge, the 1st documented case of juvenile xanthogranuloma with isolated bone marrow involvement sparing skin and viscera.

Protein kinase Cα (PKCα) regulates bone architecture and osteoblast activity.

PubMed

Galea, Gabriel L; Meakin, Lee B; Williams, Christopher M; Hulin-Curtis, Sarah L; Lanyon, Lance E; Poole, Alastair W; Price, Joanna S

2014-09-12

Bones' strength is achieved and maintained through adaptation to load bearing. The role of the protein kinase PKCα in this process has not been previously reported. However, we observed a phenotype in the long bones of Prkca(-/-) female but not male mice, in which bone tissue progressively invades the medullary cavity in the mid-diaphysis. This bone deposition progresses with age and is prevented by disuse but unaffected by ovariectomy. Castration of male Prkca(-/-) but not WT mice results in the formation of small amounts of intramedullary bone. Osteoblast differentiation markers and Wnt target gene expression were up-regulated in osteoblast-like cells derived from cortical bone of female Prkca(-/-) mice compared with WT. Additionally, although osteoblastic cells derived from WT proliferate following exposure to estradiol or mechanical strain, those from Prkca(-/-) mice do not. Female Prkca(-/-) mice develop splenomegaly and reduced marrow GBA1 expression reminiscent of Gaucher disease, in which PKC involvement has been suggested previously. From these data, we infer that in female mice, PKCα normally serves to prevent endosteal bone formation stimulated by load bearing. This phenotype appears to be suppressed by testicular hormones in male Prkca(-/-) mice. Within osteoblastic cells, PKCα enhances proliferation and suppresses differentiation, and this regulation involves the Wnt pathway. These findings implicate PKCα as a target gene for therapeutic approaches in low bone mass conditions. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Bone growth and bone development in the presence of implants or after induced leg-lengthening studied using the Oxford Scanning Proton Microprobe

NASA Astrophysics Data System (ADS)

Pålsgård, Eva; Johansson, Carina; Li, Gang; Grime, Geoff W.; Triffitt, J. T.

1997-07-01

To respond to varying environmental demands the bone tissue in the body is under continual reconstruction throughout life. It is known that metallic elements are important for maintaining normal bone structure, but their roles are not well understood. More information about the effects of metal excess or deficiency is needed to help in the development of metallic bone implants and to improve the treatment of bone fractures and defects. The Oxford Scanning Proton Microprobe (SPM) is being applied in two studies involving metal ions in bone: (1) bone regrowth and bonding to titanium bone implants may be influenced by diffusion of Ti ions into the bone. We are using microPIXE to determine the metal ion content of bone developing in contact with implants of pure Nb, Ti and Ti alloys. (2) Bone lengthening as a surgical procedure is induced by fracturing the bone and allowing it to heal with a small gap between the fractured ends created by the use of external fixators. The gap can be slowly increased during the healing process to stimulate the production of new bone. The enzymes and other constituents of the developing bone need certain metals for their function. Using experimental animals we have studied the concentrations of the metals and whether a deficiency of trace metals limits the optimum rate of bone lengthening.

Unusual localizations of unicameral bone cysts and aneurysmal bone cysts: A retrospective review of 451 cases.

PubMed

Aycan, Osman Emre; Çamurcu, İsmet Yalkın; Özer, Devrim; Arıkan, Yavuz; Kabukçuoğlu, Yavuz Selim

2015-06-01

Unicameral bone cysts (UBC) and aneurysmal bone cysts (ABC) are benign cystic lesions of bone which are easily diagnosed. However, unusual locations may lead to a false diagnosis. Therefore the aim of this retrospective study was to determine the frequency of unusual localizations. The authors studied 451 cases with histopathologically confirmed diagnosis of UBC or ABC, seen between 1981 and 2012. In the UBC group (352 cases) humerus, femur and calcaneus were found to be the most common sites, while acetabulum, scapula, scaphoid, lunatum, metacarpals, metatarsals, toe phalanges and ulna each accounted for less than 1%. In the ABC group (99 cases) the most common sites of involvement were femur, humerus and tibia, while finger phalanges, ilium, acetabulum, pubis, calcaneus, cuboid, and toe phalanges each accounted for only 1%. The differential diagnosis of cystic bone lesions should include both UBC and ABC. Pain complaints plead for the latter, except in case of fracture.

Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis

PubMed Central

Goldstein, Robert H; Reagan, Michaela R; Anderson, Kristen; Kaplan, David L; Rosenblatt, Michael

2010-01-01

American women have a nearly 25% lifetime risk of developing breast cancer, with 20–40% of these patients developing life-threatening metastases. Over 70% of patients presenting with metastases have skeletal involvement, which signals progression to an incurable stage. Tumor-stroma cell interactions are only superficially understood, specifically regarding the ability of stromal cells to affect metastasis. In vivo models show that exogenously supplied hBMSCs (human bone-marrow derived stem cells) migrate to breast cancer tumors, but no reports have shown endogenous hBMSC migration from the bone to primary tumors. Here we present a model of in vivo hBMSC migration from a physiologic human bone environment to human breast tumors. Further, hBMSCs alter tumor growth and bone metastasis frequency. hBMSCs may home to certain breast tumors based on tumor-derived TGF-β1. Moreover, at the primary tumor IL-17B/IL-17BR signaling may mediate interactions between hBMSCs and breast cancer cells (BCCs). PMID:21159629

Detecting microdamage in bone.

PubMed

Lee, T C; Mohsin, S; Taylor, D; Parkesh, R; Gunnlaugsson, T; O'Brien, F J; Giehl, M; Gowin, W

2003-08-01

Fatigue-induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre-existing microdamage sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site-specific. Cracks are discontinuities in the calcium-rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed--fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non-invasive method is needed to measure microdamage in patients. Micro-CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis.

A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation

PubMed Central

Kozhemyakina, Elena; Lassar, Andrew B.; Zelzer, Elazar

2015-01-01

Decades of work have identified the signaling pathways that regulate the differentiation of chondrocytes during bone formation, from their initial induction from mesenchymal progenitor cells to their terminal maturation into hypertrophic chondrocytes. Here, we review how multiple signaling molecules, mechanical signals and morphological cell features are integrated to activate a set of key transcription factors that determine and regulate the genetic program that induces chondrogenesis and chondrocyte differentiation. Moreover, we describe recent findings regarding the roles of several signaling pathways in modulating the proliferation and maturation of chondrocytes in the growth plate, which is the ‘engine’ of bone elongation. PMID:25715393

Enhanced bone screw fixation with biodegradable bone cement in osteoporotic bone model.

PubMed

Juvonen, Tiina; Koistinen, Arto; Kröger, Heikki; Lappalainen, Reijo

2012-09-27

The purpose of this study was to study the potential of novel biodegradable PCL bone cement to improve bone screw fixation strength in osteoporotic bone. The biomechanical properties of bone cement (ε-polycaprolactone, PCL) and fixation strength were studied using biomechanical tests and bone screws fixed in an osteoporotic bone model. Removal torques and pullout strengths were assessed for cortical, self-tapping, and cancellous screws inserted in the osteoporotic bone model (polyurethane foam blocks with polycarbonate plate) with and without PCL bone cement. Open cell and cellular rigid foam blocks with a density of 0.12 g/cm3 were used in this model. Removal torques were significantly (more than six-fold) improved with bone cement for cancellous screws. Furthermore, the bone cement improved pullout strengths three to 12 times over depending on the screw and model material. Biodegradable bone cement turned out to be a very potential material to stabilize screw fixation in osteoporotic bone. The results warrant further research before safe clinical use, especially to clarify clinically relevant factors using real osteoporotic bone under human body conditions and dynamic fatigue testing for long-term performance.

[Mechanobiology and bone metabolism: Clinical relevance for fracture treatment].

PubMed

Haffner-Luntzer, M; Liedert, A; Ignatius, A

2015-12-01

Mechanical stimuli are known to significantly influence bone metabolism and fracture healing. Various studies have demonstrated the involvement of complex molecular mechanotransduction pathways, such as the Wnt/beta-catenin, bone morphogenetic protein (BMP) and estrogen receptor signaling pathways in mechanotransduction. Mechanotransduction is influenced by aging and the comorbidities of the patient. Pharmacological modulation of signal transduction influences bone formation and the mechanosensitivity of skeletal tissue. The combination of pharmacological and biomechanical therapies may be useful for the treatment of fractures with impaired healing.

Common endocrine control of body weight, reproduction, and bone mass

NASA Technical Reports Server (NTRS)

Takeda, Shu; Elefteriou, Florent; Karsenty, Gerard

2003-01-01

Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

Optical Fourier diffractometry applied to degraded bone structure recognition

NASA Astrophysics Data System (ADS)

Galas, Jacek; Godwod, Krzysztof; Szawdyn, Jacek; Sawicki, Andrzej

1993-09-01

Image processing and recognition methods are useful in many fields. This paper presents the hybrid optical and digital method applied to recognition of pathological changes in bones involved by metabolic bone diseases. The trabecular bone structure, registered by x ray on the photographic film, is analyzed in the new type of computer controlled diffractometer. The set of image parameters, extracted from diffractogram, is evaluated by statistical analysis. The synthetic image descriptors in discriminant space, constructed on the base of 3 training groups of images (control, osteoporosis, and osteomalacia groups) by discriminant analysis, allow us to recognize bone samples with degraded bone structure and to recognize the disease. About 89% of the images were classified correctly. This method after optimization process will be verified in medical investigations.

Assessment of bone mineral status in children with Marfan syndrome

USDA-ARS?s Scientific Manuscript database

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-ßeta, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone minerali...

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

PubMed Central

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

2016-01-01

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

Treating Families of Bone Marrow Recipients and Donors

ERIC Educational Resources Information Center

Cohen, Marie; And Others

1977-01-01

Luekemia and aplastic anemia are beginning to be treated by bone marrow transplants, involving donors and recipients from the same family. Such intimate involvement in the patient's life and death struggles typically produces a family crisis and frequent maladaptive responses by various family members. (Author)

Bone scintigraphy elucidates different metabolic stages of melorheostosis.

PubMed

Izadyar, Sina; Gholamrezanezhad, Ali

2012-01-01

Melorheostosis is a rare benign non-hereditary sclerosing dysplasia involving the bone, often in a sclerotomal distribution. we report the case of a 27 years old lady with painful swelling of the left hand and forearm lasting for almost 15 years. The patient experienced aggravation of symptoms and limitation of motion during the past two months. Radiographic assessment revealed hyperostosis involving the left 3(rd) and 4(th) metacarpal bones and corresponding digits as well as the left ulna and distal humerus, with no soft tissue ossification. Angiographic and blood pool images of bone scintigraphy showed increased activity of mid-metacarpal region, corresponding to the sclerotom C-8. Delayed static views showed increased radiotracer uptake of the left 4(th) metacarpal bone and the corresponding digit as well as the left ulna and humerus, but no abnormal osteoblastic activity of the 3(rd) left metacarpal and digit. Histopathologic assessment confirmed the diagnosis of Melorheostosis. The case confirms that even in the same sclerotomal distribution, the multiple foci of involvement can present in different metabolic stages. In fact, the disease does not progress uniformly and different lesions can be seen in dissimilar stages of activity. Hence, metabolic imaging can be important to unmask which of the radiographically detected bony lesions are metabolically active and have the potential to be the source of current patient's symptoms and which of them are old, metabolically inactive and silent lesions, which are not clinically relevant to the patient's complaints.

Bone scintigraphy elucidates different metabolic stages of melorheostosis

PubMed Central

Izadyar, Sina; Gholamrezanezhad, Ali

2012-01-01

Melorheostosis is a rare benign non-hereditary sclerosing dysplasia involving the bone, often in a sclerotomal distribution. we report the case of a 27 years old lady with painful swelling of the left hand and forearm lasting for almost 15 years. The patient experienced aggravation of symptoms and limitation of motion during the past two months. Radiographic assessment revealed hyperostosis involving the left 3rd and 4th metacarpal bones and corresponding digits as well as the left ulna and distal humerus, with no soft tissue ossification. Angiographic and blood pool images of bone scintigraphy showed increased activity of mid-metacarpal region, corresponding to the sclerotom C-8. Delayed static views showed increased radiotracer uptake of the left 4th metacarpal bone and the corresponding digit as well as the left ulna and humerus, but no abnormal osteoblastic activity of the 3rd left metacarpal and digit. Histopathologic assessment confirmed the diagnosis of Melorheostosis. The case confirms that even in the same sclerotomal distribution, the multiple foci of involvement can present in different metabolic stages. In fact, the disease does not progress uniformly and different lesions can be seen in dissimilar stages of activity. Hence, metabolic imaging can be important to unmask which of the radiographically detected bony lesions are metabolically active and have the potential to be the source of current patient's symptoms and which of them are old, metabolically inactive and silent lesions, which are not clinically relevant to the patient's complaints. PMID:22514755

Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside-a Comprehensive Review.

PubMed

Alves, C Henrique; Farrell, Eric; Vis, Marijn; Colin, Edgar M; Lubberts, Erik

2016-08-01

Throughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiation and activation, and chronic inflammation is a condition that initiates systemic bone loss. Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that is characterised by active synovitis and is associated with early peri-articular bone loss. Peri-articular bone loss precedes focal bone erosions, which may progress to bone destruction and disability. The incidence of generalised osteoporosis is associated with the severity of arthritis in RA and increased osteoporotic vertebral and hip fracture risk. In this review, we will give an overview of different animal models of inflammatory arthritis related to RA with focus on bone erosion and involvement of pro-inflammatory cytokines. In addition, a humanised endochondral ossification model will be discussed, which can be used in a translational approach to answer osteoimmunological questions.

Tympanic plate fractures in temporal bone trauma: prevalence and associated injuries.

PubMed

Wood, C P; Hunt, C H; Bergen, D C; Carlson, M L; Diehn, F E; Schwartz, K M; McKenzie, G A; Morreale, R F; Lane, J I

2014-01-01

The prevalence of tympanic plate fractures, which are associated with an increased risk of external auditory canal stenosis following temporal bone trauma, is unknown. A review of posttraumatic high-resolution CT temporal bone examinations was performed to determine the prevalence of tympanic plate fractures and to identify any associated temporal bone injuries. A retrospective review was performed to evaluate patients with head trauma who underwent emergent high-resolution CT examinations of the temporal bone from July 2006 to March 2012. Fractures were identified and assessed for orientation; involvement of the tympanic plate, scutum, bony labyrinth, facial nerve canal, and temporomandibular joint; and ossicular chain disruption. Thirty-nine patients (41.3 ± 17.2 years of age) had a total of 46 temporal bone fractures (7 bilateral). Tympanic plate fractures were identified in 27 (58.7%) of these 46 fractures. Ossicular disruption occurred in 17 (37.0%). Fractures involving the scutum occurred in 25 (54.4%). None of the 46 fractured temporal bones had a mandibular condyle dislocation or fracture. Of the 27 cases of tympanic plate fractures, 14 (51.8%) had ossicular disruption (P = .016) and 18 (66.6%) had a fracture of the scutum (P = .044). Temporomandibular joint gas was seen in 15 (33%) but was not statistically associated with tympanic plate fracture (P = .21). Tympanic plate fractures are commonly seen on high-resolution CT performed for evaluation of temporal bone trauma. It is important to recognize these fractures to avoid the preventable complication of external auditory canal stenosis and the potential for conductive hearing loss due to a fracture involving the scutum or ossicular chain.

Psoralen inhibits bone metastasis of breast cancer in mice.

PubMed

Wu, Chunyu; Sun, Zhenping; Ye, Yiyi; Han, Xianghui; Song, Xiaoyun; Liu, Sheng

2013-12-01

Breast cancer is the most common female malignancy and it frequently metastasizes to bone. Metastatic breast cancer continues to be the primary cause of death for women in East and Southeast Asia. Psoralen is a furocoumarin that can be isolated from the seeds of Psoralea corylifolia L. Psoralen exhibits a wide range of biological properties and has been demonstrated as an antioxidant, antidepressant, anticancer, antibacterial, and antiviral agent. Additionally, it is involved in the formation and regulation of bone. This study investigated whether psoralen can inhibit metastasis of breast cancer to bone in vivo. Histological, molecular biological, and imaging analyses revealed that psoralen inhibits bone metastases in mice. Psoralen may function to inhibit breast cancer cell growth in the bone microenvironment and regulate the function of osteoblasts and osteoclasts in tumor-bearing mice. The results of this study suggest that psoralen is a bone-modifying agent and a potential therapeutic to treat patients with bone metastases. © 2013.

Relationship between serum leptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis.

PubMed

Shaarawy, Mohamed; Abassi, Asmaa Farid; Hassan, Hany; Salem, Mahmoud E

2003-04-01

To determine whether leptin is involved in bone remodeling in patients with postmenopausal osteoporosis. Cross-sectional study. Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University. Ninety postmenopausal osteoporotic women (37 obese and 53 nonobese) and 30 healthy premenopausal women from the same clinic served as controls. Lumbar spine bone mineral density (LS-BMD) of osteoporotic patients was more than 2.5 SD below the normal mean of healthy premenopausal women. Serum levels of leptin, osteocalcin (OC), bone alkaline phosphatase (B-ALP), urinary deoxypyridinoline (DPyr), and N-telopeptide of type 1 collagen (NTX) as well as LS-BMD using dual energy X-ray absorptiometry (DEXA). The serum leptin level in obese postmenopausal osteoporotic patients was significantly increased compared with nonobese osteoporotic patients. There were no significant differences of bone formation markers (B-ALP, OC), bone resorption markers (DPyr, NTX), or LS-BMD between the obese and nonobese groups. There were no significant correlations between serum leptin and any biomarkers of bone turnover and BMD. In postmenopausal osteoporotic patients with increased bone turnover, serum leptin concentration is not correlated with BMD or with the biomarkers of bone formation or bone resorption.

Hyperparathyroidism Mimicking Metastatic Bone Disease: A Case Report and Review of Literature.

PubMed

Gupta, Monica; Singhal, Lalita; Kumar, Akshay

2018-06-01

Multiple osteolytic lesions are usually associated with metastatic involvement of the bone; however, metabolic bone diseases should also be included in the differential diagnosis. In this study, we describe a case of primary hyperparathyroidism (PHPT) with multiple osteolytic lesions that was diagnosed initially as having metastatic bone involvement. The laboratory results showed hypercalcemia and raised alkaline phosphatase along with fibrosis in the bone marrow biopsy with no increase in tumor markers and normal serum protein electrophoresis. The parathyroid hormone levels were high, which pointed toward a diagnosis of PHPT. Sestamibi scan revealed uptake at the level of the left inferior pole of the thyroid gland, which was suggestive of parathyroid adenoma. The possibility of hyperparathyroidism should be kept in mind when a patient presents with multiple osteolytic lesions and hypercalcemia.

Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes

PubMed Central

Kokolski, Marie; Ebling, Francis J.; Henstock, James R.; Anderson, Susan I.

2017-01-01

The adipokine leptin regulates energy balance, appetite, and reproductive maturation. Leptin also acts on bone growth and remodeling, but both osteogenic and anti-osteogenic effects have been reported depending on experimental conditions. Siberian hamsters (Phodopus sungorus) have natural variation in circulating leptin concentrations, where serum leptin is significantly decreased during the short day (SD)-induced winter state. In summer long day (LD) photoperiods, appetite and body adiposity increase with associated central leptin insensitivity. This natural change in leptin secretion was exploited to investigate leptin’s effect on bone growth. Hamsters were injected with calcium-chelating fluorescent dyes to measure bone mineral apposition rate (MAR). Measurements were initially obtained from 5-week and 6-month-old animals maintained in low leptin (SD) or high leptin (LD) states. A further study investigated effects of chronic administration of recombinant mouse leptin to hamsters housed in SD and LD conditions; growth plate thickness and bone density were also assessed. As expected, a reduction in body mass was seen in hamsters exposed to SD, confirming the phenotype change in all studies. Serum leptin concentrations were significantly reduced in SD animals in all studies. MAR was reproducibly and significantly increased in the femurs of SD animals in all studies. Vitamin D and growth plate thickness were significantly increased in SD animals at 6 months. No effect on bone density was observed in any study. Taken together these data suggest that bone growth is associated with the low leptin, winter, lean state. In leptin-treated animals, there was a significant interaction effect of leptin and photoperiod. In comparison to their vehicle counterparts, SD animals had decreased and LD animals had increased MAR, which was not apparent prior to leptin administration. In conclusion, increased MAR was associated with low serum leptin levels in early life and

Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes.

PubMed

Kokolski, Marie; Ebling, Francis J; Henstock, James R; Anderson, Susan I

2017-01-01

The adipokine leptin regulates energy balance, appetite, and reproductive maturation. Leptin also acts on bone growth and remodeling, but both osteogenic and anti-osteogenic effects have been reported depending on experimental conditions. Siberian hamsters ( Phodopus sungorus ) have natural variation in circulating leptin concentrations, where serum leptin is significantly decreased during the short day (SD)-induced winter state. In summer long day (LD) photoperiods, appetite and body adiposity increase with associated central leptin insensitivity. This natural change in leptin secretion was exploited to investigate leptin's effect on bone growth. Hamsters were injected with calcium-chelating fluorescent dyes to measure bone mineral apposition rate (MAR). Measurements were initially obtained from 5-week and 6-month-old animals maintained in low leptin (SD) or high leptin (LD) states. A further study investigated effects of chronic administration of recombinant mouse leptin to hamsters housed in SD and LD conditions; growth plate thickness and bone density were also assessed. As expected, a reduction in body mass was seen in hamsters exposed to SD, confirming the phenotype change in all studies. Serum leptin concentrations were significantly reduced in SD animals in all studies. MAR was reproducibly and significantly increased in the femurs of SD animals in all studies. Vitamin D and growth plate thickness were significantly increased in SD animals at 6 months. No effect on bone density was observed in any study. Taken together these data suggest that bone growth is associated with the low leptin, winter, lean state. In leptin-treated animals, there was a significant interaction effect of leptin and photoperiod. In comparison to their vehicle counterparts, SD animals had decreased and LD animals had increased MAR, which was not apparent prior to leptin administration. In conclusion, increased MAR was associated with low serum leptin levels in early life and

Osteogenic differentiation of dura mater stem cells cultured in vitro on three-dimensional porous scaffolds of poly(ε-caprolactone) fabricated via co-extrusion and gas foaming

PubMed Central

Aronin, C.E. Petrie; Cooper, J.A.; Sefcik, L.S.; Tholpady, S.S.; Ogle, R.C.; Botchwey, E.A.

2008-01-01

A novel scaffold fabrication method utilizing both polymer blend extrusion and gas foaming techniques to control pore size distribution is presented. Seventy five per cent of all pores produced using polymer blend extrusion alone were less than 50 μm. Introducing a gas technique provided better control of pore size distribution, expanding the range from 0-50 to 0-350 μm. Varying sintering time, annealing temperature and foaming pressure also helped reduced the percentage of pore sizes below 50 μm. Scaffolds chosen for in vitro cellular studies had a pore size distribution of 0-300 μm, average pore size 66 ± 17 μm, 0.54 ± 0.02% porosity and 98% interconnectivity, measured by micro computed tomography (microCT) analysis. The ability of the scaffolds to support osteogenic differentiation and cranial defect repair was evaluated by static and dynamic (0.035 ± 0.006 m s-1 terminal velocity) cultivation with dura mater stem cells (DSCs). In vitro studies showed minimal increases in proliferation over 28 days in culture in osteogenic media. Alkaline phosphatase expression remained constant throughout the study. Moderate increases in matrix deposition, as assessed by histochemical staining and microCT analysis, occurred at later time points, days 21 and 28. Although constructs cultured dynamically showed greater mineralization than static conditions, these trends were not significant. It remains unclear whether bioreactor culture of DSCs is advantageous for bone tissue engineering applications. However, these studies show that polycaprolactone (PCL) scaffolds alone, without the addition of other co-polymers or ceramics, support long-term attachment and mineralization of DSCs throughout the entire porous scaffold. PMID:18434267

NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis

PubMed Central

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

2013-01-01

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

[Cat-scratch disease with bone compromise: atypical manifestation].

PubMed

Rodríguez C, Magdalena; Giachetto L, Gustavo; Cuneo E, Alejandro; Gutiérrez B, María del C; Shimchack R, Mario; Pírez G, M Catalina

2009-08-01

Fever, headache, myalgias and lymphadenopathy are characteristic manifestations of cat-scratch disease but other less common findings are described in 2 to 10% of cases. We report two children that presented with hepatosplenic abscesses and bone involvement. One child, had multiple areas of increased uptake in the bone scintigram with a positive serology (IgG > 1/256, IgM slightly positive). The second child had destruction of the L2 vertebral body that compromised the channel and right foramen as visualized by MRI. In both cases, bacilli were observed in the bone biopsy by Warthing-Starry stain.

Vertebroplasty and interventional radiology procedures for bone metastases.

PubMed

Laredo, Jean-Denis; Chiras, Jacques; Kemel, Salim; Taihi, Lokmane; Hamze, Bassam

2018-03-01

Advances in cancer treatments have lengthened the survival of patients with bone metastases. Optimal control of the symptoms and prevention of the complications associated with bone metastases improve quality of life. Achieving these goals increasingly involves interventional radiology procedures. These include bone consolidation and analgesic techniques such as cementoplasty (vertebroplasty at the spine); percutaneous implantation of screws, metallic reinforcement devices, or intraosseous implants; and tumor destruction using thermal methods (radiofrequency and cryotherapy), chemicals (alcohol), and drugs (chemoembolization), which have fewer indications. Here, these techniques and their indications are reviewed. Copyright © 2017. Published by Elsevier SAS.

Percutaneous magnetic resonance imaging-guided bone tumor management and magnetic resonance imaging-guided bone therapy.

PubMed

Sequeiros, Roberto Blanco; Fritz, Jan; Ojala, Risto; Carrino, John A

2011-08-01

Magnetic resonance imaging (MRI) is promising tool for image-guided therapy. In musculoskeletal setting, image-guided therapy is used to direct diagnostic and therapeutic procedures and to steer patient management. Studies have demonstrated that MRI-guided interventions involving bone, soft tissue, joints, and intervertebral disks are safe and in selected indications can be the preferred action to manage clinical situation. Often, these procedures are technically similar to those performed in other modalities (computed tomography, fluoroscopy) for bone and soft tissue lesions. However, the procedural perception to the operator can be very different to other modalities because of the vastly increased data.Magnetic resonance imaging guidance is particularly advantageous should the lesion not be visible by other modalities, for selective lesion targeting, intra-articular locations, cyst aspiration, and locations adjacent to surgical hardware. Palliative tumor-related pain management such as ablation therapy forms a subset of procedures that are frequently performed under MRI. Another suitable entity for MRI guidance are the therapeutic percutaneous osseous or joint-related benign or reactive conditions such as osteoid osteoma, epiphyseal bone bridging, osteochondritis dissecans, bone cysts, localized bone necrosis, and posttraumatic lesions. In this article, we will describe in detail the technical aspects of performing MRI-guided therapeutic musculoskeletal procedures as well as the clinical indications.

CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells.

PubMed

Wang, Tingyu; Li, Shan; Yi, Dan; Zhou, Guang-Qian; Chang, Zhijie; Ma, Peter X; Xiao, Guozhi; Chen, Di

2018-01-01

Carboxyl terminus of Hsp70-interacting protein (CHIP or STUB1) is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal (BMS) cells derived from Chip -/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip- deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip -/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.

Bone and fat connection in aging bone.

PubMed

Duque, Gustavo

2008-07-01

The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

Dural opening/removal for combined petrosal approach: technical note.

PubMed

Terasaka, Shunsuke; Asaoka, Katsuyuki; Kobayashi, Hiroyuki; Sugiyama, Taku; Yamaguchi, Shigeru

2011-03-01

Detailed descriptions of stepwise dural opening/removal for combined petrosal approach are presented. Following maximum bone work, the first dural incision was made along the undersurface of the temporal lobe parallel to the superior petrosal sinus. Posterior extension of the dural incision was made in a curved fashion, keeping away from the transverse-sigmoid junction and taking care to preserve the vein of Labbé. A second incision was made perpendicular to the first incision. After sectioning the superior petrosal sinus around the porus trigeminus, the incision was extended toward the posterior fossa dura in the middle fossa region. The tentorium was incised toward the incisura at a point just posterior to the entrance of the trochlear nerve. A third incision was made longitudinally between the superior petrosal sinus and the jugular bulb. A final incision was initiated perpendicular to the third incision in the presigmoid region and extended parallel to the superior petrosal sinus connecting the second incision. The dural complex consisting of the temporal lobe dura, the posterior fossa dura, and the freed tentorium could then be removed. In addition to extensive bone resection, our strategic cranial base dural opening/removal can yield true advantages for the combined petrosal approach.

Resection followed by vascularized bone autograft in patients with possible recurrence of malignant bone tumors after conservative treatment

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

Metaizeau, J.P.; Olive, D.; Bey, P.

1984-04-01

In conservative treatment of malignant bone tumors, assessment of the local condition is difficult. The radiological changes seen in the irradiated tumor and the frequent occurrence of pathological fractures at this site may give rise to the fear that the tumor has relapsed. Resection of the whole of the involved bone is the best way to assure adequate local control but the extent of the bone defect and the bad local conditions secondary to irradiation make reconstruction hazardous. In two patients (one with Ewing's sarcoma of the femur and one with osteogenic sarcoma of the humerus) the authors used amore » free, vascularized fibular graft for the reconstruction having obtained consolidation of the limb after resection of the irradiated tumor, with preservation of its function. The encouraging results obtained have suggested a conservative attitude as primary treatment of specific malignant bone tumors.« less

Detecting microdamage in bone

PubMed Central

Lee, TC; Mohsin, S; Taylor, D; Parkesh, R; Gunnlaugsson, T; O'Brien, FJ; Giehl, M; Gowin, W

2003-01-01

Fatigue-induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre-existing microdamage sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site-specific. Cracks are discontinuities in the calcium-rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed – fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non-invasive method is needed to measure microdamage in patients. Micro-CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis. PMID:12924817

Emergency Interventions After Severe Traumatic Brain Injury in Rats: Effect on Neuropathology and Functional Outcome

DTIC Science & Technology

2000-01-01

placed in a stereotaxic frame and a left parietal craniotomy was performed. The dura and bone flap were left in place until immediately before CCI. A...microtransducer) was inserted through a burr hole in the frontal bone into the contralateral (right) frontal cortex at the time of craniotomy ...immediately after injury) or vehicle. A separate sham group (all surgery including craniotomy , but no TBI was also studied. Brain temperature maintained at

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

Intrasinusoidal pattern of bone marrow infiltration by hepatosplenic T-cell lymphoma.

PubMed

Butler, Liesl Ann; Juneja, Surender

2018-04-01

Hepatosplenic T-cell lymphoma is a rare, aggressive form of extranodal lymphoma, which frequently involves the bone marrow. An intrasinusoidal pattern of infiltration is characteristic of the disease and is often best appreciated on immunohistochemical staining. Bone marrow biopsy can be a useful diagnostic tool.

Bone morphogenetic protein 7 (BMP-7) influences tendon-bone integration in vitro.

PubMed

Schwarting, Tim; Lechler, Philipp; Struewer, Johannes; Ambrock, Marius; Frangen, Thomas Manfred; Ruchholtz, Steffen; Ziring, Ewgeni; Frink, Michael

2015-01-01

Successful graft ingrowth following reconstruction of the anterior cruciate ligament is governed by complex biological processes at the tendon-bone interface. The aim of this study was to investigate in an in vitro study the effects of bone morphogenetic protein 7 (BMP-7) on tendon-bone integration. To study the biological effects of BMP-7 on the process of tendon-bone-integration, two independent in vitro models were used. The first model involved the mono- and coculture of bovine tendon specimens and primary bovine osteoblasts with and without BMP-7 exposure. The second model comprised the mono- and coculture of primary bovine osteoblasts and fibroblasts. Alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lactate and osteocalcin (OCN) were analyzed by ELISA. Histological analysis and electron microscopy of the tendon specimens were performed. In both models, positive effects of BMP-7 on ALP enzyme activity were observed (p<0.001). Additionally, similar results were noted for LDH activity and lactate concentration. BMP-7 stimulation led to a significant increase in OCN expression. Whereas the effects of BMP-7 on tendon monoculture peaked during an early phase of the experiment (p<0.001), the cocultures showed a maximal increase during the later stages (p<0.001). The histological analysis showed a stimulating effect of BMP-7 on extracellular matrix formation. Organized ossification zones and calcium carbonate-like structures were only observed in the BMP-stimulated cell cultures. This study showed the positive effects of BMP-7 on the biological process of tendon-bone integration in vitro. Histological signs of improved mineralization were paralleled by increased rates of osteoblast-specific protein levels in primary bovine osteoblasts and fibroblasts. Our findings indicated a role for BMP-7 as an adjuvant therapeutic agent in the treatment of ligamentous injuries, and they emphasized the importance of the transdifferentiation process of tendinous fibroblasts

Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts.

PubMed

Amiable, Nathalie; Tat, Steeve Kwan; Lajeunesse, Daniel; Duval, Nicolas; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Boileau, Christelle

2009-06-01

In osteoarthritis (OA), the subchondral bone undergoes a remodelling process involving several factors synthesized by osteoblasts. In this study, we investigated the expression, production, modulation, and role of PAR-2 in human OA subchondral bone osteoblasts. PAR-2 expression and production were determined by real-time PCR and flow cytometry, respectively. PAR-2 modulation was investigated in OA subchondral bone osteoblasts treated with IL-1 beta (100 pg/ml), TNF-alpha (5 ng/ml), TGF-beta1 (10 ng/ml), PGE(2) (500 nM), IL-6 (10 ng/ml) and IL-17 (10 ng/ml). Membranous RANKL protein was assessed by flow cytometry, and OPG, MMP-1, MMP-9, MMP-13, IL-6 and intracellular signalling pathways by specific ELISAs. Bone resorptive activity was measured by using a co-culture model of human PBMC and OA subchondral bone osteoblasts. PAR-2 expression and production (p<0.05) were markedly increased when human OA subchondral bone osteoblasts were compared to normal. On OA osteoblasts, PAR-2 production was significantly increased by IL-1 beta, TNF-alpha and PGE(2). Activation of PAR-2 with a specific agonist, SLIGKV-NH(2), induced a significant up-regulation of MMP-1, MMP-9, IL-6, and membranous RANKL, but had no effect on MMP-13 or OPG production. Interestingly, bone resorptive activity was also significantly enhanced following PAR-2 activation. The PAR-2 effect was mediated by activation of the MAP kinases Erk1/2 and JNK. This study is the first to demonstrate that PAR-2 activation plays a role in OA subchondral bone resorption via an up-regulation of major bone remodelling factors. These results shed new light on the potential of PAR-2 as a therapeutic target in OA.

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

PubMed

Haut, Roger C; Wei, Feng

2017-02-01

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

Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

PubMed Central

Mendonça, Maira L.; Batista, Sérgio L.; Nogueira-Barbosa, Marcello H.; Salmon, Carlos E.G.; de Paula, Francisco J.A.

2016-01-01

OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT) and 21 controls (CG). Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01). Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%). The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005), but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity. PMID:27626477

Evolutionary Patterns of Bone Histology and Bone Compactness in Xenarthran Mammal Long Bones

PubMed Central

Straehl, Fiona R.; Scheyer, Torsten M.; Forasiepi, Analía M.; MacPhee, Ross D.; Sánchez-Villagra, Marcelo R.

2013-01-01

Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xenarthran long bones is composed of a mixture of woven, parallel-fibered and lamellar bone. The vascular canals have a longitudinal, reticular or radial orientation and are mostly arranged in an irregular manner. Concentric rows of vascular canals and laminar organization of the tissue are only found in anteater bones. The long bones of adult specimens are marked by dense Haversian bone, a feature that has been noted for most groups of mammals. In the long bones of armadillos, secondary osteons have an oblique orientation within the three-dimensional bone tissue, thus resulting in their irregular shape when the bones are sectioned transversely. Secondary remodeling is generally more extensive in large taxa than in small taxa, and this could be caused by increased loading. Lines of arrested growth are assumed to be present in all specimens, but they are restricted to the outermost layer in bones of armadillos and are often masked by secondary remodeling in large taxa. Parameters of bone compactness show a pattern in the femur that separates Cingulata and Pilosa (Folivora and Vermilingua), with cingulates having a lower compactness than pilosans. In addition, cingulates show an allometric relationship between humeral and femoral bone compactness. PMID:23874932

Evolutionary patterns of bone histology and bone compactness in xenarthran mammal long bones.

PubMed

Straehl, Fiona R; Scheyer, Torsten M; Forasiepi, Analía M; MacPhee, Ross D; Sánchez-Villagra, Marcelo R

2013-01-01

Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xenarthran long bones is composed of a mixture of woven, parallel-fibered and lamellar bone. The vascular canals have a longitudinal, reticular or radial orientation and are mostly arranged in an irregular manner. Concentric rows of vascular canals and laminar organization of the tissue are only found in anteater bones. The long bones of adult specimens are marked by dense Haversian bone, a feature that has been noted for most groups of mammals. In the long bones of armadillos, secondary osteons have an oblique orientation within the three-dimensional bone tissue, thus resulting in their irregular shape when the bones are sectioned transversely. Secondary remodeling is generally more extensive in large taxa than in small taxa, and this could be caused by increased loading. Lines of arrested growth are assumed to be present in all specimens, but they are restricted to the outermost layer in bones of armadillos and are often masked by secondary remodeling in large taxa. Parameters of bone compactness show a pattern in the femur that separates Cingulata and Pilosa (Folivora and Vermilingua), with cingulates having a lower compactness than pilosans. In addition, cingulates show an allometric relationship between humeral and femoral bone compactness.

New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

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

Herlin, Maria, E-mail: maria.herlin@ki.se; Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi; Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu

Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serummore » levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR

Bone effects of biologic drugs in rheumatoid arthritis.

PubMed

Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

2013-01-01

Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

Unicameral bone cysts: general characteristics and management controversies.

PubMed

Pretell-Mazzini, Juan; Murphy, Robert Francis; Kushare, Indranil; Dormans, John P

2014-05-01

Unicameral bone cysts are benign bone lesions that are often asymptomatic and commonly develop in the proximal humerus and femur of skeletally immature patients. The etiology of these lesions remains unknown. Most patients present with a pathologic fracture, but these cysts can be discovered incidentally, as well. Radiographically, a unicameral bone cyst appears as a radiolucent lesion with cortical thinning and is centrally located within the metaphysis. Although diagnosis is frequently straightforward, management remains controversial. Because the results of various management methods are heterogeneous, no single method has emerged as the standard of care. New minimally invasive techniques involve cyst decompression with bone grafting and instrumentation. These techniques have yielded promising results, with low rates of complications and recurrence reported; however, prospective clinical trials are needed to compare these techniques with current evidence-based treatments.

Bone tumor

MedlinePlus

Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

Alterations in the lipids of bone caused by hypervitaminosis A and D

PubMed Central

Cruess, Richard L.; Clark, Irwin

1965-01-01

1. The total lipid, phospholipid, total and free fatty acid, free and esterified cholesterol contents of the long bones of normal, hypervitaminotic A, D and A plus D rats were determined. 2. Toxic amounts of vitamin A decreased the total fatty content, whereas toxic amounts of vitamin D increased triglycerides, esterified cholesterol and in particular the phospholipids of bone. 3. An interaction occurred between toxic amounts of vitamins A and D, which prevented, to a large extent, the alterations in bone lipids that occur in hypervitaminosis D. 4. The studies suggest an involvement of vitamin D in lipid metabolism and tend to support the idea that lipids are involved in ossification. PMID:14343141

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.

Engineered matrices for bone regeneration

NASA Astrophysics Data System (ADS)

Winn, Shelley R.; Hu, Yunhua; Pugh, Amy; Brown, Leanna; Nguyen, Jesse T.; Hollinger, Jeffrey O.

2000-06-01

Traditional therapies of autografts and allogeneic banked bone can promote reasonable clinical outcome to repair damaged bone. However, under certain conditions the success of these traditional approaches plummets, providing the incentive for researchers to develop clinical alternatives. The evolving field of tissue engineering in the musculoskeletal system attempts to mimic many of the components from the intact, healthy subject. Those components consist of a biologic scaffold, cells, extracellular matrix, and signaling molecules. The bone biomimetic, i.e., an engineered matrix, provides a porous structural architecture for the regeneration and ingrowth of osseous tissue at the site of injury. To further enhance the regenerative cascade, our strategy has involved porous biodegradable scaffolds containing and releasing signaling molecules and providing a suitable environment for cell attachment, growth and differentiation. In addition, the inclusion of genetically modified osteogenic precursor cells has brought the technology closer to developing a tissue-engineered equivalent. The presentation will describe various formulations and the methods utilized to evaluate the clinical utility of these biomimetics.

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

PubMed

Kathirvelu, D; Anburajan, M

2014-09-01

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

[Homeostasis and Disorder of Musculoskeletal System.Molecular mechanism of bone metabolism and future therapeutic strategies.

PubMed

Nakashima, Tomoki

Recent studies of mouse genetics and human gene mutations has greatly contributed to clarifying the molecular mechanism of bone metabolism. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication among bone component cells such as osteoclasts, osteoblasts, osteocytes and endothelial cells. An imbalance of this process is often linked to various bone diseases. Thus, the elucidation of the molecular mechanisms involved in bone remodeling is critical for a deeper understanding of the maintenance of healthy skeleton and bone disease.

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

PubMed Central

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

2013-01-01

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

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

Vitamin C reverses hypogonadal bone loss

USDA-ARS?s Scientific Manuscript database

Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, ...

[Bone metabolism and cardiovascular function Update. Vascular calcification as a manifestation of bone-vascular axis].

PubMed

Kurabayashi, Masahiko

2014-07-01

Vascular calcification is the major cause of cardiovascular morbidity and mortality in the patients with type 2 diabetes, chronic kidney disease and in aging patients. Regardless of the morphology and location, most evidence indicates that vascular calcification involves an organized process recapitulating many cellular and molecular events that govern skeletal bone formation. While the large body of evidence that osteoblastic and osteochondrocytic cells contribute to vascular calcification, it remains unclear how osteoclasts are differentiated from their precursors and how osteoclasts play a role in calcium reabsorption in calcifying arteries. It is reassuring that calcium paradox is not merely due to the calcium shift from bone to artery wall, but is likely due to the differential response of both osteoblasts and osteoclasts to oxidative stress between bone and artery. To date, many studies have highlighted the important role for RANK/RANKL/OPG axis as unifying theme for the apparently opposite regulation of calcification between two tissues.

Neurosurgical treatment of breast cancer metastases to the neurocranium.

PubMed

Stark, Andreas M

2010-12-16

Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4-11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

PubMed Central

Stark, Andreas M.

2011-01-01

Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy. PMID:21209717

Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss

PubMed Central

Calabrese, Gina; Mesner, Larry D.; Foley, Patricia L.; Rosen, Clifford J.; Farber, Charles R.

2016-01-01

The postmenopausal period in women is associated with decreased circulating estrogen levels, which accelerate bone loss and increase the risk of fracture. Here, we gained novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause, using co-expression network analysis. Specifically, we generated a co-expression network consisting of 53 gene modules using expression profiles from intact and OVX mice from a panel of inbred strains. The expression of four modules was altered by OVX, including module 23 whose expression was decreased by OVX across all strains. Module 23 was enriched for genes involved in the response to oxidative stress, a process known to be involved in OVX-induced bone loss. Additionally, module 23 homologs were co-expressed in human bone marrow. Alpha synuclein (Snca) was one of the most highly connected “hub” genes in module 23. We characterized mice deficient in Snca and observed a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the altered expression of specific network modules, including module 23. In summary, the results of this study suggest that Snca regulates bone network homeostasis and ovariectomy-induced bone loss. PMID:27378017

The Role of Hedgehog Signaling in Tumor Induced Bone Disease

PubMed Central

Cannonier, Shellese A.; Sterling, Julie A.

2015-01-01

Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. PMID:26343726

Effects of endocrine and inflammatory changes on markers of bone turnover following Roux-en-Y gastric bypass surgery

USDA-ARS?s Scientific Manuscript database

Bariatric surgery is associated with increased bone turnover. The mechanisms involved are unclear but may involve nutrition, mechanical unloading, altered secretion of gastrointestinal and adipose hormones and changes in inflammatory status leading to weight loss induced bone loss. We assessed marke...

[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.

Interventions for treating simple bone cysts in the long bones of children.

PubMed

Zhao, Jia-Guo; Wang, Jia; Huang, Wan-Jie; Zhang, Peng; Ding, Ning; Shang, Jian

2017-02-04

data extraction. We summarised data using risk ratios (RRs) or mean differences (MDs), as appropriate, and 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the overall quality of the evidence. In this update in 2017, we did not identify any new randomised controlled trials (RCT) for inclusion. We identified one ongoing trial that we are likely to include in a future update. Accordingly, our results are unchanged. The only included trial is a multicentre RCT conducted at 24 locations in North America and India that compared bone marrow injection with steroid (methylprednisolone acetate) injection for treating simple bone cysts. Up to three injections were planned for participants in each group. The trial involved 90 children (mean age 9.5 years) and presented results for 77 children at two-year follow-up. Although the trial had secure allocation concealment, it was at high risk of performance bias and from major imbalances in baseline characteristics. Reflecting these study limitations, we downgraded the quality of evidence by two levels to 'low' for most outcomes, meaning that we are unsure about the estimates of effect. For outcomes where there was serious imprecision, we downgraded the quality of evidence by a further level to 'very low'.The trial provided very low quality evidence that fewer children in the bone marrow injection group had radiographically assessed healing of bone cysts at two years than in the steroid injection group (9/39 versus 16/38; RR 0.55 favouring steroid injection, 95% CI 0.28 to 1.09). However, the result was uncertain and may be compatible with no difference or small benefit favouring bone marrow injection. Based on an illustrative success rate of 421 children with healed bone cysts per 1000 children treated with steroid injections, this equates to 189 fewer (95% CI 303 fewer to 38 more) children with healed bone cysts per 1000 children treated with bone

Transient Overexpression of Sonic Hedgehog Alters the Architecture and Mechanical Properties of Trabecular Bone

PubMed Central

Kiuru, Maija; Solomon, Jason; Ghali, Bassem; van der Meulen, Marjolein; Crystal, Ronald G; Hidaka, Chisa

2009-01-01

Bone formation and remodeling involve coordinated interactions between osteoblasts and osteoclasts through signaling networks involving a variety of molecular pathways. We hypothesized that overexpression of Sonic hedgehog (Shh), a morphogen with a crucial role in skeletal development, would stimulate osteoblastogenesis and bone formation in adult animals in vivo. Systemic administration of adenovirus expressing the N-terminal form of Shh into adult mice resulted in a primary increase in osteoblasts and their precursors. Surprisingly, however, this was associated with altered trabecular morphology, decreased bone volume, and decreased compressive strength in the vertebrae. Whereas no change was detected in the number of osteoclast precursors, bone marrow stromal cells from Shh-treated mice showed enhanced osteoclastogenic potential in vitro. These effects were mediated by the PTH/PTH-related protein (PTHrP) pathway as evidenced by increased sensitivity to PTH stimulation and upregulation of the PTH/PTHrP receptor (PPR). Together, these data show that Shh has stimulatory effects on osteoprogenitors and osteoblasts in adult animals in vivo, which results in bone remodeling and reduced bone strength because of a secondary increase in osteoclastogenesis. PMID:19338448

Modified Kidner procedure utilizing a Mitek bone anchor.

PubMed

Dawson, D M; Julsrud, M E; Erdmann, B B; Jacobs, P M; Ringstrom, J B

1998-01-01

The recent development of small bone suture anchors has created several potential applications in reconstructive surgery of the foot. Mitek bone anchors are simple to insert, require less aggressive dissection and surgical time than reefing of the redundant posterior tibial tendon, and are a reliable method of tendon-to-bone fixation. Mitek bone anchors are an excellent technique for the treatment of redundant tibialis posterior tendon following a modified Kidner procedure. In modified Kidner procedures involving an excessively large os tibiale externum, Mitek anchoring of the redundant tibialis posterior tendon to the navicular bone is an excellent means for secure plication of the posterior tibial tendon in cases involving intraoperative tendon laxity. A description of the Mitek Anchor System and technique of application in a modified Kinder procedure is presented. The purpose of this study was to describe patient satisfaction and long-term clinical outcomes of the modified Kinder procedure with and without the Mitek bone anchoring system. A retrospective study of the modified Kinder procedure was performed with 13 patients being evaluated, seven with Mitek anchoring and six without. The University of Maryland 100-point Painful Foot Center Scoring System was modified to be more specific to the modified Kinder procedure for assessment of subjective long-term results. Patient overall satisfaction was rated good to excellent by 85.6% of patients in the Mitek group and by 100% of patients in the non-Mitek group. Use of the Mitek anchor allowed for quicker postoperative recovery to resumption of ambulation without assistive devices (average of 3 weeks vs. 4.42 weeks) and a quicker return to pain-free ambulation in normal shoegear (average of 4 weeks vs. 6 weeks). Mitek anchoring of the tibialis posterior tendon, theoretically, increases medial arch support as evidenced by 14% of the Mitek group and 67% of the non-Mitek group requiring postoperative orthotics.

Utilization of ring-shaped bone allograft for surgical treatment of adolescent post-tubercular kyphosis: A retrospective study.

PubMed

Yin, Xiang; Liu, Peng; Liu, Yao-Yao; Fan, Wei-Li; Liu, Bai-Yi; Zhao, Jian-Hua

2017-06-01

This study aimed to investigate the mid-term outcome of ring-shaped bone allografts in the surgical treatment of adolescent post-tubercular kyphosis secondary to spinal tuberculosis.The records of adolescent patients diagnosed with spinal tuberculosis who received treatment in our department between 2009 and 2013 were retrospectively reviewed. The anterior approach was used in cases of cervical kyphosis and the posterior approach was used in cases of thoracic and lumbar kyphosis. During the surgery, the ring-shaped bone was used as a structural bone graft associated with the cancellous bone filing in the center portion of the ring shape. Cobb's angle, signs of spinal infusion on computed tomography, and complications were followed up.A total of 25 patients were included in our study. Among them, 3 involved the cervical region, 5 involved the thoracic region, 8 involved the thoracolumbar region, and 9 involved the lumbar region. The preoperative kyphosis deformity was a mean 65° Cobb's angle (40°-97°) compared to the postoperative 14° Cobb's angle (10°-21°) for an average correction of 51°. All wounds healed well without graft rejection. All patients achieved bone fusion 3 months postoperative for a 100% fusion rate.Our results show that the ring-shaped allograft bone is an effective option for the treatment of adolescent kyphosis. The ring-shaped allograft bone demonstrated satisfactory mechanical strength and vertebral fusion without mid-term metallic toxicity.

Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women.

PubMed

Bilek, Laura D; Waltman, Nancy L; Lappe, Joan M; Kupzyk, Kevin A; Mack, Lynn R; Cullen, Diane M; Berg, Kris; Langel, Meghan; Meisinger, Melissa; Portelli-Trinidad, Ashlee; Lang, Molly

2016-08-30

developing a clinical management pathway for women with low bone mass at their peak period of bone loss that would involve lifestyle modifications such as exercises prior to medications such as BPs. Clinicaltrials.gov NCT02186600 . Initial registration: 7/7/2014.

The cell biology of bone growth.

PubMed

Price, J S; Oyajobi, B O; Russell, R G

1994-02-01

The field of bone cell biology is clearly of relevance to the problem of stunting in children, as in the final analysis the cells of the growing long bone are the ultimate 'regulators'. It is the alterations in the functions of these cells that manifests as a reduction in height. Normal longitudinal growth is achieved by the coordinated recruitment, proliferation, differentiation, maturation and eventual death of the cells of growth plate and bone. Cellular activity is closely regulated by endocrine factors acting directly or indirectly, with factors produced locally and stored within the bone and cartilage microenvironment having a critical role in intercellular communication. Disruption of any of these processes can lead to growth disturbances, since it only requires a defect in a single gene to have profound effects. Studies in recent years have shed light on the biochemical and molecular effects of cytokines and growth factors and have shown that these regulatory molecules may mediate the effects of certain hormones important in controlling growth. However, the complex interrelationship of these molecules is still not clear. Notwithstanding, understanding of the mechanisms involved in bone remodelling is increasing, as this area attracts much research because of the high incidence of metabolic bone disease in Western society. Although studies of adult bone remodelling are of relevance, there is a requirement for increased research directed specifically at the mechanisms of endochondral ossification and its regulation. Longitudinal bone growth is a challenge to the cell biologist, since it is an accelerated cycle of cellular division and differentiation, within which it is not easy to separate events temporally and spatially. In addition, different regulatory mechanisms are probably important at different stages of growth. Another difficulty impeding progress in this field is the lack of appropriate animal models for research. Much information has come from

Anemia in patient with primary hyperoxaluria and bone marrow involvement by oxalate crystals.

PubMed

Mykytiv, Vitaliy; Campoy Garcia, Fiz

2018-06-01

We present a rare case of anaemia secondary to bone marrow infiltration by oxalate crystals and renal failure in a patient diagnosed with primary hyperoxaluria. In our case, the anaemia was recovered after the double liver and kidney transplantation, the latter was performed on two occasions after the failure of the first graft. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

NASA Technical Reports Server (NTRS)

Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

2003-01-01

Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

Differentiating levels of surgical experience on a virtual reality temporal bone simulator.

PubMed

Zhao, Yi C; Kennedy, Gregor; Hall, Richard; O'Leary, Stephen

2010-11-01

Virtual reality simulation is increasingly being incorporated into surgical training and may have a role in temporal bone surgical education. Here we test whether metrics generated by a virtual reality surgical simulation can differentiate between three levels of experience, namely novices, otolaryngology residents, and experienced qualified surgeons. Cohort study. Royal Victorian Eye and Ear Hospital. Twenty-seven participants were recruited. There were 12 experts, six residents, and nine novices. After orientation, participants were asked to perform a modified radical mastoidectomy on the simulator. Comparisons of time taken, injury to structures, and forces exerted were made between the groups to determine which specific metrics would discriminate experience levels. Experts completed the simulated task in significantly shorter time than the other two groups (experts 22 minutes, residents 36 minutes, and novices 46 minutes; P = 0.001). Novices exerted significantly higher average forces when dissecting close to vital structures compared with experts (0.24 Newton [N] vs 0.13 N, P = 0.002). Novices were also more likely to injure structures such as dura compared to experts (23 injuries vs 3 injuries, P = 0.001). Compared with residents, the experts modulated their force between initial cortex dissection and dissection close to vital structures. Using the combination of these metrics, we were able to correctly classify the participants' level of experience 90 percent of the time. This preliminary study shows that measurements of performance obtained from within a virtual reality simulator can differentiate between levels of users' experience. These results suggest that simulator training may have a role in temporal bone training beyond foundational training. Copyright © 2010 American Academy of Otolaryngology–Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

THE OXYTOCIN-BONE AXIS

PubMed Central

Colaianni, G.; Tamma, R.; Di Benedetto, A.; Yuen, T.; Sun, L.; Zaidi, M.; Zallone, A.

2014-01-01

We recently demonstrated a direct action of oxytocin (OT) on skeletal homeostasis mainly mediated through stimulation of osteoblasts (OBs) formation and through the reciprocal modulation of osteoclast (OCs) formation and function. Thus, mice lacking the hormone or its receptor develop a low turnover osteoporosis that worsens with age in both sexes. The skeleton of OT and OT receptor (Oxtr) null mice display a pronounced decrease in vertebral and femoral trabecular volume. At cellular level OBs from OT−/− and Oxtr−/− mice exhibit lower mineralization activity and, at mRNA level, all master genes for osteoblast differentiation are down regulated. Moreover, OT has dual effects on OCs: it increases osteoclast formation both directly, by activating NF-kB and MAP kinase signaling, and indirectly, through the up-regulation of RANK-L synthesis by OBs. On the other hand, it inhibits bone resorption by triggering cytosolic Ca2+ release and nitric oxide synthesis in mature OCs. OT is locally produced by osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. The estrogen signal involved in this feed forward circuit is non genomic, since it requires an intact MAPK kinase signal transduction pathway, instead of the classical nuclear translocation of estrogen receptor. The ability of estrogen to increase bone mass in vivo is to an extent OTR-dependent. Thus Oxtr−/− mice injected 17β-estradiol did not show any effects on bone formation parameters, while the same treatment increases trabecular and cortical bone in wild type mice. An intact OT autocrine-paracrine circuit seems to be essential for optimal skeletal remodeling. PMID:24219627

Melorheostosis: a Rare Sclerosing Bone Dysplasia.

PubMed

Kotwal, Anupam; Clarke, Bart L

2017-08-01

Melorheostosis is a rare sclerosing bone dysplasia that affects both cortical bone and adjacent soft tissue structures in a sclerotomal distribution. In this review, we describe the natural history, radiological features, proposed pathogenesis, and management options for this debilitating condition. Since its first description in 1922, about 400 cases of melorheostosis have been reported, either as single reports or in small case series. Melorheostosis affects the appendicular skeleton more commonly than the axial skeleton and usually presents with lower limb deformity. Diagnosis is based on a combination of clinical and radiological features that help differentiate this condition from other sclerosing bone dysplasias. LEM domain-containing protein 3 (LEMD3) gene mutations have been demonstrated in several familial cases, but these have been more strongly correlated with other hereditary dysplasias, such as osteopoikilosis, and are not thought to be the causative gene for melorheostosis. The exact etiology of classic sporadically occurring melorheostosis remains unknown, with possible causes being somatic LEMD3 mutations, somatic mutations in the bone morphogenetic protein/transforming growth factor-beta pathway, mutations in multiple genes, or other non-genetic causes. Management in recent years has involved nitrogen-containing bisphosphonates in addition to traditional orthopedic surgical approaches and physical therapy. Melorheostosis may present as mixed or atypical osseous involvement in addition to the classically described "dripping candle wax" appearance of hyperostosis. Some patients may have overlap with osteopoikilosis or Buschke-Ollendorff syndrome. In the future, better characterization of genetic and developmental factors predisposing to melorheostosis may lead to the development of targeted therapy for this condition, as well as for more commonly encountered skeletal abnormalities.

Temperature-dependent MR signals in cortical bone: potential for monitoring temperature changes during high-intensity focused ultrasound treatment in bone.

PubMed

Ramsay, Elizabeth; Mougenot, Charles; Kazem, Mohammad; Laetsch, Theodore W; Chopra, Rajiv

2015-10-01

Because existing magnetic resonance thermometry techniques do not provide temperature information within bone, high-intensity focused ultrasound (HIFU) exposures in bone are monitored using temperature changes in adjacent soft tissues. In this study, the potential to monitor temperature changes in cortical bone using a short TE gradient echo sequence is evaluated. The feasibility of this proposed method was initially evaluated by measuring the temperature dependence of the gradient echo signal during cooling of cortical bone samples implanted with fiber-optic temperature sensors. A subsequent experiment involved heating a cortical bone sample using a clinical MR-HIFU system. A consistent relationship between temperature change and the change in magnitude signal was observed within and between cortical bone samples. For the two-dimensional gradient echo sequence implemented in this study, a least-squares linear fit determined the percentage change in signal to be (0.90 ± 0.01)%/°C. This relationship was used to estimate temperature changes observed in the HIFU experiment and these temperatures agreed well with those measured from an implanted fiber-optic sensor. This method appears capable of displaying changes related to temperature in cortical bone and could improve the safety of MR-HIFU treatments. Further investigations into the sensitivity of the technique in vivo are warranted. © 2014 Wiley Periodicals, Inc.

Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF-β signaling.

PubMed

Zhao, Weiwei; Wang, Ting; Luo, Qiang; Chen, Yan; Leung, Victor Y L; Wen, Chunyi; Shah, Mohammed F; Pan, Haobo; Chiu, KwongYuen; Cao, Xu; Lu, William W

2016-05-01

Transforming growth factor-β (TGF-β) has been demonstrated as a potential therapeutic target in osteoarthritis. However, beneficial effects of TGF-β supplement and inhibition have both been reported, suggesting characterization of the spatiotemporal distribution of TGF-β during the whole time course of osteoarthritis is important. To investigate the activity of TGF-β in osteoarthritis progression, we collected knee joints from Dunkin-Hartley (DH) guinea pigs at 3, 6, 9, and 12-month old (n = 8), which develop spontaneous osteoarthritis in a manner extraordinarily similar to humans. Via histology and micro-computed tomography (CT) analysis, we found that the joints exhibited gradual cartilage degeneration, subchondral plate sclerosis, and elevated bone remodeling during aging. The degenerating cartilage showed a progressive switch of the expression of phosphorylated Smad2/3 to Smad1/5/8, suggesting dual roles of TGF-β/Smad signaling during chondrocyte terminal differentiation in osteoarthritis progression. In subchondral bone, we found that the locations and age-related changes of osterix(+) osteoprogenitors were in parallel with active TGF-β, which implied the excessive osteogenesis may link to the activity of TGF-β. Our study, therefore, suggests an association of cartilage degeneration and excessive bone remodeling with altered TGF-β signaling in osteoarthritis progression of DH guinea pigs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:763-770, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Bone Biopsy

MedlinePlus

... News Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging ... the limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided ...

Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal-Stem Cells Identified Candidates for Bone Regeneration.

PubMed

Chang, Chi-Chih; Venø, Morten T; Chen, Li; Ditzel, Nicholas; Le, Dang Q S; Dillschneider, Philipp; Kassem, Moustapha; Kjems, Jørgen

2018-02-07

Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin-dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs delivered locally from an implanted scaffold can provide a promising approach for enhanced bone regeneration. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation.

PubMed

Koskela, A; Koponen, J; Lehenkari, P; Viluksela, M; Korkalainen, M; Tuukkanen, J

2017-07-28

Perfluoroalkyl substances (PFAS), including two most commonly studied compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are widely distributed environmental pollutants, used extensively earlier. Due to their toxicological effects the use of PFAS is now regulated. Based on earlier studies on PFOA's distribution in bone and bone marrow in mice, we investigated PFAS levels and their possible link to bone microarchitecture of human femoral bone samples (n = 18). Soft tissue and bone biopsies were also taken from a 49-year old female cadaver for PFAS analyses. We also studied how PFOA exposure affects differentiation of human osteoblasts and osteoclasts. PFAS were detectable from all dry bone and bone marrow samples, PFOS and PFOA being the most prominent. In cadaver biopsies, lungs and liver contained the highest concentrations of PFAS, whereas PFAS were absent in bone marrow. Perfluorononanoic acid (PFNA) was present in the bones, PFOA and PFOS were absent. In vitro results showed no disturbance in osteogenic differentiation after PFOA exposure, but in osteoclasts, lower concentrations led to increased resorption, which eventually dropped to zero after increase in PFOA concentration. In conclusion, PFAS are present in bone and have the potential to affect human bone cells partly at environmentally relevant concentrations.

Microarchitecture of irradiated bone: comparison with healthy bone

NASA Astrophysics Data System (ADS)

Bléry, Pauline; Amouriq, Yves; Guédon, Jeanpierre; Pilet, Paul; Normand, Nicolas; Durand, Nicolas; Espitalier, Florent; Arlicot, Aurore; Malard, Olivier; Weiss, Pierre

2012-03-01

The squamous cell carcinomas of the upper aero-digestive tract represent about ten percent of cancers. External radiation therapy leads to esthetic and functional consequences, and to a decrease of the bone mechanical abilities. For these patients, the oral prosthetic rehabilitation, including possibilities of dental implant placement, is difficult. The effects of radiotherapy on bone microarchitecture parameters are not well known. Thus, the purpose of this study is to assess the effects of external radiation on bone micro architecture in an experimental model of 25 rats using micro CT. 15 rats were irradiated on the hind limbs by a single dose of 20 Grays, and 10 rats were non irradiated. Images of irradiated and healthy bone were compared. Bone microarchitecture parameters (including trabecular thickness, trabecular number, trabecular separation, connectivity density and tissue and bone volume) between irradiated and non-irradiated bones were calculated and compared using a Mann and Whitney test. After 7 and 12 weeks, images of irradiated and healthy bone are different. Differences on the irradiated and the healthy bone populations exhibit a statistical significance. Trabecular number, connectivity density and closed porosity are less important on irradiated bone. Trabecular thickness and separation increase for irradiated bone. These parameters indicate a decrease of irradiated bone properties. Finally, the external irradiation induces changes on the bone micro architecture. This knowledge is of prime importance for better oral prosthetic rehabilitation, including implant placement.

Experimental analysis of drilling process in cortical bone.

PubMed

Wang, Wendong; Shi, Yikai; Yang, Ning; Yuan, Xiaoqing

2014-02-01

Bone drilling is an essential part in orthopaedics, traumatology and bone biopsy. Prediction and control of drilling forces and torque are critical to the success of operations involving bone drilling. This paper studied the drilling force, torque and drilling process with automatic and manual drill penetrating into bovine cortical bone. The tests were performed on a drilling system which is used to drill and measure forces and torque during drilling. The effects of drilling speed, feed rate and drill bit diameter on force and torque were discussed separately. The experimental results were proven to be in accordance with the mathematic expressions introduced in this paper. The automatic drilling saved drilling time by 30-60% in the tested range and created less vibration, compared to manual drilling. The deviation between maximum and average force of the automatic drilling was 5N but 25N for manual drilling. To conclude, using the automatic method has significant advantages in control drilling force, torque and drilling process in bone drilling. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Unusually large solitary unicameral bone cyst: case report.

PubMed

Singh, Sandeep; Dhammi, Ish Kumar; Arora, Anil; Kumar, Sudhir

2003-01-01

A 15-year-old boy presented with complaints of pain and swelling of the right leg. Radiography revealed a large lytic lesion involving the proximal half of the tibia. The patient was taken to surgery, where the cavity was curetted and packed with allogeneic bone graft. Tissue was sent for histopathological evaluation. The patient was kept in an above-knee cast for 4 months, after which partial weight-bearing was allowed. The histopathological diagnosis was a unicameral bone cyst. A radiograph at 1 year showed incorporation of the graft, but a small part of the cavity was still visible and there was a persistent discharge. The patient was again subjected to allogeneic bone grafting in the remaining cavity. At 3.5 years of follow-up now, the patient is walking unsupported, there is no pain, and the radiograph shows complete obliteration of the cavity. Unicameral bone cysts are usually a few centimeters in size. To the best of our knowledge, a unicameral bone cyst of such a large size has never been reported in the literature.

The surgical management of fibrous dysplasia of bone.

PubMed

Stanton, Robert P; Ippolito, Ernesto; Springfield, Dempsey; Lindaman, Lynn; Wientroub, Shlomo; Leet, Arabella

2012-05-24

The surgical management of Polyostotic Fibrous Dysplasia (FD) of bone is technically demanding. The most effective methods to manage the associated bone deformity remain unclear. The marked variation in the degree and pattern of bone involvement has made it difficult to acquire data to guide the surgeon's approach to these patients. In light of the paucity of data, but need for guidance, recognized experts in the management of these patients came together at the National Institutes of Health in Bethesda, Maryland as part of an International meeting to address issues related to fibrous dysplasia of bone to discuss and refine their recommendations regarding the surgical indications and preferred methods for the management of these challenging patients. The specific challenges, recommended approaches, and "lessons learned" are presented in hopes that surgeons faced with typical deformities can be guided in the surgical reconstruction of both children and adults with FD.

Effects of active acromegaly on bone mRNA and microRNA expression patterns.

PubMed

Belaya, Zhanna; Grebennikova, Tatiana; Melnichenko, Galina; Nikitin, Alexey; Solodovnikov, Alexander; Brovkina, Olga; Grigoriev, Andrey; Rozhinskaya, Liudmila; Lutsenko, Alexander; Dedov, Ivan

2018-04-01

To evaluate the response of bone to chronic long-term growth hormone (GH) and insulin-like growth factor-1 (IGF1) excess by measuring the expression of selected mRNA and microRNA (miR) in bone tissue samples of patients with active acromegaly. Case-control study. Bone tissue samples were obtained during transsphenoidal adenomectomy from the sphenoid bone (sella turcica) from 14 patients with clinically and biochemically confirmed acromegaly and 10 patients with clinically non-functioning pituitary adenoma (NFPA) matched by sex and age. Expression of genes involved in the regulation of bone remodeling was studied using quantitative polymerase chain reaction (qPCR). Of the genes involved in osteoblast and osteoclast activity, only alkaline phosphatase (ALP) mRNA was 50% downregulated in patients with acromegaly. GH excess caused increased expression of the Wnt signaling antagonists ( DKK1) and agonists ( WNT10B) and changes in the levels of miR involved in mesenchymal stem cell commitment to chondrocytes (miR-199a-5p) or adipocytes (miR-27-5p, miR-125b-5p, miR-34a-5p, miR-188-3p) P  < 0.05; q  < 0.1. Relevant compensatory mechanisms were found through the changes in miR involved in osteoblastogenesis (miR-210-5p, miR-135a-5p, miR-211, miR-23a-3p, miR-204-5p), but the expression of TWIST1 was 50% downregulated and RUNX2 was unchanged. Acromegaly had minimal effects on tested mRNAs specific to osteoblast or osteoclast function except for downregulated ALP expression. The expressions of miR known to be involved in mesenchymal stem cell commitment and downregulated TWIST1 expression suggest acromegaly has a negative effect on osteoblastogenesis. © 2018 European Society of Endocrinology.

Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

PubMed Central

Marini, Francesca; Cianferotti, Luisella; Brandi, Maria Luisa

2016-01-01

Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles. PMID:27529237

The roles of vascular endothelial growth factor in bone repair and regeneration

PubMed Central

Hu, Kai; Olsen, Bjorn R.

2016-01-01

Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors. PMID:27353702

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

PubMed

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

2018-05-03

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

Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor.

PubMed

Panizza, Pedro Sergio Brito; de Albuquerque Cavalcanti, Conrado Furtado; Yamaguchi, Nise Hitomi; Leite, Claudia Costa; Cerri, Giovanni Guido; de Menezes, Marcos Roberto

2016-02-01

A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor

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

Panizza, Pedro Sergio Brito; Albuquerque Cavalcanti, Conrado Furtado de; Yamaguchi, Nise Hitomi

2016-02-15

A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

Bone healing and bone substitutes.

PubMed

Costantino, Peter D; Hiltzik, David; Govindaraj, Satish; Moche, Jason

2002-02-01

With the advent of new biomaterials and surgical techniques, the reconstructive surgeon has a wider range of treatment modalities for the rehabilitation and reconstruction of craniofacial skeletal deformities than ever before. These innovative substances act as true bone graft substitutes, thereby allowing the surgeon to avoid the use of autogenous bone grafts and their associated donor site morbidity. Surgeons have long been interested in producing a composite graft that can heal faster by induction, incorporate with surrounding tissues, and be remodeled to resemble native bone. Currently, there are a host of bone graft substitutes available that vary in both their composition and properties. Craniomaxillofacial surgeons must therefore become comfortable with numerous biomaterials to best tailor the treatment for each patient individually. Ongoing investigations into the next phase of tissue engineering will continue to bring us closer to the ability to regenerate or replace bone.

Wnt and the Wnt signaling pathway in bone development and disease

PubMed Central

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

2014-01-01

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

High Prevalence of Vitamin D Deficiency in Patients with Bone Tumors.

PubMed

Horas, Konstantin; Maier, Gerrit; Jakob, Franz; Maus, Uwe; Kurth, Andreas; Jakuscheit, Axel; Rudert, Maximilian; Holzapfel, Boris Michael

2017-09-14

The aim of this study was to evaluate the prevalence of vitamin D deficiency in patients with different types of bone tumors and to elucidate whether or not there are differences in prediagnostic vitamin D levels in patients with malignant compared to benign bone tumors. Prediagnostic serum 25(OH)D levels of 105 consecutive patients that presented with bone tumors and tumor-like lesions to two Orthopedic Level I University Centers in Germany between 2011 and 2016 were measured on admission. We found an alarming and widespread rate of vitamin D deficiency in patients with bone tumors. Specifically, 83% of all patients had low vitamin D levels with a mean 25(OH)D level of 19.82 ng/ml. Notably, patients diagnosed with malignant bone tumors had significantly lower vitamin D levels compared to patients with benign bone lesions (p = 0.0008). In conclusion, it is essential to assess vitamin D levels in patients with tumors involving bone. In addition, there might be an association between vitamin D deficiency and the onset or course of primary malignant bone tumors.

The bone diagnostic instrument III: Testing mouse femora

NASA Astrophysics Data System (ADS)

Randall, Connor; Mathews, Phillip; Yurtsev, Eugene; Sahar, Nadder; Kohn, David; Hansma, Paul

2009-06-01

Here we describe modifications that allow the bone diagnostic instrument (BDI) [P. Hansma et al., Rev. Sci. Instrum. 79, 064303 (2008); Rev. Sci. Instrum. 77, 075105 (2006)], developed to test human bone, to test the femora of mice. These modifications include reducing the effective weight of the instrument on the bone, designing and fabricating new probe assemblies to minimize damage to the small bone, developing new testing protocols that involve smaller testing forces, and fabricating a jig for securing the smaller bones for testing. With these modifications, the BDI was used to test the hypothesis that short-term running has greater benefit on the mechanical properties of the femur for young growing mice compared to older, skeletally mature mice. We measured elastic modulus, hardness, and indentation distance increase (IDI), which had previously been shown to be the best discriminators in model systems known to exhibit differences in mechanical properties at the whole bone level. In the young exercised murine femora, the IDI was significantly lower than in young control femora. Since IDI has a relation to postyield properties, these results suggest that exercise during bone development increases post yield mechanical competence. We were also able to measure effects of aging on bone properties with the BDI. There was a significant increase in the IDI, and a significant decrease in the elastic modulus and hardness between the young and old groups. Thus, with the modifications described here, the BDI can take measurements on mouse bones and obtain statistically significant results.

Low Bone Density

MedlinePlus

... Bone Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone ... to people with normal bone density. Detecting Low Bone Density A bone density test will determine whether ...

Gravity, Calcium, and Bone: Update, 1989

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Morey-Holton, Emily

1991-01-01

Some of the results of recent short-term flights and ground-based experiments that have contributed new insights into skeletal adaptation, calcium metabolism, and growth processes in 0 g, are highlighted. After 6 months in space, bone demineralization, invariably involving the os calcis, was found not to extend to the lumbar spine in 4 exercising cosmonauts. A flight experiment in the Space Shuttle crew has documented the early events in the calcium endocrine system during spaceflight. On the ground, brief and long-term bed rest studies of healthy volunteers in the head-down tile (HDT) model of weightlessness were completed. The skeleton of the adult male responds more rapidly to unloading than previously recognized. Regional changes in bone density can be quantified in only 30 days, are highly individual, and follow the direction of gravitational forces in the HDT model during inactivity. Bone biopsy results in healthy volunteers after bed rest differ from results in paraplegics from the same sampling site. Flight experiments in growing rats reveal changes in the composition of bone mineral and matrix in the femur postflight that were found to be highly regional and suggestive of an effect of gravity on mineral distribution. These observations may be relevant to the results from an earlier Cosmos flight where artificial gravity in space was found to maintain bone strength, but not to correct the radial growth deficit.

[Regional blood flow and bone uptake of methylene-diphosphonate-technetium-99m].

PubMed

Vattimo, A; Martini, G; Pisani, M

1983-05-30

Sudeck's atrophy of the foot is an acute, patchy osteoporosis that, on bone scan, shows an increase in both bone blood flow and local bone uptake of bone-seeking radionuclides. The purpose of this study was to evaluate the relationship between bone uptake of 99mTc-MDP and local bone blood flow. In some patients with Sudeck's atrophy of one foot we measured local bone blood flow and bone uptake of 99mTc-MDP. External counting of radioactivity, with a count-rate of 1 second was performed for 60 minutes after i.v. injection of a known dose of 99mTc-MDP in some patients with Sudeck's atrophy of the foot. The regions of interest (ROI) were selected on the basis of a bone scan performed 24 hours earlier. We assumed that the data recorded during the first seconds (7-10) reflect local blood flow and the data at 60 minutes reflect the bone uptake. The ratio between the local blood flow in the involved and healthy foot was higher than the local bone uptake ratio. The ratio between bone uptake and local bone blood flow was higher in the normal foot than in the affected one. These results suggest that the bone avidity for bone-seeking radionuclides is lower in Sudeck's atrophy than in normal bone.

Role of mastoid pneumatization in temporal bone fractures.

PubMed

Ilea, A; Butnaru, A; Sfrângeu, S A; Hedeşiu, M; Dudescu, C M; Berce, P; Chezan, H; Hurubeanu, L; Trombiţaş, V E; Câmpian, R S; Albu, S

2014-07-01

The mastoid portion of the temporal bone has multiple functional roles in the organism, including regulation of pressure in the middle ear and protection of the inner ear. We investigated whether mastoid pneumatization plays a role in the protection of vital structures in the temporal bone during direct lateral trauma. The study was performed on 20 human temporal bones isolated from cadavers. In the study group formed by 10 temporal bone samples, mastoid cells were removed and the resulting neocavities were filled. The mastoids were maintained intact in the control group. All samples were impacted at the same speed and kinetic energy. The resultant temporal bone fractures were evaluated by CT. Temporal squama fractures were 2.88 times more frequent, and mastoid fractures were 2.76 times more frequent in the study group. Facial nerve canal fractures were 6 times more frequent in the study group and involved all the segments of the facial nerve. Carotid canal fractures and jugular foramen fractures were 2.33 and 2.5 times, respectively, more frequent in the study group. The mastoid portion of the temporal bone plays a role in the absorption and dispersion of kinetic energy during direct lateral trauma to the temporal bone, reducing the incidence of fracture in the setting of direct trauma. © 2014 by American Journal of Neuroradiology.

[The injection of acrylic bone cement prevents bone collapse in the intercalar bones lacking bony support: an experimental sheep semilunar bone model].

PubMed

Unsal, Murat; Tetik, Cihangir; Erol, Bülent; Cabukoğlu, Cengiz

2003-01-01

In a sheep semilunar bone model, we investigated whether collapse in the intercalar bones lacking bony support could be prevented by the injection of acrylic bone cement. The study included 16 limbs of eight sheep. Preoperatively, anteroposterior and lateral views of the carpal joints in the fore limbs were obtained. The animals were divided into four groups. In group 1 (n=3) no surgical procedure was performed in the right semilunar bones, whereas the periosteum on the contralateral side was elevated (group 2; n=3). The first two groups were left as controls. In Group 3 (n=5) the left semilunar bones were filled with acrylic bone cement following decancellation of the bone, while the right semilunar bones were left decancellated (group 4; n=5). The sheep were monitored for three months. Radiographs of the carpal joints were obtained to evaluate collapse occurrence in the semilunar bones. Thereafter, the animals were sacrificed and the semilunar bones were excised for biomechanical and histological examinations. Osteonecrosis and cartilage damage were sought and resistance to compressive forces was investigated. Radiologically, the extent of collapse was statistically significant in the semilunar bones in group 4 (p<0.05). The use of acrylic bone cement was found to prevent collapse in group 3, with no significant difference being noted between preoperative and postoperative semilunar bone heights (p>0.05). Biomechanically, the least resistance to compressive forces was measured in group 4 (p<0.05). Histologically, cartilage damage and osteonecrosis were only seen in group 4. Our data suggest that the use of acrylic bone cement prevents collapse in the semilunar bones, without inducing any cartilage damage or osteonecrosis.

Risk assessment of bovine spongiform encephalopathy transmission through bone graft material derived from bovine bone used for dental applications.

PubMed

Sogal, A; Tofe, A J

1999-09-01

Several commercial products are currently available for clinical application as bone graft substitutes. These products can be broadly classified into two categories: synthetic and natural. Bovine bone is a popular source for several of the natural bone substitutes. The availability of bovine derived xenogenic bone substitutes has made it possible to avoid traumatic and expensive secondary surgery to obtain autogenous bone once thought essential for effective bone replacement. While autogenous bone still remains the undisputed "gold standard" in bone grafting, the realization that bone requirement in several clinical applications is as effectively met by xenografts has lead to their widespread use. But the convenience of using xenografts is tempered by the possibility of disease transmission from cattle to humans. The recent incidents of bovine spongiform encephalopathies (BSE) in humans have underscored this likelihood. In this paper, we report a risk analysis performed to assess the possibility of such disease transmission from a commercially available bone graft substitute (BGS) that is popularly used in clinical dentistry. An extensive review of current literature on the status of risk assessment of BSE transmission was conducted, and two risk assessment models were identified as applicable to the present study. Risk assessment models developed by the German Federal Ministry of Health and by the Pharmaceutical Research and Manufacturers Association of America were applied to BGS. Results from the analyses conducted using both models showed that the risk of disease (BSE) transmission from BGS was negligible and could be attributed to the stringent protocols followed in sourcing and processing of the raw bovine bone used in the commercial product. Based on the risk analysis, it is evident that the risk of BSE infection from BGS is several orders of magnitude less than that posed by the risk of death related to, lightning, tornadoes, or similar remote events

A mechano-biological model of multi-tissue evolution in bone

NASA Astrophysics Data System (ADS)

Frame, Jamie; Rohan, Pierre-Yves; Corté, Laurent; Allena, Rachele

2017-12-01

Successfully simulating tissue evolution in bone is of significant importance in predicting various biological processes such as bone remodeling, fracture healing and osseointegration of implants. Each of these processes involves in different ways the permanent or transient formation of different tissue types, namely bone, cartilage and fibrous tissues. The tissue evolution in specific circumstances such as bone remodeling and fracturing healing is currently able to be modeled. Nevertheless, it remains challenging to predict which tissue types and organization can develop without any a priori assumptions. In particular, the role of mechano-biological coupling in this selective tissue evolution has not been clearly elucidated. In this work, a multi-tissue model has been created which simultaneously describes the evolution of bone, cartilage and fibrous tissues. The coupling of the biological and mechanical factors involved in tissue formation has been modeled by defining two different tissue states: an immature state corresponding to the early stages of tissue growth and representing cell clusters in a weakly neo-formed Extra Cellular Matrix (ECM), and a mature state corresponding to well-formed connective tissues. This has allowed for the cellular processes of migration, proliferation and apoptosis to be described simultaneously with the changing ECM properties through strain driven diffusion, growth, maturation and resorption terms. A series of finite element simulations were carried out on idealized cantilever bending geometries. Starting from a tissue composition replicating a mid-diaphysis section of a long bone, a steady-state tissue formation was reached over a statically loaded period of 10,000 h (60 weeks). The results demonstrated that bone formation occurred in regions which are optimally physiologically strained. In two additional 1000 h bending simulations both cartilaginous and fibrous tissues were shown to form under specific geometrical and loading

Switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: changes in bone turnover markers and circulating sclerostin levels.

PubMed

Negredo, Eugènia; Diez-Pérez, Adolfo; Bonjoch, Anna; Domingo, Pere; Pérez-Álvarez, Núria; Gutierrez, Mar; Mateo, Gracia; Puig, Jordi; Echeverría, Patricia; Escrig, Roser; Clotet, Bonaventura

2015-07-01

Tenofovir is involved in accelerated bone mineral density (BMD) loss. We recently published a hip BMD improvement at week 48 [+2.1% (95% CI: -0.6, 4.7) (P = 0.043)] in HIV-infected patients with osteopenia/osteoporosis randomized to switch from tenofovir to abacavir (n = 26), although without reaching statistical significance compared with those who maintained tenofovir (n = 28). Here, we present changes at week 48 in bone markers [C-terminal telopeptide of collagen type 1 (CTX), osteocalcin and procollagen type 1 N propeptide (P1NP)] as well as in circulating levels of three proteins involved in bone regulation [osteoprotegerin, receptor activator for NF-κB ligand (RANKL) and sclerostin, a selective regulator of bone formation through the Wnt pathway] in 44 of these patients. χ(2) or Fisher and Student t-tests were performed according to the distribution of the variables. Bone markers decreased only in the abacavir group [mean (SD) CTX changed from 0.543 (0.495) to 0.301 (0.306) ng/mL; mean (SD) osteocalcin changed from 23.72 (22.20) to 13.95 (12.40) ng/mL; and mean (SD) P1NP changed from 54.68 (54.52) to 28.65 (27.48) ng/mL (P < 0.001 in all cases)], reaching statistical significance between the groups at week 48. Osteoprotegerin did not vary, but sclerostin significantly increased in the abacavir group [from 29.53 (27.91) to 35.56 (34.59) pmol/L, P = 0.002]. No significant differences in osteoprotegerin and sclerostin were detected between the groups at week 48. RANKL values were below the limit of detection in all samples. The switch from tenofovir to abacavir seems to induce a positive effect on bone tissue, since bone turnover markers decreased. In addition, circulating sclerostin levels increased, a change associated with improved bone properties. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Muscle-Bone Interactions in Pediatric Bone Diseases.

PubMed

Veilleux, Louis-Nicolas; Rauch, Frank

2017-10-01

Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders. When starting in utero, muscle disorders can lead to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function. Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.

Adrenarche and bone modeling and remodeling at the proximal radius: weak androgens make stronger cortical bone in healthy children.

PubMed

Remer, Thomas; Boye, Kai R; Hartmann, Michaela; Neu, Christina M; Schoenau, Eckhard; Manz, Friedrich; Wudy, Stefan A

2003-08-01

Adrenarche, the physiological increase in adrenal androgen secretion, may contribute to better bone status. Proximal radial bone and 24-h urinary steroid hormones were analyzed cross-sectionally in 205 healthy children and adolescents. Positive adrenarchal effects on radial diaphyseal bone were observed. Obviously, adrenarche is one determinant of bone mineral status in children. Increased bone mass has been reported in several conditions with supraphysiological adrenal androgen secretion during growth. However, no data are available for normal children. Therefore, our aim was to examine whether adrenal androgens within their physiological ranges may be involved in the strengthening of diaphyseal bone during growth. Periosteal circumference (PC), cortical density, cortical area, bone mineral content, bone strength strain index (SSI), and forearm cross-sectional muscle area were determined with peripheral quantitative computed tomography (pQCT) at the proximal radial diaphysis in healthy children and adolescents. All subjects, aged 6-18 years, who collected a 24-h urine sample around the time of their pQCT analysis (100 boys, 105 girls), were included in the present study, and major urinary glucocorticoid (C21) and androgen (C19) metabolites were quantified using gas chromatography-mass spectrometry. We found a significant influence of muscularity, but not of hormones, on periosteal modeling (PC) before the appearance of pubic hair (prepubarche). Similarly, no influence of total cortisol secretion (C21) was seen on the other bone variables. However, positive effects of C19 on cortical density (p < 0.01), cortical area (p < 0.001), bone mineral content (p < 0.001), and SSI (p < 0.001)--reflecting, at least in part, reduction in intracortical remodeling-were observed in prepubarchal children after muscularity or age had been adjusted for. This early adrenarchal contribution to proximal radial diaphyseal bone strength was further confirmed for all cortical variables

Bone grafts.

PubMed

Hubble, Matthew J W

2002-09-01

Bone grafts are used in musculoskeletal surgery to restore structural integrity and enhance osteogenic potential. The demand for bone graft for skeletal reconstruction in bone tumor, revision arthroplasty, and trauma surgery, couple with recent advances in understanding and application of the biology of bone transplantation, has resulted in an exponential increase in the number of bone-grafting procedures performed over the last decade. It is estimated that 1.5 million bone-grafting procedures are currently performed worldwide each year, compared to a fraction of that number 20 years ago. Major developments also have resulted in the harvesting, storage, and use of bone grafts and production of graft derivatives, substitutes, and bone-inducing agents.

Treatment of aneurysmal bone cysts of the pelvis and sacrum.

PubMed

Papagelopoulos, P J; Choudhury, S N; Frassica, F J; Bond, J R; Unni, K K; Sim, F H

2001-11-01

Aneurysmal bone cysts are benign, non-neoplastic, highly vascular bone lesions. The purpose of this study was to describe the prevalence, the clinical presentation, and the recurrence rate of aneurysmal bone cysts of the pelvis and sacrum and to examine the diagnostic and therapeutic options and prognosis for patients with this condition. Forty consecutive patients with an aneurysmal bone cyst of the pelvis and/or sacrum were treated from 1921 to 1996. Their medical records and radiographic and imaging studies were reviewed, and histological sections from the cysts were examined. Seventeen lesions were iliosacral, sixteen were acetabular, and seven were ischiopubic. Seven involved the hip joint, and two involved the sacroiliac joint. All twelve sacral lesions extended to more than one sacral segment and were associated with neurological signs and symptoms. Destructive acetabular lesions were associated with pathological fracture in five patients and with medial migration of the femoral head, hip subluxation, and hip dislocation in one patient each. The mean duration of follow-up was thirteen years (range, three to fifty-three years). Thirty-five patients who were initially treated for a primary lesion had surgical treatment (twenty-one had excision-curettage and fourteen had intralesional excision); two patients also had adjuvant radiation therapy. Of the thirty-five patients, five (14%) had a local recurrence noted less than eighteen months after the operation. Of five patients initially treated for a recurrent lesion, one had a local recurrence. At the latest follow-up examination, all forty patients were disease-free and twenty-eight (70%) were asymptomatic. There were two deep infections. Aneurysmal bone cysts of the pelvis and sacrum are usually aggressive lesions associated with substantial bone destruction, pathological fractures, and local recurrence. Current management recommendations include preoperative selective arterial embolization, excision

Effects of Spaceflight on Cells of Bone Marrow Origin

PubMed Central

Özçivici, Engin

2013-01-01

Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types. Conflict of interest:None declared. PMID:24385745

Electrospun nanofibrous 3D scaffold for bone tissue engineering.

PubMed

Eap, Sandy; Ferrand, Alice; Palomares, Carlos Mendoza; Hébraud, Anne; Stoltz, Jean-François; Mainard, Didier; Schlatter, Guy; Benkirane-Jessel, Nadia

2012-01-01

Tissue engineering aims at developing functional substitutes for damaged tissues by mimicking natural tissues. In particular, tissue engineering for bone regeneration enables healing of some bone diseases. Thus, several methods have been developed in order to produce implantable biomaterial structures that imitate the constitution of bone. Electrospinning is one of these methods. This technique produces nonwoven scaffolds made of nanofibers which size and organization match those of the extracellular matrix. Until now, seldom electrospun scaffolds were produced with thickness exceeding one millimeter. This article introduces a new kind of electrospun membrane called 3D scaffold of thickness easily exceeding one centimeter. The manufacturing involves a solution of poly(ε-caprolactone) in DMF/DCM system. The aim is to establish parameters for electrospinning in order to characterize these 3D scaffolds and, establish whether such scaffolds are potentially interesting for bone regeneration.

Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

USDA-ARS?s Scientific Manuscript database

Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

Osteosclerotic bone dysplasia (melorheostosis) of the mandible.

PubMed

Kuttenberger, J J; Hardt, N; Gebbers, J-O; Hofer, B

2006-12-01

Melorheostosis is a linear bone dysplasia of unknown origin that may be associated with soft-tissue alterations. Although any part of the skeleton can be affected, this condition is rarely observed in the craniofacial region. Only seven cases of melorheostosis with craniofacial involvement have been reported and cranial manifestation only is even rarer. To the authors' knowledge, manifestation in the mandible only has not yet been documented. A patient with isolated melorheostosis of the mandible with characteristic symptomatic bone pain is presented. The clinical, radiological and histological findings are described and possible therapeutic options are discussed.

Bone density in patients with chondromalacia patella.

PubMed

Salehi, Iraj; Khazaeli, Shabnam; Hatami, Parta; Malekpour, Mahdi

2010-06-01

Chondromalacia of the patella is the most common cause of anterior knee pain in young women. The etiology of the disease is not well-understood but the initial lesion is a disorganization of collagenous structures. Since the disease is proposed to be due to generalized constitutional disturbance, we postulated that bony structures could also be involved. To investigate this hypothesis we measured the bone density of 286 patients with the diagnosis of chondromalacia of the patella during a 4-year period using dual energy X-ray absorptiometry (DXA) method. We found a significant number of patients having low bone densities. This problem was more pronounced in men and in younger age groups. We suggest base-line bone density evaluation in all patients, treatment of osteopenia or osteoporosis in select patients and regular follow-ups using DXA.

The cellular transducer in bone: What is it?

PubMed

Taylor, David; Hazenberg, Jan; Lee, T Clive

2006-01-01

Bone is able to detect its strain environment and respond accordingly. In particular it is able to adapt to over-use and under-use by bone deposition or resorption. How can bone sense strain? Various physical mechanisms have been proposed for the so-called cellular transducer, but there is no conclusive proof for any one of them. This paper examines the theories and evidence, with particular reference to a new theory proposed by the authors, involving damage to cellular processes by microcracks. Experiments on bone samples ex-vivo showed that cracks cannot fracture osteocytes, but that cellular processes which span the crack can be broken. A theoretical model was developed for predicting the number of broken processes as a function of crack size and applied stress. This showed that signals emitted by fractured processes could be used to detect cracks which needed repairing and to provide information on the overall level of damage which could be used to initiate repair and adaptation responses.

[Xanthoma disseminatum with asymptomatic multisystem involvement].

PubMed

Zinoun, M; Hali, F; Marnissi, F; Lazaar, S; Benchikhi, H

2015-04-01

Xanthogranulomas belong to non-Langerhans histiocytosis of the second group in the Histiocyte Society classification. They comprise a heterogeneous group of rare entities frequently involving cutaneous tropism. Xanthoma disseminatum belongs to this group of non-Langerhans histiocytosis. We report a case of xanthoma disseminatum (XD) in which localized skin and mucous impairment revealed multisystem involvement. A 28-year-old man presented with a two-year history of progressive yellow-orange and infiltrated xanthomatous papulonodular lesions of the face. Lesions of the oral mucosa and genital region were seen, with no functional repercussions. No ophthalmic or other complications were found. Histopathology showed a dense histiocytic infiltrate within the dermis with Touton giant cells, foamy multinucleated giant cells and inflammatory cells, without necrobiosis. Histiocytes were positive for CD68 but negative for CD1a. Gastric and lung involvement was seen and was confirmed at histology. Bone scintigraphy showed suspicious left ulnar hyperfixation suggesting bone involvement. No monoclonal gammopathy or diabetes insipidus was seen. Our patient was treated with corticosteroids 1mg/kg/day and thalidomide 100 mg/day. The outcome was marked by regression and exfiltration of the cutaneous lesions from the second week of treatment, with subsidence continuing at 3 months. This case involves a very rare form of xanthoma disseminatum. The localized facial skin lesions revealed multifocal non-Langerhans histiocytosis that was in fact asymptomatic. The diagnosis of XD was based on clinical, histological and immunohistochemical criteria. Xanthoma disseminatum is a non-Langerhans histiocytic proliferation first described by Montgomery in 1938. This rare entity is characterized by skin and mucous membrane xanthomatosis in which the facial involvement is common, together with diabetes insipidus and normal lipid metabolism. The prognosis is determined by the presence of mucosal

Functional adaptation to mechanical loading in both cortical and cancellous bone is controlled locally and is confined to the loaded bones.

PubMed

Sugiyama, Toshihiro; Price, Joanna S; Lanyon, Lance E

2010-02-01

In order to validate whether bones' functional adaptation to mechanical loading is a local phenomenon, we randomly assigned 21 female C57BL/6 mice at 19 weeks of age to one of three equal numbered groups. All groups were treated with isoflurane anesthesia three times a week for 2 weeks (approximately 7 min/day). During each anaesthetic period, the right tibiae/fibulae in the DYNAMIC+STATIC group were subjected to a peak dynamic load of 11.5 N (40 cycles with 10-s intervals between cycles) superimposed upon a static "pre-load" of 2.0 N. This total load of 13.5 N engendered peak longitudinal strains of approximately 1400 microstrain on the medial surface of the tibia at a middle/proximal site. The right tibiae/fibulae in the STATIC group received the static "pre-load" alone while the NOLOAD group received no artificial loading. After 2 weeks, the animals were sacrificed and both tibiae, fibulae, femora, ulnae and radii analyzed by three-dimensional high-resolution (5 mum) micro-computed tomography (microCT). In the DYNAMIC+STATIC group, the proximal trabecular percent bone volume and cortical bone volume at the proximal and middle levels of the right tibiae as well as the cortical bone volume at the middle level of the right fibulae were markedly greater than the left. In contrast, the left bones in the DYNAMIC+STATIC group showed no differences compared to the left or right bones in the NOLOAD or STATIC group. These microCT data were confirmed by two-dimensional examination of fluorochrome labels in bone sections which showed the predominantly woven nature of the new bone formed in the loaded bones. We conclude that the adaptive response in both cortical and trabecular regions of bones subjected to short periods of dynamic loading, even when this response is sufficiently vigorous to stimulate woven bone formation, is confined to the loaded bones and does not involve changes in other bones that are adjacent, contra-lateral or remote to them. (c) 2009 Elsevier Inc

Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

PubMed

Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

2016-09-01

Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. Copyright © 2015 Elsevier Inc. All rights reserved.

The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

PubMed Central

Sun, Mengge; Zhou, Xiaoya; Chen, Lili; Huang, Shishu; Leung, Victor; Wu, Nan; Pan, Haobo; Zhen, Wanxin; Lu, William; Peng, Songlin

2016-01-01

MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed. PMID:27073801

Bone: from a reservoir of minerals to a regulator of energy metabolism

PubMed Central

Confavreux, Cyrille B

2011-01-01

Besides locomotion, organ protection, and calcium–phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secretion, insulin sensitivity, and pancreas β-cell proliferation) in the regulation of energy metabolism is described. Then, the connections between insulin signaling on osteoblasts and the release of uncarboxylated osteocalcin during osteoclast bone resorption through osteoprotegerin are reported. Finally, the understanding of this new bone endocrinology will provide some insights into bone, kidney, and energy metabolism in patients with chronic kidney disease. PMID:21346725

miR-218 is involved in the negative regulation of osteoclastogenesis and bone resorption by partial suppression of p38MAPK-c-Fos-NFATc1 signaling: Potential role for osteopenic diseases.

PubMed

Qu, Bo; Xia, Xun; Yan, Ming; Gong, Kai; Deng, Shaolin; Huang, Gang; Ma, Zehui; Pan, Xianming

2015-10-15

The increased osteoclastic activity accounts for pathological bone loss in diseases including osteoporosis. MicroRNAs are widely accepted to be involved in the regulation of osteopenic diseases. Recently, the low expression of miR-218 was demonstrated in CD14(+) peripheral blood mononuclear cells (PBMCs) from patients with postmenopausal osteoporosis. However, its role and the underlying mechanism in osteoporosis are still undefined. Here, an obvious decrease in miR-218 expression was observed during osteoclastogenesis under receptor activator of nuclear factor κB ligand (RANKL) stimulation, in both osteoclast precursors of bone marrow macrophages (BMMs) and RAW 264.7. Further analysis confirmed that overexpression of miR-218 obviously attenuated the formation of multinuclear mature osteoclasts, concomitant with the decrease in Trap and Cathepsin K levels, both the master regulators of osteoclastogenesis. Moreover, miR-218 up-regulation dramatically inhibited osteoclast precursor migration, actin ring formation and bone resorption. Mechanism assay demonstrated that miR-218 overexpression attenuated the expression of p38MAPK, c-Fos and NFATc1 signaling molecules. Following preconditioning with P79350, an agonist of p38MAPK, the inhibitor effect of miR-218 on osteoclastogenesis and bone-resorbing activity was strikingly ameliorated. Together, this study revealed a crucial role of miR-218 as a negative regulator for osteoclastogenesis and bone resorption by suppressing the p38MAPK-c-Fos-NFATc1 pathway. Accordingly, this research will provide a promising therapeutic agent against osteopenic diseases including osteoporosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Bone and bone turnover.

PubMed

Crofton, Patricia M

2009-01-01

Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified. Copyright (c) 2009 S. Karger AG, Basel.

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

PubMed

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

2012-04-06

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

Origins of bone repair in the armour of fossil fish: response to a deep wound by cells depositing dentine instead of dermal bone.

PubMed

Johanson, Zerina; Smith, Moya; Kearsley, Anton; Pilecki, Peter; Mark-Kurik, Elga; Howard, Charles

2013-10-23

The outer armour of fossil jawless fishes (Heterostraci) is, predominantly, a bone with a superficial ornament of dentine tubercles surrounded by pores leading to flask-shaped crypts (ampullae). However, despite the extensive bone present in these early dermal skeletons, damage was repaired almost exclusively with dentine. Consolidation of bone, by dentine invading and filling the vascular spaces, was previously recognized in Psammolepis and other heterostracans but was associated with ageing and dermal shield wear (reparative). Here, we describe wound repair by deposition of dentine directly onto a bony scaffold of fragmented bone. An extensive wound response occurred from massive deposition of dentine (reactionary), traced from tubercle pulp cavities and surrounding ampullae. These structures may provide the cells to make reparative and reactionary dentine, as in mammalian teeth today in response to stimuli (functional wear or damage). We suggest in Psammolepis, repair involved mobilization of these cells in response to a local stimulatory mechanism, for example, predator damage. By comparison, almost no new bone is detected in repair of the Psammolepis shield. Dentine infilling bone vascular tissue spaces of both abraded dentine and wounded bone suggests that recruitment of this process has been evolutionarily conserved over 380 Myr and precedes osteogenic skeletal repair.

A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow.

PubMed

Park, Il-Hyung; Micic, Ivan Dragoljub; Jeon, In-Ho

2008-02-01

The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.