Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis.

PubMed

Okumura, Takako; Murata, Yoko; Taniguchi, Kana; Murase, Akio; Nii, Aisuke

2008-06-01

Prostaglandin E2 (PGE2) produced by cyclooxygenase (COX) is a potent pro-inflammatory mediator. We have recently discovered CJ-023,423, a highly selective antagonist of EP4 receptors, one of the PGE2 receptors. This agent is suitable for exploring the effects of blocking EP4 receptors following oral administration in rats. In this study, CJ-023,423 was used in rats with adjuvant-induced arthritis (AIA) to investigate the role of the EP4 receptor in chronic inflammation and bone destruction. These effects were compared with those of rofecoxib, a selective COX-2 inhibitor. CJ-023,423 had significant inhibitory effects on paw swelling, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats. In particular, the inhibitory effect on paw swelling in AIA rats was comparable to that of rofecoxib. These results suggest that PGE2 acting via the EP4 receptor is involved in the development of chronic inflammation and bone destruction, particularly with respect to oedema in AIA rats. This is the first study to confirm the in-vivo effects of EP4 receptor blockade on inflammation and bone destruction in AIA rats with a small-molecule compound.

Analysis of imaging characteristics of primary malignant bone tumors in children

PubMed Central

Sun, Yingwei; Liu, Xueyong; Pan, Shinong; Deng, Chunbo; Li, Xiaohan; Guo, Qiyong

2017-01-01

The present study aimed to investigate the imaging characteristics of primary malignant bone tumors in children. The imaging results of 34 children with primary malignant bone tumors confirmed by histopathological diagnosis between March 2008 and January 2014 were retrospectively analyzed. In total, 25 patients had osteosarcoma, with radiography and computed tomography (CT) showing osteolytic bone destruction or/and osteoblastic bone sclerosis, an aggressive periosteal reaction, a soft-tissue mass and cancerous bone. The tumors appeared as mixed magnetic resonance imaging (MRI) signals that were inhomogeneously enhanced. A total of 5 patients presented with Ewing sarcoma, with radiography and CT showing invasive bone destruction and a soft-tissue mass. Of the 5 cases, 2 showed a laminar periosteal reaction. The tumors were shown to have mixed low signal on T1-weighted images (T1WI) and high signal on T2-weighted images (T2WI); 1 case showed marked inhomogeneous enhancement. Another 3 patients exhibited chondrosarcoma. Of these cases, 1 was adjacent to the cortex of the proximal tibia, and presented with local cortical bone destruction and a soft-tissue mass containing scattered punctate and amorphous calcifications. MRI revealed mixed low T1 signal and high T2 signals. Another case was located in the medullary cavity of the distal femur, with radiography revealing a localized periosteal reaction. The tumor appeared with mixed MRI signals, and with involvement of the epiphysis and epiphyseal plates. Radiography and CT of the third case showed bone destruction in the right pubic ramus, with patchy punctate, cambered calcifications in the soft-tissue mass. MRI of the soft-tissue mass revealed isointensity on T1WI and heterogeneous hyperintensity on T2WI. Ossifications and the septum appeared as low T1WI and T2WI. Of the 34 patients, 1 patient presented with lymphoma involving the T12, L1 and L2 vertebrae. CT showed vertebral bone destruction, a soft-tissue mass and a compression fracture of L1. MRI showed a soft-tissue mass with low T1 signal and high T2 signal and marked inhomogeneous enhancement. Overall, osteosarcoma was the most common primary malignant bone tumor, followed by Ewing sarcoma, chondrosarcoma and lymphoma. Osteoblastic or osteolytic bone destruction, an invasive periosteal reaction, soft-tissue masses, a tumor matrix and inhomogeneous enhancement were important imaging features of malignant bone tumors. PMID:29113210

Non-destructive and non-invasive observation of friction and wear of human joints and of fracture initiation by acoustic emission.

PubMed

Schwalbe, H J; Bamfaste, G; Franke, R P

1999-01-01

Quality control in orthopaedic diagnostics according to DIN EN ISO 9000ff requires methods of non-destructive process control, which do not harm the patient by radiation or by invasive examinations. To obtain an improvement in health economy, quality-controlled and non-destructive measurements have to be introduced into the diagnostics and therapy of human joints and bones. A non-invasive evaluation of the state of wear of human joints and of the cracking tendency of bones is, as of today's point of knowledge, not established. The analysis of acoustic emission signals allows the prediction of bone rupture far below the fracture load. The evaluation of dry and wet bone samples revealed that it is possible to conclude from crack initiation to the bone strength and thus to predict the probability of bone rupture.

Ewing's sarcoma of the cranial vault: a case report.

PubMed

Feki, Jihene; Guermazi, Zeineb; Kammoun, Brahim; Khanfir, Afef; Toumi, Nabil; Boudawara, Tahiya; Boudawara, Zaher; Daoud, Jamel; Frikha, Mounir

2017-12-01

Ewing's sarcoma is a malignant tumor that mainly affects young patients. It represents 10% of primary malignant tumors of the bone and 3% of malignant tumors of the child. Cranial localization is extremely rare representing less than 1% of all the localizations. We report a case of a 10-year-old girl who presented with an intracranial hypertension syndrome with left parietal mass of progressive installation. The X-ray skull showed a lytic lesion with irregular margins involving the left parietal bone. Brain magnetic resonance imaging revealed extensive parietal bone destruction involving both the inner and outer tables. The girl was operated in emergency. Histological examination concluded to Ewing's Sarcoma. The resection was incomplete (R1). The girl received induction's chemotherapy. The cerebral scanner evaluation showed no abnormalities. Then, she received consolidation's chemotherapy with concomitant local radiation therapy. Currently, the girl is in complete remission with a seven-month decline.

18F-fluorodeoxyglucose imaging of primary malignant pericardial mesothelioma with concurrent pericardial and pleural effusions and bone metastasis: A case report.

PubMed

Li, Xiaohui; Lu, Rugang; Zhao, Youcai; Wang, Feng; Shao, Guoqiang

2018-06-01

Primary malignant pericardial mesothelioma (PMPM) is an aggressive tumor that originates from the mesothelial cells of the pericardium. PMPM with extensive atrial infiltration and bone metastasis is extremely rare. The diagnosis and staging of PMPM based on anatomical imaging may be difficult when concurrent pericardial and pleural effusions are present. A 28-year-old man presented with progressive chest pain. Concurrent pericardial and pleural effusions were identified on computed tomography. On echocardiography, mild thickening and adhesions of the pericardium with the right ventricle and atrium were observed. 18 F-fluorodeoxyglucose (FDG) metabolism imaging revealed increased accumulation in the pericardium and adjacent right atrium. Ring-shaped radioactivity aggregation and bone destruction in the sacrum were demonstrated on 18 F-FDG and 99m Tc-methyl diphosphonate imaging. The diagnosis of PMPM was subsequently confirmed by pathology. The patient survived for >1.5 years with comprehensive treatment.

Determination of Small Animal Long Bone Properties Using Densitometry

NASA Technical Reports Server (NTRS)

Breit, Gregory A.; Goldberg, BethAnn K.; Whalen, Robert T.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Assessment of bone structural property changes due to loading regimens or pharmacological treatment typically requires destructive mechanical testing and sectioning. Our group has accurately and non-destructively estimated three dimensional cross-sectional areal properties (principal moments of inertia, Imax and Imin, and principal angle, Theta) of human cadaver long bones from pixel-by-pixel analysis of three non-coplanar densitometry scans. Because the scanner beam width is on the order of typical small animal diapbyseal diameters, applying this technique to high-resolution scans of rat long bones necessitates additional processing to minimize errors induced by beam smearing, such as dependence on sample orientation and overestimation of Imax and Imin. We hypothesized that these errors are correctable by digital image processing of the raw scan data. In all cases, four scans, using only the low energy data (Hologic QDR-1000W, small animal mode), are averaged to increase image signal-to-noise ratio. Raw scans are additionally processed by interpolation, deconvolution by a filter derived from scanner beam characteristics, and masking using a variable threshold based on image dynamic range. To assess accuracy, we scanned an aluminum step phantom at 12 orientations over a range of 180 deg about the longitudinal axis, in 15 deg increments. The phantom dimensions (2.5, 3.1, 3.8 mm x 4.4 mm; Imin/Imax: 0.33-0.74) were comparable to the dimensions of a rat femur which was also scanned. Cross-sectional properties were determined at 0.25 mm increments along the length of the phantom and femur. The table shows average error (+/- SD) from theory of Imax, Imin, and Theta) over the 12 orientations, calculated from raw and fully processed phantom images, as well as standard deviations about the mean for the femur scans. Processing of phantom scans increased agreement with theory, indicating improved accuracy. Smaller standard deviations with processing indicate increased precision and repeatability. Standard deviations for the femur are consistent with those of the phantom. We conclude that in conjunction with digital image enhancement, densitometry scans are suitable for non-destructive determination of areal properties of small animal bones of comparable size to our phantom, allowing prediction of Imax and Imin within 2.5% and Theta within a fraction of a degree. This method represents a considerable extension of current methods of analyzing bone tissue distribution in small animal bones.

A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis

PubMed Central

Cassat, James E.; Hammer, Neal D.; Campbell, J. Preston; Benson, Meredith A.; Perrien, Daniel S.; Mrak, Lara N.; Smeltzer, Mark S.; Torres, Victor J.; Skaar, Eric P.

2013-01-01

Summary Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection. Pathogen-induced bone destruction limits antimicrobial penetration to the infectious focus and compromises treatment of osteomyelitis. To investigate mechanisms of S. aureus-induced bone destruction, we developed a murine model of osteomyelitis. Micro-computed tomography of infected femurs revealed that S. aureus triggers profound alterations in bone turnover. The bacterial regulatory locus sae was found to be critical for osteomyelitis pathogenesis, as Sae-regulated factors promote pathologic bone remodeling and intraosseous bacterial survival. Exoproteome analyses revealed the Sae-regulated protease aureolysin as a major determinant of the S. aureus secretome and identified the phenol soluble modulins as aureolysin-degraded, osteolytic peptides that trigger osteoblast cell death and bone destruction. These studies establish a murine model for pathogen-induced bone remodeling, define Sae as critical for osteomyelitis pathogenesis, and identify protease-dependent exoproteome remodeling as a major determinant of the staphylococcal virulence repertoire. PMID:23768499

Gorham-Stout syndrome of the facial bones: a review of pathogenesis and treatment modalities and report of a case with a rare cutaneous manifestations.

PubMed

Al-Jamali, Jamil; Glaum, Ricarda; Kassem, Ahmed; Voss, Pit Jacob; Schmelzeisen, Rainer; Schön, Ralf

2012-12-01

Gorham disease is a very rare condition associated with spontaneous destruction and resorption of 1 or more bones anywhere in the body. Many authors have suggested and/or implicated trauma as the initiating factor in the majority of the reported cases. It can affect almost all bones, and a combination of bones has been reported. In the maxillofacial skeleton, the first facial case was reported by Romer in 1928. Until now, only a few cases of Gorham disease affecting the maxillofacial bones, including this case report, have been reported. We present a brief review of the pathogenesis and treatment modalities of the disease and report a very rare clinical picture of the disease affecting a young and otherwise healthy patient with massive osteolysis of the mandibular bone and extensive involvement of the mouth floor and skin of the chin, which to our knowledge, is the only case report with skin manifestation affecting the maxillofacial region. Such skin manifestations play an important role for the diagnosis and add a clue for management of such condition. Copyright © 2012 Elsevier Inc. All rights reserved.

Apple Down 152: a putative case of syphilis from sixth century AD Anglo-Saxon England.

PubMed

Cole, Garrard; Waldron, Tony

2011-01-01

This report describes a putative case of a treponemal infection observed on a skeleton of a young male adult from the Apple Down Anglo-Saxon cemetery dating to the sixth century AD, accompanied by grave goods indicative of a high status burial. The skeleton is well preserved and almost complete. The pathological evidence includes an extensive area of lytic destruction to the frontal bone of the skull, widespread profuse bilateral symmetrical periosteal reaction affecting scapulae, clavicles, arms, legs, hands, feet and ribs. There is also evidence of gummatous destruction on some of the long bones. Application of a differential diagnosis of all probable diseases exhibiting the individual symptoms leads to a clear conclusion that the person was infected with a treponemal pathogen. The skeleton shows none of the stigmata associated with the congenital form of treponemal disease. We propose that the evidence suggests a possible case of venereal syphilis rather than one of the endemic forms of treponemal disease. This diagnosis is based on the geographical pathogen range, the apparent low prevalence of the disease, significant social upheaval at the time, the high social status and early age of death of the individual. Copyright © 2010 Wiley-Liss, Inc.

Exceptional case of bone resorption in an osteo-odonto-keratoprosthesis. A scanning electron microscopy and X-ray microanalysis study

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

Caiazza, S.; Falcinelli, G.; Pintucci, S.

1990-01-01

This article reports the findings of investigations on an osteo-odonto-keratoprosthesis in an eye that was enucleated owing to severe complications 12 years after implantation. Scanning electron microscopy and electron probe X-ray microanalysis showed extensive resorption of the bone that was used as a supporting element in the kind of transcorneal prosthesis developed by Strampelli. The destructive process, in addition to surgical trauma, has been associated with the early and recurrent bacterial infections relating to the presence of Staphylococcus epidermidis. The need to control the occurrence of primary bacterial infections in traumatized tissues during operations as well as further infectious situations,more » given the enhanced antibiotic-resistence of bacteria, is emphasized.« less

Association of magnetic resonance imaging findings and histologic diagnosis in dogs with nasal disease: 78 cases (2001-2004).

PubMed

Miles, Macon S; Dhaliwal, Ravinder S; Moore, Michael P; Reed, Ann L

2008-06-15

OBJECTIVE-To determine whether magnetic resonance imaging (MRI) features correlated with histologic diagnosis in dogs with nasal disease. DESIGN-Retrospective case series. ANIMALS-78 Dogs undergoing MRI for evaluation of nasal disease. PROCEDURES-Medical records and MRI reports of dogs were reviewed to identify MRI features associated with histologic diagnosis. Features evaluated were presence of a mass effect, frontal sinus involvement, sphenoid sinus involvement, maxillary recess involvement, nasopharyngeal infiltration by soft tissue, nasal turbinate destruction, vomer bone lysis, paranasal bone destruction, cribriform plate erosion, and lesion extent (ie, unilateral vs bilateral). RESULTS-33 Dogs had neoplastic disease, 38 had inflammatory rhinitis, and 7 had fungal rhinitis. Lesion extent was not significantly associated with histologic diagnosis. Absence of a mass effect was significantly associated with inflammatory disease. However, presence of a mass was not specific for neoplasia. In dogs with evidence of a mass on magnetic resonance (MR) images, nasal turbinate destruction, frontal sinus invasion, and maxillary recess invasion were not useful in distinguishing neoplastic from nonneoplastic disease, but cribriform plate erosion, vomer bone lysis, paranasal bone destruction, sphenoid sinus invasion, and nasopharyngeal invasion were. CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that in dogs with nasal disease, the lack of a mass effect on MR images was significantly associated with inflammatory disease. In dogs with a mass effect on MR images, vomer bone lysis, cribriform plate erosion, paranasal bone destruction, sphenoid sinus invasion by a mass, and nasopharyngeal invasion by a mass were significantly associated with a diagnosis of neoplasia.

Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

PubMed Central

Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

2012-01-01

Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

Primary non-Hodgkin lymphoma of the right femur and subsequent metastasis to the left femur: A case report and literature review.

PubMed

Hu, Jing-Yu; Yu, Dan; Wu, Yao-Hui

2018-04-01

Non-Hodgkin lymphoma of the bone is rare and typically causes an extensive bone lesion. The present study describes a case of diffuse large B-cell primary non-Hodgkin lymphoma of the bone, which occurred in the right femur, and was initially treated with surgery and chemotherapy. Following a 7-year period of complete remission, a new, similar lesion was identified in the left femur. With both lesions, there was no accompanying destruction of any other bones or organ involvement. Metastasis of PLB to the contralateral side is extremely rare and, to the best of our knowledge, this is the first report of this particular presentation in China or worldwide. We hypothesized that the present situation arose due to mechanisms involving the tumor microenvironment, circulating tumor cells, lymphocyte homing and self-seeding. The present report describes the case in detail, and discusses the possible underlying mechanisms and their potential contribution to the treatment of non-Hodgkin lymphoma, as well as the prevention of metastasis and recurrence, which may be of considerable clinical significance.

Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

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

Nakamura, Ryosuke; Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Kayamori, Kou

Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and themore » bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction.« less

Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis.

PubMed

Hendrix, Andrew S; Spoonmore, Thomas J; Wilde, Aimee D; Putnam, Nicole E; Hammer, Neal D; Snyder, Daniel J; Guelcher, Scott A; Skaar, Eric P; Cassat, James E

2016-09-01

Staphylococcus aureus osteomyelitis is a common and debilitating invasive infection of bone. Treatment of osteomyelitis is confounded by widespread antimicrobial resistance and the propensity of bacteria to trigger pathological changes in bone remodeling that limit antimicrobial penetration to the infectious focus. Adjunctive therapies that limit pathogen-induced bone destruction could therefore limit morbidity and enhance traditional antimicrobial therapies. In this study, we evaluate the efficacy of the U.S. Food and Drug Administration-approved, nonsteroidal anti-inflammatory (NSAID) compound diflunisal in limiting S. aureus cytotoxicity toward skeletal cells and in preventing bone destruction during staphylococcal osteomyelitis. Diflunisal is known to inhibit S. aureus virulence factor production by the accessory gene regulator (agr) locus, and we have previously demonstrated that the Agr system plays a substantial role in pathological bone remodeling during staphylococcal osteomyelitis. Consistent with these observations, we find that diflunisal potently inhibits osteoblast cytotoxicity caused by S. aureus secreted toxins independently of effects on bacterial growth. Compared to commonly used NSAIDs, diflunisal is uniquely potent in the inhibition of skeletal cell death in vitro Moreover, local delivery of diflunisal by means of a drug-eluting, bioresorbable foam significantly limits bone destruction during S. aureus osteomyelitis in vivo Collectively, these data demonstrate that diflunisal potently inhibits skeletal cell death and bone destruction associated with S. aureus infection and may therefore be a useful adjunctive therapy for osteomyelitis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

PubMed

Body, Jean-Jacques

2012-03-01

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

Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma.

PubMed

Morisawa, Ayaka; Okui, Tatsuo; Shimo, Tsuyoshi; Ibaragi, Soichiro; Okusha, Yuka; Ono, Mitsuaki; Nguyen, Thi Thu Ha; Hassan, Nur Mohammad Monsur; Sasaki, Akira

2018-03-01

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically where one of the mechanisms responsible for the invasion into facial bones occurs via the activation of osteoclasts. Copper has been demonstrated to play a key role in skeletal remodeling. However, the role of copper in cancer-associated bone destruction is thus far unknown. Lysyl oxidase (LOX) is a copper-dependent enzyme that promotes osteoclastogenesis. In the present study, we investigated the effects of copper on HNSCC with bone invasion by the copper chelator, ammonium tetrathiomolybdate (TM) in vitro and in vivo. We demonstrate that TM blocks the proliferation of HNSCC cells, inhibits LOX activation and decreases the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoblasts and osteocytes, subsequently suppressing bone destruction. These findings suggest that copper is a potential target for the treatment of HNSCCs associated with bone destruction.

Solitary juvenile xanthogranuloma of the temporal muscle and bone penetrating the dura mater in a 2-month-old boy.

PubMed

Cornips, Erwin M J; Cox, Kimberly E M; Creytens, David H K V; Granzen, Bernd; Weber, Jacobiene W; Ter Laak-Poort, Mariel P

2009-12-01

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder primarily observed during the first 2 years of life. Most patients present with a solitary cutaneous lesion; however, others present with extracutaneous manifestations or even with systemic involvement. The authors describe a 2-month-old boy in whom was diagnosed a unifocal extracutaneous JXG involving the temporal bone. Unlike 3 other cases of solitary JXGs of the temporal bone in the literature, the present case involved destruction of the dura mater and leptomeningeal enhancement surrounding the entire temporal lobe. The lesion did not regress after an initial biopsy procedure and had to be removed more radically because of progressive mass effect on the brain. The child recently underwent a reconstructive skull procedure and is doing well almost 2 years postoperatively without evidence of disease. This case demonstrates that even in instances of extensive disease a favorable outcome is possible without chemotherapy.

Water extract of the fruits of Alpinia oxyphylla inhibits osteoclast differentiation and bone loss.

PubMed

Ha, Hyunil; Shim, Ki-Shuk; Kim, Taesoo; Lee, Chung-Jo; Park, Ji Hyung; Kim, Han Sung; Ma, Jin Yeul

2014-09-23

Excessive bone resorption by osteoclasts causes pathological bone destruction, seen in various bone diseases. There is accumulating evidence that certain herbal extracts have beneficial effects on bone metabolism. The fruits of Alpinia oxyphylla has been traditionally used for the treatment of diarrhea and enuresis. In this study, we investigated the effects of water extract of the fruits of Alpinia oxyphylla (WEAO) on osteoclast differentiation and osteoclast-mediated bone destruction. For osteoclast differentiation assay, mouse bone marrow-derived macrophages (BMMs) were cultured in the presence of RANKL and M-CSF. RANKL signaling pathways and gene expression of transcription factors regulating osteoclast differentiation were investigated by real-time PCR and Western blotting. A constitutively active form of NFATc1 was retrovirally transduced into BMMs. Bone resorbing activity of mature osteoclast was examined on a plate coated with an inorganic crystalline calcium phosphate. The in vivo effect against bone destruction was assessed in a murine model of RANKL-induced osteoporosis by micro-computed tomography and bone metabolism marker analyses. WEAO dose-dependently inhibited RANKL-induced osteoclast differentiation from BMMs by targeting the early stages of osteoclast differentiation. WEAO inhibited RANKL-induced expression of NFATc1, the master regulator of osteoclast differentiation. Overexpression of a constitutively active form of NFATc1 blunted the inhibitory effect of WEAO on osteoclast differentiation, suggesting that NFATc1 is a critical target of the inhibitory action of WEAO. WEAO inhibited RANKL-induced expression of c-Fos, an upstream activator of NFATc1, by suppressing the classical NF-κB signaling pathway. WEAO also inhibited RANKL-induced down-regulation of Id2 and MafB, negative regulators of NFATc1. WEAO does not directly affect bone resorbing activity of mature osteoclasts. In accordance with the in vitro results, WEAO attenuated RANKL-induced bone destruction in mice by inhibiting osteoclast differentiation. This study demonstrates that WEAO exhibits a protective effect against bone loss by inhibiting RANKL-induced osteoclast differentiation. These findings suggest that WEAO might be useful for the prevention and treatment of bone diseases associated with excessive bone resorption.

Multiple non-syndromic odontogenic keratocysts in three siblings

PubMed Central

Nirwan, Amit; Wanjari, Sangeeta Panjab; Saikhedkar, Rashmi; Karun, Vinayak

2013-01-01

Occurrence of multiple cysts (MC) involving the jaw is rare. When multiple, it is usually associated with a syndrome. Occurrence of MC without syndromic association is extremely rare. Multiple odontogenic cysts mostly could be odontogenic keratocysts or dentigerous cysts. Odontogenic keratocyst shows involvement of mandible over maxilla, with peak incidence in second and third decade and it is exceedingly rare before 10 years of age. However multiple odontogenic keratocysts found in children are often reflective of nevoid basal cell carcinoma syndrome. Here is a case report which documents multiple jaw cysts involving both the jaws, in three siblings of ages 10, 13 and 17 years with negative parental history. All three reported cases were free of any systemic involvement. As odontogenic keratocyst spreads through bone marrow, destruction is more before any clinical manifestation. Therefore, early detection and intervention are essential in preventing extensive destruction. PMID:23505078

The treatment of recurrent chronic infected knee arthroplasty with a 2-stage procedure.

PubMed

Antoci, Valentin; Phillips, Matthew J; Antoci, Valentin; Krackow, Kenneth A

2009-01-01

We report the case of a patient with recurrent periprosthetic infections after total knee arthroplasty associated with bone destruction and massive bone loss that was successfully treated with a 2-stage procedure-resection arthroplasty with insertion of an antibiotic-impregnated cement rod-spacer and systemic antibiotics and then a resection arthrodesis of the knee with the use of an intercalary allograft fixed with a long intramedullary nail. This technique is a viable option for the treatment of recurrent periprosthetic infections after total knee arthroplasty associated with bone destruction, massive bone loss, and severe instability.

Kinetic examination of femoral bone modeling in broilers.

PubMed

Prisby, R; Menezes, T; Campbell, J; Benson, T; Samraj, E; Pevzner, I; Wideman, R F

2014-05-01

Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute to subsequent pathology of the femoral head in fast-growing broilers.

Bone structure regeneration after low induction magnetic field treatment in teeth chosen for extraction.

PubMed

Opalko, K; Dojs, A

2006-01-01

The aim of the work was to use and to evaluate the usefulness of the slow variable magnetic fields to aid the treatment of the teeth chosen for extraction. The marginal paradontium of periapical bone of teeth was in a state of extensive destruction. The teeth were chosen for extraction. 13 patients were chosen. 10 of them had with endo-perio changes and 3 suffered from full tooth luxation and had the teeth replanted. Those people were to have an extraction procedure or were declared as impossible to treat in other dental offices. Patients underwent non-aggressive skaling, endodontic treatment and were exposed to slow variable magnetic fields generated by Viofor JPS, accordingly to methods and parameters suggested by Department of Propaedeutics in Dentistry of Pomeranian Medical University in Szczecin. The process of healing of changes was evaluated radiologically. RTG done after 2 weeks and after 2 months were evaluated in respect of bone regeneration. They show the bone structure concentration. A RTG evaluation after half a year, two and three years show a preservation of the bone structure concentration. The use of slow variable magnetic fields contributed to bone structure regeneration and to preserve teeth with recorded endo-perio syndrome. Endodontic treatment of replanted teeth, aided with magnetostimulation has stopped the osteolisis process.

Hyoid Bone and Thyroid Cartilage Metastases from Sigmoid Colon Adenocarcinoma: A Case Report.

PubMed

Bracanovic, Djurdja; Vukovic, Vesna; Janovic, Aleksa; Radosavljevic, Davorin; Rakocevic, Zoran

2017-05-05

Secondary tumours of the hyoid bone and thyroid cartilage are extremely rare. In this paper, we present a case of the hyoid bone and thyroid cartilage metastases in a patient treated for sigmoid colon adenocarcinoma. Four years after sigmoid colon adenocarcinoma was diagnosed and treated with surgery and chemotherapy, the patient developed bone metastases in the left sacroiliac joint and right proximal humerus. Although the patient did not complain of any related symptoms, in a bone scintigraphy the accumulation of Technetium-99m was incidentally detected in the two sites of the anterior neck. On ultrasound examination there were two hyperechoic and heterogeneous masses with calcifications placed in front of the hyoid bone and thyroid cartilage. Computerized tomography demonstrated massive hyoid bone and thyroid cartilage destruction. In patients with progressive sigmoid colon adenocarcinoma, destruction of the hyoid bone and thyroid cartilage could be suspected for metastases.

Autocrine inhibition of the c-fms proto-oncogene reduces breast cancer bone metastasis assessed with in vivo dual-modality imaging.

PubMed

Jeffery, Justin J; Lux, Katie; Vogel, John S; Herrera, Wynetta D; Greco, Stephen; Woo, Ho-Hyung; AbuShahin, Nisreen; Pagel, Mark D; Chambers, Setsuko K

2014-04-01

Breast cancer cells preferentially home to the bone microenvironment, which provides a unique niche with a network of multiple bidirectional communications between host and tumor, promoting survival and growth of bone metastases. In the bone microenvironment, the c-fms proto-oncogene that encodes for the CSF-1 receptor, along with CSF-1, serves as one critical cytokine/receptor pair, functioning in paracrine and autocrine fashion. Previous studies concentrated on the effect of inhibition of host (mouse) c-fms on bone metastasis, with resulting decrease in osteolysis and bone metastases as a paracrine effect. In this report, we assessed the role of c-fms inhibition within the tumor cells (autocrine effect) in the early establishment of breast cancer cells in bone and the effects of this early c-fms inhibition on subsequent bone metastases and destruction. This study exploited a multidisciplinary approach by employing two non-invasive, in vivo imaging methods to assess the progression of bone metastases and bone destruction, in addition to ex vivo analyses using RT-PCR and histopathology. Using a mouse model of bone homing human breast cancer cells, we showed that an early one-time application of anti-human c-fms antibody delayed growth of bone metastases and bone destruction for at least 31 days as quantitatively measured by bioluminescence imaging and computed tomography, compared to controls. Thus, neutralizing human c-fms in the breast cancer cell alone decreases extent of subsequent bone metastasis formation and osteolysis. Furthermore, we are the first to show that anti-c-fms antibodies can impact early establishment of breast cancer cells in bone.

Smad4 is required to inhibit osteoclastogenesis and maintain bone mass.

PubMed

Morita, Mayu; Yoshida, Shigeyuki; Iwasaki, Ryotaro; Yasui, Tetsuro; Sato, Yuiko; Kobayashi, Tami; Watanabe, Ryuichi; Oike, Takatsugu; Miyamoto, Kana; Takami, Masamichi; Ozato, Keiko; Deng, Chu-Xia; Aburatani, Hiroyuki; Tanaka, Sakae; Yoshimura, Akihiko; Toyama, Yoshiaki; Matsumoto, Morio; Nakamura, Masaya; Kawana, Hiromasa; Nakagawa, Taneaki; Miyamoto, Takeshi

2016-10-12

Bone homeostasis is maintained as a delicate balance between bone-resorption and bone-formation, which are coupled to maintain appropriate bone mass. A critical question is how bone-resorption is terminated to allow bone-formation to occur. Here, we show that TGFβs inhibit osteoclastogenesis and maintain bone-mass through Smad4 activity in osteoclasts. We found that latent-TGFβ1 was activated by osteoclasts to inhibit osteoclastogenesis. Osteoclast-specific Smad4 conditional knockout mice (Smad4-cKO) exhibited significantly reduced bone-mass and elevated osteoclast formation relative to controls. TGFβ1-activation induced expression of Irf8 and Bcl6, both of which encode factors inhibiting osteoclastogenesis, by blocking their negative regulator, Prdm1, in osteoclasts in a Smad4-dependent manner. Reduced bone-mass and accelerated osteoclastogenesis seen in Smad4-cKO were abrogated by Prdm1 deletion. Administration of latent-TGFβ1-Fc to wild-type mice antagonized LPS-induced bone destruction in a model of activated osteoclast-mediated bone destruction. Thus, latent-TGFβ1-Fc could serve as a promising new therapeutic agent in bone diseases marked by excessive resorption.

Intrinsic qualities of primate bones as predictors of skeletal element representation in modern and fossil carnivore feeding assemblages.

PubMed

Carlson, Kristian J; Pickering, Travis Rayne

2003-04-01

Plio-Pleistocene faunal assemblages from Swartkrans Cave (South Africa) preserve large numbers of primate remains. Brain, C.K., 1981. The Hunters or the Hunted? An Introduction to African Cave Taphonomy. University of Chicago Press, Chicago suggested that these primate subassemblages might have resulted from a focus by carnivores on primate predation and bone accumulation. Brain's hypothesis prompted us to investigate, in a previous study, this taphonomic issue as it relates to density-mediated destruction of primate bones (J. Archaeol. Sci. 29, 2002, 883). Here we extend our investigation of Brain's hypothesis by examining additional intrinsic qualities of baboon bones and their role as mediators of skeletal element representation in carnivore-created assemblages. Using three modern adult baboon skeletons, we collected data on four intrinsic bone qualities (bulk bone mineral density, maximum length, volume, and cross-sectional area) for approximately 81 bones per baboon skeleton. We investigated the relationship between these intrinsic bone qualities and a measure of skeletal part representation (the percentage minimum animal unit) for baboon bones in carnivore refuse and scat assemblages. Refuse assemblages consist of baboon bones not ingested during ten separate experimental feeding episodes in which individual baboon carcasses were fed to individual captive leopards and a spotted hyena. Scat assemblages consist of those baboon bones recovered in carnivore regurgitations and feces resulting from the feeding episodes. In refuse assemblages, volume (i.e., size) was consistently the best predictor of element representation, while cross-sectional area was the poorest predictor in the leopard refuse assemblage and bulk bone mineral density (i.e., a measure of the proportion of cortical to trabecular bone) was the poorest predictor in the hyena refuse assemblage. In light of previous documentation of carnivore-induced density-mediated destruction to bone assemblages, we interpret the current findings as suggestive of the secondary importance of bulk bone mineral density to other intrinsic qualities of skeletal elements (e.g., size, maximum dimension, and average cross-sectional area). It is only when skeletal elements are too large for consumption (e.g., many long bones) that they are fragmented following intra-element patterns of density-mediated carnivore destruction. There appears to be a size threshold beneath which bulk bone mineral density contributes little to mediating carnivore destruction of carcasses. Thus, depending on body size of the predator, body size of the prey, and specific size of the element, bulk bone mineral density may play little or no role of primary importance in mediating the destruction of skeletal elements. We compare patterns in modern comparative assemblages to patterns in primate fossil assemblages from Swartkrans. One of the fossil assemblages, Swartkrans Member 1, Hanging Remnant, most closely approximates a hyena (possibly refuse) assemblage pattern, while the Swartkrans Member 2 assemblage most closely approximates a leopard (possibly scat) assemblage pattern. The Swartkrans Member 1, Lower Bank, assemblage does not closely approximate any of our modern comparative assemblage patterns.

Different clinical presentation and management of temporal bone fibrous dysplasia in children.

PubMed

Mierzwiński, Józef; Kosowska, Justyna; Tyra, Justyna; Haber, Karolina; Drela, Maria; Paczkowski, Dariusz; Burduk, Paweł

2018-01-15

Fibrous dysplasia is a slowly progressive benign fibro-osseous disorder that involves one or multiple bones with a unilateral distribution in most cases. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse histopathology. Temporal bone involvement is the least frequently reported type, especially in children. We reviewed available articles regarding fibrous dysplasia with temporal bone involvement in children and added four patients aged 7 to 17 years who were diagnosed and treated in our institution from 2006 to 2017. The patients' clinical picture comprised head deformity, external canal stenosis, headache, progressive conductive and/or sensorineural hearing loss, tinnitus, and sudden deafness. Two patients had experienced severe episodic vertigo with nausea and vomiting. Two were referred to us with external canal obstruction and secondary cholesteatoma formation with broad middle ear destruction. One was diagnosed with acute mastoiditis and intracranial complications. Optimal management of fibrous dysplasia is unclear and can be challenging, especially in children. In our two patients with disease expansion and involvement of important structures, surgical treatment was abandoned and a "wait-and-scan" policy was applied. The other two were qualified for surgical treatment. One patient underwent two surgeries: modified lateral petrosectomy (canal left open) with pathological tissue removal, cavity obliteration, and subsequent tympanoplasty. Another patient with extensive destruction of the left temporal bone underwent canal wall down mastoidectomy with perisinus abscess drainage and revision 12 months later. Tympanoplasty was unsatisfactory in both patients because of slow progression of the middle ear pathology. None of our patients underwent pharmacological treatment. In younger patients, observation and a "wait-and-scan" protocol is relevant until significant function, or cosmetic deficits are obvious. Surgery is not preferred and should be delayed until puberty because fibrous dysplasia has a tendency to stabilize after adolescence. In patients with severe symptoms medical treatment can be implemented, but safety of this treatment in children remain controversial.

Microbial osteolysis in an Early Pleistocene hominin (Paranthropus robustus) from Swartkrans, South Africa.

PubMed

Grine, Frederick E; Bromage, Timothy G; Daegling, David J; Burr, David B; Brain, Charles K

2015-08-01

Microbiological degradation is one of the most important factors responsible for the destruction of bone in archaeological contexts. Microscopic focal destruction (MFD) is the most prevalent form of microbial tunneling and is encountered very commonly in human bones from archaeological sites, whereas animal bones from these same sites show significantly better preservation if they were deposited in a fragmentary (e.g., butchered) state. Similarly, most fossils show either no evidence or only minor traces of bacterial osteolysis. These observations and experimental evidence point to an endogenous origin for osteolytic bacteria, suggesting that bone bioerosion could potentially aid in reconstructing early taphonomic events. We here report extensive MFD in the mandibular corpus of a small (presumptive female) individual of the hominin Paranthropus robustus from the Early Pleistocene site of Swartkrans, South Africa. The specimen (SKX 5013) derives in situ from the Member 2 deposit, which is dated to ca. 1.5-1.0 Ma. Examination of sections from the corpus by backscattered electron microscopy reveals numerous small linear longitudinal and budded tunneling cavities, which tend to be concentrated around Haversian canals and are more abundant closer to the endosteal aspect of the section. The taphonomy of Swartkrans has been the subject of intense investigation, and given the possibility that different agents of accumulation may have been responsible for the faunal and hominin fossils in the different members at the site, the observation that a specimen of P. robustus from Member 2 displays significant microbial osteolysis is of potential interest. A study of the prevalence of this process in adequately large samples of the animal bones from these units may yield novel insights and provide refinement of our understanding of their taphonomic histories. Such observations might well reveal differences among the various members that could provide another valuable source of osteoarchaeological information for the site. Copyright © 2015 Elsevier Ltd. All rights reserved.

Destructive bone disease in early syphilis.

PubMed

Dismukes, W E; Delgado, D G; Mallernee, S V; Myers, T C

1976-12-06

Although destructive bone disease is a well-known complication of tertiary syphilis, osteitis or osteomyelitis are not commonly recognized as complications of early (primary or secondary) syphillis. A patient with secondary syphilis characterized by generalized lymphadenopathy, perianal condyloma lata, and positive rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption (FTA-ABS) tests also complained of headache, right should pain, and right anterior chest pain and swelling. Roentgenograms showed mottled osteolytic lesions consistent with previously described luetic bone disease. Biopsy confirmed the diagnosis of syphilitic osteomyelitis, and treatment with penicillin resulted in prompt resolution of symptoms.

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 ...

Cherubism Mice Also Deficient in c-Fos Exhibit Inflammatory Bone Destruction Executed by Macrophages That Express MMP14 Despite the Absence of TRAP+ Osteoclasts.

PubMed

Kittaka, Mizuho; Mayahara, Kotoe; Mukai, Tomoyuki; Yoshimoto, Tetsuya; Yoshitaka, Teruhito; Gorski, Jeffrey P; Ueki, Yasuyoshi

2018-01-01

Currently, it is believed that osteoclasts positive for tartrate-resistant acid phosphatase (TRAP+) are the exclusive bone-resorbing cells responsible for focal bone destruction in inflammatory arthritis. Recently, a mouse model of cherubism (Sh3bp2 KI/KI ) with a homozygous gain-of-function mutation in the SH3-domain binding protein 2 (SH3BP2) was shown to develop auto-inflammatory joint destruction. Here, we demonstrate that Sh3bp2 KI/KI mice also deficient in the FBJ osteosarcoma oncogene (c-Fos) still exhibit noticeable bone erosion at the distal tibia even in the absence of osteoclasts at 12 weeks old. Levels of serum collagen I C-terminal telopeptide (ICTP), a marker of bone resorption generated by matrix metalloproteinases (MMPs), were elevated, whereas levels of serum cross-linked C-telopeptide (CTX), another resorption marker produced by cathepsin K, were not increased. Collagenolytic MMP levels were increased in the inflamed joints of the Sh3bp2 KI/KI mice deficient in c-Fos. Resorption pits contained a large number of F4/80+ macrophages and genetic depletion of macrophages rescued these erosive changes. Importantly, administration of NSC405020, an MMP14 inhibitor targeted to the hemopexin (PEX) domain, suppressed bone erosion in c-Fos-deficient Sh3bp2 KI/KI mice. After activation of the NF-κB pathway, macrophage colony-stimulating factor (M-CSF)-dependent macrophages from c-Fos-deficient Sh3bp2 KI/KI mice expressed increased amounts of MMP14 compared with wild-type macrophages. Interestingly, receptor activator of NF-κB ligand (RANKL)-deficient Sh3bp2 KI/KI mice failed to show notable bone erosion, whereas c-Fos deletion did restore bone erosion to the RANKL-deficient Sh3bp2 KI/KI mice, suggesting that osteolytic transformation of macrophages requires both loss-of-function of c-Fos and gain-of-function of SH3BP2 in this model. These data provide the first genetic evidence that cells other than osteoclasts can cause focal bone destruction in inflammatory bone disease and suggest that MMP14 is a key mediator conferring pathological bone-resorbing capacity on c-Fos-deficient Sh3bp2 KI/KI macrophages. In summary, the paradigm that osteoclasts are the exclusive cells executing inflammatory bone destruction may need to be reevaluated based on our findings with c-Fos-deficient cherubism mice lacking osteoclasts. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Effects of letrozole on breast cancer micro-metastatic tumor growth in bone and lung in mice inoculated with murine 4T1 cells.

PubMed

Wang, Wendan; Belosay, Aashvini; Yang, Xujuan; Hartman, James A; Song, Huaxin; Iwaniec, Urszula T; Turner, Russell T; Churchwell, Mona I; Doerge, Daniel R; Helferich, William G

2016-06-01

Breast cancer (BC) is the leading cancer in women worldwide. Metastasis occurs in stage IV BC with bone and lung being common metastatic sites. Here we evaluate the effects of the aromatase inhibitor letrozole on BC micro-metastatic tumor growth in bone and lung metastasis in intact and ovariectomized (OVX) mice with murine estrogen receptor negative (ER-) BC cells inoculated in tibia. Forty-eight BALB/c mice were randomly assigned to one of four groups: OVX, OVX + Letrozole, Intact, and Intact + Letrozole, and injected with 4T1 cells intra-tibially. Letrozole was subcutaneously injected daily for 23 days at a dose of 1.75 µg/g body weight. Tumor progression was monitored by bioluminescence imaging (BLI). Following necropsy, inoculated tibiae were scanned via µCT and bone response to tumor was scored from 0 (no ectopic mineralization/osteolysis) to 5 (extensive ectopic mineralization/osteolysis). OVX mice had higher tibial pathology scores indicative of more extensive bone destruction than intact mice, irrespective of letrozole treatment. Letrozole decreased serum estradiol levels and reduced lung surface tumor numbers in intact animals. Furthermore, mice receiving letrozole had significantly fewer tumor colonies and fewer proliferative cells in the lung than OVX and intact controls based on H&E and Ki-67 staining, respectively. In conclusion, BC-inoculated OVX animals had higher tibia pathology scores than BC-inoculated intact animals and letrozole reduced BC metastases to lungs. These findings suggest that, by lowering systemic estrogen level and/or by interacting with the host organ, the aromatase inhibitor letrozole has the potential to reduce ER- BC metastasis to lung.

Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow

USDA-ARS?s Scientific Manuscript database

Osteoporosis is characterized by destruction of bone architecture, resulting in decreased bone mass density (BMD) and increased fracture susceptibility. While current therapies focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabol...

The role of internal fixation for long bone metastasis prior to impending fracture: an experimental model.

PubMed

Ibrahim, Mohammad; Terai, Hidetomi; Yamada, Kentaro; Suzuki, Akinobu; Toyoda, Hiromitsu; Nakamura, Hiroaki

2013-07-01

Patients with long bone metastasis have many therapeutic options, including surgery. However, the appropriate time for surgical intervention and the use of internal fixation prior to impending fracture remains controversial. The purpose of this study was to establish a long bone metastatic model with internal fixation, and to determine whether prophylactic internal fixation for long bone metastasis prior to impending fracture would affect bone destruction, tumor progression, and mortality. We implanted VX2 tumor cells into the tibiae of 45 rabbits divided equally into three groups: internal fixation, control, and sham groups. Rabbits were monitored by X-ray and computed tomography, and blood serum levels were examined every 2 weeks. Computed tomography data revealed significantly higher bone destruction in rabbit tibiae in the sham and control groups compared with those in the fixation group; there were volumetric bone losses of 0.2, 0.4, and 2.3% in the fixation, sham, and control groups, respectively, at 3 weeks, which increased to 1.2, 2.5, and 6.1% at 5 weeks. Rabbits in the fixation group showed significantly prolonged survival (64.5 ± 13.5 days) in comparison with rabbits in the sham group (50.3 ± 11.6 days) and control group (38.2 ± 4.9 days). Our results suggest that prophylactic internal fixation may hinder bone destruction and tumor progression, thus extending the survival period for patients with long bone metastasis.

Hamster and Murine Models of Severe Destructive Lyme Arthritis

PubMed Central

Munson, Erik; Nardelli, Dean T.; Du Chateau, Brian K.; Callister, Steven M.; Schell, Ronald F.

2012-01-01

Arthritis is a frequent complication of infection in humans with Borrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ-) deficient mice with viable B. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology. PMID:22461836

Aggressive intraosseous lipoma of the intermediate phalanges of the thumb.

PubMed

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

2018-07-01

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

The Immediate Aesthetic and Functional Restoration of Maxillary Incisors Compromised by Periodontitis Using Short Implants with Single Crown Restorations: A Minimally Invasive Approach and Five-Year Follow-Up

PubMed Central

Marincola, Mauro; Lombardo, Giorgio; Pighi, Jacopo; Corrocher, Giovanni; Mascellaro, Anna; Lehrberg, Jeffrey; Nocini, Pier Francesco

2015-01-01

The functional and aesthetic restoration of teeth compromised due to aggressive periodontitis presents numerous challenges for the clinician. Horizontal bone loss and soft tissue destruction resulting from periodontitis can impede implant placement and the regeneration of an aesthetically pleasing gingival smile line, often requiring bone augmentation and mucogingival surgery, respectively. Conservative approaches to the treatment of aggressive periodontitis (i.e., treatments that use minimally invasive tools and techniques) have been purported to yield positive outcomes. Here, we report on the treatment and five-year follow-up of patient suffering from aggressive periodontitis using a minimally invasive surgical technique and implant system. By using the methods described herein, we were able to achieve the immediate aesthetic and functional restoration of the maxillary incisors in a case that would otherwise require bone augmentation and extensive mucogingival surgery. This technique represents a conservative and efficacious alternative to the aesthetic and functional replacement of teeth compromised due to aggressive periodontitis. PMID:26649207

Adipose, Bone and Myeloma: Contributions from the Microenvironment

PubMed Central

McDonald, Michelle; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R.

2017-01-01

Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide [1]. Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90% of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies. PMID:27343063

In vivo visualisation of different modes of action of biological DMARDs inhibiting osteoclastic bone resorption.

PubMed

Matsuura, Yoshinobu; Kikuta, Junichi; Kishi, Yuika; Hasegawa, Tetsuo; Okuzaki, Daisuke; Hirano, Toru; Minoshima, Masafumi; Kikuchi, Kazuya; Kumanogoh, Atsushi; Ishii, Masaru

2018-04-28

Osteoclasts play critical roles in inflammatory bone destruction. Precursor cell migration, cell differentiation, and functional cell activation are all in play. Biological disease-modifying antirheumatic drugs (DMARDs) have been shown to significantly inhibit both bone erosion as well as synovitis, although how such agents reduce osteoclastic bone destruction in vivo has not been fully explained. Here, we used an intravital time-lapse imaging technique to directly visualise mature osteoclasts and their precursors, and explored how different biological DMARDs acted in vivo . Lipopolysaccharide (LPS) was injected into the calvarial periosteum of fluorescent reporter mice to induce inflammatory bone destruction. Time-lapse imaging was performed via intravital multiphoton microscopy 5 days after LPS injection. Biological DMARDs, including monoclonal antibodies (mAbs) against the interleukin (IL) 6 receptor (IL-6R) and tumour necrosis factor α (TNFα), or cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-Ig, were intraperitoneally administered at the time of LPS injection. We determined CD80/86 expression levels in mature osteoclasts and their precursors by flow cytometry, quantitative PCR and immunohistochemistry. Of the biologicals tested, anti-IL-6R and anti-TNFα mAbs affected mature osteoclasts and switched bone-resorbing osteoclasts to non-resorbing cells. CTLA4-Ig had no action on mature osteoclasts but mobilised osteoclast precursors, eliminating their firm attachment to bone surfaces. In agreement with these results, CD80/86 (the target molecules of CTLA4-Ig) were prominently expressed only in osteoclast precursor cells, being suppressed during osteoclast maturation. Intravital imaging revealed that various biological DMARDs acted at specific therapeutic time points during osteoclastic bone destruction, with different efficacies. These results enable us to grasp the real modes of action of drugs, optimising the usage of drug regimens. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

IL-17 receptor A signaling is protective in infection-stimulated periapical bone destruction.

PubMed

AlShwaimi, Emad; Berggreen, Ellen; Furusho, Hisako; Rossall, Jonathan Caleb; Dobeck, Justine; Yoganathan, Subbiah; Stashenko, Philip; Sasaki, Hajime

2013-08-15

IL-17 is a pleiotropic cytokine produced by Th17 T cells that induces a myriad of proinflammatory mediators. However, different models of inflammation report opposite functional roles of IL-17 signal in terms of its effects on bone destruction. In this study we determined the role of IL-17RA signal in bone resorption stimulated by dentoalveolar infections. Infrabony resorptive lesions were induced by surgical pulp exposure and microbial infection of mouse molar teeth. IL-17 was strongly induced in periapical tissues in wild-type (WT) mice by 7 d after the infection but was not expressed in uninfected mice. Dentoalveolar infections of IL-17RA knockout (KO) mice demonstrated significantly increased bone destruction and more abscess formation in the apical area compared with WT mice. Infected IL-17RA KO mice exhibited significantly increased neutrophils and macrophages compared with the WT littermates at day 21, suggesting a failure of transition from acute to chronic inflammation in the IL-17RA KO mice. The expression of IL-1 (both α and β isoforms) and MIP2 were significantly upregulated in the IL-17RA KO compared with WT mice at day 21 postinfection. The development of periapical lesions in IL-17RA KO mice was significantly attenuated by neutralization of IL-1β and MIP2. Taken together, these results demonstrate that IL-17RA signal seems to be protective against infection-induced periapical inflammation and bone destruction via suppression of neutrophil and mononuclear inflammation.

Primary Signet Ring Cell Carcinoma of Rectum Diagnosed by Boring Biopsy in Combination with Endoscopic Mucosal Resection.

PubMed

Hirata, Yoshito; Kanno, Keishi; Kishikawa, Nobusuke; Tomoda, Shinji; Kimura, Kazuki; Kobayashi, Tomoki; Miyamori, Daisuke; Otani, Yuichiro; Mizooka, Masafumi; Arihiro, Koji; Oka, Shiro; Tanaka, Shinji; Tazuma, Susumu

2018-01-01

A 46-year-old man with severe back pain visited our hospital. Magnetic resonance imaging revealed extensive bone metastasis and rectal wall thickness. Colonoscopy revealed circumferential stenosis with edematous mucosa, suggesting colon cancer. However, histological findings of biopsy specimens revealed inflammatory cells but no malignant cells. The patient underwent endoscopic ultrasound, which demonstrated edematous wall thickness without destruction of the normal layer structure. After unsuccessful detection of neoplastic cells by boring biopsies, we performed endoscopic mucosal resection followed by boring biopsies that finally revealed signet ring cell carcinoma. Herein, we present a case and provide a review of the literature.

Total Saponin from Anemone flaccida Fr. Schmidt Prevents Bone Destruction in Experimental Rheumatoid Arthritis via Inhibiting Osteoclastogenesis.

PubMed

Liu, Chunfang; Yang, Yue; Sun, Danni; Wang, Chao; Wang, Hui; Jia, Shiwei; Liu, Liang; Lin, Na

2015-12-01

Anemone flaccida Fr. Schmidt is used in the clinical compound prescription for the treatment of rheumatoid arthritis (RA) in China and has the traditional use of draining dampness, diminishing swelling, and relieving pain. Total saponins (TS) are the characteristic components and also the main active ingredients of A. flaccida. Previous reports indicated that TS possess anti-inflammatory and immunoregulatory properties; however, the effects of TS on bone destruction of RA have not been evaluated. In this study, our data first showed the therapeutic effects of TS on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) rats. Then, by microfocal computed tomography (CT) quantification, TS significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints both at peri-articular and extra-articular locations. TS also diminished the level of the bone resorption marker CTX-I and simultaneously increased the bone formation marker osteocalcin in sera of CIA rats. Interestingly, TS prevented bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of nuclear factor-κF (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in inflamed joints and sera of CIA rats. This was further confirmed in the co-culture system of human fibroblast-like synovial and peripheral blood mononuclear cells. In addition, TS inhibited the levels of pro-inflammatory cytokines implicated in bone resorption, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα), IL-6, IL-17, and IL-23 in sera and joints. These findings offer convincing evidence that TS attenuate RA partially by preventing both focal bone destruction and systemic bone loss. This anti-erosive effect results in part from inhibiting osteoclastogenesis by regulating the RANKL/RANK/OPG signaling pathway. The suppression of systemic and local pro-osteoclastogenic cytokines by TS was also highly effective.

Prevaccination with SRL172 (heat-killed Mycobacterium vaccae) inhibits experimental periodontal disease in Wistar rats

PubMed Central

Breivik, T; Rook, G A W

2000-01-01

Periodontal disease is a bacterial dental plaque-induced destructive inflammatory condition of the tooth-supporting tissues, which is thought to be mediated by T lymphocytes secreting T helper 2 (Th2) cytokines, resulting in recruitment of high numbers of antibody-producing B lymphocytes/plasma cells as well as polymorphonuclear leucocytes (PMN) secreting tissue-destructive components, such at matrix metalloproteinases and reactive oxygen metabolites into the gingival connective tissues. One treatment strategy may be to down-regulate the Th2 response to those dental plaque microorganisms which induce the destructive inflammatory response. In this study we have examined the effects of a potent down-regulator of Th2 responses on ligature-induced periodontal disease in an experimental rat model. A single s.c. injection into Wistar rats of 0·1 or 1 mg of SRL172, a preparation of heat-killed Mycobacterium vaccae (NCTC 11659), 13 days before application of the ligature, significantly reduced the subsequent destruction of the tooth-supporting tissues, as measured by loss of periodontal attachment fibres (P < 0·001) and bone (P < 0·002). This protective effect occurred not only on the experimental (ligatured) side but also on the control unligatured side. SRL172 has undergone extensive toxicological studies and safety assessments in humans, and it is suggested that it may provide a safe and novel therapeutic approach to periodontal disease. PMID:10844524

A comparative analysis of microscopic alterations in modern and ancient undecalcified and decalcified dry bones.

PubMed

Caruso, Valentina; Cummaudo, Marco; Maderna, Emanuela; Cappella, Annalisa; Caudullo, Giorgio; Scarpulla, Valentina; Cattaneo, Cristina

2018-02-01

The present study aims to evaluate the preservation of the microstructure of skeletal remains collected from four different known burial sites (archaeological and contemporary). Histological analysis on undecalcified and decalcified thin sections was performed in order to assess which of the two techniques is more affected by taphonomic insults. A histological analysis was performed on both undecalcified and decalcified thin sections of 40 long bones and the degree of diagenetic change was evaluated using transmitted and polarized light microscopy according to the Oxford Histological Index (OHI). In order to test the optical behavior of bone tissue, thin sections were observed by polarized light microscopy and the intensity of birefringence was evaluated. The more ancient samples are generally characterized by a low OHI (0-1) with extensive microscopic focal destruction; recent samples exhibited a better preservation of bone micromorphology. When comparing undecalcified to decalcified thin sections, the latter showed an amelioration in the conservation of microscopic structure. As regards the birefringence, it was very low in all the undecalcified thin sections, whereas decalcification process seems to improve its visibility. The preservation of the bone microscopic structure appears to be influenced not only by age, but also by the burial context. Undecalcified bones appear to be more affected by taphonomical alterations, probably because of the thickness of the thin sections; on the contrary, decalcified thin sections proved to be able to tackle this issue allowing a better reading of the bone tissue. © 2017 Wiley Periodicals, Inc.

The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK activation in osteoclast precursors

PubMed Central

Kitano, Victor J.; Shimada, Jun

2018-01-01

Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS). Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells. However, the effects of sudachitin on inflammatory bone destruction and osteoclastogenesis remain unknown. In calvaria inflamed by a local lipopolysaccharide (LPS) injection, inflammation-induced bone destruction and the accompanying elevated expression of osteoclastogenesis-related genes were reduced by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited osteoclast formation in cultures of isolated osteoblasts and osteoclast precursors. However, sudachitin rather increased the expression of receptor activator of NF-κB ligand (RANKL), which is an important molecule triggering osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of additional target cells. When osteoclast formation was induced from osteoclast precursors derived from bone marrow cells in the presence of soluble RANKL and macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis without influencing cell viability. Consistently, the expression of osteoclast differentiation-related molecules including c-fos, NFATc1, cathepsin K and osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our findings suggest that sudachitin is a useful agent for the treatment of anti-inflammatory bone destruction. PMID:29342179

The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK activation in osteoclast precursors.

PubMed

Ohyama, Yoko; Ito, Junta; Kitano, Victor J; Shimada, Jun; Hakeda, Yoshiyuki

2018-01-01

Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS). Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells. However, the effects of sudachitin on inflammatory bone destruction and osteoclastogenesis remain unknown. In calvaria inflamed by a local lipopolysaccharide (LPS) injection, inflammation-induced bone destruction and the accompanying elevated expression of osteoclastogenesis-related genes were reduced by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited osteoclast formation in cultures of isolated osteoblasts and osteoclast precursors. However, sudachitin rather increased the expression of receptor activator of NF-κB ligand (RANKL), which is an important molecule triggering osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of additional target cells. When osteoclast formation was induced from osteoclast precursors derived from bone marrow cells in the presence of soluble RANKL and macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis without influencing cell viability. Consistently, the expression of osteoclast differentiation-related molecules including c-fos, NFATc1, cathepsin K and osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our findings suggest that sudachitin is a useful agent for the treatment of anti-inflammatory bone destruction.

The sound of orthopaedic surgery--the application of acoustic emission technology in orthopaedic surgery: a review.

PubMed

Rashid, Mustafa S; Pullin, Rhys

2014-01-01

Acoustic emission technology has been developed and extensively used as a non-destructive method of testing within engineering. In recent years, acoustic emission has gained popularity within the field of Orthopaedic research in a variety of situations. It is an attractive method in the detection of flaws within structures due its high sensitivity and non-destructive nature. The aim of this article is firstly to critically review the research conducted using acoustic emission testing in a variety of Orthopaedic-related situations and to present the technique to the wider Orthopaedic community. A summary of the principles and practical aspects of using acoustic emission testing are outlined. Acoustic emission has been validated as a method of early detection of aseptic loosening in femoral components in total hip arthroplasty in several well-conducted in vitro studies [1-3]. Other studies have used acoustic emission to detect microdamage in bone and to assess the biomechanical properties of bone and allografts [9]. Researchers have also validated the use of acoustic emission to detect and monitor fracture healing [4]. Several studies have applied acoustic emission to spinal surgery and specifically to assess the biomechanical environment in titanium mesh cages used in spinal surgery [10, 11]. Despite its growing popularity within Orthopaedic research, acoustic emission remains are relatively unfamiliar technique to the majority of Orthopaedic surgeons.

Fabrication method, structure, mechanical, and biological properties of decellularized extracellular matrix for replacement of wide bone tissue defects.

PubMed

Anisimova, N Y; Kiselevsky, M V; Sukhorukova, I V; Shvindina, N V; Shtansky, D V

2015-09-01

The present paper was focused on the development of a new method of decellularized extracellular matrix (DECM) fabrication via a chemical treatment of a native bone tissue. Particular attention was paid to the influence of chemical treatment on the mechanical properties of native bones, sterility, and biological performance in vivo using the syngeneic heterotopic and orthotopic implantation models. The obtained data indicated that after a chemical decellularization treatment in 4% aqueous sodium chlorite, no noticeable signs of the erosion of compact cortical bone surface or destruction of trabeculae of spongy bone in spinal channel were observed. The histological studies showed that the chemical treatment resulted in the decellularization of both bone and cartilage tissues. The DECM samples demonstrated no signs of chemical and biological degradation in vivo. Thorough structural characterization revealed that after decellularization, the mineral frame retained its integrity with the organic phase; however clotting and destruction of organic molecules and fibers were observed. FTIR studies revealed several structural changes associated with the destruction of organic molecules, although all organic components typical of intact bone were preserved. The decellularization-induced structural changes in the collagen constituent resulted changed the deformation under compression mechanism: from the major fracture by crack propagation throughout the sample to the predominantly brittle fracture. Although the mechanical properties of radius bones subjected to decellularization were observed to degrade, the mechanical properties of ulna bones in compression and humerus bones in bending remained unchanged. The compressive strength of both the intact and decellularized ulna bones was 125-130 MPa and the flexural strength of humerus bones was 156 and 145 MPa for the intact and decellularized samples, respectively. These results open new avenues for the use of DECM samples as the replacement of wide bone tissue defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Destructive discovertebral degenerative disease of the lumbar spine.

PubMed

Charran, A K; Tony, G; Lalam, R; Tyrrell, P N M; Tins, B; Singh, J; Eisenstein, S M; Balain, B; Trivedi, J M; Cassar-Pullicino, V N

2012-09-01

The uncommon variant of degenerative hip joint disease, termed rapidly progressive osteoarthritis, and highlighted by severe joint space loss and osteochondral disintegration, is well established. We present a similar unusual subset in the lumbar spine termed destructive discovertebral degenerative disease (DDDD) with radiological features of vertebral malalignment, severe disc resorption, and "bone sand" formation secondary to vertebral fragmentation. Co-existing metabolic bone disease is likely to promote the development of DDDD of the lumbar spine, which presents with back pain and sciatica due to nerve root compression by the "bone sand" in the epidural space. MRI and CT play a complimentary role in making the diagnosis.

Forensic microradiology: micro-computed tomography (Micro-CT) and analysis of patterned injuries inside of bone.

PubMed

Thali, Michael J; Taubenreuther, Ulrike; Karolczak, Marek; Braun, Marcel; Brueschweiler, Walter; Kalender, Willi A; Dirnhofer, Richard

2003-11-01

When a knife is stabbed in bone, it leaves an impression in the bone. The characteristics (shape, size, etc.) may indicate the type of tool used to produce the patterned injury in bone. Until now it has been impossible in forensic sciences to document such damage precisely and non-destructively. Micro-computed tomography (Micro-CT) offers an opportunity to analyze patterned injuries of tool marks made in bone. Using high-resolution Micro-CT and computer software, detailed analysis of three-dimensional (3D) architecture has recently become feasible and allows microstructural 3D bone information to be collected. With adequate viewing software, data from 2D slice of an arbitrary plane can be extracted from 3D datasets. Using such software as a "digital virtual knife," the examiner can interactively section and analyze the 3D sample. Analysis of the bone injury revealed that Micro-CT provides an opportunity to correlate a bone injury to an injury-causing instrument. Even broken knife tips can be graphically and non-destructively assigned to a suspect weapon.

Adipose, Bone, and Myeloma: Contributions from the Microenvironment.

PubMed

McDonald, Michelle M; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R

2017-05-01

Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide (Podar et al. in Expert Opin Emerg Drugs 14:99-127, 2009). Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90 % of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes, and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies.

Correlation between Volume of Apical Periodontitis Determined by Cone-beam Computed Tomography Analysis and Endotoxin Levels Found in Primary Root Canal Infection.

PubMed

Cardoso, Flávia G R; Ferreira, Nádia S; Martinho, Frederico C; Nascimento, Gustavo G; Manhães, Luiz R C; Rocco, Marco A; Carvalho, Cláudio A T; Valera, Marcia C

2015-07-01

This clinical study was conducted to correlate the levels of endotoxins and bacterial counts found in primary endodontic infection with the volume of periapical bone destruction determined by cone-beam computed tomography (CBCT) analysis. Moreover, the levels of bacteria and endotoxins were correlated with the development of clinical features. Twenty-four root canals with primary endodontic disease and apical periodontitis were selected. Clinical features such as pain on palpation, pain on percussion, and previous episode of pain were recorded. The volume (cubic millimeters) of periapical bone destruction was determined by CBCT analysis. Endotoxins and bacterial samplings were collected by using sterile/apyrogenic paper points. Endotoxins were quantified by using limulus amebocyte lysate assay (KQCL test), and bacterial count (colony-forming units [CFU]/mL) was determined by using anaerobic culture techniques. Data were analyzed by Pearson correlation and multiple logistic regression (P < .05). Endotoxins and bacteria were detected in 100% of the root canal samples (24 of 24), with median values of 10.92 endotoxin units (EU)/mL (1.75-128 EU/mL) and 7.5 × 10(5) CFU/mL (3.20 × 10(5)-8.16 × 10(6) CFU/mL), respectively. The median volume of bone destruction determined by CBCT analysis was 100 mm(3) (10-450 mm(3)). The multiple regression analysis revealed a positive correlation between higher levels of endotoxins present in root canal infection and larger volume of bone destruction (P < .05). Moreover, higher levels of endotoxins were also correlated with the presence of previous pain (P < .05). Our findings revealed that the levels of endotoxins found in root canal infection are related to the volume of periapical bone destruction determined by CBCT analysis. Moreover, the levels of endotoxin are related to the presence of previous pain. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Bizarre parosteal osteochondromatous proliferation (Nora's lesion): a retrospective study of 12 cases, 2 arising in long bones.

PubMed

Abramovici, Luigia; Steiner, German C

2002-12-01

Twelve cases of bizarre parosteal osteochondromatous proliferation (BPOP), also known as Nora's lesion, are reported. Ten lesions were located in the small bones of the hands, and 2 were located in long bones (femur and proximal tibia). Patient age ranged from 12 to 63 years (average, 30.3 years). Radiography of the lesions in the hand bones showed calcific masses attached to the underlying cortex, without interruption of the latter. The long bone lesions revealed unusual findings. In the femur, BPOP presented with extensive cortical destruction and was suggestive of a malignant lesion. This presentation has not been described to date. In the tibia, the lesion was located in the soft tissue without cortical attachment. This type of BPOP probably represents an immature lesion that over time will mature to solid cortical attachment. On histologic examination, all lesions demonstrated 3 distinct components with variable degrees of representation: (1) hypercellular cartilage with calcification and ossification, with the calcified cartilage having a characteristic basophilic tinctorial quality; (2) cancellous bone undergoing maturation; and (3) spindle cell stroma without cytologic atypia. In 1 case with a long-standing history, the cartilaginous component was minimal. BPOP, together with florid reactive periostitis and turret exostosis, may represent different stages in the development of a posttraumatic proliferative process. BPOP apparently arises from the periosteal tissues through a process of cartilaginous metaplasia. Copyright 2002, Elsevier Science (USA). All rights reserved.

Murine models of breast cancer bone metastasis

PubMed Central

Wright, Laura E; Ottewell, Penelope D; Rucci, Nadia; Peyruchaud, Olivier; Pagnotti, Gabriel M; Chiechi, Antonella; Buijs, Jeroen T; Sterling, Julie A

2016-01-01

Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats. In this methods review, we characterize the bone phenotype of commonly utilized human- and murine-derived breast cell lines that elicit osteoblastic and/or osteolytic destruction of bone in mice and report methods for optimizing tumor-take in murine models of bone metastasis. We then provide protocols for four of the most common xenograft and syngeneic inoculation routes for modeling breast cancer metastasis to the skeleton in mice, including the intra-cardiac, intra-arterial, orthotopic and intra-tibial methods of tumor cell injection. Recommendations for in vivo and ex vivo assessment of tumor progression and bone destruction are provided, followed by discussion of the strengths and limitations of the available tools and translational models that aid investigators in the study of breast cancer metastasis to bone. PMID:27867497

Transdifferentiation of myoblasts into osteoblasts - possible use for bone therapy.

PubMed

Lin, Daphne P L; Carnagarin, Revathy; Dharmarajan, Arun; Dass, Crispin R

2017-12-01

Transdifferentiation is defined as the conversion of one cell type to another and is an ever-expanding field with a growing number of cells found to be capable of such a process. To date, the fact remains that there are limited treatment options for fracture healing, osteoporosis and bone repair post-destruction by bone tumours. Hence, this review focuses on the transdifferentiation of myoblast to osteoblast as a means to further understand the transdifferentiation process and to investigate a potential therapeutic option if successful. The potent osteoinductive effects of the bone morphogenetic protein-2 are largely implicated in the transdifferentiation of myoblast to osteoblast. Bone morphogenetic protein-2-induced activation of the Smad1 protein ultimately results in JunB synthesis, the first transcriptional step in myoblast dedifferentiation. The upregulation of the activating protein-1 binding activity triggers the transcription of the runt-related transcription factor 2 gene, a transcription factor that plays a major role in osteoblast differentiation. This potential transdifferentiation treatment may be utilised for dental implants, fracture healing, osteoporosis and bone repair post-destruction by bone tumours. © 2017 Royal Pharmaceutical Society.

Prostaglandin PGE2: a possible mechanism for bone destruction in calcinosis circumscripta.

PubMed

Caniggia, A; Gennari, C; Vattimo, A; Runci, F; Bombardieri, S

1978-02-28

A patient showed evident osteolysis in phalanges and heavy periarticular calcium deposits of the fingers, wrists and toes which avidly took up 47Ca. The dense, white, tooth-paste like fluid contained in the periarticular calcium deposits has been studied by two different X-ray diffraction methods, by Ubatuba's bioassay for prostaglandin, by thin layer chromatography and by mass spectrometry. The calcium deposits were hydroxyapatite and prostaglandin PGE2 was detected in them. The bone resorption stimulating activity of PGE2 would be expected to result in increased bone destruction with release of calcium salts and this could be a working hypothesis of the pathogenesis of calcinosis circumscripta.

Desmoplastic fibroma of the distal tibia: A case report of a minimally invasive histological diagnosis

PubMed Central

Levrini, Gabriele; Pattacini, Pierpaolo

2016-01-01

Desmoplastic fibroma (DF) is a benign, rare fibroblastic intraosseous neoplasm histologically resembling a desmoid soft tissue tumor. Although classified as benign, DF frequently exhibits an aggressive behavior, has a moderate-to-high recurrence rate, and often causes pathological fractures and extensive bone destruction. This case report presents an incidentally detected DF of the tibia, which was diagnosed using a minimally invasive approach. A 36-year-old African female patient was referred to the Department of Diagnostic Imaging of Arcispedale Santa Maria Nuova-IRCCS (Reggio Emilia, Italy), to be examined by a computed tomography scan on an outpatient basis, after an x-ray examination of the tibia, which was performed after an injury to exclude the presence of a fracture, revealed a hyperlucency of unknown origin. The aim of this study was to discuss the clinical, histological, immunohistochemical and radiographic characteristics of this rare neoplasm, with a focus on image-guided bone biopsy. PMID:27882239

Inhibitory effects of incadronate on the progression of rat experimental periodontitis by porphyromonas gingivalis infection.

PubMed

Tani-Ishii, Nobuyuki; Minamida, Genshi; Saitoh, Daisuke; Chieda, Keiko; Omuro, Hiromasa; Sugaya, Akira; Hamada, Nobushiro; Takahashi, Yusuke; Kiyohara, Shiro; Kashima, Isamu; Teranaka, Toshio; Umemotot, Toshio

2003-05-01

Incadronate (YM175, disodium cycloheptylaminomethylenediphosphonate monohydrate), a bisphosphonate, has been suggested to prevent the bone resorption associated with periodontitis by inhibiting osteoclast activity. The purpose of this study was to investigate the effect of incadronate in preventing periodontal destruction in rats with Porphyromonas gingivalis-induced periodontitis. Periodontitis was induced in 35 Wister rats by inoculating P. gingivalis into the oral cavity and feeding the rats a soft diet for 4 weeks. Incadronate or placebo was administered to the oral cavity of the rats 2 days per week for 2, 4, or 8 weeks. P. gingivalis infection resulted in destruction of the periodontal ligament, reduced bone density, and caused inflammatory cell migration. Radiographic, morphometric, and histological results showed that incadronate had the ability to increase the bone mineral density (quantum level score; cortex 518.9 [placebo 612.8]; sponge 579.8 [placebo 672.0]) and to prevent periodontal ligament destruction (width 0.16 mm [placebo 0.20 mm]; area 0.36 mm2 [placebo 0.54 mm2]) after 8 weeks' administration. Furthermore, the polymorphonuclear leukocyte (PMN) infiltration in gingival tissue was significantly decreased. These results showed that incadronate inhibits bone resorption and PMN migration in P. gingivalis-induced periodontitis.

Anti-rheumatic drug iguratimod (T-614) alleviates cancer-induced bone destruction via down-regulating interleukin-6 production in a nuclear factor-κB-dependent manner.

PubMed

Sun, Yue; Ye, Da-Wei; Zhang, Peng; Wu, Ying-Xing; Wang, Bang-Yan; Peng, Guang; Yu, Shi-Ying

2016-10-01

Cytokines are believed to be involved in a "vicious circle" of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose (30 μg/mL) iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.

A Non-Destructive Method for Distinguishing Reindeer Antler (Rangifer tarandus) from Red Deer Antler (Cervus elaphus) Using X-Ray Micro-Tomography Coupled with SVM Classifiers

PubMed Central

Lefebvre, Alexandre; Rochefort, Gael Y.; Santos, Frédéric; Le Denmat, Dominique; Salmon, Benjamin; Pétillon, Jean-Marc

2016-01-01

Over the last decade, biomedical 3D-imaging tools have gained widespread use in the analysis of prehistoric bone artefacts. While initial attempts to characterise the major categories used in osseous industry (i.e. bone, antler, and dentine/ivory) have been successful, the taxonomic determination of prehistoric artefacts remains to be investigated. The distinction between reindeer and red deer antler can be challenging, particularly in cases of anthropic and/or taphonomic modifications. In addition to the range of destructive physicochemical identification methods available (mass spectrometry, isotopic ratio, and DNA analysis), X-ray micro-tomography (micro-CT) provides convincing non-destructive 3D images and analyses. This paper presents the experimental protocol (sample scans, image processing, and statistical analysis) we have developed in order to identify modern and archaeological antler collections (from Isturitz, France). This original method is based on bone microstructure analysis combined with advanced statistical support vector machine (SVM) classifiers. A combination of six microarchitecture biomarkers (bone volume fraction, trabecular number, trabecular separation, trabecular thickness, trabecular bone pattern factor, and structure model index) were screened using micro-CT in order to characterise internal alveolar structure. Overall, reindeer alveoli presented a tighter mesh than red deer alveoli, and statistical analysis allowed us to distinguish archaeological antler by species with an accuracy of 96%, regardless of anatomical location on the antler. In conclusion, micro-CT combined with SVM classifiers proves to be a promising additional non-destructive method for antler identification, suitable for archaeological artefacts whose degree of human modification and cultural heritage or scientific value has previously made it impossible (tools, ornaments, etc.). PMID:26901355

Peculiarities of the bone tissue resorption under microgravity conditions

NASA Astrophysics Data System (ADS)

Rodionova, N.; Oganov, V.; Polkovenko, O.; Nitsevich, T.

The actual problem - peculiarities of resorptive processes in the spongiose of thingbones - we studied with the use of tranmissive electron microscopy in experiments on rats (American space station SLS-2) and on monkeys Macaca mulatt? (BION-11). Animals were onboard during 2 weeks. There was established, that the resorption happen with osteoclasts participation. They can create groups of cells. In the osteoclasts population we indicated not typical for the control (ground experiment) "giant" cells, which have on ultrathin sections 5-6 nuclei, many lysosomes, well developed "light" zone and "brush-border". The destruction of minera lized matrix in bone lacunas also happens by the way of osteolytic activity of osteocytes. Lysosome ferments of osteocytes are secreted by the eczocytosis. The osteocytic osteolysis, as well as the osteoclastic one can be seen as a physiological, gormon-dependent mechanism of resorption. The presence of a considerable number of neutrophiles, which enter in some zones of resorption is also typical. When these neutrophiles destruct, they release lysosomic ferments that dissolve the bone matrix. In some zones of resorption we noted the presence of the row from collagen fibrils, which loosed crystals , on mineralized matrix borders. The cell detritus is noted in zones of surface dissolving among crystallic conglomerates. It certificates the processes of osteogenic cells destruction that happen here. So, under the microgravity conditions in zones of adaptive remodeling of the spongiose the processes of the bone tissue resorption happen by some ways, namely: by the functional activization of osteoclasts; by the osteocytic osteolysis increasing; as a result of hydrolytic activity of neutrophiles, entering in these zones, and also by the local demineralization and further destruction of bone matrix surface zones.

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

PubMed

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

2015-10-01

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

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

PubMed Central

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

2015-01-01

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

Could Biomarkers of Bone, Cartilage or Synovium Turnover Be Used for Relapse Prediction in Rheumatoid Arthritis Patients?

PubMed Central

Dénarié, Delphine; Constant, Elodie; Thomas, Thierry

2014-01-01

Objective. The aim of this review is to clarify the usefulness of bone, cartilage, and synovial biomarker in the management of rheumatoid arthritis (RA) therapy in remission. Synovial Biomarkers. High MMP-3 levels are associated with joint progression in RA patients, but there is no data about their utility in clinical remission. IIINys and Glc-Gal-PYD seem to be more specific to synovium, but more studies are required. Cartilage Biomarkers. Unbalance between cartilage break-down biomarkers (urinary CTX II and COMP) and cartilage formation biomarker (PIIANP) was described. This unbalance is also associated with joint destruction and prognosis of destruction. No data are available on patients in remission. Bone Biomarkers. RA activity is correlated with an increase of bone resorption markers such as CTX I, PYD, and TRACP 5b and a decrease of bone formation markers such as OC and BALP. RA therapies seem to improve bone turnover in limiting bone resorption. There is no study about bone marker utility in remission. Conclusion. Biomarkers seem to correlate with RA activity and progression. They also could be used to manage RA therapies, but we need more data on RA remission to predict relapse. PMID:24744505

Bone as a secondary missile: an experimental study in the fragmenting of bone by high-velocity missiles.

PubMed

Amato, J J; Syracuse, D; Seaver, P R; Rich, N

1989-05-01

Destruction to soft tissues by bone fragments has been described in the literature. Civilian and military injuries have been reported in which bone fragments have acted as secondary missiles. This experimental study demonstrates, in detail, the formation of the temporary cavity within bone and the forward motion of these bone spicules. The knowledge of the ballistics will assist in the treatment of wounds caused by high-velocity missiles.

Retrospective review of 50 canine nasal tumours evaluated by low-field magnetic resonance imaging.

PubMed

Avner, A; Dobson, J M; Sales, J I; Herrtage, M E

2008-05-01

Low-field magnetic resonance imaging machines are being used more often in veterinary practice for the investigation of sinonasal disease. The aim of this retrospective study was to describe and characterise the low-field magnetic resonance imaging features of nasal tumours in dogs. The Queen's Veterinary School Hospital magnetic resonance imaging database (2001-2005) was searched for dogs with a magnetic resonance imaging diagnosis of a nasal tumour. Fifty cases with histological diagnosis of nasal tumour were found. The appearance and extent of the nasal tumour as well as the involvement of adjacent anatomic structures were examined against a checklist. The most common magnetic resonance imaging findings were as follows. (1) Soft tissue mass replacing the destroyed nasal conchae and/or ethmoturbinates (98 per cent of cases). (2) Nasal septum destruction (68 per cent of cases). (3) Retained secretions with or without mass caudally in frontal sinuses (62 per cent of cases). (4) Nasal/frontal bone destruction (52 per cent of cases). Low-field magnetic resonance imaging allowed differentiation of tumour tissue from retained secretions or necrotic tissue. Magnetic resonance imaging was invaluable in assessing the extension of the tumour into the maxillary recesses, caudal recesses, nasopharynx, adjacent bones and cranial cavity. The tumour often extended caudally into the frontal sinuses, nasopharynx and perhaps most importantly into the caudal recesses. Tumour extension into the cranial cavity was not common (16 per cent), and only three of these cases showed neurological signs. However, 54 per cent of cases showed focal meningeal (dural) hyperintensity, although the significance of this is unclear. A significant difference (P<0.05) in tumour signal intensity between the sarcomas and carcinomas was found. The use of a low-field magnetic resonance imaging technique is excellent for the diagnosis and determination of extent of sinonasal tumours.

[Multiple myeloma with significant multifocal osteolysis in a dog without a detectible gammopathy].

PubMed

Souchon, F; Koch, A; Sohns, A

2013-01-01

Description of a variant of multiple myeloma in a dog lacking the gammopathy normally associated with this type of neoplasm. A Border Collie mongrel was presented with symptoms of progressive hind-leg weakness, lethargy and tiredness, which had started to appear 6 weeks previously. Radiographic examination showed small osteolytic areas in the spinal column, but also diffuse small areas of increased opacity as well as evidence of decreased bone density in the pelvis and of both femoral necks. Moderate regenerative anaemia, hypogammopathy and hypercalcaemia were diagnosed. Computed tomography scans displayed multifocal osteolysis and bone destruction in the skull, spinal column, scapulae, proximal humeri, pelvis and femoral necks. H&E staining of the biopsies showed bone destruction and monomorphic plasmacyotid cell populations, causing infiltrative bone marrow lesions and osteolysis. In many areas neoplastic plasma cell infiltration of the bone marrow was 70% and in some areas reached 100%. The diagnosis was non-secretory multiple myeloma without apparent secretion of paraproteins into the blood.

The effect of intramedullary bone endoscopy on the endosteal blood supply in long bones. An experimental study in sheep.

PubMed

Herget, Georg W; Haberstroh, Jörg; Südkamp, Norbert; Riede, Ursus; Oberst, Michael

2011-02-01

This study investigated whether the Intramedullary Bone Endoscopy (IBE) procedure within the cavity of an intact long bone will interfere with the local endosteal blood supply. In a sheep model, 10 animals underwent the IBE procedure with complete perioperative anaesthesiology monitoring. After the femora were harvested, histological analysis was performed to examine destruction of the endosteum and consecutive reduction in perfusion. Only one animal showed evidence of detachment of the endosteum with destruction of several microns of the endosteum, although this did not interfere with the cortical perfusion. None of the vessels were occluded by fat or other causes of occlusion, e.g. blood coagulation. Our findings indicate that with the IBE procedure under visual control there is a potential risk to damage the endosteum. However, the interference was limited to a small part of the endosteum and did not lead to a reduction in the cortical perfusion. Clinical use could be in localized intramedullary lesions such as osteomyelitis or benign bone tumours.

Comparison of destructive periodontal disease in blue iris mink to PCB 126-induced mandibular and maxillary squamous epithelial proliferation in natural dark mink.

PubMed

Ellick, Rachel M; Fitzgerald, Scott D; Link, Jane E; Bursian, Steven J

2013-01-01

Mink (Mustela vison) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like chemicals have been reported to develop mandibular and maxillary squamous cell proliferation that results in the destruction of alveolar bone and eventual tooth loss. This jaw lesion has been reported in wild mink collected from areas contaminated with TCDD-like compounds and is a potential biomarker for exposure to these chemicals. The blue iris strain of domestic mink is prone to develop severe periodontal disease, which results in destruction of bone and tooth loss that is grossly similar to the lesion induced by exposure to TCDD-like chemicals. A histological assessment of jaws from blue iris mink and natural dark mink exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) was done to determine whether the oral lesions are similar. The jaw tissue from the blue iris mink had lesions indicative of lymphoplasmacytic gingivitis and osteomyelitis, caused by inflammation entering the dental sulcus, while the jaw tissue from the mink exposed to PCB 126 exhibited squamous epithelial proliferation. Therefore, it was determined that the tooth loss and bone destruction seen in these mink are of different origin despite the similarity of the gross clinical signs.

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

PubMed

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

2006-11-01

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

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.

Dental extraction following zoledronate, induces osteonecrosis in rat's jaw.

PubMed

Vidal-Gutiérrez, X; Gómez-Clavel, J-F; Gaitán-Cepeda, L-A

2017-03-01

Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time. Thirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson's trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes. At two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups. The animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models.

[Metabolic status and bone mineral density in patients with pseudarthrosis of long bones in hyperhomocysteinemia].

PubMed

Bezsmertnyĭ, Iu O

2013-06-01

In article described research of the metabolic status and bone mineral density in 153 patients with with pseudarthrosis of long bones, in individuals with consolidated fractures and healthy people. The violations of reparative osteogenesis at hyperhomocysteinemia are accompanied by disturbances of the functional state of bone tissue, inhibition of biosynthetic and increased destruction processes, reduced bone mineral density in the formation of osteopenia and osteoporosis. The degree and direction of change of bone depends on the type of violation of reparative osteogenesis.

[Bone structure in rheumatoid arthritis].

PubMed

Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

2013-07-01

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

Checking collagen preservation in archaeological bone by non-destructive studies (Micro-CT and IBA)

NASA Astrophysics Data System (ADS)

Beck, L.; Cuif, J.-P.; Pichon, L.; Vaubaillon, S.; Dambricourt Malassé, A.; Abel, R. L.

2012-02-01

The material to be studied is a piece of human skull discovered (1999) in Pleistocene sediments from the Orsang river (Gujarat state, India). From anatomical view point, this skull is highly composite: modern Homo sapiens characters are associated to undoubtedly more ancient features. Absolute dating by 14C is critical to understand this discovery. Prior to dating measurements, non-destructive studies have been carried out. Micro-CT reconstruction (X-ray microtomography) and Ion Beam Analysis (IBA) have been undertaken to check the structural preservation of the fossil and the collagen preservation. PIXE elemental map was used to select well-preserved bone area. RBS/EBS and NRA were used for light element quantification, in particular C, N and O contents. We also demonstrate that the PIXE-RBS/EBS combination is a effective tool for the whole characterization of archaeological and recent bones by analysing in one experiment both mineral and organic fractions. We have shown that the archaeological bone, a fragment of the potentially oldest modern Indian, is enough preserved for radiocarbon dating. We propose that Elastic Backscattering Spectrometry (EBS) using 3 MeV protons could be a good non destructive alternative to conventional CHN method using Carbon-Hydrogen-Nitrogen analyzer for measuring C and N before 14C dating.

[CHRONIC PERIODONTITIS WITH SYMPTOMATIC HYPERTROPHIC GINGIVITIS: CASE REPORT AND REVIEW OF THE LITERATURE].

PubMed

Shinkevich, V; Udaltsova, K; Pisarenko, E; Kolomiets, S; Khmil, T

2015-12-01

Gingivitis in traditional national dentistry referred to independent diseases or symptomatic condition in periodontitis and classified morphologically. The diagnostic features of the diseases are characteristic, but the clinical presentation of symptomatic gingivitis and patterns of bone destructions may vary between patients. Successful treatment of the disease depends from proper diagnosis and advanced disease stages, but for symptomatic gingivitis that accompanying chronic periodontitis, protocols include surgical excision. Despite of the high prevalence of chronic generalized periodontitis, its active treatment often start in severe destruction and bone loss (2-3 stage severity). Today etiotropic antimicrobial therapy is real way to control microbial biofilm and has solid evidence base. Applying of etiotropic antimicrobial therapy as systemic azithromycin with timely treatment of mild to moderate periodontal and bone destruction may reduce severe periodontitis incidence of and treatment-related complications in the future. This paper attempts to describe the clinical diagnostic features and the current treatment options along with a suggested protocol for comprehensive management of chronic generalized periodontitis and hypertrophic gingivitis patient with case reports and a brief review.

Contrast Agents for Micro-Computed Tomography of Microdamage in Bone

DTIC Science & Technology

2011-01-01

solution from DI water (or PBS). For the second model, a 5 mm cube of cortical bone tissue was embedded in polymethylmethacrylate and sectioned...radiography1 and as a radiopacifer in polymethylmethacrylate bone cement.2 Current commercial products for either application use microscale BaSO4 particles... polymethylmethacrylate bone cement (Lewis, 1997). The objective of this study was to non-destructively and three-dimensionally image microdamage

Myostatin is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice.

PubMed

Dankbar, Berno; Fennen, Michelle; Brunert, Daniela; Hayer, Silvia; Frank, Svetlana; Wehmeyer, Corinna; Beckmann, Denise; Paruzel, Peter; Bertrand, Jessica; Redlich, Kurt; Koers-Wunrau, Christina; Stratis, Athanasios; Korb-Pap, Adelheid; Pap, Thomas

2015-09-01

Myostatin (also known as growth and differentiation factor 8) is a secreted member of the transforming growth factor-β (TGF-β) family that is mainly expressed in skeletal muscle, which is also its primary target tissue. Deletion of the myostatin gene (Mstn) in mice leads to muscle hypertrophy, and animal studies support the concept that myostatin is a negative regulator of muscle growth and regeneration. However, myostatin deficiency also increases bone formation, mainly through loading-associated effects on bone. Here we report a previously unknown direct role for myostatin in osteoclastogenesis and in the progressive loss of articular bone in rheumatoid arthritis (RA). We demonstrate that myostatin is highly expressed in the synovial tissues of RA subjects and of human tumor necrosis factor (TNF)-α transgenic (hTNFtg) mice, a model for human RA. Myostatin strongly accelerates receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast formation in vitro through transcription factor SMAD2-dependent regulation of nuclear factor of activated T-cells (NFATC1). Myostatin deficiency or antibody-mediated inhibition leads to an amelioration of arthritis severity in hTNFtg mice, chiefly reflected by less bone destruction. Consistent with these effects in hTNFtg mice, the lack of myostatin leads to increased grip strength and less bone erosion in the K/BxN serum-induced arthritis model in mice. The results strongly suggest that myostatin is a potent therapeutic target for interfering with osteoclast formation and joint destruction in RA.

CypD-mPTP axis regulates mitochondrial functions contributing to osteogenic dysfunction of MC3T3-E1 cells in inflammation.

PubMed

Gan, Xueqi; Zhang, Ling; Liu, Beilei; Zhu, Zhuoli; He, Yuting; Chen, Junsheng; Zhu, Junfei; Yu, Haiyang

2018-04-20

Bone is a dynamic organ, the bone-forming osteoblasts and bone-resorbing osteoclasts form the physiological basis of bone remodeling process. During pathological process of numerous inflammatory diseases, these two aspects are uncoupled and the balance is usually tipped in favor of bone destruction. Evidence suggests that the inflammatory destruction of bone is mainly attributed to oxidative stress and is closely related to mitochondrial dysfunction. The mechanisms underlying osteogenic dysfunction in inflammation still need further investigation. Reactive oxygen species (ROS) is associated with mitochondrial dysfunction and cellular damage. Here, we reported an unexplored role of cyclophilin D (CypD), the major modulator of mitochondrial permeability transition pore (mPTP), and the CypD-mPTP axis in inflammation-induced mitochondrial dysfunction and bone damage. And the protective effects of knocking down CypD by siRNA interference or the addition of cyclosporin A (CsA), an inhibitor of CypD, were evidenced by rescued mitochondrial function and osteogenic function of osteoblast under tumor necrosis factor-α (TNF-α) treatment. These findings provide new insights into the role of CypD-mPTP-dependent mitochondrial pathway in the inflammatory bone injury. The protective effect of CsA or other moleculars affecting the mPTP formation may hold promise as a potential novel therapeutic strategy for inflammation-induced bone damage via mitochondrial pathways.

[Destructive mastoiditis with thrombosis of the sigmoid sinus in a 8 year-old child presenting with concomitant chicken pox].

PubMed

Bogomil'skiĭ, M R; Polunin, M M; Ivanenko, A M; Poliakov, A A

2014-01-01

The specific clinical feature of mastoidities that developed in a patient presenting with chicken pox was the rapid progress in temporal bone destruction with partial thrombosis of the sigmoid sinusis in the absence of typical manifestations of mastoiditis. The pronounced destructive changes found in a series of CT images were regarded as the indications for urgent antromastoidotomy with the puncture of the sigmoid sinusis.

Bone sialoprotein in laboratory diagnostic work-up of osteoarthritis.

PubMed

Lis, Kinga

2008-01-01

Changes in osteoarthritis joint appear in the articular cartilage, synovium and in subchondral bone. It is necessary to find, apart from markers of cartilage destruction, a sensitive and specific biochemical marker which would reflect the metabolism as well as degradation of subchondral bone. Bone sialoprotein is mostly synthesized in osseous tissue found directly under the surface of joint cartilage. As a result, it is being increasingly perceived as a valuable marker of the metabolism rate of this layer of bone. Bone sialoprotein seems to be of use as a marker for subchondral bone degradation rate in laboratory diagnostic work-up of osteoarthritis.

[Dopamine receptor signaling regulates human osteoclastogenesis].

PubMed

Hanami, Kentaro; Nakano, Kazuhisa; Tanaka, Yoshiya

2013-01-01

Although the central nervous system and the neurotransmitters are known to control not only the immune system but also the homeostasis of bone mass, their pathological relevance to bone disorders remains unclear. Osteoclasts in the synovium of rheumatoid arthritis (RA) play an important role in bone destruction. It is known that increased sympathetic nervous activity increases both differentiation and function of osteoclasts, which leads to bone loss. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. We previously reported that dopamine plays an important role in IL-6-IL-17 axis and subsequent joint destruction in RA. The major source of dopamine in the synovial tissue of RA was dendritic cells (DCs) that stored and secreted dopamine. Dopamine released by DCs bounded to D1-like dopamine receptors on T cells and induced activation of cAMP and differentiation to Th17 cells via IL-6 production We here overview the interplay among the immune system, bone metabolism and neurologic system shedding light upon dopaminergic signals upon osteoclastogenesis.

Interventional radiology in bone metastases.

PubMed

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

2017-11-01

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

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

Assessment of skeletal changes after post-mortem exposure to fire as an indicator of decomposition stage.

PubMed

Keough, N; L'Abbé, E N; Steyn, M; Pretorius, S

2015-01-01

Forensic anthropologists are tasked with interpreting the sequence of events from death to the discovery of a body. Burned bone often evokes questions as to the timing of burning events. The purpose of this study was to assess the progression of thermal damage on bones with advancement in decomposition. Twenty-five pigs in various stages of decomposition (fresh, early, advanced, early and late skeletonisation) were exposed to fire for 30 min. The scored heat-related features on bone included colour change (unaltered, charred, calcined), brown and heat borders, heat lines, delineation, greasy bone, joint shielding, predictable and minimal cracking, delamination and heat-induced fractures. Colour changes were scored according to a ranked percentage scale (0-3) and the remaining traits as absent or present (0/1). Kappa statistics was used to evaluate intra- and inter-observer error. Transition analysis was used to formulate probability mass functions [P(X=j|i)] to predict decomposition stage from the scored features of thermal destruction. Nine traits displayed potential to predict decomposition stage from burned remains. An increase in calcined and charred bone occurred synchronously with advancement of decomposition with subsequent decrease in unaltered surfaces. Greasy bone appeared more often in the early/fresh stages (fleshed bone). Heat borders, heat lines, delineation, joint shielding, predictable and minimal cracking are associated with advanced decomposition, when bone remains wet but lacks extensive soft tissue protection. Brown burn/borders, delamination and other heat-induced fractures are associated with early and late skeletonisation, showing that organic composition of bone and percentage of flesh present affect the manner in which it burns. No statistically significant difference was noted among observers for the majority of the traits, indicating that they can be scored reliably. Based on the data analysis, the pattern of heat-induced changes may assist in estimating decomposition stage from unknown, burned remains. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

SPECT imaging in evaluating extent of malignant external otitis: case report

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

English, R.J.; Tu'Meh, S.S.; Piwnica-Worms, D.

1987-03-01

Otitis externa, a benign inflammatory process of the external auditory canal, is general responsive to local therapy. Some patients however, develop a less controllable disease leading to chondritis and osteomyelitis of the base of the skull. The direct invasive characteristic of the disease has led to the descriptive term malignant external otitis (MEO), more appropriately called necrotizing or invasive external otitis. Malignant external otitis is caused by an aggressive pseudomonas or proteus infection that almost exclusively occurs in elderly diabetic patients. The primary imaging modalities previously used in the diagnosis and evaluation of MEO were standard planar scintigraphic techniques withmore » technetium-99M (/sup 99m/Tc) bone agents and gallium-67 (/sup 67/Ga), and pluridirectional tomography. The advent of high resolution computed tomography (CT) effectively allowed demonstration of the soft tissue extension and bone destruction associated with MEO, but still suffered from the low sensitivity constraints of all radiographic techniques in determining early inflammatory bone involvement. Recent work suggests that scintigraphic detection of MEO with /sup 99m/Tc-MDP and /sup 67/Ga, combined with the cross-sectional resolution of single photon emission computed tomography (SPECT) may be of value in planning treatment of this inflammatory condition.« less

Rib fractures and death from deletion of osteoblast βcatenin in adult mice is rescued by corticosteroids.

PubMed

Duan, JinZhu; Lee, Yueh; Jania, Corey; Gong, Jucheng; Rojas, Mauricio; Burk, Laurel; Willis, Monte; Homeister, Jonathon; Tilley, Stephen; Rubin, Janet; Deb, Arjun

2013-01-01

Ribs are primarily made of cortical bone and are necessary for chest expansion and ventilation. Rib fractures represent the most common type of non-traumatic fractures in the elderly yet few studies have focused on the biology of rib fragility. Here, we show that deletion of βcatenin in Col1a2 expressing osteoblasts of adult mice leads to aggressive osteoclastogenesis with increased serum levels of the osteoclastogenic cytokine RANKL, extensive rib resorption, multiple spontaneous rib fractures and chest wall deformities. Within days of osteoblast specific βcatenin deletion, animals die from respiratory failure with a vanishing rib cage that is unable to sustain ventilation. Increased bone resorption is also observed in the vertebrae and femur. Treatment with the bisphosphonate pamidronate delayed but did not prevent death or associated rib fractures. In contrast, administration of the glucocorticoid dexamethasone decreased serum RANKL and slowed osteoclastogenesis. Dexamethasone preserved rib structure, prevented respiratory compromise and strikingly increased survival. Our findings provide a novel model of accelerated osteoclastogenesis, where deletion of osteoblast βcatenin in adults leads to rapid development of destructive rib fractures. We demonstrate the role of βcatenin dependent mechanisms in rib fractures and suggest that glucocorticoids, by suppressing RANKL, may have a role in treating bone loss due to aggressive osteoclastogenesis.

Rib Fractures and Death from Deletion of Osteoblast βcatenin in Adult Mice Is Rescued by Corticosteroids

PubMed Central

Duan, JinZhu; Lee, Yueh; Jania, Corey; Gong, Jucheng; Rojas, Mauricio; Burk, Laurel; Willis, Monte; Homeister, Jonathon; Tilley, Stephen; Rubin, Janet; Deb, Arjun

2013-01-01

Ribs are primarily made of cortical bone and are necessary for chest expansion and ventilation. Rib fractures represent the most common type of non-traumatic fractures in the elderly yet few studies have focused on the biology of rib fragility. Here, we show that deletion of βcatenin in Col1a2 expressing osteoblasts of adult mice leads to aggressive osteoclastogenesis with increased serum levels of the osteoclastogenic cytokine RANKL, extensive rib resorption, multiple spontaneous rib fractures and chest wall deformities. Within days of osteoblast specific βcatenin deletion, animals die from respiratory failure with a vanishing rib cage that is unable to sustain ventilation. Increased bone resorption is also observed in the vertebrae and femur. Treatment with the bisphosphonate pamidronate delayed but did not prevent death or associated rib fractures. In contrast, administration of the glucocorticoid dexamethasone decreased serum RANKL and slowed osteoclastogenesis. Dexamethasone preserved rib structure, prevented respiratory compromise and strikingly increased survival. Our findings provide a novel model of accelerated osteoclastogenesis, where deletion of osteoblast βcatenin in adults leads to rapid development of destructive rib fractures. We demonstrate the role of βcatenin dependent mechanisms in rib fractures and suggest that glucocorticoids, by suppressing RANKL, may have a role in treating bone loss due to aggressive osteoclastogenesis. PMID:23393600

Radiation injury to the temporal bone

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

Guida, R.A.; Finn, D.G.; Buchalter, I.H.

1990-01-01

Osteoradionecrosis of the temporal bone is an unusual sequela of radiation therapy to the head and neck. Symptoms occur many years after the radiation is administered, and progression of the disease is insidious. Hearing loss (sensorineural, conductive, or mixed), otalgia, otorrhea, and even gross tissue extrusion herald this condition. Later, intracranial complications such as meningitis, temporal lobe or cerebellar abscess, and cranial neuropathies may occur. Reported here are five cases of this rare malady representing varying degrees of the disease process. They include a case of radiation-induced necrosis of the tympanic ring with persistent squamous debris in the external auditorymore » canal and middle ear. Another case demonstrates the progression of radiation otitis media to mastoiditis with bony sequestration. Further progression of the disease process is seen in a third case that evolved into multiple cranial neuropathies from skull base destruction. Treatment includes systemic antibiotics, local wound care, and debridement in cases of localized tissue involvement. More extensive debridement with removal of sequestrations, abscess drainage, reconstruction with vascularized tissue from regional flaps, and mastoid obliteration may be warranted for severe cases. Hyperbaric oxygen therapy has provided limited benefit.« less

Spontaneous osteosarcoma of the femur in a non-obese diabetic mouse

PubMed Central

Hong, Sunhwa; Lee, Hyun-A; Choe, Ohmok; Chung, Youngho

2011-01-01

An abnormal swelling was identified in the distal portion of the right femur in a 1-year-old non-obese diabetic (NOD) mouse. Grossly, a large mass of the distal femur was observed in the right femur. Lesions were poorly marginated, associated with destruction of the cancellous and cortical elements of the bone, and showed ossification within the soft tissue component. Histologically, the tumor was identified as a poorly differentiated sarcoma. Histopathologic examination of the bone masses revealed invasive proliferation of poorly differentiated neoplastic mesenchymal cells forming streams, bundles, and nests, which resulted in destruction of normal bone. Neoplastic cells exhibited random variation in cellular appearance and arrangement, as well as matrix composition and abundance. Haphazard and often intermingling patterns of osteogenic, chondroblastic, lipoblastic, and angiogenic tissues were present. Larger areas of neoplastic bone and hyaline cartilage contained multiple large areas of hemorrhage and necrosis bordered by neoplastic cells. The mass was diagnosed as an osteosarcoma. To our knowledge, this is the first spontaneous osteosarcoma in an NOD mouse. PMID:21998615

Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

PubMed Central

Gómez-Clavel, José-Francisco; Gaitán-Cepeda, Luis-Alberto

2017-01-01

Background Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time. Material and Methods Thirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson’s trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes. Results At two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups. Conclusions The animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models. Key words:Bisphosphonates, osteonecrosis, dental extractions, animal model, BRONJ. PMID:28160593

A method to score radiographic change in psoriatic arthritis.

PubMed

Wassenberg, S; Fischer-Kahle, V; Herborn, G; Rau, R

2001-06-01

Radiographic features of psoriatic arthritis (PsA) are very characteristic and differ from those observed in rheumatoid arthritis, especially in two aspects: 1) the distribution of affected joints (i.e. DIP joints), 2) the presence of destructive changes and bone proliferation at the same time. A scoring method for PsA, therefore, has to account for these characteristics of PsA. To develop, describe and validate a method for scoring radiographic changes in patients with PsA. Forty joints of the hands and feet are scored for destruction and proliferation. In the destruction score (DS) grading on a 0-5 scale is based on the amount of joint surface destruction: 0 = normal, 1 = one or more erosions with an interruption of the cortical plate of > 1 mm with destruction of the total joint surface up to 10%, 2 = 11-25%, 3 = 26-50%, 4 = 51-75%, 5 = > 75% joint surface destruction. The proliferation score (PS) sums up any kind of bony proliferation typical for PsA; graded 0-4: 0 = normal, 1 = bony proliferation of 1-2 mm or bone growth < 25% of the original size (diameter), 2 = bony proliferation 2-3 mm or bone growth 25-50%, 3 = bony proliferation > 3 mm or bone growth > 50%, 4 = bony ankylosis. The DS (0-200) and the PS (0-160) can be summed up to the total score (0-360). VALIDATION OF THE METHOD: To validate the method x-rays of 20 patients with active PsA taken 3 years apart were read twice in pairs, knowing the chronological order but not knowing demographic, clinical or laboratory data of the patients. The data were analyzed with a hierarchical analysis of variance model. There was good agreement between the first and the second reading of the same rater and between the two raters regarding the destruction score. The agreement regarding the proliferation score was lower but still acceptable. The reliability of the method to describe change over time--relation of progression (intra-patient variance) to the measurement error (inter-rater variance)--was 3.9 for the DS, 2.8 for the PS and 4.1 for the total score. The minimal detectable change when the readings of two raters were compared (inter-rater MDC) was 5.8, 5.0 and 4.6%, respectively of the maximum possible score for the destruction, the proliferation and the total score. These data compare very well with the results of standard scoring methods in rheumatoid arthritis. We propose a method for scoring radiographic change in psoriatic arthritis which reliably quantifies the progression of the disease seen on radiographs.

Mathematical modeling of bone marrow--peripheral blood dynamics in the disease state based on current emerging paradigms, part I.

PubMed

Afenya, Evans K; Ouifki, Rachid; Camara, Baba I; Mundle, Suneel D

2016-04-01

Stemming from current emerging paradigms related to the cancer stem cell hypothesis, an existing mathematical model is expanded and used to study cell interaction dynamics in the bone marrow and peripheral blood. The proposed mathematical model is described by a system of nonlinear differential equations with delay, to quantify the dynamics in abnormal hematopoiesis. The steady states of the model are analytically and numerically obtained. Some conditions for the local asymptotic stability of such states are investigated. Model analyses suggest that malignancy may be irreversible once it evolves from a nonmalignant state into a malignant one and no intervention takes place. This leads to the proposition that a great deal of emphasis be placed on cancer prevention. Nevertheless, should malignancy arise, treatment programs for its containment or curtailment may have to include a maximum and extensive level of effort to protect normal cells from eventual destruction. Further model analyses and simulations predict that in the untreated disease state, there is an evolution towards a situation in which malignant cells dominate the entire bone marrow - peripheral blood system. Arguments are then advanced regarding requirements for quantitatively understanding cancer stem cell behavior. Among the suggested requirements are, mathematical frameworks for describing the dynamics of cancer initiation and progression, the response to treatment, the evolution of resistance, and malignancy prevention dynamics within the bone marrow - peripheral blood architecture. Copyright © 2016 Elsevier Inc. All rights reserved.

Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits.

PubMed

He, Yi-Xin; Liu, Jin; Guo, Baosheng; Wang, Yi-Xiang; Pan, Xiaohua; Li, Defang; Tang, Tao; Chen, Yang; Peng, Songlin; Bian, Zhaoxiang; Liang, Zicai; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

2015-03-09

To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement &Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement &Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.

Guided tissue regeneration with heterologous materials in primary subtalar arthrodesis: a case report.

PubMed

Frangez, Igor; Kasnik, Tea; Cimerman, Matej; Smrke, Dragica Maja

2016-05-03

Calcaneal fractures are relatively rare and difficult to treat. Treatment options vary based on the type of fracture and the surgeon's experiences. In recent years, surgical procedures have increasingly been used due to the better long-term results. We present a case where guided tissue regeneration was performed in a calcaneal fracture that needed primary subtalar arthrodesis. We used the principles of guided tissue regeneration from oral surgery to perform primary subtalar arthrodesis and minimize the risk of non-union. We used a heterologous collagen membrane, which acts as a mechanical barrier and protects the bone graft from the invasion of unwanted cells that could lead to non-union. The collagenous membrane also has osteoconductive properties and is therefore able to increase the osteoblast proliferation rate. A 62-year-old Caucasian woman sustained multiple fractures of her lower limbs and spine after a fall from a ladder. Her left calcaneus had a comminuted multifragmental fracture (Sanders type IV) with severe destruction of the cartilage of her subtalar joint and depression of the Böhler's angle. Therefore, we performed primary arthrodesis of her subtalar joint with elevation of the Böhler's angle using a 7.3 mm titanium screw, a heterologous cortico-cancellous collagenated pre-hydrated bone mix, a heterologous cancellous collagenated bone wedge, and a heterologous collagen membrane (Tecnoss®, Italy). The graft was fully incorporated 12 weeks after the procedure and a year and a half later our patient walks without limping. We present a new use of guided tissue regeneration with heterologous materials that can be used to treat extensive bone defects after bone injuries. We believe that guided tissue regeneration using heterologous materials, including a heterologous collagen membrane that presents a mechanical barrier between soft tissues and bone as well as a stimulative component that enhances bone formation, could be more often used in bone surgery.

Aneurysmal bone cyst of the scapula. A case report.

PubMed

Megas, Panagiotis; Papathanassiou, Zafiria G; Kasimatis, George; Papachristou, Dionysios J

2009-10-01

Aneurysmal bone cyst (ABC) is an uncommon, benign but locally destructive bone lesion of unknown origin. Differential diagnosis can be challenging as it shares common radiological and pathological features with other benign and malignant bone lesions. The degree of diagnostic difficulty grows even more when an unusual location has to be taken into account. We report a rare and challenging case of a large primary ABC located at the scapula of a young male, who was surgically treated with subtotal removal of the scapula.

Specific destruction of islet transplants in NOD<-->C57BL/6 and NOD<-->C3H/Tif embryo aggregation chimeras irrespective of allelic differences in beta-cell antigens.

PubMed

Leijon, K; Hillörn, V; Bergqvist, I; Holmberg, D

1995-06-01

We have tested the hypothesis that allelic differences in the antigens expressed by the beta-cells of the islets of Langerhans influence the development of insulitis in the non-obese diabetic (NOD) mouse. Islets of Langerhans from NOD, C57BL/6 and C3H/Tif mice were transplanted under the kidney capsule of NOD<-->C57BL/6 and NOD<-->C3H/Tif embryo aggregation (EA) chimeras and the infiltration was scored 5-7 weeks later. Mononuclear cell infiltration of pancreatic islets was observed in 60% of the NOD<-->C57BL/6 and in 55% of the NOD<-->C3H/Tif EA chimeras. All transplanted EA chimeras that developed insulitis also displayed mononuclear cell infiltrates in the transplants, irrespective of the origin of the transplanted islets. In contrast, no infiltration of transplants was detected in EA chimeras scoring negative for insulitis. These results demonstrate that the specific destruction of islet transplants does not require the expression of NOD specific antigens by the islets. Moreover, the beta-cell destruction appears not to be restricted to NOD-MHC. The correlation between insulitis and transplant beta-cell destruction suggests the possibility that the development of insulitis is a prerequisite for transplant specific destruction. MHC restricted destruction may, therefore, precede the beta-cell destruction of transplanted islets. The chimerism among the mononuclear cells infiltrating the islet transplants was found to correlate with the overall haematopoetic chimerism in each of the individual EA chimeras. This observation suggests that NOD bone marrow, as well as non-NOD bone marrow, generates cells contributing to the beta-cell destruction process.

Safflower bud inhibits RANKL-induced osteoclast differentiation and prevents bone loss in ovariectomized mice.

PubMed

Choi, Joo-Hee; Lim, Seul-Ki; Kim, Dong-Il; Park, Min-Jung; Kim, Young-Kuk; Lee, An-Chul; Kim, Young-Min; Yang, Soo-Jin; Park, Jong-Hwan

2017-10-15

The powder and extract of safflower seeds are known to be effective in the prevention of bone loss in ovariectomized animals. However, the inhibitory effect and molecular mechanisms of safflower bud (SB), the germinated safflower, on bone destruction is unclear. The present study was designed to investigate the inhibitory effect and molecular mechanism of SB on osteoclastic differentiation and on bone loss in ovarietomized (OVX) mice. Osteoclastogenesis was determined by TRAP staining, F-actin ring formation, and bone resorption assay. NF-κB and MAPKs activation was analyzed by transfection assay and Western blot, respectively. Real-time PCR was performed to examine the expression of osteoclastogenesis-related genes. Histological changes, increases in TRAP-positive cells, and cathepsin K expression were examined in the metaphysis of OVX mice. Density of bone marrow was evaluated by µCT. SB inhibited the RANKL-induced differentiation of BMDMs into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by SB in RANKL-treated BMDMs. In addition, SB decreased the activation of NF-κB and MAPKs and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. Feeding of SB-included diet prevented bone loss in OVX mice. The number of TRAP-positive cells and level of protein expression of cathepsin K was reduced and bone mineral density was increased in the metaphysis of mice fed SB compared with OVX mice. These findings suggest that SB can be a preventive and therapeutic candidate for destructive bone diseases. Copyright © 2017. Published by Elsevier GmbH.

Application of VNIR hyperspectral imaging for non-destructive prediction of pH, color, and drip loss of chicken breast fillets

USDA-ARS?s Scientific Manuscript database

Non-destructive and rapid prediction of quality attributes of chicken breast fillets using visible and near-infrared (VNIR) hyperspectral imaging (400-1000 nm) was carried out in this work. All hyperspectral images were acquired for bone (dorsal) side of chicken breast. A forward principal component...

Staphylococcus aureus Biofilms Decrease Osteoblast Viability, Inhibits Osteogenic Differentiation, and Increases Bone Resorption in vitro

DTIC Science & Technology

2013-06-01

severe and often debilitating disease characterized by inflammatory destruction of bone. Despite treatment, chronic infection often develops which is...biofilms may contribute to bone loss during chronic osteomyelitis simultaneously by: (1) reducing osteoblast viability and osteogenic potential thereby...accounting for more than half of all cases [1]. Despite treatment and surgical intervention up to 30% of osteomyelitis cases progress into a chronic

Osteomyelitis of the hyoid bones in two calves.

PubMed

Nuss, Karl; Malbon, Alexandra J; Braun, Ueli; Ringer, Simone; Muggli, Evelyne; Kircher, Patrick; Willmitzer, Florian

2015-09-22

Two calves were referred because of ptyalism and difficulty opening the mouth (Calf 1) and for elective umbilical hernia surgery under inhalation anaesthesia (Calf 2). Additional clinical signs were increased breath sounds and swelling in the region of the mandibular angle in Calf 1. Ultrasonography and endoscopy revealed oral inflammation and abscessation in the area of the base of the tongue in both calves. Infection of the hyoid apparatus was suspected based on ultrasonographic findings and confirmed by means of computed tomography. In Calf 1, there was no response to treatment with systemic antibiotics, nonsteroidal anti-inflammatory drugs and local lavage, and Calf 2 was not treated. Both calves were euthanized because of a poor prognosis and the diagnoses confirmed during postmortem examination. In Calf 1, the abscess was associated with complete destruction of the left epihyoid bone and partial destruction of the left stylohyoid and ceratohyoid bones. In Calf 2, the abscess was located at the distal end of the right stylohyoid bone near the epihyoid bone. Stomatitis or laryngeal and pharyngeal abscessation caused by sharp feed particles are common in cattle and infection of the hyoid apparatus should be included in the differential diagnosis.

Cartilage and bone damage in rheumatoid arthritis

PubMed Central

Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Nieciecki, Michał; Sudoł-Szopińska, Iwona

2018-01-01

Rheumatoid arthritis (RA), which is a chronic inflammatory disease with a multifactorial aetiology, leads to partial or permanent disability in the majority of patients. It is characterised by persistent synovitis and formation of pannus, i.e. invasive synovial tissue, which ultimately leads to destruction of the cartilage, subchondral bone, and soft tissues of the affected joint. Moreover, inflammatory infiltrates in the subchondral bone, which can lead to inflammatory cysts and later erosions, play an important role in the pathogenesis of RA. These inflammatory infiltrates can be seen in magnetic resonance imaging (MRI) as bone marrow oedema (BME). BME is observed in 68–75% of patients in early stages of RA and is considered a precursor of rapid disease progression. The clinical significance of synovitis and bone marrow oedema as precursors of erosions is well established in daily practice, and synovitis, BME, cysts, hyaline cartilage defects and bone erosions can be detected by ultrasonography (US) and MRI. A less explored subject is the inflammatory and destructive potential of intra- and extra-articular fat tissue, which can also be evaluated in US and MRI. Finally, according to certain hypotheses, hyaline cartilage damage may trigger synovitis and lead to irreversible joint damage, and MRI may be used for preclinical detection of cartilage biochemical abnormalities. This review discusses the pathomechanisms that lead to articular cartilage and bone damage in RA, including erosion precursors such as synovitis and osteitis and panniculitis, as well as the role of imaging techniques employed to detect early cartilage damage and bone erosions. PMID:29853727

cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

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

Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui

2010-07-23

Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cellsmore » and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.« less

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing.

PubMed

Xu, M T; Sun, S; Zhang, L; Xu, F; Du, S L; Zhang, X D; Wang, D W

2016-01-01

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

[Interventional radiology in bone metastases].

PubMed

Chiras, Jacques; Cormier, Evelyne; Baragan, Hector; Jean, Betty; Rose, Michèle

2007-02-01

Interventional radiology takes a large place in the treatment of bone metastases by numerous techniques, percutaneous or endovascular. Vertebroplasty appears actually as the most important technique for stabilisation of spine metastases as it induces satisfactory stabilisation of the vertebra and offer clear improvement of the quality of life. Due to the success of this technique cementoplasty of other bones, mainly pelvic girdle, largely develop. The heath due to the polymerisation of the cement induce carcinolytic effect but this effect is not as important as that can be created with radiofrequency destruction. This last technique appears actually as the most important development to destroy definitively some bone metastases and replace progressively alcoholic destruction of such lesions. Angiographic techniques appear more confidential but endovascular embolization is very useful to diminish the risk of surgical treatment of hyper vascular metastases. Chemoembolization is actually developped to associate the relief of pain induced by endovascular embolization and the carcinolytic effect obtained by local endovascular chemotherapy. All these techniques should develop largely during the next years and their efficacy and safety should improve largely by treating earlier the metastasis.

Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

PubMed Central

Soenjaya, Y.; Foster, B.L.; Nociti, F.H.; Ao, M.; Holdsworth, D.W.; Hunter, G.K.; Somerman, M.J.

2015-01-01

Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp-/- mice. PMID:26130257

The hemoglobin receptor protein of porphyromonas gingivalis inhibits receptor activator NF-kappaB ligand-induced osteoclastogenesis from bone marrow macrophages.

PubMed

Fujimura, Yuji; Hotokezaka, Hitoshi; Ohara, Naoya; Naito, Mariko; Sakai, Eiko; Yoshimura, Mamiko; Narita, Yuka; Kitaura, Hideki; Yoshida, Noriaki; Nakayama, Koji

2006-05-01

Extracellular proteinaceous factors of Porphyromonas gingivalis, a periodontal pathogen, that influence receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced osteoclastogenesis from bone marrow macrophages were investigated. The culture supernatant of P. gingivalis had the ability to inhibit RANKL-induced in vitro osteoclastogenesis. A major protein of the culture supernatant, hemoglobin receptor protein (HbR), suppressed RANKL-induced osteoclastogenesis in a dose-dependent fashion. HbR markedly inhibited RANKL-induced osteoclastogenesis when present in the culture for the first 24 h after addition of RANKL, whereas no significant inhibition was observed when HbR was added after 24 h or later, implying that HbR might interfere with only the initial stage of RANKL-mediated differentiation. HbR tightly bound to bone marrow macrophages and had the ability to induce phosphorylation of ERK, p38, NF-kappaB, and Akt. RANKL-induced phosphorylation of ERK, p38, and NF-kappaB was not suppressed by HbR, but that of Akt was markedly suppressed. HbR inhibited RANKL-mediated induction of c-Fos and NFATc1. HbR could induce beta interferon (IFN-beta) from bone marrow macrophages, but the induction level of IFN-beta might not be sufficient to suppress RANKL-mediated osteoclastogenesis, implying presence of an IFN-beta-independent pathway in HbR-mediated inhibition of osteoclastogenesis. Since rapid and extensive destruction of the alveolar bone causes tooth loss, resulting in loss of the gingival crevice that is an anatomical niche for periodontal pathogens such as P. gingivalis, the suppressive effect of HbR on osteoclastogenesis may help the microorganism exist long in the niche.

The anti-allergic compound tranilast attenuates inflammation and inhibits bone destruction in collagen-induced arthritis in mice

PubMed Central

Shiota, N; Kovanen, PT; Eklund, KK; Shibata, N; Shimoura, K; Niibayashi, T; Shimbori, C; Okunishi, H

2010-01-01

Background and purpose: Recent findings suggest the importance of mast cells in the pathogenesis of rheumatoid arthritis and their potential as a therapeutic target. Tranilast is an anti-allergic compound with a potent membrane-stabilizing effect on mast cells and a wide range of anti-inflammatory effects, thus may be advantageous in the treatment of arthritis. Here, we have evaluated the effects of tranilast on the progression of collagen-induced arthritis in mice. Experimental approach: Tranilast (400 mg·kg−1·day−1) was orally administered for 8 weeks to mice with established collagen-induced arthritis. Arthritis was assessed by clinical signs and X-ray scores. In paw tissue, the numbers of mast cells and osteoclasts were measured by histological analysis, and several inflammatory factors were assessed by RT-PCR and Western blot analysis.* Key results: TNF-α-positive mast cells were present extensively throughout the inflamed synovium of vehicle-treated arthritic mice, with some mast cells in close proximity to osteoclasts in areas of marked bone and cartilage destruction. Tranilast significantly reduced clinical and X-ray scores of arthritis and decreased numbers of TNF-α-positive mast cells and mRNA levels of TNF-α, chymase (mouse mast cell protease 4), tryptase (mouse mast cell protease 6), stem cell factor, interleukin-6, cathepsin-K, receptor activator of nuclear factor-κB, and of receptor activator of nuclear factor-κB-ligand, but increased interleukin-10 mRNA level in paws of arthritic mice. Osteoclast numbers were decreased by treatment with tranilast. Conclusions and implications: Tranilast possesses significant anti-rheumatic efficacy and, probably, this therapeutic effect is partly mediated by inhibition of mast cell activation and osteoclastogenesis. PMID:20067475

[Charcot foot treated by correction and arthrodesis of the hindfoot].

PubMed

Wagner, Andreas; Fuhrmann, Renée; Roth, Andreas

2005-10-01

First patient: neuropathic osteoarthropathy with severely deformed foot, plantar ulceration and recurrent purulent infections. Second patient: diabetic osteoarthropathy with pathologic fracture. First patient: 50-year-old man with hereditary sensory and motor neuropathy, plantar ulceration, equinus of the hindfoot, and extensive destruction of all bones of the foot. Recurrent infections necessitated repeated surgical interventions during the last 7 years. At the time of admission purulent infection of the foot. Healing after debridement including a resection of metatarsal bones and part of sequestrated bones of the foot. Patient was left with a severe equinus of the hindfoot. Orthopedic shoes with or without below-knee orthesis. Lengthening of the Achilles tendon and plantar alignment of the calcaneus. Arthrodesis of the hindfoot. Below-knee amputation, if necessary as a primary procedure to combat infection. Arthrodesis of the hindfoot after realignment; an amputation of the foot was refused. Two-stage procedure: treatment of infection followed by astragalectomy and tibiocalcaneal arthrodesis achieved with cancellous lag screws. Bridging of the area of resection with a segment of the fibula. Bony fusion and full load bearing in an orthopedic shoe after 3 months. Recurrence of ulcerations after 20 and 27 months due to wear of ill-fitting shoes. The accompanying purulent process forced the authors to resort to a below-knee amputation and fitting of a prosthesis. Second patient: of this patient only radiographs with a retrograde introduced intramedullary nail are shown.

Bone volume fraction and structural parameters for estimation of mechanical stiffness and failure load of human cancellous bone samples; in-vitro comparison of ultrasound transit time spectroscopy and X-ray μCT.

PubMed

Alomari, Ali Hamed; Wille, Marie-Luise; Langton, Christian M

2018-02-01

Conventional mechanical testing is the 'gold standard' for assessing the stiffness (N mm -1 ) and strength (MPa) of bone, although it is not applicable in-vivo since it is inherently invasive and destructive. The mechanical integrity of a bone is determined by its quantity and quality; being related primarily to bone density and structure respectively. Several non-destructive, non-invasive, in-vivo techniques have been developed and clinically implemented to estimate bone density, both areal (dual-energy X-ray absorptiometry (DXA)) and volumetric (quantitative computed tomography (QCT)). Quantitative ultrasound (QUS) parameters of velocity and attenuation are dependent upon both bone quantity and bone quality, although it has not been possible to date to transpose one particular QUS parameter into separate estimates of quantity and quality. It has recently been shown that ultrasound transit time spectroscopy (UTTS) may provide an accurate estimate of bone density and hence quantity. We hypothesised that UTTS also has the potential to provide an estimate of bone structure and hence quality. In this in-vitro study, 16 human femoral bone samples were tested utilising three techniques; UTTS, micro computed tomography (μCT), and mechanical testing. UTTS was utilised to estimate bone volume fraction (BV/TV) and two novel structural parameters, inter-quartile range of the derived transit time (UTTS-IQR) and the transit time of maximum proportion of sonic-rays (TTMP). μCT was utilised to derive BV/TV along with several bone structure parameters. A destructive mechanical test was utilised to measure the stiffness and strength (failure load) of the bone samples. BV/TV was calculated from the derived transit time spectrum (TTS); the correlation coefficient (R 2 ) with μCT-BV/TV was 0.885. For predicting mechanical stiffness and strength, BV/TV derived by both μCT and UTTS provided the strongest correlation with mechanical stiffness (R 2 =0.567 and 0.618 respectively) and mechanical strength (R 2 =0.747 and 0.736 respectively). When respective structural parameters were incorporated to BV/TV, multiple regression analysis indicated that none of the μCT histomorphometric parameters could improve the prediction of mechanical stiffness and strength, while for UTTS, adding TTMP to BV/TV increased the prediction of mechanical stiffness to R 2 =0.711 and strength to R 2 =0.827. It is therefore envisaged that UTTS may have the ability to estimate BV/TV along with providing an improved prediction of osteoporotic fracture risk, within routine clinical practice in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis.

PubMed

Orlandi, A; Oliva, F; Taurisano, G; Candi, E; Di Lascio, A; Melino, G; Spagnoli, L G; Tarantino, U

2009-04-01

Osteoarthritis is a progressive joint disease characterized by cartilage degradation and bone remodeling. Transglutaminases catalyze a calcium-dependent transamidation reaction that produces covalent cross-linking of available substrate glutamine residues and modifies the extracellular matrix. Increased transglutaminases-mediated activity is reported in osteoarthritis, but the relative contribution of transglutaminases-2 (TG2) is uncertain. We describe TG2 expression in human femoral osteoarthritis and in wild-type and homozygous TG2 knockout mice after surgically-induced knee joint instability. Increased TG2 levels were observed in human and wild-type murine osteoarthritic cartilage compared to the respective controls. Histomorphometrical but not X-ray investigation documented in osteoarthritic TG2 knockout mice reduced cartilage destruction and an increased osteophyte formation compared to wild-type mice. These differences were associated with increased TGFbeta-1 expression. In addition to confirming its important role in osteoarthritis development, our results demonstrated that TG2 expression differently influences cartilage destruction and bone remodeling, suggesting new targeted TG2-related therapeutic strategies.

Multimodal-3D imaging based on μMRI and μCT techniques bridges the gap with histology in visualization of the bone regeneration process.

PubMed

Sinibaldi, R; Conti, A; Sinjari, B; Spadone, S; Pecci, R; Palombo, M; Komlev, V S; Ortore, M G; Tromba, G; Capuani, S; Guidotti, R; De Luca, F; Caputi, S; Traini, T; Della Penna, S

2018-03-01

Bone repair/regeneration is usually investigated through X-ray computed microtomography (μCT) supported by histology of extracted samples, to analyse biomaterial structure and new bone formation processes. Magnetic resonance imaging (μMRI) shows a richer tissue contrast than μCT, despite at lower resolution, and could be combined with μCT in the perspective of conducting non-destructive 3D investigations of bone. A pipeline designed to combine μMRI and μCT images of bone samples is here described and applied on samples of extracted human jawbone core following bone graft. We optimized the coregistration procedure between μCT and μMRI images to avoid bias due to the different resolutions and contrasts. Furthermore, we used an Adaptive Multivariate Clustering, grouping homologous voxels in the coregistered images, to visualize different tissue types within a fused 3D metastructure. The tissue grouping matched the 2D histology applied only on 1 slice, thus extending the histology labelling in 3D. Specifically, in all samples, we could separate and map 2 types of regenerated bone, calcified tissue, soft tissues, and/or fat and marrow space. Remarkably, μMRI and μCT alone were not able to separate the 2 types of regenerated bone. Finally, we computed volumes of each tissue in the 3D metastructures, which might be exploited by quantitative simulation. The 3D metastructure obtained through our pipeline represents a first step to bridge the gap between the quality of information obtained from 2D optical microscopy and the 3D mapping of the bone tissue heterogeneity and could allow researchers and clinicians to non-destructively characterize and follow-up bone regeneration. Copyright © 2017 John Wiley & Sons, Ltd.

Relationships of bone characteristics in MYO9B deficient femurs.

PubMed

Kim, Do-Gyoon; Jeong, Yong-Hoon; McMichael, Brooke K; Bähler, Martin; Bodnyk, Kyle; Sedlar, Ryan; Lee, Beth S

2018-08-01

The objective of this study was to examine relationships among a variety of bone characteristics, including volumetric, mineral density, geometric, dynamic mechanical analysis, and static fracture mechanical properties. As MYO9B is an unconventional myosin in bone cells responsible for normal skeletal growth, bone characteristics of wild-type (WT), heterozygous (HET), and MYO9B knockout (KO) mice groups were compared as an animal model to express different bone quantity and quality. Forty-five sex-matched 12-week-old mice were used in this study. After euthanization, femurs were isolated and scanned using microcomputed tomography (micro-CT) to assess bone volumetric, tissue mineral density (TMD), and geometric parameters. Then, a non-destructive dynamic mechanical analysis (DMA) was performed by applying oscillatory bending displacement on the femur. Finally, the same femur was subject to static fracture testing. KO group had significantly lower length, bone mineral density (BMD), bone mass and volume, dynamic and static stiffness, and strength than WT and HET groups (p < 0.019). On the other hand, TMD parameters of KO group were comparable with those of WT group. HET group showed volumetric, geometric, and mechanical properties similar to WT group, but had lower TMD (p < 0.014). Non-destructive micro-CT and DMA parameters had significant positive correlations with strength (p < 0.015) without combined effect of groups and sex on the correlations (p > 0.077). This comprehensive characterization provides a better understanding of interactive behavior between the tissue- and organ-level of the same femur. The current findings elucidate that MYO9B is responsible for controlling bone volume to determine the growth rate and fracture risk of bone. Copyright © 2018 Elsevier Ltd. All rights reserved.

Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice.

PubMed

Kim, Sun-Jin; Uehara, Hisanori; Karashima, Takashi; Shepherd, David L; Killion, Jerald J; Fidler, Isaiah J

2003-03-01

We determined whether blockade of the epidermal growth factor receptor (EGF-R) signaling pathway by oral administration of the EGF-R tyrosine kinase inhibitor (PKI 166) alone or in combination with injectable Taxol inhibits the growth of PC-3MM2 human prostate cancer cells in the bone of nude mice. Male nude mice implanted with PC-3MM2 cells in the tibia were treated with oral administrations of PKI 166 or PKI 166 plus injectable Taxol beginning 3 days after implantation. The incidence and size of bone tumors and destruction of bone were determined by digitalized radiography. Expression of epidermal growth factor (EGF), EGF-R, and activated EGF-R in tumor cells and tumor-associated endothelial cells was determined by immunohistochemistry. Oral administration of PKI 166 or PKI 166 plus injectable Taxol reduced the incidence and size of bone tumors and destruction of bone. Immunohistochemical analysis revealed that PC-3MM2 cells growing adjacent to the bone expressed high levels of EGF and activated EGF-R, whereas tumor cells in the adjacent musculature did not. Moreover, endothelial cells within the bone tumor lesions, but not in uninvolved bone or tumors in the muscle, expressed high levels of activated EGF-R. Treatment with PKI 166 and more so with PKI 166 plus Taxol significantly inhibited phosphorylation of EGF-R on tumor and endothelial cells and induced significant apoptosis and endothelial cells within tumor lesions. These data indicate that endothelial cells exposed to EGF produced by tumor cells express activated EGF-R and that targeting EGF-R can produce significant therapeutic effects against prostate cancer bone metastasis.

Complicated coexisting pyogenic and tuberculous otitis media affecting the temporozygomatic, infratemporal, and parotid areas: report of a rare entity.

PubMed

Brar, Tripti; Mrig, Sumit; Passey, J C; Agarwal, A K; Jain, Shayma

2013-01-01

We report an unusual case in which a 28-year-old woman presented with a long-standing history of ear discharge, hearing loss, facial weakness with ipsilateral facial swelling and cellulitis, a postauricular fistula, and an abscess of the temporozygomatic, infratemporal, and parotid areas. The pus stained positive for bacteria and acid-fast bacilli, and culture was positive for Proteus vulgaris and mycobacteria. Based on these findings, a diagnosis of tuberculous otitis media with complications was made. Computed tomography showed extensive destruction of the tympanic and mastoid part of the temporal bone, as well as lytic lesions in the skull. The patient was placed on antituberculosis drug therapy. Although her facial nerve palsy and hearing loss persisted, she otherwise responded well and did not require surgery.

[Osteostimulating effect of bone xenograft on bone tissue regeneration].

PubMed

Balin, V N; Balin, D V; Iordanishvili, A K; Musikin, M I

2015-01-01

The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures.

Advanced Functional Nanomaterials for Biological Processes

DTIC Science & Technology

2014-01-01

of this project, we performed research in the area of tissue engineering/bone regeneration and cancer nanotechnology . The primary focus of the tissue...photoacoustic approach. 15. SUBJECT TERMS: Tissue Engineering, Cancer detection, Cancer destruction, Nanoparticles 16. SECURITY CLASSIFICATION OF: 17...Nanocomposite Materials with Drug Delivery Capabilities for Tissue Engineering and Bone Regeneration; and B. Multifunctional Nanoparticles for Cancer Early

Validating in vivo Raman spectroscopy of bone in human subjects

NASA Astrophysics Data System (ADS)

Esmonde-White, Francis W. L.; Morris, Michael D.

2013-03-01

Raman spectroscopy can non-destructively measure properties of bone related to mineral density, mineral composition, and collagen composition. Bone properties can be measured through the skin in animal and human subjects, but correlations between the transcutaneous and exposed bone measurements have only been reported for human cadavers. In this study, we examine human subjects to collect measurements transcutaneously, on surgically exposed bone, and on recovered bone fragments. This data will be used to demonstrate in vivo feasibility and to compare transcutaneous and exposed Raman spectroscopy of bone. A commercially available Raman spectrograph and optical probe operating at 785 nm excitation are used for the in vivo measurements. Requirements for applying Raman spectroscopy during a surgery are also discussed.

Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL

PubMed Central

Kassem, Ali; Lindholm, Catharina; Lerner, Ulf H

2016-01-01

Severe Staphylococcus aureus (S. aureus) infections pose an immense threat to population health and constitute a great burden for the health care worldwide. Inter alia, S. aureus septic arthritis is a disease with high mortality and morbidity caused by destruction of the infected joints and systemic bone loss, osteoporosis. Toll-Like receptors (TLRs) are innate immune cell receptors recognizing a variety of microbial molecules and structures. S. aureus recognition via TLR2 initiates a signaling cascade resulting in production of various cytokines, but the mechanisms by which S. aureus causes rapid and excessive bone loss are still unclear. We, therefore, investigated how S. aureus regulates periosteal/endosteal osteoclast formation and bone resorption. S. aureus stimulation of neonatal mouse parietal bone induced ex vivo bone resorption and osteoclastic gene expression. This effect was associated with increased mRNA and protein expression of receptor activator of NF-kB ligand (RANKL) without significant change in osteoprotegerin (OPG) expression. Bone resorption induced by S. aureus was abolished by OPG. S. aureus increased the expression of osteoclastogenic cytokines and prostaglandins in the parietal bones but the stimulatory effect of S. aureus on bone resorption and Tnfsf11 mRNA expression was independent of these cytokines and prostaglandins. Stimulation of isolated periosteal osteoblasts with S. aureus also resulted in increased expression of Tnfsf11 mRNA, an effect lost in osteoblasts from Tlr2 knockout mice. S. aureus stimulated osteoclastogenesis in isolated periosteal cells without affecting RANKL-stimulated resorption. In contrast, S. aureus inhibited RANKL-induced osteoclast formation in bone marrow macrophages. These data show that S. aureus enhances bone resorption and periosteal osteoclast formation by increasing osteoblast RANKL production through TLR2. Our study indicates the importance of using different in vitro approaches for studies of how S. aureus regulates osteoclastogenesis to obtain better understanding of the complex mechanisms of S. aureus induced bone destruction in vivo. PMID:27311019

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.

[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.

Multiple Myeloma, Version 2.2016

PubMed Central

Anderson, Kenneth C.; Alsina, Melissa; Atanackovic, Djordje; Biermann, J. Sybil; Chandler, Jason C.; Costello, Caitlin; Djulbegovic, Benjamin; Fung, Henry C.; Gasparetto, Cristina; Godby, Kelly; Hofmeister, Craig; Holmberg, Leona; Holstein, Sarah; Huff, Carol Ann; Kassim, Adetola; Krishnan, Amrita Y.; Kumar, Shaji K.; Liedtke, Michaela; Lunning, Matthew; Raje, Noopur; Singhal, Seema; Smith, Clayton; Somlo, George; Stockerl-Goldstein, Keith; Treon, Steven P.; Weber, Donna; Yahalom, Joachim; Shead, Dorothy A.; Kumar, Rashmi

2016-01-01

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM. PMID:26553768

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

PubMed

Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

2016-01-01

Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease.

PubMed

Kajiya, Mikihito; Giro, Gabriela; Taubman, Martin A; Han, Xiaozhe; Mayer, Marcia P A; Kawai, Toshihisa

2010-11-08

Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal bacteria in the onset and progression of periodontal disease (PD) are well documented. However, the mechanism underlying the engagement of periodontal bacteria in RANKL-mediated alveolar bone resorption remains unclear. Therefore, this review article addresses three critical subjects. First, we discuss earlier studies of immune intervention, ultimately leading to the identification of bacteria-reactive lymphocytes as the cellular source of osteoclast-induction factor lymphokine (now called RANKL) in the context of periodontal bone resorption. Next, we consider (1) the effects of periodontal bacteria on RANKL production from a variety of adaptive immune effector cells, as well as fibroblasts, in inflamed periodontal tissue and (2) the bifunctional roles (upregulation vs. downregulation) of LPS produced from periodontal bacteria in a RANKL-induced osteoclast-signal pathway. Future studies in these two areas could lead to new therapeutic approaches for the management of PD by down-modulating RANKL production and/or RANKL-mediated osteoclastogenesis in the context of host immune responses against periodontal pathogenic bacteria.

Quantification of osteolytic bone lesions in a preclinical rat trial

NASA Astrophysics Data System (ADS)

Fränzle, Andrea; Bretschi, Maren; Bäuerle, Tobias; Giske, Kristina; Hillengass, Jens; Bendl, Rolf

2013-10-01

In breast cancer, most of the patients who died, have developed bone metastasis as disease progression. Bone metastases in case of breast cancer are mainly bone destructive (osteolytic). To understand pathogenesis and to analyse response to different treatments, animal models, in our case rats, are examined. For assessment of treatment response to bone remodelling therapies exact segmentations of osteolytic lesions are needed. Manual segmentations are not only time-consuming but lack in reproducibility. Computerized segmentation tools are essential. In this paper we present an approach for the computerized quantification of osteolytic lesion volumes using a comparison to a healthy reference model. The presented qualitative and quantitative evaluation of the reconstructed bone volumes show, that the automatically segmented lesion volumes complete missing bone in a reasonable way.

Variability of morphometric parameters of human trabecular tissue from coxo-arthritis and osteoporotic samples.

PubMed

Marinozzi, Franco; Marinozzi, Andrea; Bini, Fabiano; Zuppante, Francesca; Pecci, Raffaella; Bedini, Rossella

2012-01-01

Morphometric and architectural bone parameters change in diseases such as osteoarthritis and osteoporosis. The mechanical strength of bone is primarily influenced by bone quantity and quality. Bone quality is defined by parameters such as trabecular thickness, trabecular separation, trabecular density and degree of anisotropy that describe the micro-architectural structure of bone. Recently, many studies have validated microtomography as a valuable investigative technique to assess bone morphometry, thanks to micro-CT non-destructive, non-invasive and reliability features, in comparison to traditional techniques such as histology. The aim of this study is the analysis by micro-computed tomography of six specimens, extracted from patients affected by osteoarthritis and osteoporosis, in order to observe the tridimensional structure and calculate several morphometric parameters.

Validation of cortical bone mineral density distribution using micro-computed tomography.

PubMed

Mashiatulla, Maleeha; Ross, Ryan D; Sumner, D Rick

2017-06-01

Changes in the bone mineral density distribution (BMDD), due to disease or drugs, can alter whole bone mechanical properties such as strength, stiffness and toughness. The methods currently available for assessing BMDD are destructive and two-dimensional. Micro-computed tomography (μCT) has been used extensively to quantify the three-dimensional geometry of bone and to measure the mean degree of mineralization, commonly called the tissue mineral density (TMD). The TMD measurement has been validated to ash density; however parameters describing the frequency distribution of TMD have not yet been validated. In the current study we tested the ability of μCT to estimate six BMDD parameters: mean, heterogeneity (assessed by the full-width-at-half-maximum (FWHM) and the coefficient of variation (CoV)), the upper and lower 5% cutoffs of the frequency distribution, and peak mineralization) in rat sized femoral cortical bone samples. We used backscatter scanning electron microscopy (bSEM) as the standard. Aluminum and hydroxyapatite phantoms were used to identify optimal scanner settings (70kVp, and 57μA, with a 1500ms integration time). When using hydroxyapatite samples that spanned a broad range of mineralization levels, high correlations were found between μCT and bSEM for all BMDD parameters (R 2 ≥0.92, p<0.010). When using cortical bone samples from rats and various species machined to mimic rat cortical bone geometry, significant correlations between μCT and bSEM were found for mean mineralization (R 2 =0.65, p<0.001), peak mineralization (R 2 =0.61, p<0.001) the lower 5% cutoff (R 2 =0.62, p<0.001) and the upper 5% cutoff (R 2 =0.33, p=0.021), but not for heterogeneity, measured by FWHM (R 2 =0.05, p=0.412) and CoV (R 2 =0.04, p=0.469). Thus, while mean mineralization and most parameters used to characterize the BMDD can be assessed with μCT in rat sized cortical bone samples, caution should be used when reporting the heterogeneity. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnetic resonance imaging features of esthesioneuroblastoma in three dogs and one cat.

PubMed

Söffler, Charlotte; Hartmann, Antje; Gorgas, Daniela; Ludewig, Eberhard; von Pückler, Kerstin; Kramer, Martin; Schmidt, Martin J

2016-10-12

Esthesioneuroblastoma is a rare malignant intranasal tumor that originates from the olfactory neuroepithelium of the upper nasal cavity, and can destroy the cribriform plate and expand into the neurocranium. Descriptions of the magnetic resonance features of esthesioneuroblastomas in animals are scarce. The objectives of this study were to report the magnetic resonance imaging features of esthesioneuroblastomas in order to determine distinct imaging characteristics that may help distinguish it from other intracranial tumor types. Magnetic resonance images of four patients with confirmed esthesioneuroblastomas were reviewed and compared with previously reported cases. The esthesioneuroblastomas appeared as oval-shaped, solitary lesions in the caudal nasal cavity that caused osteolysis of the cribriform plate and extended into the brain in all cases. Signal intensity was variable. Contrast enhancement was mild and varied from homogeneous to heterogeneous. A peripheral cystic component was found in two patients and was reported in only one previous case. Mass effect and white matter edema were marked to severe. Osteolysis of facial bones and extension into the facial soft tissues or retrobulbar space were not present in any of the cases, although this has been reported in the literature. A definitive diagnosis of esthesioneuroblastoma based on signal intensity or contrast behavior was not possible. Nevertheless, the presence of a mass in the caudal nasal cavity with extension into the neurocranium seems to be a feature highly suspicious of esthesioneuroblastoma. In contrast to other extra-cranial lesions, the extra-cranial mass was relatively small and destruction of facial bones seems to be rare.

Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activation.

PubMed

Kong, Xiangying; Wu, Wenbin; Yang, Yue; Wan, Hongye; Li, Xiaomin; Zhong, Michun; Zhao, Hongyan; Su, Xiaohui; Jia, Shiwei; Ju, Dahong; Lin, Na

2015-03-15

Osteoclasts, bone-specialized multinucleated cells, are responsible for bone destructive diseases such as rheumatoid arthritis and osteoporosis. Natural plant-derived products have received substantial attention given their potential therapeutic and preventive activities against bone destructive diseases. In the present study, we investigated the effects of total saponin (TS) from Anemone flaccida Fr. Schmidt, on receptor activator of nuclear factor-κB ligand (RANKL)-induced in vitro osteoclast differentiation. We observed that TS concentration-dependently inhibited RANKL-induced osteoclast formation from RAW 264.7 cell and bone marrow-derived macrophages (BMMs), as well as decreased extent of actin ring formation and lacunar resorption. The RANKL-stimulated expression of osteoclast-related transcription factors were also diminished by TS. Moreover, TS blocked the RANKL-triggered TRAF6 expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and IκB-α, and inhibited NF-κB p65 DNA binding activity. Furthermore, TS almost abrogated the nuclear factor of activated T cells (NFATc1) and c-Fos expression. Taken together, our results demonstrated that TS suppresses RANKL-induced osteoclast differentiation and inflammatory bone loss via the down-regulation of TRAF6 level, suppression of JNK and p38 MAPKs and NF-κB activation, and subsequent decreased expression of c-Fos and NFATc1. Therefore, TS may be a potential agent and needs to be more evaluated in vivo or in clinical trials to become a therapeutic for lytic bone diseases.

Efficacy of anti-IL-23 monotherapy versus combination therapy with anti-IL-17 in estrogen deficiency induced bone loss conditions.

PubMed

Shukla, Priyanka; Mansoori, Mohd Nizam; Singh, Divya

2018-05-01

Recent studies have identified that Interleukin (IL)-23/IL-17 axis plays crucial role in pathogenesis of inflammation and bone destruction. IL-23 is thought to promote joint destruction in arthritis by stimulating Th17 cells. IL-23 directly mediates bone loss by inducing osteoclastogenesis and receptor activator of kappa B ligand (RANKL) expression in T cells. IL-23 also promotes tartrate-resistant acid phosphatase (TRAP) activity of osteoclast in osteoblast-osteoclast co-culture. The role of IL-23 has not been studied in estrogen deficiency induced bone loss. Here, we study the effect of IL-23 neutralization in ovariectomized (Ovx) estrogen deficient mice on various immune and skeletal parameters. We also determine whether the combination of anti-IL-23 and anti-IL17 has enhanced osteoprotective effects compared to monotherapies. Treatment of anti-IL-23 and its combination with anti-IL-17 suppressed Th17 cell differentiation and promoted development of T regulatory cells. Anti-IL-23 and its combination with anti-IL-17 prevented bone loss. However, the individual monotherapies of anti-IL-23 and anti-IL-17 were more effective than combination therapy. Treatment of IL-17 and IL-23 cytokines to bone marrow stromal cells led to increased differentiation towards osteoblast lineage. Double neutralization of IL-23 and IL-17 might be inhibiting this phenomenon thus producing less potent effects. Our studies thus support bone protective effects of anti-IL-23 and that the monotherapies of neutralizing antibodies against IL-17 and IL-23 may be a more accepted mode of treatment in management of post-menopausal bone loss rather than combination therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

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-curettage, and bone-grafting.

Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features.

PubMed

Lee, Byung-Do; Park, Moo-Rim; Kwon, Kyung-Hwan

2015-09-01

A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

Long-term overexpression of human granulocyte colony-stimulating factor in transgenic mice: persistent neutrophilia with no increased mortality for more than one year.

PubMed

Serizawa, I; Amano, K; Ishii, H; Ichikawa, T; Kusaka, M; Taguchi, T; Kiyokawa, N; Fujimoto, J

2000-06-01

To investigate possible adverse consequences of persistent neutrophil overproduction, mice transgenic for human granulocyte colony-stimulating factor (hG-CSF) were studied for more than 1 year. They showed marked granulocytopoiesis and neutrophilia. Continuous medullary and extramedullary granulocytopoiesis resulted in marked changes in bone and liver. In the liver, haemorrhage and focal necrosis and a few haemangiosarcomas were present, presumably caused by the destructive granulocytopoiesis. Despite the high incidence of lung infiltration by mature neutrophils, lung lesions rarely appeared. Although there was a persistent increase in neutrophils, mortality of the mice did not differ from that of non-transgenic littermates at least within 1 year after birth. Factors other than overproduction of G-CSF and extensive neutrophilia could be required for the development of neutrophil-mediated acute and chronic tissue damage. Copyright 2000 Academic Press.

A recurrent central giant cell granuloma in a young patient and orthodontic treatment: a case report.

PubMed

Patel, Devaki; Minhas, Gursharan; Johnson, Paul

2016-12-01

Central giant cell granuloma (CGCG) is an uncommon benign intraosseous lesion of the jaw, found predominantly in children and young adults below 30 years of age. The purpose of this article was to present a summary of the current literature and a case report of an 11-year-old boy diagnosed with an aggressive CGCG involving the anterior maxilla that was removed in 2004 and subsequently recurred almost 3 years later in 2006. The presenting features of the patient and the effect of combined surgical and orthodontic treatment for this condition are discussed. This case shows how the dentition was successfully maintained with conservative surgery and orthodontic treatment in spite of the extensive destruction of the supporting bone, and the importance of long-term follow-up. The report also reminds orthodontic practitioners that rare pathological conditions can occur in their child patient groups.

Cost-effective non-surgical treatment of chronic pressure ulcers in the community.

PubMed

Dale, Megan; Cox-Martin, Bill; Shaw, Paula; Carolan-Rees, Grace

2014-03-01

The Salisbury Pressure Ulcer Outreach Service successfully treats patients with chronic pressure ulcers that have not healed during routine community treatment. These patients have grade 4 pressure ulcers, involving extensive destruction, or damage to muscle and bone. A combination of scientific, seating and tissue viability expertise with a holistic approach results in non-surgical healing for 70% of patients. For those who still require surgery, outcomes are more successful with this approach, resulting in low recurrence rates. Prior to creation of the outreach service, patients were referred directly for surgical closure, resulting in high recurrence levels and long waiting lists. The authors compared costs of the Pressure Ulcer Outreach Service with the previous system of surgical closure. The model base case found that the Pressure Ulcer Outreach Service saved £8588 per patient, and that cost savings could be even greater if the outreach service was extended into preventative work.

Neuropathic Arthropathy of the Glenohumeral Joint A Review of the Literature.

PubMed

Santiesteban, Lauren; Mollon, Brent; Zuckerman, Joseph D

2018-06-01

Neuropathic arthropathy, also known as Charcot arthropathy, is a degenerative disorder most commonly characterized by rapid destruction of the joint with extensive involvement of the bone and soft tissue. The underlying pathophysiology is thought to be due to loss of nociception (pain sensation), most frequently caused by diabetes mellitus, syphilitic myelopathy, or syringomyelia. A neuropathic shoulder is rare, with historic case series forming the bulk of the literature. The purpose of this review is to better understand the pathogenesis, clinical presentation, and management of neuropathic arthropathy of the glenohumeral joint. It should be stressed that the identification and management of the underlying etiology is paramount if the disease process is to be positively impacted. Although the mainstay of orthopedic management is non-surgical, little evidence exists to support the use of any specific therapeutic intervention. Recent literature suggests surgical reconstruction may be considered in very select patients.

[Expression of S100A8 and A100A9 in giant cell tumor of bone and its relation with CT and MR imaging findings].

PubMed

Liao, Jin-sheng; Ding, Xiao-yi; Xu, Shun-liang

2015-05-01

To investigate the mRNA and protein expression levels of S100A8 and S100A9 in giant cell tumor (GCT) of bone, and its relation with radiological findings and biological behavior. Forty three patient with GCT of bone admitted in Ruijin Hospital Shanghai Jiaotong University School of Medicine from January 2009 to June 2012 were enrolled in the study. The expression levels of S100A8 and S100A9 mRNA and protein were detected by using semiquantitative RT-PCR and Western blotting in 43 specimens of GCT and 6 specimens of normal bone marrow. The CT and MRI findings of patients were retrospectively reviewed, its relation with tissue expression of S100A8 and S100A9 was analyzed. Among 43 GCT cases 40 showed positive expression of S100A8 and S100A9 mRNA and protein, and the expression levels were significantly higher than those in normal bone marrow P<0.05). The expression level of S100A8 protein was significantly different in bone GCT with different composition ratio on MRI (P<0.05).The expression level of S100A9 protein was significantly different in GCT with different degree of bone destruction on CT scan (P<0.05). The expression of S100A8 and S100A9 mRNA and protein is up-regulated in GCT of bone. The expression of S100A8 and S100A9 is associated with the real composition ratio and the degree of bone destruction, respectively, indicating that S100A8 and S100A9 may be involved in the biological behavior of bone GCT.

Primary bone tumors of adulthood

PubMed Central

Teo, Harvey E L; Peh, Wilfred C G

2004-01-01

Imaging plays a crucial role in the evaluation of primary bone tumors in adults. Initial radiographic evaluation is indicated in all cases with suspected primary bone tumors. Radiographs are useful for providing the diagnosis, a short list of differential diagnosis or at least indicating the degree of aggressiveness of the lesion. More detailed information about the lesion, such as cortical destruction or local spread, can be obtained using cross-sectional imaging techniques such as computed tomography and magnetic resonance imaging. This article discusses the characteristic features of the more common primary bone tumors of adulthood, and also the pre-treatment evaluation and staging of these lesions using imaging techniques. PMID:18250012

Determination of Corrosion Rate of Artificial Bone Made of Metal at Different pH Conditions using X-Ray Radiography

NASA Astrophysics Data System (ADS)

Sutikno; Handayani, L.; Edi, S. S.; Susilo; Elvira

2018-03-01

The purpose of this research is to observe the mechanism and the rate of corrosion of artificial bone made of metal by using x-ray radiography technique. Artificial bones can be made of metallic materials and composites which are biomaterials. The most commonly used metal for bone graft is stainless steel. The interaction between artificial bone and human tissue will have important medical impacts that need to be observed and examined. This interaction can be a mechanical or chemical interaction. X-ray radiography technique is selected because it uses non-destructive method. This method is done by x-ray radiation exposure on the observed body part. The bone density and bone fracture can be seen on the resulted radiographic film or image on the monitor screen.

The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases

PubMed Central

Boucharaba, Ahmed; Serre, Claire-Marie; Guglielmi, Julien; Bordet, Jean-Claude; Clézardin, Philippe; Peyruchaud, Olivier

2006-01-01

Platelet-derived lysophosphatidic acid (LPA) supports the progression of breast and ovarian cancer metastasis to bone. The mechanisms through which LPA promotes bone metastasis formation are, however, unknown. Here we report that silencing of the type 1 LPA receptor (LPA1) in cancer cells blocks the production of tumor-derived cytokines that are potent activators of osteoclast-mediated bone destruction and significantly reduces the progression of osteolytic bone metastases. Moreover, functional blockade of LPA action on its cognate receptor LPA1 using a pharmacological antagonist mimics the effects of silencing LPA1 in tumor cells in vitro and substantially reduces bone metastasis progression in animals. Overall, these results suggest that inhibition of platelet-derived LPA action on LPA1 expressed by tumor cells may be a promising therapeutic target for patients with bone metastases. PMID:16769891

Aneurysmal Bone Cysts of the Spine: Two Case Reports

PubMed Central

Ozdemir, Seymen; Ozden, Ferhat; Kacira, Ozlem Kitiki; Kacira, Tibet

2014-01-01

Aneurysmal bone cysts are rare entities which causes expansile and destructive bone lesions characterized by reactive proliferation of connective tissue. They usually grow rapidly with hypervascularity. In clinical practice they can be easily misdiagnosed due to the rare occurance and having no such typical findings as radiologically. Most cases have uncommon pain symptoms, but rarely, if fractures occur, neurological findings can be seen and the surgical treatment, if needed, could be difficult. We will discuss our evaluations to two cases that we experienced in our clinic in this report. PMID:25620988

Aneurysmal bone cysts of the spine: two case reports.

PubMed

Ozdemir, Seymen; Yaldiz, Can; Ozden, Ferhat; Kacira, Ozlem Kitiki; Kacira, Tibet

2014-12-01

Aneurysmal bone cysts are rare entities which causes expansile and destructive bone lesions characterized by reactive proliferation of connective tissue. They usually grow rapidly with hypervascularity. In clinical practice they can be easily misdiagnosed due to the rare occurance and having no such typical findings as radiologically. Most cases have uncommon pain symptoms, but rarely, if fractures occur, neurological findings can be seen and the surgical treatment, if needed, could be difficult. We will discuss our evaluations to two cases that we experienced in our clinic in this report.

Harnessing and Modulating Inflammation in Strategies for Bone Regeneration

PubMed Central

Mountziaris, Paschalia M.; Spicer, Patrick P.; Kasper, F. Kurtis

2011-01-01

Inflammation is an immediate response that plays a critical role in healing after fracture or injury to bone. However, in certain clinical contexts, such as in inflammatory diseases or in response to the implantation of a biomedical device, the inflammatory response may become chronic and result in destructive catabolic effects on the bone tissue. Since our previous review 3 years ago, which identified inflammatory signals critical for bone regeneration and described the inhibitory effects of anti-inflammatory agents on bone healing, a multitude of studies have been published exploring various aspects of this emerging field. In this review, we distinguish between regenerative and damaging inflammatory processes in bone, update our discussion of the effects of anti-inflammatory agents on bone healing, summarize recent in vitro and in vivo studies demonstrating how inflammation can be modulated to stimulate bone regeneration, and identify key future directions in the field. PMID:21615330

Solid variant of aneurysmal bone cyst of the thoracic spine: a case report

PubMed Central

2011-01-01

Introduction The solid variant of aneurysmal bone cyst is rare, and only 13 cases involving the spine have been reported to date, including seven in the thoracic vertebrae. The diagnosis is difficult to secure radiographically before biopsy or surgery. Case report An 18-year-old Hispanic man presented to our facility with a one-year history of left chest pain without any significant neurological deficits. An MRI scan demonstrated a 6 cm diameter enhancing multi-cystic mass centered at the T6 vertebral body with involvement of the left proximal sixth rib and extension into the pleural cavity; the spinal cord was severely compressed with evidence of abnormal T2 signal changes. Our patient was taken to the operating room for a total spondylectomy of T6 with resection of the left sixth rib from a single-stage posterior-only approach. The vertebral column was reconstructed in a 360° manner with an expandable titanium cage and pedicle screw fixation. Histologically, the resected specimen showed predominant solid fibroblastic proliferation, with minor foci of reactive osteoid formation, an area of osteoclastic-like giant cells, and cyst-like areas filled with erythrocytes and focal hemorrhage, consistent with a predominantly solid variant of aneurysmal bone cyst. At 16 months after surgery, our patient remains neurologically intact with resolution of his chest and back pain. Conclusions Because of its rarity, location, and radical treatment approach, we considered this case worthy of reporting. The solid variant of aneurysmal bone cyst is difficult to diagnose radiologically before biopsy or surgery, and we hope to remind other physicians that it should be included in the differential diagnosis of any lytic expansile destructive lesion of the spine. PMID:21718507

Management bone loss of the proximal femur in revision hip arthroplasty: Update on reconstructive options

PubMed Central

Sakellariou, Vasileios I; Babis, George C

2014-01-01

The number of revision total hip arthroplasties is expected to rise as the indications for arthroplasty will expand due to the aging population. The prevalence of extensive proximal femoral bone loss is expected to increase subsequently. The etiology of bone loss from the proximal femur after total hip arthroplasty is multifactorial. Stress shielding, massive osteolysis, extensive loosening and history of multiple surgeries consist the most common etiologies. Reconstruction of extensive bone loss of the proximal femur during a revision hip arthroplasty is a major challenge for even the most experienced orthopaedic surgeon. The amount of femoral bone loss and the bone quality of the remaining metaphyseal and diaphyseal bone dictate the selection of appropriate reconstructive option. These include the use of impaction allografting, distal press-fit fixation, allograft-prosthesis composites and tumor megaprostheses. This review article is a concise review of the current literature and provides an algorithmic approach for reconstruction of different types of proximal femoral bone defects. PMID:25405090

A novel classification of frontal bone fractures: The prognostic significance of vertical fracture trajectory and skull base extension.

PubMed

Garg, Ravi K; Afifi, Ahmed M; Gassner, Jennifer; Hartman, Michael J; Leverson, Glen; King, Timothy W; Bentz, Michael L; Gentry, Lindell R

2015-05-01

The broad spectrum of frontal bone fractures, including those with orbital and skull base extension, is poorly understood. We propose a novel classification scheme for frontal bone fractures. Maxillofacial CT scans of trauma patients were reviewed over a five year period, and frontal bone fractures were classified: Type 1: Frontal sinus fracture without vertical extension. Type 2: Vertical fracture through the orbit without frontal sinus involvement. Type 3: Vertical fracture through the frontal sinus without orbit involvement. Type 4: Vertical fracture through the frontal sinus and ipsilateral orbit. Type 5: Vertical fracture through the frontal sinus and contralateral or bilateral orbits. We also identified the depth of skull base extension, and performed a chart review to identify associated complications. 149 frontal bone fractures, including 51 non-vertical frontal sinus (Type 1, 34.2%) and 98 vertical (Types 2-5, 65.8%) fractures were identified. Vertical fractures penetrated the middle or posterior cranial fossa significantly more often than non-vertical fractures (62.2 v. 15.7%, p = 0.0001) and had a significantly higher mortality rate (18.4 v. 0%, p < 0.05). Vertical fractures with frontal sinus and orbital extension, and fractures that penetrated the middle or posterior cranial fossa had the strongest association with intracranial injuries, optic neuropathy, disability, and death (p < 0.05). Vertical frontal bone fractures carry a worse prognosis than frontal bone fractures without a vertical pattern. In addition, vertical fractures with extension into the frontal sinus and orbit, or with extension into the middle or posterior cranial fossa have the highest complication rate and mortality. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

A systematic examination of the bone destruction pattern of the two-shot technique

PubMed Central

Stoetzer, Marcus; Stoetzer, Carsten; Rana, Majeed; Zeller, Alexander; Hanke, Alexander; Gellrich, Nils-Claudius; von See, Constantin

2014-01-01

Introduction: The two-shot technique is an effective stopping power method. The precise mechanisms of action on the bone and soft-tissue structures of the skull; however, remain largely unclear. The aim of this study is to compare the terminal ballistics of the two-shot and single-shot techniques. Materials and Methods: 40 fresh pigs’ heads were randomly divided into 4 groups (n = 10). Either a single shot or two shots were fired at each head with a full metal jacket or a semi-jacketed bullet. Using thin-layer computed tomography and photography, the diameter of the destruction pattern and the fractures along the bullet path were then imaged and assessed. Results: A single shot fired with a full metal jacket bullet causes minor lateral destruction along the bullet path. With two shots fired with a full metal jacket bullet, however, the maximum diameter of the bullet path is significantly greater (P < 0.05) than it is with a single shot fired with a full metal jacket bullet. In contrast, the maximum diameter with a semi-jacketed bullet is similar with the single-shot and two-shot techniques. Conclusion: With the two-shot technique, a full metal jacket bullet causes a destruction pattern that is comparable to that of a single shot fired with a semi-jacketed bullet. PMID:24812454

Emerging treatments for postmenopausal osteoporosis – focus on denosumab

PubMed Central

Geusens, Piet

2009-01-01

The pathway of the receptor activator of the nuclear factor κB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget’s disease of bone, rheumatoid arthritis [RA], metastatic bone disease). Clinical trials indicate that denosumab, a RANKL-specific recombinant humanized monoclonal antibody, is effective in suppressing bone resorption, resulting in increase in bone mineral density (BMD) in post-menopausal women with low BMD, and has the potential to prevent progression of erosions in RA and of skeletal-related events in metastatic bone disease. The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study. In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed. PMID:19554095

Genetics Home Reference: Diamond-Blackfan anemia

MedlinePlus

... developing certain cancers, including a cancer of blood-forming tissue known as acute myeloid leukemia (AML) and ... proteins may increase the self-destruction of blood-forming cells in the bone marrow, resulting in anemia. ...

Giant cell angiofibroma of the scalp: A benign rare neoplasm with bone destruction

PubMed Central

Arifin, Muhammad Z.; Tjahjono, Firman P.; Faried, Ahmad; Gill, Arwinder S.; Cahyadi, Alexander; Hernowo, Bethy S.

2013-01-01

Background: The incidence of extraorbital giant cell angiofibroma (GCA) is rare, with only one case located in the scalp reported in the literature. The morphological hallmark is histopathological examination showing richly vascularized pattern-less spindle cell proliferation containing pseudovascular spaces and floret-like multinucleate giant cells. Case Description: We report a case of a 30-year-old female with a primary complaint of a painless solitary nodule arising on the left parietal region of the scalp. Complete tumor removal through surgical intervention was achieved, and the postoperative period was uneventful. Conclusion: Diagnosing a highly vascularized tumor in the head and neck is challenging. Our case is unique in that it is presented as a GCA of the scalp, which is an extremely rare clinical entity, and also demonstrated bone destruction. PMID:24231802

Finite element tension analysis of the supporting tissues of a maxillary canine.

PubMed

Kalachev, Y S; Ralev, R D; Iordanov, P I

2001-01-01

The distribution of masticatory load on the teeth and the arising force tensions in them are factors that determine the origine of destructive processes in their periodontium. The development of mathematical models and application of new computer technologies make possible their precise study. They are still not thoroughly studied. To study the tensions, originating in the periodontium of a canine tooth during occlusal load by the modern method of finite elements (MFE). A three-dimensional model of a maxillary canine is built by MFE containing 304 finite elements with six varieties of geometrical form, linked in 1409 nodes. It is supposed that the tooth is fixed firmly to the outer surface of the periodontal membrane to the alveolar bone and is loaded in the lingual wall by a force perpendicular to its longitudinal axis and directed from the lingual to the vestibular wall. As a result of the calculations according to MFE the tension state of dental tissues is calculated for diferent degrees of destruction of the alveolar bone. It was established that with the increase of destruction of the alveolar bone for one and the same masticatory load, the tensions in the periodontal membrane also increase. The maximal tensions act in the apex of the root and around the clinical neck of the teeth. The results obtained provide precise information of distribution of force tensions in the periodontium of maxillary canines during occlusal load. They serve as a serious theoretical base for future investigations.

Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction

PubMed Central

Danilin, Sabrina; Merkel, Alyssa R.; Johnson, Joshua R.; Johnson, Rachelle W.; Edwards, James R.; Sterling, Julie A.

2012-01-01

Myeloid-derived suppressor cells (MDSCs), identified as Gr1+CD11b+ cells in mice, expand during cancer and promote tumor growth, recurrence and burden. However, little is known about their role in bone metastases. We hypothesized that MDSCs may contribute to tumor-induced bone disease, and inoculated breast cancer cells into the left cardiac ventricle of nude mice. Disease progression was monitored weekly by X-ray and fluorescence imaging and MDSCs expansion by fluorescence-activated cell sorting. To explore the contribution of MDSCs to bone metastasis, we co-injected mice with tumor cells or PBS into the left cardiac ventricle and Gr1+CD11b+ cells isolated from healthy or tumor-bearing mice into the left tibia. MDSCs didn’t induce bone resorption in normal mice, but increased resorption and tumor burden significantly in tumor-bearing mice. In vitro experiments showed that Gr1+CD11b+ cells isolated from normal and tumor-bearing mice differentiate into osteoclasts when cultured with RANK ligand and macrophage colony-stimulating factor, and that MDSCs from tumor-bearing mice upregulate parathyroid hormone-related protein (PTHrP) mRNA levels in cancer cells. PTHrP upregulation is likely due to the 2-fold increase in transforming growth factor β expression that we observed in MDSCs isolated from tumor-bearing mice. Importantly, using MDSCs isolated from GFP-expressing animals, we found that MDSCs differentiate into osteoclast-like cells in tumor-bearing mice as evidenced by the presence of GFP+TRAP+ cells. These results demonstrate that MDSCs expand in breast cancer bone metastases and induce bone destruction. Furthermore, our data strongly suggest that MDSCs are able to differentiate into osteoclasts in vivo and that this is stimulated in the presence of tumors. PMID:23264895

NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice.

PubMed

Bast, Antje; Kubis, Helen; Holtfreter, Birte; Ribback, Silvia; Martin, Heiner; Schreiner, Helen C; Dominik, Malte J; Breitbach, Katrin; Dombrowski, Frank; Kocher, Thomas; Steinmetz, Ivo

2017-02-01

Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans-induced periodontitis. NADPH oxidase-deficient (gp91 phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional micro-computed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91 phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91 phox KO mice. Only infected gp91 phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis. Copyright © 2017 American Society for Microbiology.

NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice

PubMed Central

Bast, Antje; Kubis, Helen; Holtfreter, Birte; Ribback, Silvia; Martin, Heiner; Schreiner, Helen C.; Dominik, Malte J.; Breitbach, Katrin; Dombrowski, Frank; Kocher, Thomas

2016-01-01

ABSTRACT Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans-induced periodontitis. NADPH oxidase-deficient (gp91phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional micro-computed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91phox KO mice. Only infected gp91phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis. PMID:27849181

Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes.

PubMed

Glowacki, Andrew J; Yoshizawa, Sayuri; Jhunjhunwala, Siddharth; Vieira, Andreia E; Garlet, Gustavo P; Sfeir, Charles; Little, Steven R

2013-11-12

The hallmark of periodontal disease is the progressive destruction of gingival soft tissue and alveolar bone, which is initiated by inflammation in response to an invasive and persistent bacterial insult. In recent years, it has become apparent that this tissue destruction is associated with a decrease in local regulatory processes, including a decrease of forkhead box P3-expressing regulatory lymphocytes. Accordingly, we developed a controlled release system capable of generating a steady release of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22), composed of a degradable polymer with a proven track record of clinical translation, poly(lactic-co-glycolic) acid. We have previously shown that this sustained presentation of CCL22 from a point source effectively recruits regulatory T cells (Tregs) to the site of injection. Following administration of the Treg-recruiting formulation to the gingivae in murine experimental periodontitis, we observed increases in hallmark Treg-associated anti-inflammatory molecules, a decrease of proinflammatory cytokines, and a marked reduction in alveolar bone resorption. Furthermore, application of the Treg-recruiting formulation (fabricated with human CCL22) in ligature-induced periodontitis in beagle dogs leads to reduced clinical measures of inflammation and less alveolar bone loss under severe inflammatory conditions in the presence of a diverse periodontopathogen milieu.

Non-destructive elemental analysis of vertebral body trabecular bone using muonic X-rays.

PubMed

Hosoi, Y; Watanabe, Y; Sugita, R; Tanaka, Y; Nagamine, K; Ono, T; Sakamoto, K

1995-12-01

Non-destructive elemental analysis with muonic X-rays was performed on human vertebral bone and lumbar torso phantoms. It can provide quantitative information on all elements in small deep-seated localized volumes. The experiment was carried out using the superconducting muon channel at TRIUMF in Vancouver, Canada and a lithium drifted germanium detector with an active area of 18.5 cm2. The muon channel produced backward-decayed negative muons with wide kinetic energy range from 0.5 to 54.2 MeV. The muon beam was collimated to a diameter of 18 mm. The number of incoming muons was about 4 x 10(6) approximately 5 x 10(7) per data point. In the measurements with human vertebral bones fixed with neutralized formaldehyde, the correlation coefficient between calcium content measured by muons and by atomic absorption analysis was 0.99 and the level of significance was 0.0003. In the measurements with lumbar torso phantoms, the correlation coefficient between calcium content measured by muons and by atomic absorption analysis was 0.99 and the level of significance was 0.02. The results suggest that elemental analysis in vertebral body trabecular bone using muonic X-rays closely correlates with measurements by atomic absorption analysis.

Primary malignant perivascular epithelioid cell neoplasm (PEComa) of the bone mimicking granular cell tumor in core biopsy: A case report and literature review

PubMed Central

Sadigh, Sam; Shah, Preya; Weber, Kristy; Sebro, Ronnie; Zhang, Paul J.

2018-01-01

The present study investigated the case of a 46-year-old female with primary malignant perivascular epithelioid cell neoplasm (PEComa) of the femur. The patient presented with a 5-month history of right distal thigh pain following trauma. Radiographs of the right distal femur revealed a mixed lytic and sclerotic lesion with subtle areas of cortical destruction and soft tissue extension, consistent with an aggressive tumor. A core biopsy revealed an epithelioid tumor with granular cell features, but a definitive diagnosis could not be made. Due to the aggressive features on radiologic evaluation, the patient underwent a resection of the distal femur and reconstruction with a distal femoral megaprosthesis and hinged knee replacement. The post-resection pathology led to a final diagnosis of primary bone PEComa, with histologic features including epithelioid, granular cell and spindled cell morphologies and biphasic immunoreactivity for melanocytic and smooth muscle markers. The large tumor size (>5 cm), rapid mitotic rate, infiltrative growth pattern, high nuclear grade and cellularity, and the presence of necrosis rendered this a malignant PEComa. The present study discussed the case, including radiographic (radiographs, magnetic resonance imaging and positron emission tomography scans) and histologic appearance and a literature review. PMID:29435023

Telangiectatic osteosarcoma of the patella.

PubMed

Shehadeh, Ahmad M; Haiba, Moutaz A; Henshaw, Robert M; Lack, Ernest

2008-08-01

Although osteosarcoma is the most common primary malignancy of bone, it has only been reported to arise from the patella in a handful of cases. Telangiectatic osteosarcoma accounts for <5% of all osteosarcomas, and it is distinguished histologically by spaces, often blood filled, separated by septa containing highly malignant cells and radiographically by a predominately lytic and/or expansile component. Telangiectatic osteosarcoma can be radiologically confused with aneurysmal bone cyst or giant cell tumor. A 22-year-old otherwise healthy man presented with increasing pain, swelling, and limited flexion of the right knee after failing physical therapy for anterior knee pain. Standard anteroposterior and lateral radiographs demonstrated a diffuse destructive process involving the majority of the patella (including loss of the inferior patellar cortex) and a lytic lesion of the proximal tibia. Apparent osteoid matrix was visible in the soft tissue extension along the inferior pole of the patella. A computed tomography scan of the chest showed 2 pulmonary nodules consistent with metastatic disease. Evaluation of core needle biopsy showed osteosarcoma with telangiectatic features. Given that the majority of the tumor involved the patella/extensor mechanism, it was clear that the tumor originated in the patella. This case presents the first published report of a telangiectatic osteosarcoma arising from the patella.

Forensic genetic analysis of bone remain samples.

PubMed

Siriboonpiputtana, T; Rinthachai, T; Shotivaranon, J; Peonim, V; Rerkamnuaychoke, B

2018-03-01

DNA typing from degraded human remains is still challenging forensic DNA scientists not only in the prospective of DNA purification but also in the interpretation of established DNA profiles and data manipulation, especially in mass fatalities. In this report, we presented DNA typing protocol to investigate many skeletal remains in different degrees of decomposing. In addition, we established the grading system aiming for prior determination of the association between levels of decomposing and overall STR amplification efficacy. A total of 80 bone samples were subjected to DNA isolation using the modified DNA IQ™ System (Promega, USA) for bone extraction following with STR analysis using the AmpFLSTR Identifiler ® (Thermo Fisher Scientific, USA). In low destruction group, complete STR profiles were observed as 84.4% whereas partial profiles and non-amplified were found as 9.4% and 6.2%, respectively. Moreover, in medium destruction group, both complete and partial STR profiles were observed as 31.2% while 37.5% of this group was unable to amplify. Nevertheless, we could not purify DNA and were unable to generate STR profile in any sample from the high destroyed bone samples. Compact bones such as femur and humerus have high successful amplification rate superior than loose/spongy bones. Furthermore, costal cartilage could be a designate specimen for DNA isolation in a case of the body that was discovered approximately to 3 days after death which enabled to isolate high quality and quantity of DNA, reduce time and cost, and do not require special tools such as freezer mill. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of electromagnetic radiation exposure on bone mineral density, thyroid, and oxidative stress index in electrical workers

PubMed Central

Kunt, Halil; Şentürk, İhsan; Gönül, Yücel; Korkmaz, Mehmet; Ahsen, Ahmet; Hazman, Ömer; Bal, Ahmet; Genç, Abdurrahman; Songur, Ahmet

2016-01-01

Background In the literature, some articles report that the incidence of numerous diseases increases among the individuals who live around high-voltage electric transmission lines (HVETL) or are exposed vocationally. However, it was not investigated whether HVETL affect bone metabolism, oxidative stress, and the prevalence of thyroid nodule. Methods Dual-energy X-ray absorptiometry (DEXA) bone density measurements, serum free triiodothyronine (FT3), free thyroxine (FT4), RANK, RANKL, osteoprotegerin (OPG), alkaline phosphatase (ALP), phosphor, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were analyzed to investigate this effect. Results Bone mineral density levels of L1–L4 vertebrae and femur were observed significantly lower in the electrical workers. ALP, phosphor, RANK, RANKL, TOS, OSI, and anteroposterior diameter of the left thyroid lobe levels were significantly higher, and OPG, TAS, and FT4 levels were detected significantly lower in the study group when compared with the control group. Conclusion Consequently, it was observed that the balance between construction and destruction in the bone metabolism of the electrical workers who were employed in HVETL replaced toward destruction and led to a decrease in OPG levels and an increase in RANK and RANKL levels. In line with the previous studies, long-term exposure to an electromagnetic field causes disorders in many organs and systems. Thus, it is considered that long-term exposure to an electromagnetic field affects bone and thyroid metabolism and also increases OSI by increasing the TOS and decreasing the antioxidant status. PMID:26929645

Histologic analysis of a failing three-part dental implant: a human case report.

PubMed

Landi, Luca; Manicone, Paolo Francesco; Piccinelli, Stefano; Raia, Roberto

2005-12-01

Two failing implants were removed for prosthetic reasons from the maxilla of a 60-year-old woman. The implants were clinically immobile but presented clear signs of peri-implant mucositis and bone destruction. One of the two implants was harvested together with the surrounding bone and analyzed histologically. The implant was threaded and consisted of three distinct components screwed together in a telescopic fashion. Histologically, bone loss reached the fourth thread, while apical to the fourth thread, osseointegration between the host bone and the implant surface was recognizable. The implant parts were not completely seated into each other, and the resulting gap was colonized by host bone. Newly formed alveolar bone penetrated deep into the implant body cavity and appeared similar in nature to the alveolar bone surrounding the implant. Histologic findings are discussed in reference to the ability of such an implant to withstand biomechanical loading over time.

Unicameral (simple) bone cysts.

PubMed

Baig, Rafath; Eady, John L

2006-09-01

Since their original description by Virchow, simple bone cysts have been studied repeatedly. Although these defects are not true neoplasms, simple bone cysts may create major structural defects of the humerus, femur, and os calcis. They are commonly discovered incidentally when x-rays are taken for other reasons or on presentation due to a pathologic fracture. Various treatment strategies have been employed, but the only reliable predictor of success of any treatment strategy is the age of the patient; those being older than 10 years of age heal their cysts at a higher rate than those under age 10. The goal of management is the formation of a bone that can withstand the stresses of use by the patient without evidence of continued bone destruction as determined by serial radiographic follow-up. The goal is not a normal-appearing x-ray, but a functionally stable bone.

Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases.

PubMed

Kawatani, Makoto; Osada, Hiroyuki

2009-11-01

Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to have efficacy for treating bone metastases in many types of cancer, and the development of various molecularly targeted agents is currently proceeding. Thus, inhibition of osteoclast function is now established as an important treatment strategy for bony metastases. This review focuses on promising small molecules that disrupt osteoclast function and introduces our chemical/biological approach for identifying osteoclast-targeting small molecular inhibitors.

The potential role of free chitosan in bone trauma and bone cancer management.

PubMed

Tan, Mei L; Shao, Peng; Friedhuber, Anna M; van Moorst, Mallory; Elahy, Mina; Indumathy, Sivanjah; Dunstan, Dave E; Wei, Yongzhong; Dass, Crispin R

2014-09-01

Bone defects caused by fractures or cancer-mediated destruction are debilitating. Chitosan is commonly used in scaffold matrices for bone healing, but rarely as a free drug. We demonstrate that free chitosan promotes osteoblast proliferation and osteogenesis in mesenchymal stem cells, increases osteopontin and collagen I expression, and reduces osteoclastogenesis. Chitosan inhibits invasion of endothelial cells, downregulating uPA/R, MT1-MMP, cdc42 and Rac1. Better healing of bone fractures with greater trabecular bone formation was observed in mice treated with chitosan. Chitosan induces apoptosis in osteotropic prostate and breast cancer cells via caspase-2 and -3 activation, and reduces their establishment in bone. Chitosan is pro-apoptotic in osteosarcoma cells, but not their normal counterpart, osteoblasts, or chondrosarcoma cells. Systemic delivery of chitosan does not perturb angiogenesis, bone volume or instinctive behaviour in pregnant mice, but decreases foetal length and changes pancreatic secretory acini. With certain controls in place, chitosan could be useful for bone trauma management. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma.

PubMed

Morris, Emma V; Edwards, Claire M

2018-06-26

Obesity has become a global epidemic influencing the establishment and progression of a wide range of diseases, such as diabetes, cardiovascular disease, and cancer. In 2016, International Agency for Research on Cancer reported that obesity is now associated with 13 different cancers, one of which is multiple myeloma (MM), a destructive cancer of plasma cells that predominantly reside in the bone marrow. Obesity is the accumulation of excess body fat, which causes metabolic, endocrine, immunologic, and inflammatory-like changes. Obesity is usually associated with an increase in visceral and/or subcutaneous fat; however, an additional fat depot that also responds to diet-induced changes is bone marrow adipose tissue (BMAT). There have been several studies over the past few decades that have identified BMAT as a key driver in MM progression. Adipocytes secrete numerous adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, which when secreted at normal controlled levels have protective properties. However, in obesity these levels of secretion change, coupled with an increase in adipocyte number and size causing a profound and lasting effect on the bone microenvironment, contributing to MM cell growth, survival, and migration as well as potentially fueling bone destruction. Obesity is a modifiable risk factor making it an attractive option for targeted therapy. This review discusses the link between obesity, monoclonal gammopathy of undetermined significance (a benign condition that precedes MM), and myeloma, and the contribution of key adipokines to disease establishment and progression. © 2018 Wiley Periodicals, Inc.

Co-existent sickle cell disease and juvenile rheumatoid arthritis. Two cases with delayed diagnosis and severe destructive arthropathy.

PubMed

Nistala, K; Murray, K J

2001-09-01

We describe 2 pediatric patients with sickle cell disease (SCD) who developed seropositive juvenile rheumatoid arthritis (JRA). Both patients have severe joint damage, the compound effect of both disease processes. The bone and cartilage destruction, which poses serious therapeutic challenges, highlights the difficulty of making a diagnosis of chronic inflammatory disease in the setting of SCD. There may be a correlation between increased levels of tumor necrosis factor-alpha in the synovial tissue of joints damaged by arthritis and local sickling. The resultant ischemia and corresponding inflammatory infiltrates could in turn worsen existing synovial proliferation and cartilage destruction as well as trigger further sickling.

Non-destructive and destructive investigation of aged-in-the field carbon FRP-wrapped columns.

DOT National Transportation Integrated Search

2011-06-01

The common practice of applying deicing salts on highway bridges increases the potential of reinforcing steel in these structures to experience extensive corrosion in the decks as well as the substructure. A new rehabilitation method which is believe...

[Breast cancer metastasis in distal phalanx of the big toe. Case report].

PubMed

Carlesimo, B; Tempesta, M; Fioramonti, P; Bistoni, G; Ruggiero, M; Marchetti, F

2009-01-01

Breast cancer represents the most prevalent malignancies in women and bone is the first site of metastasis in 26-50% of cases. Usually metastasis involve limbs in 16%. We present a rare case of 47-year-old woman, who underwent to monolateral mastectomy for lobular cancer. After 8 years from surgery, she presented pain, swelling and functional limitations, gradually increasing, to the left big toe. X-rays and MRI showed a lucent area of bone destruction on the shaft of the distal phalanx of the left big toe. Surgical biopsy on the excised bone assessed for breast cancer metastasis.

Reconstructing the Life of an Unknown (ca. 500 Years-Old South American Inca) Mummy – Multidisciplinary Study of a Peruvian Inca Mummy Suggests Severe Chagas Disease and Ritual Homicide

PubMed Central

Panzer, Stephanie; Peschel, Oliver; Haas-Gebhard, Brigitte; Bachmeier, Beatrice E.; Pusch, Carsten M.; Nerlich, Andreas G.

2014-01-01

The paleopathological, paleoradiological, histological, molecular and forensic investigation of a female mummy (radiocarbon dated 1451–1642 AD) provides circumstantial evidence for massive skull trauma affecting a young adult female individual shortly before death along with chronic infection by Trypanosoma cruzi (Chagas disease). The mummy (initially assumed to be a German bog body) was localized by stable isotope analysis to South America at/near the Peruvian/Northern Chilean coast line. This is further supported by New World camelid fibers attached to her plaits, typical Inca-type skull deformation and the type of Wormian bone at her occiput. Despite an only small transverse wound of the supraorbital region computed tomography scans show an almost complete destruction of face and frontal skull bones with terrace-like margins, but without evidence for tissue reaction. The type of destruction indicates massive blunt force applied to the center of the face. Stable isotope analysis indicates South American origin: Nitrogen and hydrogen isotope patterns indicate an extraordinarily high marine diet along with C4-plant alimentation which fits best to the coastal area of Pacific South America. A hair strand over the last ten months of her life indicates a shift to a more “terrestric” nutrition pattern suggesting either a move from the coast or a change in her nutrition. Paleoradiology further shows extensive hypertrophy of the heart muscle and a distended large bowel/rectum. Histologically, in the rectum wall massive fibrosis alternates with residual smooth muscle. The latter contains multiple inclusions of small intracellular parasites as confirmed by immunohistochemical and molecular ancient DNA analysis to represent a chronic Trypanosoma cruzi infection. This case shows a unique paleopathological setting with massive blunt force trauma to the skull nurturing the hypothesis of a ritual homicide as previously described in South American mummies in an individual that suffered from severe chronic Chagas disease. PMID:24586848

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.

Cancer pain physiology

PubMed Central

Falk, Sarah; Bannister, Kirsty

2014-01-01

Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells. This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined to the mouse femur. This model prompted related approaches, and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer-induced bone pain results in progressive bone destruction, elevated osteoclast activity and distinctive nocifensive behaviours (indicating the triad of ongoing, spontaneous and movement-induced hyperalgesia). In addition, cancer cells induce an inflammatory infiltrate and release growth factors, cytokines, interleukins, chemokines, prostanoids and endothelins, resulting in a reduction of pH to below 5 and direct deformation of primary afferents within bone. These peripheral changes, in turn, drive hypersensitivity of spinal cord sensory neurons, many of which project to the parts of the brain involved in the emotional response to pain. Within the spinal cord, a unique neuronal function reorganization within segments of the dorsal horn of the spinal cord receiving nociceptive input from the bone are discussed. Changes in certain neurotransmitters implicated in brain modulation of spinal function are also altered with implications for the affective components of cancer pain. Treatments are described in terms of mechanistic insights and in the case of opioids, which modulate pain transmission at spinal and supraspinal sites, their use can be compromised by opioid-induced hyperalgesia. We discuss evidence for how this comes about and how it may be treated. PMID:26516549

Particle-induced osteolysis in three-dimensional micro-computed tomography.

PubMed

Wedemeyer, Christian; Xu, Jie; Neuerburg, Carl; Landgraeber, Stefan; Malyar, Nasser M; von Knoch, Fabian; Gosheger, Georg; von Knoch, Marius; Löer, Franz; Saxler, Guido

2007-11-01

Small-animal models are useful for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening after total joint replacement. Microstructural changes associated with particle-induced osteolysis have been extensively explored using two-dimensional (2D) techniques. However, relatively little is known regarding the 3D dynamic microstructure of particle-induced osteolysis. Therefore, we tested micro-computed tomography (micro-CT) as a novel tool for 3D analysis of wear debris-mediated osteolysis in a small-animal model of particle-induced osteolysis. The murine calvarial model based on polyethylene particles was utilized in 14 C57BL/J6 mice randomly divided into two groups. Group 1 received sham surgery, and group 2 was treated with polyethylene particles. We performed 3D micro-CT analysis and histological assessment. Various bone morphometric parameters were assessed. Regression was used to examine the relation between the results achieved by the two methods. Micro-CT analysis provides a fully automated means to quantify bone destruction in a mouse model of particle-induced osteolysis. This method revealed that the osteolytic lesions in calvaria in the experimental group were affected irregularly compared to the rather even distribution of osteolysis in the control group. This is an observation which would have been missed if histomorphometric analysis only had been performed, leading to false assessment of the actual situation. These irregularities seen by micro-CT analysis provide new insight into individual bone changes which might otherwise be overlooked by histological analysis and can be used as baseline information on which future studies can be designed.

Lessons from rare diseases of cartilage and bone.

PubMed

Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan

2015-06-01

Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction. Copyright © 2015 Elsevier Ltd. All rights reserved.

IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats

PubMed Central

Yago, Toru; Nanke, Yuki; Kawamoto, Manabu; Furuya, Takefumi; Kobashigawa, Tsuyoshi; Kamatani, Naoyuki; Kotake, Shigeru

2007-01-01

This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction. IL-23 induced human osteoclastogenesis in cultures of PBMC in the absence of osteoblasts or exogenous soluble-receptor activator of NF-kappaB ligand (RANKL). This IL-23-induced osteoclastogenesis was inhibited by osteoprotegerin, anti-IL-17 antibody, and etanercept, suggesting that RANKL, IL-17, and TNF-alpha are involved. In addition, we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23. The inductive effect of IL-17 and the inhibitory effect of IFN-gamma on osteoclastogenesis indicate that the balance of these two cytokines is particularly important. We also demonstrated that IL-23 administered at a later stage significantly reduced paw volume in rats with collagen-induced arthritis, in a dose-dependent manner. Furthermore, anti-IL-23 antibody reduced synovial tissue inflammation and bone destruction in these rats. These findings suggest that IL-23 is important in human osteoclastogenesis and that neutralizing IL-23 after onset of collagen-induced arthritis has therapeutic potential. Thus, controlling IL-23 production and function could be a strategy for preventing inflammation and bone destruction in patients with rheumatoid arthritis. PMID:17888176

IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats.

PubMed

Yago, Toru; Nanke, Yuki; Kawamoto, Manabu; Furuya, Takefumi; Kobashigawa, Tsuyoshi; Kamatani, Naoyuki; Kotake, Shigeru

2007-01-01

This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction. IL-23 induced human osteoclastogenesis in cultures of PBMC in the absence of osteoblasts or exogenous soluble-receptor activator of NF-kappaB ligand (RANKL). This IL-23-induced osteoclastogenesis was inhibited by osteoprotegerin, anti-IL-17 antibody, and etanercept, suggesting that RANKL, IL-17, and TNF-alpha are involved. In addition, we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23. The inductive effect of IL-17 and the inhibitory effect of IFN-gamma on osteoclastogenesis indicate that the balance of these two cytokines is particularly important. We also demonstrated that IL-23 administered at a later stage significantly reduced paw volume in rats with collagen-induced arthritis, in a dose-dependent manner. Furthermore, anti-IL-23 antibody reduced synovial tissue inflammation and bone destruction in these rats. These findings suggest that IL-23 is important in human osteoclastogenesis and that neutralizing IL-23 after onset of collagen-induced arthritis has therapeutic potential. Thus, controlling IL-23 production and function could be a strategy for preventing inflammation and bone destruction in patients with rheumatoid arthritis.

[Clinical, pathological and imaging features of primary pelvic Ewing's sarcoma].

PubMed

Liu, J; Chen, Y; Ling, X L; Gong, Y; Ding, J P; Zhang, Z K; Wang, Y J

2016-07-19

To explore the clinical, pathological and imaging features of Ewing's sarcoma in pelvis and to improve knowledge and diagnosis of the disease. A retrospective analysis of the clinical, pathological and imaging data of pathologically confirmed 13 cases of Ewing's sarcoma in pelvis was carried out between May 2008 and March 2016 in the Affiliated Hospital of Hangzhou Normal University, the Third Hospital of Hebei Medical University and the Second Hospital of Hebei Medical University. The median age 13 cases of pelvic primary Ewing's sarcoma was 17 years old.The X-ray and CT imagings showed osteolytic and mixed bone destruction, CT showed mixed type in 10 cases, 8 cases of bone tumors as a flocculent, 10 cases of bone expansion failure, 10 cases of periosteal reaction, the layered 5 cases, radial in 5 cases.Thirteen cases showed soft tissue mass, soft tissue mass was equal or slightly lower density.Four cases showed heterogeneous contrast enhancement.The lesions showed low signal in T1WI and mixed high signal in T2WI of magnetic resonance imaging(MRI). The boundary of the lesions were obscure, and 5 cases had patchy necrosis area, and 9 cases had incomplete false capsule, surrounding soft tissue was violated.Four cases showed heterogeneous contrast enhancement after MRI enhancement scan. The age of onset of Ewing's sarcoma of the pelvis is more concentrated in about 15 years.The imaging feaures are mixed bone destruction and more bone is swelling and permeability damage, soft tissue mass is larger, bone tumor is cloudy or acicular, periosteal reaction in a layered and radial, most cases show that the false envelope is not complete.Combined with clinical and imaging examination, the diagnosis of the disease can be made.

Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes

PubMed Central

Glowacki, Andrew J.; Yoshizawa, Sayuri; Jhunjhunwala, Siddharth; Vieira, Andreia E.; Garlet, Gustavo P.; Sfeir, Charles; Little, Steven R.

2013-01-01

The hallmark of periodontal disease is the progressive destruction of gingival soft tissue and alveolar bone, which is initiated by inflammation in response to an invasive and persistent bacterial insult. In recent years, it has become apparent that this tissue destruction is associated with a decrease in local regulatory processes, including a decrease of forkhead box P3-expressing regulatory lymphocytes. Accordingly, we developed a controlled release system capable of generating a steady release of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22), composed of a degradable polymer with a proven track record of clinical translation, poly(lactic-co-glycolic) acid. We have previously shown that this sustained presentation of CCL22 from a point source effectively recruits regulatory T cells (Tregs) to the site of injection. Following administration of the Treg-recruiting formulation to the gingivae in murine experimental periodontitis, we observed increases in hallmark Treg-associated anti-inflammatory molecules, a decrease of proinflammatory cytokines, and a marked reduction in alveolar bone resorption. Furthermore, application of the Treg-recruiting formulation (fabricated with human CCL22) in ligature-induced periodontitis in beagle dogs leads to reduced clinical measures of inflammation and less alveolar bone loss under severe inflammatory conditions in the presence of a diverse periodontopathogen milieu. PMID:24167272

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.

Cyclophilin A (CypA) is associated with the inflammatory infiltration and alveolar bone destruction in an experimental periodontitis

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

Liu, Lihua; Li, Chengzhang, E-mail: l56cz@hotmail.com; Department of Periodontology, School and Hospital of Stomatology, Wuhan University, 237 Luo Yu Road, Hongshan District, Wuhan 430079

2010-01-01

Background and objective: CypA is able to regulate inflammatory responses and MMPs production via interaction with its cell surface receptor, EMMPRIN. This study aimed to address the possible association of CypA with pathological inflammation and destruction of periodontal tissues, and whether CypA-EMMPRIN interaction exists in periodontitis. Materials and methods: Experimental periodontitis was induced by ligation according to our previous method. Histological and radiographic examinations were performed. Western blot was used to detect CypA and EMMPRIN expressions in gingival tissues. Immunohistochemistry was applied for CypA, EMMPRIN, MMP-1, MMP-2, MMP-9, as well as cell markers of macrophage, lymphocyte and neutrophil. CypA expression,more » alveolar bone loss, and inflammatory infiltrations were quantified followed by correlation analyses. Results: Western blot revealed that CypA and EMMRPIN expressions were dramatically elevated in inflamed gingival tissues (ligature group) as compared to healthy gingival tissues (control group). The enhanced CypA and EMMPRIN expressions were highly consistent in cell localization on seriate sections. They were permanently co-localized in infiltrating macrophages and lymphocytes, as well as osteoclasts and osteoblasts in interradicular bone, but rarely expressed by infiltrating neutrophils. MMP-1, MMP-2, and MMP-9 expressions were also sharply increased in inflamed gingiva. MMP-2 and MMP-9 were mainly over-expressed by macrophages, while MMP-1 was over-produced by fibroblasts and infiltrating cells. The number of CypA-positive cells was strongly correlated with the ACJ-AC distance (r = 0.839, p = 0.000), the number of macrophages (r = 0.972, p = 0.000), and the number of lymphocytes (r = 0.951, p = 0.000). Conclusion: CypA is associated with the inflammatory infiltration and alveolar bone destruction of periodontitis. CypA-EMMPRIN interaction may exist in these pathological processes.« less

Spontaneous and bilateral avascular necrosis of the navicula: Müller-Weiss disease.

PubMed

Aktaş, Erdem; Ayanoğlu, Tacettin; Hatipoğlu, Yasin; Kanatlı, Ulunay

2016-12-01

Although, trauma, foot deformity (pesplanovalgus), systemic diseases such as diabetes mellitus and lupus, drugs (steroids, antineoplastic) and excessive alcohol consumption have all been accused in the etiology of avascular necrosis of the tarsal bones, spontaneous avascular necrosis of the navicular bone, especially in adults, is a rare entity. In this article, we report a 50-year-old female patient with bilateral, spontaneous avascular necrosis of the navicular bone and related severe talonavicular arthrosis. Clinical and radiological findings were concordant with Müller-Weiss disease, which is a rare disease with complex idiopathic foot condition of the adult tarsal navicular bone characterized by progressive navicular fragmentation and talonavicular joint destruction. The patient was successfully treated with two-staged bilateral talonavicular arthrodesis.

Microsurgical and Endoscopic Anatomy for Intradural Temporal Bone Drilling and Applications of the Electromagnetic Navigation System: Various Extensions of the Retrosigmoid Approach.

PubMed

Matsushima, Ken; Komune, Noritaka; Matsuo, Satoshi; Kohno, Michihiro

2017-07-01

The use of the retrosigmoid approach has recently been expanded by several modifications, including the suprameatal, transmeatal, suprajugular, and inframeatal extensions. Intradural temporal bone drilling without damaging vital structures inside or beside the bone, such as the internal carotid artery and jugular bulb, is a key step for these extensions. This study aimed to examine the microsurgical and endoscopic anatomy of the extensions of the retrosigmoid approach and to evaluate the clinical feasibility of an electromagnetic navigation system during intradural temporal bone drilling. Five temporal bones and 8 cadaveric cerebellopontine angles were examined to clarify the anatomy of retrosigmoid intradural temporal bone drilling. Twenty additional cerebellopontine angles were dissected in a clinical setting with an electromagnetic navigation system while measuring the target registration errors at 8 surgical landmarks on and inside the temporal bone. Retrosigmoid intradural temporal bone drilling expanded the surgical exposure to allow access to the petroclival and parasellar regions (suprameatal), internal acoustic meatus (transmeatal), upper jugular foramen (suprajugular), and petrous apex (inframeatal). The electromagnetic navigation continuously guided the drilling without line of sight limitation, and its small devices were easily manipulated in the deep and narrow surgical field in the posterior fossa. Mean target registration error was less than 0.50 mm during these procedures. The combination of endoscopic and microsurgical techniques aids in achieving optimal exposure for retrosigmoid intradural temporal bone drilling. The electromagnetic navigation system had clear advantages with acceptable accuracy including the usability of small devices without line of sight limitation. Copyright © 2017 Elsevier Inc. All rights reserved.

Yin and Yang of mesenchymal stem cells and aplastic anemia

PubMed Central

Broglie, Larisa; Margolis, David; Medin, Jeffrey A

2017-01-01

Acquired aplastic anemia (AA) is a bone marrow failure syndrome characterized by peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without treatment, most commonly from infection or hemorrhage. Current treatments focus on suppressing immune-mediated destruction of bone marrow stem cells or replacing hematopoietic stem cells (HSCs) by transplantation. Our incomplete understanding of the pathogenesis of AA has limited development of targeted treatment options. Mesenchymal stem cells (MSCs) play a vital role in HSC proliferation; they also modulate immune responses and maintain an environment supportive of hematopoiesis. Some of the observed clinical manifestations of AA can be explained by mesenchymal dysfunction. MSC infusions have been shown to be safe and may offer new approaches for the treatment of this disorder. Indeed, infusions of MSCs may help suppress auto-reactive, T-cell mediated HSC destruction and help restore an environment that supports hematopoiesis. Small pilot studies using MSCs as monotherapy or as adjuncts to HSC transplantation have been attempted as treatments for AA. Here we review the current understanding of the pathogenesis of AA and the function of MSCs, and suggest that MSCs should be a target for further research and clinical trials in this disorder. PMID:29321823

A Novel Videography Method for Generating Crack-Extension Resistance Curves in Small Bone Samples

PubMed Central

Katsamenis, Orestis L.; Jenkins, Thomas; Quinci, Federico; Michopoulou, Sofia; Sinclair, Ian; Thurner, Philipp J.

2013-01-01

Assessment of bone quality is an emerging solution for quantifying the effects of bone pathology or treatment. Perhaps one of the most important parameters characterising bone quality is the toughness behaviour of bone. Particularly, fracture toughness, is becoming a popular means for evaluating bone quality. The method is moving from a single value approach that models bone as a linear-elastic material (using the stress intensity factor, K) towards full crack extension resistance curves (R-curves) using a non-linear model (the strain energy release rate in J-R curves). However, for explanted human bone or small animal bones, there are difficulties in measuring crack-extension resistance curves due to size constraints at the millimetre and sub-millimetre scale. This research proposes a novel “whitening front tracking” method that uses videography to generate full fracture resistance curves in small bone samples where crack propagation cannot typically be observed. Here we present this method on sharp edge notched samples (<1 mm×1 mm×Length) prepared from four human femora tested in three-point bending. Each sample was loaded in a mechanical tester with the crack propagation recorded using videography and analysed using an algorithm to track the whitening (damage) zone. Using the “whitening front tracking” method, full R-curves and J-R curves could be generated for these samples. The curves for this antiplane longitudinal orientation were similar to those found in the literature, being between the published longitudinal and transverse orientations. The proposed technique shows the ability to generate full “crack” extension resistance curves by tracking the whitening front propagation to overcome the small size limitations and the single value approach. PMID:23405186

Lupus pernio: a clinico-radiological study of thirty-five cases.

PubMed

Spiteri, M A; Matthey, F; Gordon, T; Carstairs, L S; James, D G

1985-03-01

Thirty-five patients with lupus pernio were observed in a series of 818 patients with clinical and histological evidence of sarcoidosis. This analysis provides the natural history of lupus pernio and its associated clinico-radiographic features. There was intrathoracic involvement in 74% of patients, upper respiratory tract disease in 54%, reticulo-endothelial involvement in 54%, bone cysts in 43% and ocular lesions in 37%. It predominated in West Indies-born women. Histological confirmation was easily obtained by nasal mucosal biopsy and this could be repeated serially to evaluate the response to various treatments. Nasal bone radiographs showed destruction of the nasal bones, porosis and alteration in bone texture. Peripheral bone cysts were evident in 50% of patients who were radiographed, and in about 50% of these patients, the cysts were found in both hands and feet.

Management of Recurrent Post-partum Pregnancy Tumor with Localized Chronic Periodontitis.

PubMed

Reddy, N Raghavendra; Kumar, P Mohan; Selvi, Tamil; Nalini, H Esther

2014-05-01

Pregnancy tumor is a benign, hyperplastic lesion of the gingiva, considered to be reactive or traumatic rather than neoplastic in nature. The term pyogenic granuloma is a misnomer as it is not filled with pus or granulomatous tissue histologically. It is multi factorial in nature, which shows an exaggerated response to stimuli such as low grade or chronic irritation, trauma or hormonal variations. Higher levels of sex hormones during pregnancy produce effects on sub gingival microflora, the immune system, the vasculature and specific cells of periodontium which in turn in the presence of local irritants exaggerate the lesion. Since the lesion is clinically indistinguishable from other type of hyperplastic conditions, histological findings are required for proper diagnosis. We present a case report of recurrent pyogenic tumor which showed the evidence of pre-existing localized periodontitis with extensive horizontal bone destruction. The lesion was excised by electrocautery combined with conventional flap procedure after parturition period. During 3 and 6 months follow-up period post-operative healing showed satisfactory results without recurrence.

Disseminated talc granulomatosis. An unusual finding in a patient with acquired immunodeficiency syndrome and fatal cytomegalovirus infection.

PubMed

Lewis, J H; Sundeen, J T; Simon, G L; Schulof, R S; Wand, G S; Gelfand, R L; Miller, H; Garrett, C T; Jannotta, F S; Orenstein, J M

1985-02-01

The association of disseminated magnesium silicate talc granulomatosis and acquired immunodeficiency syndrome is reported in a male homosexual who used intravenous drugs and who died of overwhelming cytomegalovirus (CMV) infection. Autopsy findings included widespread deposition of talc crystals in the lungs, liver, lymph nodes, bone marrow, and spleen. Typical CMV inclusions were seen in the lungs, kidneys, adrenal glands, gastrointestinal tract, and right eye. There was no evidence of malignancy. Analysis of peripheral blood neutrophil function revealed impaired chemotaxis and chemokinesis, but opsonophagocytosis had remained normal. The CMV infection in the small bowel was extensive and resulted in severe destruction of the muscularis propria and neural plexi, leading to marked dilatation and persistent diarrhea. The terminal course was marked by intractable hypotension, pneumonitis, and malnutrition, which could be attributed respectively to CMV involvement of the adrenal glands, lungs, and small bowel. The etiology and possible role of systemic talc granulomatosis in the development of immunosuppressive illness is reported herein.

Amyloid-producing odontogenic tumour (calcifying epithelial odontogenic tumour) in the mandible of a Bengal tiger (Panthera tigris tigris).

PubMed

Kang, M-S; Park, M-S; Kwon, S-W; Ma, S-A; Cho, D-Y; Kim, D-Y; Kim, Y

2006-01-01

A 13-year-old male tiger (Panthera tigris tigris) had a marked mandibular swelling noticed 12 months earlier and associated with progressive anorexia and weight loss. Radiological and post-mortem examination revealed a mass (13x15 cm) which was firm and poorly defined, with destruction of the adjacent bone tissue. Histologically, the mass was poorly demarcated, with infiltrative growth, and composed of nests, cords and islands of epithelial cells with characteristic basal cell features. Also observed were extensive squamous metaplasia, ghost cells, stellate reticulum, and fibroblastic connective tissue stroma containing inflammatory cells. A prominent feature of this tumour consisted of abundant nodular deposits of congophilic amyloid-like material with partial mineralization (Liesegang rings). Immunohistochemically, the neoplastic cells and the amyloid-like material were positive for pancytokeratin and negative for vimentin. The findings supported the diagnosis of an amyloid-producing odontogenic tumour (APOT), also known as calcifying epithelial odontogenic tumour in man and animals.

Treatment outcomes of temporal bone osteoradionecrosis.

PubMed

Kammeijer, Quinten; van Spronsen, Erik; Mirck, Piet G B; Dreschler, Wouter A

2015-04-01

To investigate the clinical relevance of the classification systems used for temporal bone osteoradionecrosis (ORN) and to define a treatment protocol for temporal bone ORN. Retrospective case series. Amsterdam, department of otorhinolaryngology and head and neck surgery. Classification of temporal bone ORN was performed through use of clinical data and radiologic imaging. Outcomes of conservative and surgical treatment were investigated and compared for different grades of ORN. Of the 49 ears included in this study, 35 were primarily treated conservatively. At start of conservative treatment, 23 were classified as a localized and 8 as a diffuse form of ORN; 4 could not be classified. There was a significant difference in clinical outcome between the localized and diffuse forms of ORN (χ(2) = 5.862, P = .015), and mastoid air cell destruction on preoperative computed tomography scan was found to be a significant predictor for a negative outcome of conservative treatment (χ(2) = 4.34, P = .037). Fourteen ears with diffuse ORN were primarily treated surgically, and 11 were secondarily treated surgically following a period of conservative treatment. Twenty-two patients were treated with subtotal petrosectomy, of which 20 were cured. Three patients were treated with canal wall down mastoidectomy, and 2 had recurrence of disease. Ramsden's classification system is clinically relevant in predicting conservative treatment outcomes. Mastoid air cell destruction on computed tomography differentiates between the localized and diffuse forms of ORN. Given our results and experience with treating temporal bone ORN, we propose a treatment protocol. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Non-inflammatory destructive periodontal disease: a clinical, microbiological, immunological and genetic investigation

PubMed Central

REPEKE, Carlos Eduardo; CARDOSO, Cristina Ribeiro; CLAUDINO, Marcela; SILVEIRA, Elcia Maria; TROMBONE, Ana Paula Favaro; CAMPANELLI, Ana Paula; SILVA, João Santana; MARTINS JÚNIOR, Walter; GARLET, Gustavo Pompermaier

2012-01-01

Periodontitis comprises a group of multifactorial diseases in which periodontopathogens accumulate in dental plaque and trigger host chronic inflammatory and immune responses against periodontal structures, which are determinant to the disease outcome. Although unusual cases of non-inflammatory destructive periodontal disease (NIDPD) are described, their pathogenesis remains unknown. A unique NIDPD case was investigated by clinical, microbiological, immunological and genetic tools. The patient, a non-smoking dental surgeon with excessive oral hygiene practice, presented a generalized bone resorption and tooth mobility, but not gingival inflammation or occlusion problems. No hematological, immunological or endocrine alterations were found. No periodontopathogens (A. actinomycetemcomitans, P. gingivalis, F. nucleatum and T. denticola) or viruses (HCMV, EBV-1 and HSV-1) were detected, along with levels of IL-1β and TNF-α in GCF compatible with healthy tissues. Conversely ALP, ACP and RANKL GCF levels were similar to diseased periodontal sites. Genetic investigation demonstrated that the patient carried some SNPs, as well HLA-DR4 (*0404) and HLA-B27 alleles, considered risk factors for bone loss. Then, a less vigorous and diminished frequency of toothbrushing was recommended to the patient, resulting in the arrest of alveolar bone loss, associated with the return of ALP, ACP and RANKL in GCF to normality levels. In conclusion, the unusual case presented here is compatible with the previous description of NIDPD, and the results that a possible combination of excessive force and frequency of mechanical stimulation with a potentially bone loss prone genotype could result in the alveolar bone loss seen in NIDPD. PMID:22437688

Decursin from Angelica gigas suppresses RANKL-induced osteoclast formation and bone loss.

PubMed

Wang, Xin; Zheng, Ting; Kang, Ju-Hee; Li, Hua; Cho, Hyewon; Jeon, Raok; Ryu, Jae-Ha; Yim, Mijung

2016-03-05

Osteoclasts are the only cells capable of breaking down bone matrix, and excessive activation of osteoclasts is responsible for bone-destructive diseases. In this study, we investigated the effects of decursin from extract of Angelica gigas root on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation using mouse bone marrow-derived macrophages (BMMs). Decursin inhibited RANKL-induced osteoclast formation without cytotoxicity. In particular, decursin maintains the characteristics of macrophages by blocking osteoclast differentiation by RANKL. Furthermore, the RANKL-stimulated bone resorption was diminished by decursin. Mechanistically, decursin blocked the RANKL-triggered ERK mitogen-activated protein kinases (MAPK) phosphorylation, which results in suppression of c-Fos and the nuclear factor of activated T cells (NFATc1) expression. In accordance with the in vitro study, decursin reduced lipopolysaccharide (LPS)- or ovariectomy (OVX)-induced bone loss in vivo. Therefore, decursin exerted an inhibitory effect on osteoclast formation and bone loss in vitro and in vivo. Decursin could be useful for the treatment of bone diseases associated with excessive bone resorption. Copyright © 2016 Elsevier B.V. All rights reserved.

Radiographic bone loss in a Scottish non-smoking Type 1 Diabetes mellitus population; a Bitewing Radiographic Study.

PubMed

Plessas, Anastasios; Robertson, Douglas P; Hodge, Penny J

2018-05-15

The dental complications of uncontrolled diabetes include reduced salivary flow rate, candidiasis and periodontal manifestations. A recent meta-analysis concluded that diabetes patients have a significantly higher severity, but not extent, of destructive periodontal disease than non-diabetes people. The authors reported that most type-1 diabetes studies using dental radiographic data have not controlled for confounding factors such as smoking. The aim of this cross-sectional study was to compare radiographic alveolar bone loss between type 1 diabetes (T1DM) and non-diabetes (NDM) participants in a Scottish non-smoking population. Digital bitewing radiographs for 174 Scottish adult never or ex-smoker (> 5 years) participants (108 T1DM, 66 NDS), recruited from outpatient clinics throughout Greater Glasgow and Clyde, were included in the analysis. A single blinded, trained and calibrated examiner recorded the radiographic bone loss seen on bitewing radiographs using the digital screen caliper. The bone loss was measured as the distance between the cemento-enamel junction (CEJ) and the deepest radiographic alveolar bone margin interproximally of each tooth. T1DM participants had more radiographic alveolar bone loss throughout the all teeth measured (median:1.27 mm vs 1.06 mm, P < 0.001) and more than a two fold increase in the risk of having sites with ≥2 mm periodontal destruction (OR = 2.297, 95%CI 1.058-4.986, P = 0.036) compared with non-diabetes subjects. Patients suffering from type 1 diabetes are at higher risk of periodontitis even when controlling for multiple possible confounding factors and this difference can be detected on routine dental radiographs at an early stage. These data confirm radiographically the previously reported association between T1DM and periodontal bone loss. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

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

PubMed Central

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

2014-01-01

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

Surprising origin of two carved bones donated to the Buchenwald Memorial Museum.

PubMed

Gapert, René

2018-03-28

Unidentified bones were donated to the Buchenwald Memorial Museum in Weimar, Germany. The donor thought the bones may have belonged to internees of the concentration camp and had been decoratively carved by camp personnel. Non-destructive forensic anthropological examination was carried out on the bones to identify their possible origin. Comparative human and non-human bones samples were used to determine the provenance of the bones and the anatomical region they may have come from. Literature and internet searches were conducted to trace the origin of the carved motifs on the bones. The bones were determined to belong to the lower limb region of bovids. The carvings were found to correspond with those of existing bone examples found in some museums in the UK. They were traced to German prisoners of war dating to the First World War. An in-depth examination of the donated bones revealed their non-human provenance. It further showed that no link existed between the bones, internees of the concentration camp, and the time of the camp's existence. It was discovered that they belonged to the period 1914-1918 and form an important part of German prisoner of war history in the UK.

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

NASA Astrophysics Data System (ADS)

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

2014-11-01

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

Wound ballistics of injuries caused by handguns with different types of projectiles.

PubMed

von See, Constantin; Stuehmer, Alexander; Gellrich, Nils-Claudius; Blum, Katrin S; Bormann, Kai-Hendrik; Rücker, Martin

2009-07-01

There are considerable differences in the shape and composition of military and civilian projectiles. Five different projectiles with the same kinetic energy were fired into the heads of freshly sacrificed pigs (n=30) through the submental region in the occipital direction. Computed tomography (CT) and 3D face scans of the animal skulls were obtained before and after firing. The image data sets were fused and provided the basis for a quantitative analysis of destruction patterns. As a result of the destruction of the parietal bone at the potential exit site, there were significant volume difference between the Action 4 (6.45 +/- 3.42 ml) and the Hydra-Shok projectile (12.71 +/- 2.86 ml). The partial metal-jacketed projectile showed a minor increase in volume (4.89 +/- 1.47 ml) and a partial loss of soft projectile components. Radiology showed differences between the various projectiles in fragmentation and bone and soft-tissue destruction. Although the projectiles had the same kinetic energy, there were considerable differences in injury patterns between full metal-jacketed projectiles, which are the only projectiles permitted for military use under the Geneva Conventions, and the other investigated projectiles. These injuries present a major medical challenge to both first responders and surgeons.

Hominid cranial bone structure: a histological study of Omo 1 specimens from Ethiopia using different microscopic techniques.

PubMed

Bartsiokas, Antonis

2002-05-01

The microstructure of a hominid cranial vault has not previously been studied to determine its tissue histology, and differences in comparison with that of modern humans. We selected the parietals of Omo-Kibish 1, regarded as one of the oldest (about 130,000 years old) anatomically modern humans, and Omo 1 (Howell), which is a very recent human (about 2,000 years old)-both from the same area of Ethiopia. A combination of macrophotography, polarizing microscopy in the incident and transmission illumination mode, and confocal laser scanning microscopy (CLSM) was employed to examine thin sections, as well as polished and unpolished block faces of unembedded bone fragments, to minimize specimen destruction as much as possible. The methods enabled remarkably detailed information on bone microstructure and remodeling to be gleaned from tiny fragments of bone. The best method for examining fossilized human bones was shown to be that of incident light microscopy, which was the least destructive while producing the most amount of information. Unless the above methods are used, bone-filling minerals, such as calcite, can cause erroneous estimations of bone thickness, as observations with the naked eye or even a magnifying glass cannot determine the limit between the cortex and the diploe. This is particularly important for sciences such as paleoanthropology, in which, for instance, a thick cranial bone of Homo erectus may be confused with a pathological one of H. sapiens and vice versa. Cross sections of parietal bones revealed differences between Omo-Kibish 1 and Omo 1 (Howell) in diploic histology and in the relative thickness between the cortex and diploe, with the former specimen having an H. erectus ratio despite its H. sapiens gross anatomy. Omo-Kibish 1 may still retain some affinities with H. erectus despite its being classified as H. sapiens. Newly described histological structures, such as the reverse type II osteons, the multicanalled osteons, and the osteocytomata are presented here. A modern human skeletal anatomy does not necessarily imply a modern human cranial bone histology. The outer circumferential lamellae of cranial bones are in essence growth lines. Cranial histology of hominids may provide useful information concerning their taxonomy and life history, including such factors as growth rate, developmental stress, and diet. Copyright 2002 Wiley-Liss, Inc.

Septal Cartilage/Ethmoid Bone Composite Graft: A New and Improved Method for the Correction Underdeveloped Nasal Septum in Patients with Short Noses.

PubMed

Lee, Soo Hyang; Koo, Mun Geun; Kang, Eun Taek

2017-04-01

Septal extension grafts are an effective means of extending nasal length in patients with a short nose. However, such grafts can be challenging in patients who only have small quantities of weak septal cartilage, such as some East Asian patients. We developed a rhinoplasty technique using ethmoid bone to create a cartilage-bone complex to overcome this issue, allowing adequate nasal lengthening. Sixty-four women with short noses and inadequate septal cartilage determined by preoperative computed tomography underwent septal extension grafting with a cartilage-bone complex between January 2009 and December 2014. Septal cartilage and ethmoid bone were harvested during open rhinoplasty and secured to the septal cartilage. Most patients were in their twenties or thirties. All patients underwent septal extension grafting using a cartilage-bone complex and dorsal augmentation with silicone implants. Short nasal length, decreased nasolabial angle and increased nostril show, were rectified. There was no recurrence during a mean follow-up period of 12.3 months, although one patient (1.5%) requested revision surgery. Septal extension grafting with a cartilage-bone complex can be used to correct a short nose, especially in Asians who have relatively small amounts of septal cartilage. The ethmoid bone augments the inadequate septum and provides structural support. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Diagnosis and treatment of diffuse tenosynovial giant cell tumor arising from temporomandibular joints].

PubMed

Meng, J H; Guo, Y X; Luo, H Y; Guo, C B; Ma, X C

2016-12-18

To retrospectively analyze the clinical features, treatment and prognosis to the diffuse tenosynovial giant cell tumor (D-TSGCT) arising from the temporomandibular joint (TMJ), and to give a reference for the early diagnosis and treatment of this disease. In this study, 15 patients finally diagnosed as D-TSGCT of TMJ histopathologically at the Peking University Hospital of Stomatology from October 2003 to August 2015 were selected and reviewed. Their clinical manifestations, imaging and histological features, diagnoses and differential diagnoses, treatments and follow-ups were summarized and discussed. D-TSGCT of TMJ showed obvious female predominance (12/15), the main symptoms included painful preauricular swelling or mass, limited mouth-opening and mandibular deviation with movement. D-TSGCT on computed tomography (CT) scan often showed ill-defined soft tissue masses around TMJ, enhancement after contrast administration, usually with widening of the joint spaces and with bone destruction of the condyle, the fossa and even the skull base. On magnetic resonance images (MRI), the majority of lesions on T1 weighted images and T2 weighted images both showed the characteristics of low signals (6/11). The lesions could extend beyond the joints (9/11) and into the infratemporal fossa (4/11) and the middle cranial fossa (4/11). Surgical resection was performed in 14 cases and biopsy in 1 case. Postoperative radiotherapy was performed in 3 cases. In follow-ups, 3 cases showed recurrence postoperatively. D-TSGCT arising from TMJ should be differentiated with TMJ disorders, other tumors and tumor-like lesions of TMJ and parotid neoplasms, etc. CT and MRI examinations have important values in the diagnosis and treatment design of D-TSGCT. Because of the local aggressive and extensive behavior, complete resection should be performed as soon as possible. Postoperative radiotherapy was helpful for the extensive lesions including destruction of skull base and may be a good supplementary therapy. Because of the possibility of recurrence and malignancy, long-term follow-up was suggested.

The physiopathology of avascular necrosis of the femoral head: an update.

PubMed

Guerado, Enrique; Caso, Enrique

2016-12-01

The physiopathology of the femoral head bone necrosis is similar for children and for adults. The disease is characterized by apoptosis of bone cells - bone marrow and bone forming cells-resulting in head collapse with a subsequent lesion of the overlying cartilage, and therefore flattening of the rounded surface shape of the head articulating with the acetabulum, provoking, eventually, secondary osteoarthritis. When the disease becomes clinically evident already destructive phenomena have occurred and collapse will eventually ensue. In children, because epiphyseal cartilage has growth capabilities, lost epiphyseal height can be recovered, however in adults collapse is irreversible. In this paper the physiopathology of this disease is examined as well as its implication for treatment. Prevention by genetic studies is discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Vertebral aneurysmatic bone cyst: study of three cases].

PubMed

Vale, Benjamim Pessoa; Alencar, Francisco José; de Aguiar, Guilherme Brasileiro; de Almeida, Bruno Ribeiro

2005-12-01

Aneurysmatic bone cyst is a hypervascularized, benign lesion locally destructive by its progressive growth with greater incidence in the second decade of life. It lodges preferably in the long bones and vertebrae. The clinical picture varies from pain to local edema and even neurological symptoms when in vertebral location. Three cases of vertebral aneurysmatic bone cyst occurring in childhood and all with neurologic deficit symptoms are described. Computerized tomography and/or magnetic resonance imaging confirmed the diagnosis. Patients underwent surgery to remove the tumor. In one of the cases, pre-operative selective arterial embolization of the lesion was performed. The three patients progressed satisfactorily with neurological improvement, which demonstrated the efficiency of the microsurgical technique for the resection of the spinal tumor. The evolution of the cases and the current treatment are discussed.

Electromagnetic irradiation may be a new approach to therapy for peri-implantitis.

PubMed

Cao, Zhensheng; Chen, Yijia; Chen, Yuxue; Zhao, Qing; Xu, Xiaomei; Chen, Yangxi

2012-03-01

Peri-implantitis can lead to bone destruction around a dental implant through inflammation and immune reactions caused by bacteria adhering to the surface of the implant abutment. Electromagnetic irradiation can inhibit bacterial growth, increase bone formation, decrease bone resorption and reduce the inflammatory response. Our hypothesis is that electromagnetic irradiation may be a new treatment approach for peri-implantitis and may simultaneously maintain bone mass around the dental implant. The results would be more significant when combined with other agents, because the effect of some antibiotics and anti-inflammatory drugs is strengthened by electromagnetic irradiation. This non-invasive therapy is expected to be conducted in a convenient manner, and even by patients at home, thereby facilitating the prevention and treatment of peri-implantitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Primary pericranial Ewing's sarcoma on the temporal bone: A case report.

PubMed

Kawano, Hiroto; Nitta, Naoki; Ishida, Mitsuaki; Fukami, Tadateru; Nozaki, Kazuhiko

2016-01-01

Primary Ewing's sarcoma originating in the pericranium is an extremely rare disease entity. A 9-year-old female patient was admitted to our department due to a left temporal subcutaneous mass. The mass was localized under the left temporal muscle and attached to the surface of the temporal bone. Head computed tomography revealed a mass with bony spicule formation on the temporal bone, however, it did not show bone destruction or intracranial invasion. F-18 fluorodeoxyglucose positron emission tomography showed no lesions other than the mass on the temporal bone. Magnetic resonance imaging showed that the mass was located between the temporal bone and the pericranium. The mass was completely resected with the underlying temporal bone and the overlying deep layer of temporal muscle, and was diagnosed as primary Ewing's sarcoma. Because the tumor was located in the subpericranium, we created a new classification, "pericranial Ewing's sarcoma," and diagnosed the present tumor as pericranial Ewing's sarcoma. We herein present an extremely rare case of primary pericranial Ewing's sarcoma that developed on the temporal bone.

Metal ions from S‐PRG filler have the potential to prevent periodontal disease

PubMed Central

Iwamatsu‐Kobayashi, Yoko; Abe, Syouta; Fujieda, Yoshiyasu; Orimoto, Ai; Kanehira, Masafumi; Handa, Keisuke; Venkataiah, Venkata Suresh; Zou, Wei; Ishikawa, Masaki

2017-01-01

Abstract The surface pre‐reacted glass ionomer (S‐PRG) filler, a component of composite resin, is capable of releasing metal ions that possess antibacterial activity against caries and periodontal pathogens. Although S‐PRG has been suggested to be involved in oral disease prevention, no reports have been published regarding its preventive effect on periodontal disease in vivo. The present study investigated whether the eluate from S‐PRG (S‐PRG eluate) has a suppressive effect on tissue destruction induced in a mouse model of ligature‐induced periodontal disease. Twenty‐seven C57BL/6 mice were divided into three groups of nine animals each, no ligature group (Lig(−)), ligature group (Lig(+)S‐PRG(−)) and ligature with S‐PRG eluate group (Lig(+)S‐PRG(+)). Alveolar bone loss was evaluated using micro‐computed tomography scanning. Histologic changes were detected by hematoxylin and eosin staining. The infiltration of inflammatory cells was assessed by Ly6G and F4/80 staining immunohistochemically. The distribution of metal ions was detected by time‐of‐flight secondary ion mass spectrometry. S‐PRG eluate clearly inhibited alveolar bone loss and bone density. The histological analysis revealed that S‐PRG eluate reduced destruction of the collagen bundle in the periodontal ligament and the infiltration of inflammatory cells. Immunohistochemical analysis showed that the S‐PRG eluate significantly suppressed the number of infiltrating neutrophils and macrophages. Time‐of‐flight secondary ion mass spectrometry analysis revealed that more boron ions were present in the Lig(+)S‐PRG(+) group than in the Lig(+)S‐PRG(−) group. Our results suggest that the S‐PRG eluate has a preventive effect against tissue destruction in periodontal disease through its anti‐inflammatory effects in vivo. PMID:29744190

Shoulder arthrodesis with a reconstruction plate

PubMed Central

Byeon, Hwa Kyo

2008-01-01

From 1995 to 2005, arthrodesis with a reconstruction plate was performed for eight shoulders. The average follow-up period was 44 months. The indications for shoulder arthrodesis were joint destruction as a sequel of tuberculous arthritis, malignant bone tumour, pyogenic arthritis, failed arthrodesis and paralysis of the brachial plexus. The evaluation criteria included bony union and pain. Two cases of malignant tumour required an homologous bone graft due to severe bone deficit—a fracture that occurred in the distal part of the arthrodesed shoulder after removing the plate. With the exception of these two cases, severe pain or other complications did not occur in any other case. Shoulder arthrodesis with a reconstruction plate was judged to be a useful method for glenohumeral salvage in cases without severe bone deficit. Further, additional treatment methods should be considered to prevent fracture that may occur as a result of severe bone deficit. PMID:18716728

Cochlear pathology in chronic suppurative otitis media.

PubMed

Walby, A P; Barrera, A; Schuknecht, H F

1983-01-01

Chronic suppurative otitis media (COM) is reported to cause elevation of bone-conduction thresholds either by damage to cochlear sensorineural structures or by alteration in the mechanics of sound transmission in the ear. A retrospective study was made of the medical records of 87 patients with unilateral uncomplicated COM to document that abnormality in bone conduction does exist. In a separate study the cochlear pathology in 12 pairs of temporal bones with unilateral COM was studied by light microscopy. Infected ears showed higher than normal mean bone-conduction thresholds by amounts ranging from 1 dB at 500 Hz to 9.5 dB at 4,000 Hz. The temporal bones showed no greater loss of specialized sensorineural structures in infected ears than in normal control ears. Because there is no evidence that COM caused destruction of hair cells or cochlear neurons, alteration in the mechanics of sound transmission becomes a more plausible explanation for the hearing losses.

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.

[Reconstruction of tangential and circular infected bone defects].

PubMed

Schmidt, H G; Neikes, M; Zimmer, W

1987-12-01

In the treatment of bone infections the reconstruction and rehabilitation of bone defects is a problem that often requires treatment secondary to curative treatment of the infection. For the reconstruction of smaller and more extensive defects we used predominantly (92.7%) autogenous (autologous) untreated spongiosa and in only 7% of the cases allogenic (homologous) spongiosa from an organ bank, this being added if necessary. Recently the additionally introduced vascularized bone chip has become a useful extension of the therapy concept. The problems and complications of defect reconstruction are demonstrated for 705 cases of bone infection with 472 defects of different sizes, based on a comprehensive classification with defect calculation. Surgical technical approach and special aspects of after-treatment are described, as well as the results for every group of cases. We achieved stability and freedom from infection in a total of 93.7% of the patients. As was to be expected, the problems grow with the size of the defect. Particularly problematic are joint infections with adjacent extensive circular defect.

Expression profile of osteoprotegerin, RANK and RANKL genes in the femoral head of patients with avascular necrosis.

PubMed

Samara, Stavroula; Dailiana, Zoe; Chassanidis, Christos; Koromila, Theodora; Papatheodorou, Loukia; Malizos, Konstantinos N; Kollia, Panagoula

2014-02-01

Femoral head avascular necrosis (AVN) is a recalcitrant disease of the hip that leads to joint destruction. Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B (RANK) and RANK ligand (RANKL) regulate the balance between osteoclasts-osteoblasts. The expression of these genes affects the maturation and function of osteoblasts-osteoclasts and bone remodeling. In this study, we investigated the molecular pathways leading to AVN by studying the expression profile of OPG, RANK and RANKL genes. Quantitative Real Time-PCR was performed for evaluation of OPG, RANK and RANKL expression. Analysis was based on parallel evaluation of mRNA and protein levels in normal/necrotic sites of 42 osteonecrotic femoral heads (FHs). OPG and RANKL protein levels were estimated by western blotting. The OPG mRNA levels were higher (insignificantly) in the necrotic than the normal site (p > 0.05). Although the expression of RANK and RANKL was significantly lower than OPG in both sites, RANK and RANKL mRNA levels were higher in the necrotic part than the normal (p < 0.05). Protein levels of OPG and RANKL showed no remarkable divergence. Our results indicate that differential expression mechanisms for OPG, RANK and RANKL that could play an important role in the progress of bone remodeling in the necrotic area, disturbing bone homeostasis. This finding may have an effect on the resulting bone destruction and the subsequent collapse of the hip joint. Copyright © 2013. Published by Elsevier Inc.

Atypical hereditary sensory and autonomic neuropathy type IV with neither mental retardation nor pain insensitivity.

PubMed

Jung, Chae Lim; Ki, Chang-Seok; Kim, Byoung Joon; Lee, Jong-Hyuck; Sung, Ki-Sun; Kim, Jong-Won; Park, Youn-Soo

2013-12-01

Hereditary sensory and autonomic neuropathy type IV is an autosomal recessive disorder characterized by severe mental retardation and self-mutilation-related complications. Recently, we investigated a 16-year-old Korean boy with normal intelligence. He had preserved pain sensation but was suspected of having hereditary sensory and autonomic neuropathy type IV because of the recurrent bone fractures and painless joint destruction in the absence of any predisposing medical conditions. Genetic analysis of the NTRK1 gene revealed compound heterozygous mutations including c.851-33T>A and c.2303C>T (p.Pro768Leu) in the NTRK1 gene. The p.Pro768Leu mutation has been identified in 2 Japanese patients with a mild phenotype. Therefore, although it is rare, hereditary sensory and autonomic neuropathy type IV should be considered in patients with recurrent bone fractures and painless joint destruction who do not have any predisposing conditions even when they do not have typical clinical features such as mental retardation or pain insensitivity.

Direct dating of human fossils.

PubMed

Grün, Rainer

2006-01-01

The methods that can be used for the direct dating of human remains comprise of radiocarbon, U-series, electron spin resonance (ESR), and amino acid racemization (AAR). This review gives an introduction to these methods in the context of dating human bones and teeth. Recent advances in ultrafiltration techniques have expanded the dating range of radiocarbon. It now seems feasible to reliably date bones up to 55,000 years. New developments in laser ablation mass spectrometry permit the in situ analysis of U-series isotopes, thus providing a rapid and virtually non-destructive dating method back to about 300,000 years. This is of particular importance when used in conjunction with non-destructive ESR analysis. New approaches in AAR analysis may lead to a renaissance of this method. The potential and present limitations of these direct dating techniques are discussed for sites relevant to the reconstruction of modern human evolution, including Florisbad, Border Cave, Tabun, Skhul, Qafzeh, Vindija, Banyoles, and Lake Mungo. (c) 2006 Wiley-Liss, Inc.

[Secondary telangiectatic osteosarcoma of the left femur. A case presentation of an unusual course of disease].

PubMed

Zajonz, D; Werner, M; Panzert, S; Strübing, A S; Tiepolt, S; Fabsits, E; Brandmaier, P; Heyde, C-E; Prietzel, T

2014-05-01

This article presents the unusual case of a 73-year-old male patient who was treated with primary interlocking nailing after a pathological femoral fracture. Despite comprehensive diagnostics including several biopsies, a tumor could not be detected. In 2008 when progressive cystic femoral destruction leading to loosening of the nail necessitated a partial femoral prosthesis, an osteosarcoma could first be diagnosed in the resected bone. Advanced progression of the tumor required an extended hip exarticulation. During the current restaging of the now 84-year-old patient no tumor could be detected. When a malignancy cannot be excluded even by repeated biopsies of radiologically suspicious structures, an adequate tumor staging followed by close monitoring should be carried out. For a clinically silent, long-term course of cystic destruction of a long bone over several years, an age over 60 years and a lack of distant metastases, an atypical osteosarcoma should be considered in the differential diagnosis.

Zingiber officinale: A Potential Plant against Rheumatoid Arthritis

PubMed Central

Al-Nahain, Abdullah; Jahan, Rownak

2014-01-01

Rheumatoid arthritis (RA) is an autoimmune disease particularly affecting elderly people which leads to massive bone destruction with consequent inflammation, pain, and debility. Allopathic medicine can provide only symptomatic relief. However, Zingiber officinale is a plant belonging to the Zingiberaceae family, which has traditionally been used for treatment of RA in alternative medicines of many countries. Many of the phytochemical constituents of the rhizomes of this plant have therapeutic benefits including amelioration of RA. This review attempts to list those phytochemical constituents with their reported mechanisms of action. It is concluded that these phytochemicals can form the basis of discovery of new drugs, which not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction. As the development of RA is a complex process, further research should be continued towards elucidating the molecular details leading to RA and drugs that can stop or reverse these processes by phytoconstituents of ginger. PMID:24982806

Bone structure studies with holographic interferometric nondestructive testing and x-ray methods

NASA Astrophysics Data System (ADS)

Silvennoinen, Raimo; Nygren, Kaarlo; Rouvinen, Juha; Petrova, Valentina V.

1994-02-01

Changes in the biomechanics and in the molecular texture and structure of isolated radioulnar bones of subadult European moose (Alces alces L.) collected in various environmentally polluted areas of Finland were investigated by means of holographic interferometric non- destructive testing (HNDT), radiological, morphometrical, and x-ray diffraction methods. By means of small caudal-cranial bending forces, the surface movements of the lower end (distal epiphysis) of the radial bone were recorded with the HNDT method. To study bone molecular texture and structure changes under external compressing forces, the samples for x-ray diffraction analysis were taken from the upper end of the ulnar bone (olecranon tip). Results showed that the bones obtained from the Harjavalta area and those of North Karelian moose showing malnutrition and healing femoral fractures produced different HNDT pictures compared with the four normally developed North Karelian moose. In the x-ray diffraction, the Harjavalta samples showed changes in molecular texture and structure compared with the samples from the apparently normal North Karelian animals.

Changed morphology and mechanical properties of cancellous bone in the mandibular condyles of edentate people.

PubMed

Giesen, E B W; Ding, M; Dalstra, M; van Eijden, T M G J

2004-03-01

Since edentate subjects have a reduced masticatory function, it can be expected that the morphology of the cancellous bone of their mandibular condyles has changed according to the altered mechanical environment. In the present study, the morphology of cylindrical cancellous bone specimens of the mandibular condyles of edentate subjects (n = 25) was compared with that of dentate subjects (n = 24) by means of micro-computed tomography and by the application of Archimedes' principle. Stiffness and strength were determined by destructive mechanical testing. Compared with dentate subjects, it appeared that, in edentate subjects, the bone was less dense and the trabecular structure was less plate-like. The regression models of stiffness and strength built from bone volume fraction and the trabecular orientation relative to the axis of the specimen were similar for both dentate and edentate subjects. This indicates that, under reduced mechanical load, the fundamental relationship between bone morphology and mechanical properties does not change.

Giant cell tumour 2nd metatarsal-Result with en-bloc excision and autologous fibular grafting.

PubMed

Agarwal, Saurabh; Chawla, Sumit; Agarwal, Sippy; Agarwal, Puneet

2015-12-01

Giant cell tumour (GCT) of the small bones is relatively uncommon tumour. It occurs most commonly in the distal portions of femur and radius and proximal end of tibia. GCT of small bones presents at advanced stages with major bony destruction. These tumours represent more aggressive course; associated with increased local recurrence rates (40%) and metastasis. Various treatment modalities like en-bloc resection, cryosurgery, intralesional curettage with burring/phenolization or bone cement are available. In our case en-bloc resection with reconstruction using nonvascular autogenous fibular strut graft was used in patient of 2nd metatarsal GCT and a favourable functional outcome was observed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes.

PubMed

Espinoza, J Luis; Kotecha, Ritesh; Nakao, Shinji

2017-01-01

Acquired bone marrow failure syndromes encompass a unique set of disorders characterized by a reduction in the effective production of mature cells by the bone marrow (BM). In the majority of cases, these syndromes are the result of the immune-mediated destruction of hematopoietic stem cells or their progenitors at various stages of differentiation. Microbial infection has also been associated with hematopoietic stem cell injury and may lead to associated transient or persistent BM failure, and recent evidence has highlighted the potential impact of commensal microbes and their metabolites on hematopoiesis. We summarize the interactions between microorganisms and the host immune system and emphasize how they may impact the development of acquired BM failure.

Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes

PubMed Central

Espinoza, J. Luis; Kotecha, Ritesh; Nakao, Shinji

2017-01-01

Acquired bone marrow failure syndromes encompass a unique set of disorders characterized by a reduction in the effective production of mature cells by the bone marrow (BM). In the majority of cases, these syndromes are the result of the immune-mediated destruction of hematopoietic stem cells or their progenitors at various stages of differentiation. Microbial infection has also been associated with hematopoietic stem cell injury and may lead to associated transient or persistent BM failure, and recent evidence has highlighted the potential impact of commensal microbes and their metabolites on hematopoiesis. We summarize the interactions between microorganisms and the host immune system and emphasize how they may impact the development of acquired BM failure. PMID:28286502

IMAGING DIAGNOSIS-MAGNETIC RESONANCE IMAGING FEATURES OF CRANIOMANDIBULAR OSTEOPATHY IN AN AIREDALE TERRIER.

PubMed

Matiasovic, Matej; Caine, Abby; Scarpante, Elena; Cherubini, Giunio Bruto

2016-05-01

An Airedale Terrier was presented for evaluation of depression and reluctance to be touched on the head. Magnetic resonance (MR) imaging of the head was performed. The images revealed bone lesions affecting the calvarium at the level of the coronal suture and left mandibular ramus, with focal cortical destruction, expansion, and reactive new bone formation. Skull lesions were hypointense on T1-weighted sequences, hyperintense on T2-weighted sequences, and showed an intense and homogeneous enhancement after gadolinium administration. Reactive new bone formation and periosteal proliferation were confirmed histopathologically. The clinical signs, imaging findings, and histopathological examination were consistent with craniomandibular osteopathy. © 2015 American College of Veterinary Radiology.

Identification of Prevotella in pedal osteomyelitis of a diabetic patient.

PubMed

Dominiak, Barbara J; Oxberry, William; Chen, Patrick C

2003-01-01

Osteomyelitis in a diabetic patient with a nonhealing foot ulcer, multiple medical conditions, and recurrent hospitalization for antibiotic therapy was found to be associated with gram-negative bacteria Prevotella melanginoganica and Prevotella melaninoganica hemagglutinating variant. Those organisms were identified due to the morphologically distinct features in electron microscopy and sequencing of the genes after Polymerase chain reaction amplification from the pathological material. The bacteria invaded the bone and resided in osteocyte, osteoblast, and endothelial cells. The bacteria are usually associated with periodontal plaques, causing inflammation and destruction of gingival tissue and resorption of the alveolar bone. This is the first ultrastructural and molecular study of a diabetic bone lesion with anaerobic bacterial infection.

Non-destructive inspection in industrial equipment using robotic mobile manipulation

NASA Astrophysics Data System (ADS)

Maurtua, Iñaki; Susperregi, Loreto; Ansuategui, Ander; Fernández, Ane; Ibarguren, Aitor; Molina, Jorge; Tubio, Carlos; Villasante, Cristobal; Felsch, Torsten; Pérez, Carmen; Rodriguez, Jorge R.; Ghrissi, Meftah

2016-05-01

MAINBOT project has developed service robots based applications to autonomously execute inspection tasks in extensive industrial plants in equipment that is arranged horizontally (using ground robots) or vertically (climbing robots). The industrial objective has been to provide a means to help measuring several physical parameters in multiple points by autonomous robots, able to navigate and climb structures, handling non-destructive testing sensors. MAINBOT has validated the solutions in two solar thermal plants (cylindrical-parabolic collectors and central tower), that are very demanding from mobile manipulation point of view mainly due to the extension (e.g. a thermal solar plant of 50Mw, with 400 hectares, 400.000 mirrors, 180 km of absorber tubes, 140m height tower), the variability of conditions (outdoor, day-night), safety requirements, etc. Once the technology was validated in simulation, the system was deployed in real setups and different validation tests carried out. In this paper two of the achievements related with the ground mobile inspection system are presented: (1) Autonomous navigation localization and planning algorithms to manage navigation in huge extensions and (2) Non-Destructive Inspection operations: thermography based detection algorithms to provide automatic inspection abilities to the robots.

Endoscopic treatment by snare electrocoagulation prior to Nd:YAG laser photocoagulation in 85 voluminous colorectal villous adenomas.

PubMed

Aubert, A; Meduri, B; Fritsch, J; Aime, F; Baglin, A; Barbagelata, M

1991-05-01

The association of endoscopic resection with Nd:YAG laser photocoagulation was used to treat benign colorectal villous adenomas. Eight-five patients were included: 49 with surgical contraindications, 35 for whom surgical resection appeared to be too hazardous, and 1 who refused surgery. Forty-five tumors had an axial extension between 1 and 3 cm, and 40 tumors had an axial extension of at least 4 cm. Diathermic snare resection was performed to remove large tumoral fragments prior to laser photocoagulation of the residual flat lesions. Treatments were repeated every 15 days until total tumor destruction was achieved. A carcinoma was detected in biopsy specimens obtained during endoscopic treatment of five patients. Two patients were lost to follow-up. Treatment results could be analyzed in 78 patients. Successful treatment was achieved in 67 patients. Tumor destruction was complete in 77 percent of patients who had lesions of at least 4 cm diameter and in 93 percent of patients with smaller lesions. The axial extension of the tumor was the main factor affecting the results of treatment. No major complications occurred. During the average 103-week follow-up period, 21 percent of the patients with total tumor destruction had a recurrence. The risk of recurrence was correlated with the number of initial treatment sessions and previous surgery treatment. It would appear that the treatment with endoscopic resection prior to Nd:YAG laser photocoagulation is a safe and effective method in the destruction of colorectal villous adenomas.

Novel Therapy for Bone Regeneration in Large Segmental Defects

DTIC Science & Technology

2016-10-01

reamed and nonreamed intrame- dullary nailing on fracture healing. Clin Orthop Relat Res. 1998;355(Suppl):S230–8. 37. Pape HC, Giannoudis PV. Fat embolism ...extension period (Year 4). 15. SUBJECT TERMS Bone healing, bone morphogenetic protein (BMP), thrombopoietin (TPO), therapy, fracture healing, bone...Bone healing, bone morphogenetic protein (BMP), thrombopoietin (TPO), therapy, fracture healing, bone regeneration, minipig, pig 3. OVERALL PROJECT

Roughness and wettability effect on histological and mechanical response of self-drilling orthodontic mini-implants.

PubMed

Espinar-Escalona, Eduardo; Bravo-Gonzalez, Luis-Alberto; Pegueroles, Marta; Gil, Francisco Javier

2016-06-01

Self-drilling orthodontic mini-implants can be used as temporary devices for orthodontic treatments. Our main goal was to evaluate surface characteristics, roughness and wettability, of surface modified mini-implants to increase their stability during orthodontic treatment without inducing bone fracture and tissue destruction during unscrewing. Modified mini-implants by acid etching, grit-blasting and its combination were implanted in 20 New Zealand rabbits during 10 weeks. After that, the bone-to-implant (BIC) parameter was determined and the torque during unscrewing was measured. The surface characteristics, roughness and wettability, were also measured, onto modified Ti c.p. discs. Acid-etched mini-implants (R a ≈ 1.7 μm, contact angle (CA) ≈ 66°) significantly improved the bone-to-implant parameter, 26 %, compared to as-machined mini-implants (R a ≈ 0.3 μm, CA ≈ 68°, BIC = 19 %) due to its roughness. Moreover, this surface treatment did not modify torque during unscrewing due to their statistically similar wettability (p > 0.05). Surface treatments with higher roughness and hydrophobicity (R a ≈ 4.5 μm, CA ≈ 74°) lead to a greater BIC and to a higher removal torque during unscrewing, causing bone fracture, compared to as-machined mini-implants. Based on these in vivo findings, we conclude that acid-etching surface treatment can support temporary anchoring of titanium mini-implants. This treatment represents a step forward in the direction of reducing the time prior to mini-implant loading by increasing their stability during orthodontic treatment, without inducing bone fracture and tissue destruction during unscrewing.

Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis.

PubMed

Ford, Caleb A; Cassat, James E

2017-09-01

Osteomyelitis, a common and debilitating invasive infection of bone, is a frequent complication following orthopedic surgery and causes pathologic destruction of skeletal tissues. Bone destruction during osteomyelitis results in necrotic tissue, which is poorly penetrated by antibiotics and can serve as a nidus for relapsing infection. Osteomyelitis therefore frequently necessitates surgical debridement procedures, which provide a unique opportunity for targeted delivery of antimicrobial and adjunctive therapies. Areas covered: Following surgical debridement, tissue voids require implanted materials to facilitate the healing process. Antibiotic-loaded, non-biodegradable implants have been the standard of care. However, a new generation of biodegradable, osteoconductive materials are being developed. Additionally, in the face of widespread antimicrobial resistance, alternative therapies to traditional antibiotic regimens are being investigated, including bone targeting compounds, antimicrobial surface modifications of orthopedic implants, and anti-virulence strategies. Expert commentary: Recent advances in biodegradable drug delivery scaffolds make this technology an attractive alternative to traditional techniques for orthopedic infection that require secondary operations for removal. Advances in novel treatment methods are expanding the arsenal of viable antimicrobial treatment strategies in the face of widespread drug resistance. Despite a need for large scale clinical investigations, these strategies offer hope for future treatment of this difficult invasive disease.

Advances in the Local and Targeted Delivery of Anti-infective Agents for Management of Osteomyelitis

PubMed Central

Ford, Caleb A.; Cassat, James E.

2018-01-01

Structured Abstract Introduction Osteomyelitis, a common and debilitating invasive infection of bone, is a frequent complication following orthopedic surgery and causes pathologic destruction of skeletal tissues. Bone destruction during osteomyelitis results in necrotic tissue, which is poorly penetrated by antibiotics and can serve as a nidus for relapsing infection. Osteomyelitis therefore frequently necessitates surgical debridement procedures, which provide a unique opportunity for targeted delivery of antimicrobial and adjunctive therapies. Areas Covered Following surgical debridement, tissue voids require implanted materials to facilitate the healing process. Antibiotic-loaded, non-biodegradable implants have been the standard of care. However, a new generation of biodegradable, osteoconductive materials are being developed. Additionally, in the face of widespread antimicrobial resistance, alternative therapies to traditional antibiotic regimens are being investigated, including bone targeting compounds, antimicrobial surface modifications of orthopedic implants, and anti-virulence strategies. Expert Commentary Recent advances in biodegradable drug delivery scaffolds make this technology an attractive alternative to traditional techniques for orthopedic infection that require secondary operations for removal. Advances in novel treatment methods are expanding the arsenal of viable antimicrobial treatment strategies in the face of widespread drug resistance. Despite a need for large scale clinical investigations, these strategies offer hope for future treatment of this difficult invasive disease. PMID:28837368

Integrated approach to pain management for a patient with multiple bone metastases of uterine cervical cancer.

PubMed

Qin, De-An; Song, Jie-Fu; Song, Li-Ping; Feng, Gui-Sheng

2018-05-01

Background Pain management for multiple bone metastases is complex and often requires multidisciplinary treatment. We herein describe patient-centered multidisciplinary pain management for metastatic cancer. A 61-year-old woman with multiple bone metastases of uterine cervical cancer developed intractable low back pain. After external beam radiotherapy failed, we performed lumbar spinal intralesional curettage, pedicle screw fixation, and nerve decompression. However, the neuralgia persisted. We then percutaneously injected epirubicin into the intervertebral foramina under computed tomography guidance for L5 dorsal root ganglion destruction. Osteoplasty was performed under C-arm X-ray guidance; however, the sacrum was mistaken for the ilium, and treatment was ineffective. We administered zoledronic acid and strontium-89. The last resort was outpatient implantation of an epidural bupivacaine-morphine infusion system. A visual analog scale (VAS) was used for pain evaluation. Lumbar spinal intralesional curettage and fixation, epirubicin-induced ganglion destruction, and administration of zoledronic acid and strontium-89 decreased her VAS pain score from 7-8 to 3-4. Radiotherapy and nerve decompression and release were ineffective, as was osteoplasty because of the location error. The epidural infusion system decreased the VAS score from 7-8 to 2-3 and was highly efficient. Conclusions Multidisciplinary integrated treatment for metastatic cancer can be effective.

The pleotropic role of statins: Could it be the imminent host modulation agent in periodontics?

PubMed

Grover, Harpreet Singh; Luthra, Shailly; Maroo, Shruti; Maroo, Niteeka

2013-03-01

Periodontal disease is a chronic inflammatory disease which represents a primarily anaerobic Gram-negative oral infection that results in gingival inflammation, loss of attachment, bone destruction. Bacterial endotoxins in the form of lipopolysaccharides (LPS) that are instrumental in generating a host-mediated tissue destructive immune response by mobilizing their defensive cells and releasing cytokines like Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6), which lead to tissue destruction by stimulating the production of the collagenolytic enzymes: Matrix metalloproteinases (MMPs). Since the host-mediated tissue destruction is to be controlled, various means have been employed for modulating this response. Statins, 3-hydroxy-3-methylglutarylcoenzyme A (HMG CoA) reductase inhibitors, besides having lipid-lowering abilities also have antioxidant, antithrombotic, anti-inflammatory, immunomodulatory and osteomodulatory properties. All of these pleiotropic effects of statins point out to it perhaps becoming the novel host modulation agent in periodontics.

The pleotropic role of statins: Could it be the imminent host modulation agent in periodontics?

PubMed Central

Grover, Harpreet Singh; Luthra, Shailly; Maroo, Shruti; Maroo, Niteeka

2013-01-01

Periodontal disease is a chronic inflammatory disease which represents a primarily anaerobic Gram-negative oral infection that results in gingival inflammation, loss of attachment, bone destruction. Bacterial endotoxins in the form of lipopolysaccharides (LPS) that are instrumental in generating a host-mediated tissue destructive immune response by mobilizing their defensive cells and releasing cytokines like Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6), which lead to tissue destruction by stimulating the production of the collagenolytic enzymes: Matrix metalloproteinases (MMPs). Since the host-mediated tissue destruction is to be controlled, various means have been employed for modulating this response. Statins, 3-hydroxy-3-methylglutarylcoenzyme A (HMG CoA) reductase inhibitors, besides having lipid-lowering abilities also have antioxidant, antithrombotic, anti-inflammatory, immunomodulatory and osteomodulatory properties. All of these pleiotropic effects of statins point out to it perhaps becoming the novel host modulation agent in periodontics. PMID:23946727

Metal-on-Metal Hip Retrieval Analysis: A Case Report

PubMed Central

Pace, Thomas B.; Rusaw, Kara A.; Minette, Lawrence J.; Shirley, Brayton R.; Snider, Rebecca G.; DesJardins, John D.

2013-01-01

This is a case report involving a single case with severe bone and soft tissue destruction in a young male patient with a 10-year-metal on-metal total hip arthroplasty. Following complete aseptic erosion of the affected hip greater trochanter and abductor muscles, the hip was revised for recurrent instability. Histological examination of the patient's periprosthetic tissues, serological studies, and review of recent medical reports of similar cases were used to support an explanation of the destructive process and better contribute to our understanding of human reaction to metal debris in some patients following metal-on-metal hip arthroplasty. PMID:23840999

Neuroimaging findings of extensive sphenoethmoidal dysplasia in NF1.

PubMed

Tam, Allison; Sliepka, Joseph M; Bellur, Sunil; Bray, Collin Douglas; Lincoln, Christie M; Nagamani, Sandesh C S

2018-05-16

Whereas isolated sphenoid wing dysplasia (SWD) is a well-known clinical feature in neurofibromatosis 1 (NF1), extensive cranial defects involving multiple bones have been rarely reported in this disorder. In this report, we describe the clinical course of a 20-year-old male with NF1 and an extensive cranial bone dysplasia. The large sphenoethmoidal defect was associated with transethmoidal and orbital cephalocele as well as inferolateral herniation of the frontal lobe. In spite of the large defect, the individual did not have any symptoms or complications resulting from the osteopathy. We review the current knowledge of the pathogenesis and management of cranial bone dysplasia in NF1. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of TGF-β in breast cancer bone metastases

PubMed Central

Chiechi, Antonella; Waning, David L.; Stayrook, Keith R.; Buijs, Jeroen T.; Guise, Theresa A.; Mohammad, Khalid S.

2014-01-01

Breast cancer is the most prevalent cancer among females worldwide leading to approximately 350,000 deaths each year. It has long been known that cancers preferentially metastasize to particular organs, and bone metastases occur in ~70% of patients with advanced breast cancer. Breast cancer bone metastases are predominantly osteolytic and accompanied by increased fracture risk, pain, nerve compression and hypercalcemia, causing severe morbidity. In the bone matrix, transforming growth factor-β (TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteoclastic bone resorption. TGF-β, in turn, stimulates bone metastatic tumor cells to secrete factors that further drive osteolytic bone destruction adjacent to the tumor. Thus, TGF-β is a crucial factor responsible for driving the feed-forward vicious cycle of cancer growth in bone. Moreover, TGF-β activates epithelial-to-mesenchymal transition, increases tumor cell invasiveness and angiogenesis and induces immunosuppression. Blocking the TGF-β signaling pathway to interrupt this vicious cycle between breast cancer and bone offers a promising target for therapeutic intervention to decrease skeletal metastasis. This review will describe the role of TGF-β in breast cancer and bone metastasis, and pre-clinical and clinical data will be evaluated for the potential use of TGF-β inhibitors in clinical practice to treat breast cancer bone metastases. PMID:24558636

Inflammatory arthritis and systemic bone loss are attenuated by gastrointestinal helminth parasites.

PubMed

Sarter, Kerstin; Kulagin, Manuel; Schett, Georg; Harris, Nicola L; Zaiss, Mario M

2017-05-01

Infections with different helminth species have been observed to ameliorate a variety of chronic inflammatory diseases. Herein, we show that the natural murine helminth species, Heligmosomoides polygyrus bakeri (Hp) is capable of attenuating disease severity in two different inflammatory arthritis models. Furthermore, we show that excretory-secretory (ES) products from Hp directly suppress osteoclast differentiation in vitro. Taken together, these results demonstrate that helminth infections can dampen autoimmune diseases and highlight a previously unrecognized and important role for ES products, by directly impacting on bone destruction.

Childhood bone tuberculosis from Roman Pécs, Hungary.

PubMed

Hlavenková, L; Teasdale, M D; Gábor, O; Nagy, G; Beňuš, R; Marcsik, A; Pinhasi, R; Hajdu, T

2015-02-01

A child from a Roman necropolis in Pécs, Hungary (4th century CE) was initially diagnosed with severe spinal osteomyelitis. The post-cranial skeleton displayed bone alterations in the lower thoracic and upper lumbar segments, including vertebral body destruction, collapse and sharp kyphosis, and additional multiple rib lesions, suggesting a most likely diagnosis of pulmonary and spinal tuberculosis. This study discusses a number of selected diagnoses in the context of our pathological findings, complementing the macroscopic examination with radiological and biomolecular analyses. Copyright © 2014 Elsevier GmbH. All rights reserved.

En bloc resection of huge cemento-ossifying fibroma of mandible: avoiding lower lip split incision.

PubMed

Ayub, Tahera; Katpar, Shahjahan; Shafique, Salman; Mirza, Talat

2011-05-01

Cemento-ossifying Fibroma (COF) is an osteogenic benign neoplasm affecting the jaws and other craniofacial bones. It commonly presents as a progressively slow growing pathology, which can sometimes attain an enormous size, causing facial deformity. A case of a huge cemento-ossifying fibroma, appearing as a mandibular dumbell tumour in a male patient is documented, which caused massive bone destruction and deformity. It was surgically removed by performing en bloc resection of mandible avoiding the splitting of lower lip incision technique, thereby maintaining his normal facial appearance.

Ultrastructural changes in osteocytes in microgravity conditions

NASA Astrophysics Data System (ADS)

Rodionova, N. V.; Oganov, V. S.; Zolotova, N. V.

We examined the histology and morphometry of biosamples (biopsies) of the iliac crest of monkeys, flown 14 days aboard the "Bion-11", using electron microscopy. We found, that some young osteocytes take part in the activization of collagen protein biosynthesis in the adaptive remodeling process of the bone tissue to microgravity conditions. Osteocyte lacunae filled with collagen fibrils; this correlates with fibrotic osteoblast reorganization in such zones. The osteolytic activity in mature osteocytes is intensified. As a result of osteocyte destruction, the quantity of empty osteocytic lacunae in the bone tissue increases.

Primary sacral hydatid cyst. A case report.

PubMed

Joshi, Nayana; Hernandez-Martinez, Alejandro; Seijas-Vazquez, Roberto

2007-10-01

This case report highlights an unusual osseous spinal presentation of a well described disease, hydatidosis. A 59-year-old woman presented with increasing back pain and bilateral radiculopathy. Examination disclosed symptoms of spinal stenosis and urinary incontinence. Radiographs showed an expansive lytic lesion affecting the pelvic bones with destruction of the bone cortex. Laboratory analyses were performed and the patient underwent CT and MRI studies. Serology for Echinococcus was positive. When assessing sciatica, low back pain or lower limb weakness the pelvic cavity should be examined for hidden disease that might explain the neurological symptoms. Hydatid disease of bone should be considered in the differential diagnosis of any bone mass discovered in the human body. Diagnosis was delayed in this case because the pelvic cavity was not studied when radiculopathy symptoms started and there was no coexisting visceral involvement.

High resolution MRI imaging at 9.4 Tesla of the osteochondral unit in a translational model of articular cartilage repair.

PubMed

Goebel, Lars; Müller, Andreas; Bücker, Arno; Madry, Henning

2015-04-16

Non-destructive structural evaluation of the osteochondral unit is challenging. Here, the capability of high-field magnetic resonance imaging (μMRI) at 9.4 Tesla (T) was explored to examine osteochondral repair ex vivo in a preclinical large animal model. A specific aim of this study was to detect recently described alterations of the subchondral bone associated with cartilage repair. Osteochondral samples of medial femoral condyles from adult ewes containing full-thickness articular cartilage defects treated with marrow stimulation were obtained after 6 month in vivo and scanned in a 9.4 T μMRI. Ex vivo imaging of small osteochondral samples (typical volume: 1-2 cm(3)) at μMRI was optimised by variation of repetition time (TR), time echo (TE), flip angle (FA), spatial resolution and number of excitations (NEX) from standard MultiSliceMultiEcho (MSME) and three-dimensional (3D) spoiled GradientEcho (SGE) sequences. A 3D SGE sequence with the parameters: TR = 10 ms, TE = 3 ms, FA = 10°, voxel size = 120 × 120 × 120 μm(3) and NEX = 10 resulted in the best fitting for sample size, image quality, scanning time and artifacts. An isovolumetric voxel shape allowed for multiplanar reconstructions. Within the osteochondral unit articular cartilage, cartilaginous repair tissue and bone marrow could clearly be distinguished from the subchondral bone plate and subarticular spongiosa. Specific alterations of the osteochondral unit associated with cartilage repair such as persistent drill holes, subchondral bone cysts, sclerosis of the subchondral bone plate and of the subarticular spongiosa and intralesional osteophytes were precisely detected. High resolution, non-destructive ex vivo analysis of the entire osteochondral unit in a preclinical large animal model that is sufficient for further analyses is possible using μMRI at 9.4 T. In particular, 9.4 T is capable of accurately depicting alterations of the subchondral bone that are associated with osteochondral repair.

Extensive BMI Gain in Puberty is Associated with Lower Increments in Bone Mineral Density in Estonian Boys with Overweight and Obesity: A 3-Year Longitudinal Study.

PubMed

Mengel, Eva; Tillmann, Vallo; Remmel, Liina; Kool, Pille; Purge, Priit; Lätt, Evelin; Jürimäe, Jaak

2017-08-01

The aim of this 3-year prospective study was to examine changes in bone mineral characteristics during pubertal maturation in boys with different BMI values at the beginning of puberty and with different BMI increments during puberty. 26 boys with overweight and obesity (OWB) and 29 normal weight boys (NWB) were studied yearly for 3 years from the age of 11 years to measure the changes in different bone mineral characteristics. The OWB group was further divided into two subgroups according to extensive or non-extensive BMI increment during 3-year period. OWB had higher (P < 0.01) baseline total body (TB) bone mineral density (BMD), TB bone mineral content (BMC), TB BMC for height, lumbar spine (LS) BMD, and LS BMC compared to NWB. Throughout the study period, OWB gained more TB BMD (P = 0.0001), TB BMC (P = 0.0048), TB BMC for height (P = 0.0124), LS BMD (P = 0.0029), and LS BMC (P = 0.0022) compared to NWB. Also during the study period, TB BMD (P = 0.0065), TB BMC (P = 0.0141), TB BMC for height (P = 0.0199), LS BMD (P = 0.0066), LS apparent volumetric BMD (BMAD) (P = 0.0075), and LS BMC (P = 0.017) increased significantly less in those OWB whose BMI increased more extensively. Extensive BMI gain is associated with lower increments in bone mineral characteristics in boys with overweight and obesity. Unfavorable increment in total body fat mass and percentage during pubertal years could be one reason for that.

A Gift or a Waste? Quintavalle, Surplus Embryos and the Abortion Act 1967.

PubMed

Cherkassky, Lisa

2017-07-01

The destruction of an embryo must be justified in law. This is to prevent frivolous wastage and to show the respect afforded by the Warnock Report (1984). For example, embryonic destruction during pregnancy is underpinned by the Abortion Act 1967, and embryonic destruction during fertility treatment is regulated by the Human Fertilisation and Embryology Act 1990. However, following the appeal decision in R (Quintavalle) v Human Fertilisation and Embryology Authority (and Secretary of State for Health) [2005] 2 A.C. 561, embryos can now be created for a bone marrow tissue match to a sick sibling under the Human Fertility and Embryology Act 1990 according to the subjective desires of the mother. This opens the door to the first example of embryonic destruction on unique social-eugenic grounds with no clear lawful justification. It is argued that these embryos should be afforded a unique destruction provision under an amended version of section 1(1)(a) of the Abortion Act 1967 in light of their 'social-eugenic' nature. This would protect the Human Fertilisation and Embryology Authority from accusations of undercover eugenic practices and reinstate the respect shown towards embryos in law.

Comparison of mechanical behavior between implant-simulated bone tissue and implant-jaw bone tissue interfaces based on Pull Out testing

NASA Astrophysics Data System (ADS)

Lopez, C.; Muñoz, J. C.; Pinillos, J. C.

2013-11-01

The main purpose of this research was to achieve a better understanding of the relationship within the mechanical properties of human cadaver jaw bone with kind D2 density regarding a substitute polymer to simulate bone tissue, proposed by the ASTM, to evaluate orthopedic implants. However, despite the existence of several densities of foams and his mechanical characterization has been classified into different degrees of tissue densities to simulate cancellous and cortical bone, the value of the densities are different contrasted with the densities of bone tissue, making difficult to establish direct relationship about mechanical behavior between the polymer and the bone material, and therefore no clear criteria known for choosing the polymeric foam which describes the mechanical behavior of tissue for a specific or particular study. To understand such behavior from bone tissue regarding the polymer samples, on this research was a dental implant inserted into the samples, and subjected to destructive Pull Out test according to ASTM F543The Pull Out strength was compared between implant-jawbone and implant-rigid polyurethane foam interfaces. Thus, the test pieces with mechanical behavior similar to bone tissue, enabling an approximation to choose degree appropriate of polymer to replace the bone tissue in future trials biomechanical.

Changes in the population of perivascular cells in the bone tissue remodeling zones under microgravity

NASA Astrophysics Data System (ADS)

Katkova, Olena; Rodionova, Natalia; Shevel, Ivan

2016-07-01

Microgravity and long-term hypokinesia induce reduction both in bone mass and mineral saturation, which can lead to the development of osteoporosis and osteopenia. (Oganov, 2003). Reorganizations and adaptive remodeling processes in the skeleton bones occur in the topographical interconnection with blood capillaries and perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel, Fee, 1980; Rodionova, 1989, 2006) have shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic. Hence the study of populations of perivascular stromal cells in areas of destructive changes is actual. Perivascular cells from metaphysis of the rat femoral bones under conditions of modeling microgravity were studied using electron microscopy and cytochemistry (hindlimb unloading, 28 days duration) and biosatellite «Bion-M1» (duration of flight from April 19 till May 19, 2013 on C57, black mice). It was revealed that both control and test groups populations of the perivascular cells are not homogeneous in remodeling adaptive zones. These populations comprise of adjacent to endothelium poorly differentiated forms and isolated cells with signs of differentiation (specific increased volume of rough endoplasmic reticulum in cytoplasm). Majority of the perivascular cells in the control group (modeling microgravity) reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In poorly differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of experimental animals reaction to the alkaline phosphatase is registered not in all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. Under microgravity some poorly differentiated perivascular cells reveal signs of destruction. Thus it was found that number of the alkaline phosphatase containing cells (i.e. osteogenic cells) declines in perivascular cells population. It is one of the mechanisms of the osteogenic process decrease of intensity in bones because of lessening support loading on the bone skeleton. In the adaptive remodeling zones of bone tissue (near the vascular canals) in experiments fibroblasts and fibrosis zones were found - areas filled with non-mineralized collagen fibrils on the bones surfaces. Hence it should be considered that decrease (removal) of support loading slows down osteogenic differentiation of the part of perivascular cells and stimulates differentiation of the fibroblast cells. Obtained data is considered as one of the cellular mechanisms of the adaptive reactions development in spongy bone under microgravity which could lead to the bone mass loss.

Telangiectatic osteosarcoma.

PubMed

Sangle, Nikhil A; Layfield, Lester J

2012-05-01

Osteosarcoma is one of the most common primary malignant bone tumors in children and adolescents. Telangiectatic osteosarcoma is an unusual variant of osteosarcoma, forming 3% to 10% of all osteosarcomas. Radiographically, these tumors appear as purely lytic destructive lesions located in the metaphyses of long bones. The location and x-ray appearance of telangiectatic osteosarcomas are reminiscent of an aneurysmal bone cyst and can test the acumen of a diagnostic radiologist. Distinguishing between the two entities microscopically can also be quite challenging. Telangiectatic osteosarcoma shows dilated blood-filled spaces lined or traversed by septa containing atypical stromal cells, with or without production of a lacelike osteoid matrix. This review highlights the diagnostic features of telangiectatic osteosarcoma and discusses differential diagnostic considerations, treatment options, and prognostic implications.

Protective Effect of Deer Bone Oil on Cartilage Destruction in Rats with Monosodium Iodoacetate (MIA)-Induced Osteoarthritis.

PubMed

Choi, Hyeon-Son; Im, Suji; Park, Je Won; Suh, Hyung Joo

2016-01-01

The anti-osteoarthritic activity of the methanol fraction of deer bone oil extract (DBO-M) was evaluated in interleukin (IL)-1β-inflamed primary rabbit chondrocytes and in rats with monosodium iodoacetate (MIA)-induced osteoarthritis. The active compound in DBO-M was analyzed using a direct infusion liquid chromatography quadrupole (LCQ) ion-trap electrospray ionization (ESI)-mass spectrometer (MS). DBO-M significantly suppressed the IL-1β-induced sulfated-glycosaminoglycan (s-GAG) release from chondrocyte, and lowered mRNA levels of the collagen-degrading enzymes matrix metalloproteinase (MMP)-1 and MMP-3 in a dose-dependent manner. Upon treatment with high doses of DBO-M, the levels of IL-1β, tumor necrosis factor (TNF)-α, and IL-6 decreased by around 40, 70, and 50%, respectively, compared to the control in the serum of rats with MIA-induced osteoarthritis. Bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) increased by over 40% in rats treated with DBO-M compared to the values reported for the MIA-treated control group, while trabecular separation (Tb.Sp) showed a significant decrease (ca. 38%), as confirmed through micro-computed tomography (CT) analysis of MIA-induced destruction of articular bones. Furthermore, direct infusion ESI-MS analysis showed that DBO-M contains gangliosides, which are glycosphingolipids with monosialic acid (GM3), as a major compound. Our results suggest that DBO-M effectively improves MIA-induced osteoarthritis by suppressing inflammatory responses, and that gangliosides could be one of the DBO-derived anti-inflammatory components.

View of the rotunda extension and west wall of the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View of the rotunda extension and west wall of the north wing from the north. The damage visible in the photograph resulted from both general neglect and a destructive fire in February 2003 set by arsonists - U. S. Naval Asylum, Biddle Hall, Gray's Ferry Avenue, Philadelphia, Philadelphia County, PA

Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration.

PubMed

Rubessa, Marcello; Polkoff, Kathryn; Bionaz, Massimo; Monaco, Elisa; Milner, Derek J; Holllister, Scott J; Goldwasser, Michael S; Wheeler, Matthew B

2017-10-02

Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

Ptychographic X-ray nanotomography quantifies mineral distributions in human dentine

NASA Astrophysics Data System (ADS)

Zanette, I.; Enders, B.; Dierolf, M.; Thibault, P.; Gradl, R.; Diaz, A.; Guizar-Sicairos, M.; Menzel, A.; Pfeiffer, F.; Zaslansky, P.

2015-03-01

Bones are bio-composites with biologically tunable mechanical properties, where a polymer matrix of nanofibrillar collagen is reinforced by apatite mineral crystals. Some bones, such as antler, form and change rapidly, while other bone tissues, such as human tooth dentine, develop slowly and maintain constant composition and architecture for entire lifetimes. When studying apatite mineral microarchitecture, mineral distributions or mineralization activity of bone-forming cells, representative samples of tissue are best studied at submicrometre resolution while minimizing sample-preparation damage. Here, we demonstrate the power of ptychographic X-ray tomography to map variations in the mineral content distribution in three dimensions and at the nanometre scale. Using this non-destructive method, we observe nanostructures surrounding hollow tracts that exist in human dentine forming dentinal tubules. We reveal unprecedented quantitative details of the ultrastructure clearly revealing the spatially varying mineralization density. Such information is essential for understanding a variety of natural and therapeutic effects for example in bone tissue healing and ageing.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

PubMed

Wagner, A; Sachse, A; Keller, M; Aurich, M; Wetzel, W-D; Hortschansky, P; Schmuck, K; Lohmann, M; Reime, B; Metge, J; Arfelli, F; Menk, R; Rigon, L; Muehleman, C; Bravin, A; Coan, P; Mollenhauer, J

2006-03-07

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

NASA Astrophysics Data System (ADS)

Wagner, A.; Sachse, A.; Keller, M.; Aurich, M.; Wetzel, W.-D.; Hortschansky, P.; Schmuck, K.; Lohmann, M.; Reime, B.; Metge, J.; Arfelli, F.; Menk, R.; Rigon, L.; Muehleman, C.; Bravin, A.; Coan, P.; Mollenhauer, J.

2006-03-01

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis

PubMed Central

Xu, Xin; Jia, Xiaoyue; Mo, Longyi; Liu, Chengcheng; Zheng, Liwei; Yuan, Quan; Zhou, Xuedong

2017-01-01

Postmenopausal osteoporosis (PMO) is a prevalent metabolic bone disease characterized by bone loss and structural destruction, which increases the risk of fracture in postmenopausal women. Owing to the high morbidity and serious complications of PMO, many efforts have been devoted to its prophylaxis and treatment. The intestinal microbiota is the complex community of microorganisms colonizing the gastrointestinal tract. Probiotics, which are dietary or medical supplements consisting of beneficial intestinal bacteria, work in concert with endogenous intestinal microorganisms to maintain host health. Recent studies have revealed that bone loss in PMO is closely related to host immunity, which is influenced by the intestinal microbiota. The curative effects of probiotics on metabolic bone diseases have also been demonstrated. The effects of the intestinal microbiota on bone metabolism suggest a promising target for PMO management. This review seeks to summarize the critical effects of the intestinal microbiota and probiotics on PMO, with a focus on the molecular mechanisms underlying the pathogenic relationship between bacteria and host, and to define the possible treatment options. PMID:28983411

A giant cranial aneurysmal bone cyst associated with fibrous dysplasia.

PubMed

Składzieriń, J; Olés, K; Zagólski, O; Moskała, M; Sztuka, M; Strek, P; Wierzchowski, W; Tomik, J

2008-01-01

An aneurysmal bone cyst (ABC) is a rare, benign fibro-osseous lesion, considered a vascular phenomenon secondary to fibrous dysplasia or a giant-cell tumour, and occurs mainly in long bones and vertebrae. In this case report a 16-year-old male presented with massive epistaxis. He was admitted with a 3-year history of chronic rhinitis, headaches, right ocular pain and recurrent epistaxis. CT scans showed a predominantly cystic, expansive mass obstructing both nasal cavities, extending to all paranasal sinuses and both orbits, with evidence of anterior cranial fossa skull base destruction. The patient underwent a craniofacial resection of the tumour performed with an external approach and an immediate reconstruction of the dural defect. Histology confirmed the lesion was an ABC associated with fibrous dysplasia. The patient's recovery was complete. A large facial aneurysmal bone cyst can damage the facial skeleton and skull base, and requires excision by a combined external approach.

The effect of antiresorptives on bone quality.

PubMed

Recker, Robert R; Armas, Laura

2011-08-01

Currently, antiresorptive therapy in the treatment and prevention of osteoporosis includes bisphosphonates, estrogen replacement, selective estrogen receptor modulators (raloxifene), and denosumab (a human antibody that inactivates RANKL). The original paradigm driving the development of antiresorptive therapy was that inhibition of bone resorption would allow bone formation to continue and correct the defect. However, it is now clear increases in bone density account for little of the antifracture effect of these treatments. We examined the antifracture benefit of antiresorptives deriving from bone quality changes. We searched the archive of nearly 30,000 articles accumulated over more than 40 years in our research center library using a software program (Refman™). Approximately 250 publications were identified in locating the 69 cited here. The findings document antiresorptive agents are not primarily anabolic. All cause a modest increase in bone density due to a reduction in the bone remodeling space; however, the majority of their efficacy is due to suppression of the primary cause of osteoporosis, ie, excessive bone remodeling not driven by mechanical need. All of them improve some element(s) of bone quality. Antiresorptive therapy reduces risk of fracture by improving bone quality through halting removal of bone tissue and the resultant destruction of microarchitecture of bone and, perhaps to some extent, by improving the intrinsic material properties of bone tissue. Information presented here may help clinicians to improve selection of patients for antiresorptive therapy by avoiding them in cases clearly not due to excessive bone remodeling.

Practical use of imaging technique for management of bone and soft tissue tumors.

PubMed

Miwa, Shinji; Otsuka, Takanobu

2017-05-01

Imaging modalities including radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are necessary for the diagnosis of bone and soft tissue tumors. The history of imaging began with the discovery of X-rays in the 19th century. The development of CT, MRI, ultrasonography, and positron emission tomography (PET) have improved the management of bone and soft tissue tumors. X-ray imaging and CT scans enable the evaluation of bone destruction, periosteal reaction, sclerotic changes in lesions, condition of cortical bone, and ossification. MRI enables the assessment of tissue characteristics, tumor extent, and the reactive areas. Functional imaging modalities including 201 thallium ( 201 Tl) scintigraphy can be used to differentiate benign lesions from malignant lesions and to assess chemotherapeutic effects. Real-time assessment of soft tissue tumors by ultrasonography enables accurate and safe performance of surgery and biopsy. This article describes useful imaging modalities and characteristic findings in the management of bone and soft tissue tumors. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Retinitis pigmentosa, Coats disease and uveitis.

PubMed

Solomon, A; Banin, E; Anteby, I; Benezra, D

1999-01-01

To study the anamnestic immune response to retinal specific antigens of two patients suffering from a rare triad of retinitis pigmentosa, Coats disease and uveitis. 17-year-old girl presented with an acute episode of panuveitis, and her 19-year-old brother suffered from chronic uveitis. On examination, both patients showed retinal vascular changes and subretinal exudations typical of Coats disease, with bone-spicule pigmentary changes as observed in retinitis pigmentosa. All routine examinations were unrevealing. However, the peripheral lymphocytes from these two siblings gave a specific anamnestic response to retinal antigens in vitro. A stimulation index of 4.6 was obtained when the sister's lymphocytes were stimulated with interphotoreceptor binding protein, IRBP--during the acute stage of the uveitis. The brother's lymphocytes showed a stimulation index of 2.7 towards S-Ag during the chronic phase of his uveitic condition. These results indicate that autoimmunity towards retinal antigens may play some role in specific types of retinitis pigmentosa. Whether these autoimmune reactions are a primary pathological mechanism or are secondary to the extensive destruction of the photoreceptor layer resulting from the retinitis pigmentosa remains debatable.

Problems in determination of skeletal lead burden in archaeological samples: An example from the First African Baptist Church population

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

Whittmers Jr., L. E.; Aufderheide, A. C.; Pounds, Joel G.

2008-08-01

Human bone lead content has been demonstrated to be related to socioeconomic status, occupation and other social and environmental correlates. Skeletal tissue samples from 135 individuals from an early nineteenth century Philadelphia cemetery (First African Baptist Church) were studied by electrothermal atomic absorption spectrometry and x-ray fluorescence for lead content. High bone lead levels led to investigation of possible diagenetic effects. These were investigated by several different approaches including distribution of lead within bone by x-ray fluorescence, histological preservation, soil lead concentration and acidity as well as location and depth of burial. Bone lead levels were very high in themore » children, exceeding those of the adult population that were buried in the cemetery, and also those of present day adults. The antemortem age-related increase in bone lead, reported in other studies, was not evidenced in this population. Lead was even deposited in areas of taphonomic bone destruction. Synchrotron x-ray fluorescence studies revealed no consistent pattern of lead microdistribution within the bone. Our conclusions are that postmortem diagenesis of lead ion has penetrated these archaeological bones to a degree that makes their original bone lead content irretrievable by any known method. Increased bone porosity is most likely responsible for the very high levels of lead found in bones of newborns and children.« less

Problems in Determination of Skeletal Lead Burden in Archaeological Samples: An Example From the First African Baptist Church Population

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

Whittmers Jr., L. E.; Aufderheide, A. C.; Pounds, Joel G.

2008-08-01

ABSTRACT Human bone lead content has been demonstrated to be related to socioeconomic status, occupation and other social and environmental correlates. Skeletal tissue samples from 135 individuals from an early nineteenth century Philadelphia cemetery (First African Baptist Church) were studied by electrothermal atomic absorption spectrometry and x-ray fluorescence for lead content. High bone lead levels led to investigation of possible diagenetic effects. These were investigated by several different approaches including distribution of lead within bone by x-ray fluorescence, histological preservation, soil lead concentration and acidity as well as location and depth of burial. Bone lead levels were very high inmore » children, exceeding those of the adult population that were buried in the cemetery, and also those of present day adults. The antemortem age-related increase in bone lead, reported in other studies, was not evidenced in this population. Lead was even deposited in areas of taphonomic bone destruction. Synchrotron x-ray fluorescence studies revealed no consistent pattern of lead microdistribution within the bone. Our conclusions are that postmortem diagenesis of lead ion has penetrated these archaeological bones to a degree that makes their original bone lead content irretrievable by any known method. Increased bone porosity is most likely responsible for the very high levels of lead found in bones of newborns and children.« less

[A case of Bezold's abscess associated with cholesteatoma].

PubMed

Furukawa, K; Arai, E; Kobayashi, T; Takasaka, T

1992-12-01

Since the advent of antibiotics, otogenic complications have decreased considerably. However, incomplete antibiotic therapy has altered the clinical course of middle ear disease so as to be more insidious. This paper reports a case of Bezold's abscess associated with cholesteatoma. A 48-year-old man visited our hospital presenting with a 4-day history of right otorrhea and a tender swelling in the right neck. Physical examination showed a febrile patient (38.8 degrees C) with right facial paresis and trismus. A hyperemic, hard and tender swelling was observed in his right neck from the lateral cervical to the mental region. The tympanic membrane was invisible because of granulation and swelling of the posterior wall of the external auditory canal. Intravenous clindamycin and ceftazidime therapy was started immediately. A CT-scan revealed a diffuse shadow with bony destruction in the right mastoid cortex. Extensive abscess formation was also found in the right sternocleidomastoid muscle, in the anterior neck and in the posterior neck. He was diagnosed as having Bezold's abscess associated with cholesteatoma. Radical mastoidectomy and drainage of the neck abscess was performed on the third day under general anesthesia. The mastoid cavity was found to be filled with pus and cholesteatoma debris. A small area of defective bone was found at the mastoid tip, through which there were communications between the mastoid cavity and the abscesses in the neck. Bony destruction was also found in the horizontal and vertical portion of the facial canal. Bacteroides and three kinds of gram-negative rods were cultured from the mastoid cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed Central

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

2017-01-01

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

A sonic tool for spinal fusion.

PubMed

Weis, E B

1977-01-01

The application of sonic energy to bone cutting problems is reported. The basic principle of the resonant tool, its adaptation for surgery, the experimental results of its use in animals, and clinical experience are reported. This sonic tool is found to introduce no significant tissue destruction. It does have several desirable characteristics for routine use in orthopedics.

The effects of corrosive substances on human bone, teeth, hair, nails, and soft tissue.

PubMed

Hartnett, Kristen M; Fulginiti, Laura C; Di Modica, Frank

2011-07-01

This research investigates the effects of household chemicals on human tissues. Five different human tissues (bone, tooth, hair, fingernails, and skin/muscle/fat) were immersed into six different corrosive agents. These agents consisted of hydrochloric acid, sulfuric acid, lye, bleach, organic septic cleaner, and Coca-Cola(®) soda. Tap water was used as a control. Tissue samples were cut to consistent sizes and submerged in the corrosive liquids. Over time, the appearance, consistency, and weight were documented. Hydrochloric acid was the most destructive agent in this study, consuming most tissues within 24 h. Sulfuric acid was the second most destructive agent in this study. Bleach, lye, and cola had no structural effects on the hard tissues of the body, but did alter the appearance or integrity of the hair, nails, or flesh in some way. The organic septic cleaner and tap water had no effect on any of the human tissue tested during the timeframe of the study. 2011 American Academy of Forensic Sciences. Published 2011. This article is a U.S. Government work and is in the public domain in the U.S.A.

Fatigue-type stress fractures of the lower limb associated with fibrous cortical defects/non-ossifying fibromas in the skeletally immature.

PubMed

Shimal, A; Davies, A M; James, S L J; Grimer, R J

2010-05-01

To investigate the association of a fatigue-type stress fracture and a fibrous cortical defect/non-ossifying fibroma (FCD/NOF) of the lower limb long bones in skeletally immature patients. The patient database of a specialist orthopaedic oncology centre was searched to determine the number of skeletally immature patients (

Regulation of bone by the adaptive immune system in arthritis

PubMed Central

2011-01-01

Studies on the immune regulation of osteoclasts in rheumatoid arthritis have promoted the new research field of 'osteoimmunology', which investigates the interplay between the skeletal and immune systems at the molecular level. Accumulating evidence lends support to the theory that bone destruction associated with rheumatoid arthritis is caused by the enhanced activity of osteoclasts, resulting from the activation of a unique helper T cell subset, 'Th17 cells'. Understanding the interaction between osteoclasts and the adaptive immune system in rheumatoid arthritis and the molecular mechanisms of Th17 development will lead to the development of potentially effective therapeutic strategies. PMID:21635718

[Effects of T helper 1 cells and T helper 17 cells secreting cytokines on rat models of experimental periodontitis].

PubMed

Wang, Z X; Yang, L; Tan, J Y; Chen, L L

2017-12-09

Objectvie: To investigate the effects of secreting cytokines interferon-gamma (IFN-γ) and interleukin-17 (IL-17) of T helper 1 cells (Th1) and T helper 17 cells (Th17) on the peripheral blood and alveolar bone destruction, so as to provide a new explanation for cellular immunity-mediated alveolar bone destruction. Methods: Eighteen eight-week-old male Sprague-Dawley rats were divided, randomly and equally, into 3 groups: lipopolysaccharide (LPS) group, ligation group and normal control group. In the LPS group, Escherichia coli LPS was injected into the alveolar mucosa on the buccalmedian site of the left upper first molar, while the right upper first molar was injected with equal volume of physiological saline as self-controls. The injections were performed every other day for four times totally. In the ligation group, the left upper first molars were ligatured with 0.2 mm orthodontic cords, while the right upper first molars were left untreated as self-controls, and supplemented with high-sugar diet to promote the periodontitis status. The rats in normal control group were fed normally. The concentrations of IFN-γ and IL-17 in peripheral blood were measured using enzyme linked immunosorbent assay (ELISA) method at the fourth week after the start of injection and at the eighth week after ligation. The histological of periodontal tissues were observed after hematoxylin-eosin (HE) staining and osteoclast count was performed under light microscope. The histological of osteoclasts were observed after tartrate-resistant acid phosphatase (TRAP) staining. Expression of IFN-γ and IL-17 were detected by immunohistochemical assay. Results: The concentrations of IFN-γ in peripheral blood of LPS group [(185.0±50.7) ng/L] and ligation group [(202.9±60.4) ng/L] were significantly higher than that of normal control group [(106.3±17.2) ng/L]( P< 0.05). Meanwhile, histological examination showed inflammatory cells infiltration in the gingival epithelium, the height reduction of alveolar bone accompanied with absorption lacuna. There were significantly higher HE and TRAP stained osteoclasts in LPS group (9.50±1.05) and ligation group (10.83±1.17) than that in controlgroup (0.33±0.52)( P< 0.05). Moreover, the expressions of IL-17 in alveolar bone absorption area of LPS group and ligation group were significantly stronger than that in control group ( P< 0.05). Conclusions: The rat models of experimental periodontitis and alveolar bone resorption could be successfully established by means of ligationand LPS injection, respectively. The periodontal inflammatory responses were related to secreting cytokines IFN-γ and IL-17 of Th1 and Th17 cells, while Th17 cells might exert a positive effect on alveolar bone destruction.

Specific Biomimetic Hydroxyapatite Nanotopographies Enhance Osteoblastic Differentiation and Bone Graft Osteointegration

PubMed Central

Loiselle, Alayna E.; Wei, Lai; Faryad, Muhammad; Paul, Emmanuel M.; Lewis, Gregory S.; Gao, Jun; Lakhtakia, Akhlesh

2013-01-01

Impaired healing of cortical bone grafts represents a significant clinical problem. Cadaveric bone grafts undergo extensive chemical processing to decrease the risk of disease transmission; however, these processing techniques alter the bone surface and decrease the osteogenic potential of cells at the healing site. Extensive work has been done to optimize the surface of bone grafts, and hydroxyapatite (HAP) and nanotopography both increase osteoblastic differentiation. HAP is the main mineral component of bone and can enhance osteoblastic differentiation and bone implant healing in vivo, while nanotopography can enhance osteoblastic differentiation, adhesion, and proliferation. This is the first study to test the combined effects of HAP and nanotopographies on bone graft healing. With the goal of identifying the optimized surface features to improve bone graft healing, we tested the hypothesis that HAP-based nanotopographic resurfacing of bone grafts improves integration of cortical bone grafts by enhancing osteoblastic differentiation. Here we show that osteoblastic cells cultured on processed bones coated with specific-scale (50–60 nm) HAP nanotopographies display increased osteoblastic differentiation compared to cells on uncoated bone, bones coated with poly-l-lactic acid nanotopographies, or other HAP nanotopographies. Further, bone grafts coated with 50–60-nm HAP exhibited increased formation of new bone and improved healing, with mechanical properties equivalent to live autografts. These data indicate the potential for specific HAP nanotopographies to not only increase osteoblastic differentiation but also improve bone graft incorporation, which could significantly increase patient quality of life after traumatic bone injuries or resection of an osteosarcoma. PMID:23510012

Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium.

PubMed

Palapattu, Ganesh S; Meeker, Alan; Harris, Timothy; Collector, Michael I; Sharkis, Saul J; DeMarzo, Angelo M; Warlick, Christopher; Drake, Charles G; Nelson, William G

2006-08-01

Using various nonphysiological tissue injury/repair models numerous studies have demonstrated the capacity of bone marrow derived cells to contribute to the repopulation of epithelial tissues following damage. To investigate whether this phenomenon might also occur during periods of physiological tissue degeneration/regeneration we compared the ability of bone marrow derived cells to rejuvenate the prostate gland in mice that were castrated and then later treated with dihydrotestosterone vs mice with prostate epithelium that had been damaged by lytic virus infection. Using allogenic bone marrow grafts from female donor transgenic mice expressing green fluorescent protein transplanted into lethally irradiated males we were able to assess the contributions of bone marrow derived cells to recovery of the prostatic epithelium in 2 distinct systems, including 1) surgical castration followed 1 week later by dihydrotestosterone replacement and 2) intraprostatic viral injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-->C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days following intraprostatic viral injection. Prostate tissue immunofluorescence was performed with antibodies against the epithelial marker cytokeratin 5/8, the hematopoietic marker CD45 and green fluorescent protein. Mice that sustained prostate injury from vaccinia virus infection with concomitant severe inflammation and glandular disruption showed evidence of bone marrow derived cell reconstitution of prostate epithelium, that is approximately 4% of all green fluorescent protein positive cells in the epithelial compartment 14 days after injury expressed cytokeratin 5/8, similar to the proportion of green fluorescent protein positive cells in the prostate that no longer expressed the hematopoietic marker CD45. When prostatic degeneration/regeneration was triggered by androgen deprivation and reintroduction, no green fluorescent protein positive prostate epithelial cells were detected. These findings are consistent with a requirement for inflammation associated architectural destruction for the bone marrow derived cell contribution to the regeneration of prostate epithelium.

Host response mechanisms in periodontal diseases

PubMed Central

SILVA, Nora; ABUSLEME, Loreto; BRAVO, Denisse; DUTZAN, Nicolás; GARCIA-SESNICH, Jocelyn; VERNAL, Rolando; HERNÁNDEZ, Marcela; GAMONAL, Jorge

2015-01-01

Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells). Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs) and bone-resorbing osteoclasts (OCLs). This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as a stage that presents a significantly host immune and inflammatory response to the microbial challenge that determine of susceptibility to develop the destructive/progressive periodontitis under the influence of multiple behavioral, environmental and genetic factors. PMID:26221929

Beauty parlor stroke syndrome due to a bone fragment from an osteophyte of the atlas: case report.

PubMed

Kameda, Takuya; Otani, Koji; Tamura, Takamitsu; Konno, Shinichi

2018-04-01

Beauty parlor stroke syndrome (BPSS) is a rare condition characterized by mechanical impingement of a vertebral artery (VA) during neck rotation and/or hyperextension followed by vertebrobasilar insufficiency. However, there have been no reports of BPSS in which the cause of mechanical impingement was identified and no cases for which surgical treatment was reported. The authors report the case of a 56-year-old Japanese man who presented with presyncope that occurred during cervical extension. Given the possibility of vertebrobasilar insufficiency, digital subtraction angiography and CT angiography were performed. These studies revealed that the right VA was hypoplastic and the left VA was dominant. Moreover, in the position of cervical extension, the dominant left VA showed constriction caused by a bone fragment of an osteophyte of the atlas. Removal of the bone fragment was performed. Postoperative left vertebral angiography showed improvement of blood flow in the extended position, and the presyncope completely disappeared. The pathomechanism of this case was a bone fragment compressing the left VA in the C-1 groove during neck extension. In BPSS patients with recurrent transient symptoms, the possibility of this mechanism of VA constriction by a free bone fragment should be considered.

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.

Determination of mechanical stiffness of bone by pQCT measurements: correlation with non-destructive mechanical four-point bending test data.

PubMed

Martin, Daniel E; Severns, Anne E; Kabo, J M J Michael

2004-08-01

Mechanical tests of bone provide valuable information about material and structural properties important for understanding bone pathology in both clinical and research settings, but no previous studies have produced applicable non-invasive, quantitative estimates of bending stiffness. The goal of this study was to evaluate the effectiveness of using peripheral quantitative computed tomography (pQCT) data to accurately compute the bending stiffness of bone. Normal rabbit humeri (N=8) were scanned at their mid-diaphyses using pQCT. The average bone mineral densities and the cross-sectional moments of inertia were computed from the pQCT cross-sections. Bending stiffness was determined as a function of the elastic modulus of compact bone (based on the local bone mineral density), cross-sectional moment of inertia, and simulated quasistatic strain rate. The actual bending stiffness of the bones was determined using four-point bending tests. Comparison of the bending stiffness estimated from the pQCT data and the mechanical bending stiffness revealed excellent correlation (R2=0.96). The bending stiffness from the pQCT data was on average 103% of that obtained from the four-point bending tests. The results indicate that pQCT data can be used to accurately determine the bending stiffness of normal bone. Possible applications include temporal quantification of fracture healing and risk management of osteoporosis or other bone pathologies.

[Penetrating injury of the lungs and multiple injuries of lower extremities caused by aircraft bombs splinters].

PubMed

Golubović, Zoran; Stanić, Vojkan; Trenkić, Srbobran; Stojiljković, Predrag; Stevanović, Goran; Lesić, Aleksandar; Golubović, Ivan; Milić, Dragan; Visnjić, Aleksandar; Najman, Stevo

2010-08-01

Injuries caused by aircraft bombs cause severe damages to the human body. They are characterized by massive destruction of injured tissues and organs, primary contamination by polymorph bacterial flora and modified reactivity of the body. Upon being wounded by aircraft bombs projectiles a victim simultaneously sustains severe damages of many organs and organ systems due to the fact that a large number of projectiles at the same time injure the chest, stomach, head and extremities. We presented a patient, 41 years of age, injured by aircraft bomb with hemo-pneumothorax and destruction of the bone and soft tissue structures of the foot, as well as the treatment result of such heavy injuries. After receiving thoracocentesis and short reanimation, the patient underwent surgical procedure. The team performed thoracotomy, primary treatment of the wound and atypical resection of the left lung. Thoracic drains were placed. The wounds on the lower leg and feet were treated primarily. Due to massive destruction of bone tissue of the right foot by cluster bomb splinters, and impossibility of reconstruction of the foot, guillotine amputation of the right lower leg was performed. Twelve days after the wounding caused by cluster bomb splinters, soft tissue of the left lower leg was covered by Tirsch free transplant and the defect in the area of the left foot was covered by dorsalis pedis flap. The transplant and flap were accepted and the donor sites were epithelized. Twenty-six days following the wounding reamputation was performed and amputation stump of the right lower leg was closed. The patient was given a lower leg prosthesis with which he could move. Upon being wounded by aircraft bomb splinters, the injured person sustains severe wounds of multiple organs and organ systems due to simultaneous injuries caused by a large number of projectiles. It is necessary to take care of the vital organs first because they directly threaten the life of the wounded patient. Despite adequate surgical treatment of war wounds of the feet, because of massive defect of bone and soft tissue, amputation may be the only rational solution of the treatment. The resection of the lung may be succesfull method for the severe destruction of the lung.

The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats

PubMed Central

SUN, Xiaolei; Fengbo, LI; Xinlong, MA; Jianxiong, MA; ZHAO, Bin; ZHANG, Yang; Yanjun, LI; Jianwei, LV; MENG, Xinmin

2015-01-01

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increased the risk of fracture. Previous studies have demonstrated the effect of naringin (NG) or treadmill exercise (EX) on osteoporosis, however, reports about effects of NG plus EX on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized (OVX) rats. Three months after bilateral ovariectomy, Seventy-five rats were randomly assigned to the following treatment groups: OVX, sham-operated (SHAM), NG, EX, or NG plus EX treatment. Treatments were administered for 60 days. Bone metabolism, bone mineral density, trabecular bone parameters, immunohistochemistry, and the bone strength were evaluated. Compared to the OVX groups, all treatments increased bone volume (BV/TV), trabecula number (Tb.N), trabecula thickness (Tb.Th), bone mineral density (BMD), and mechanical strength. NG + EX showed the strongest effects on BV/TV, Tb.Th, and biomechanical strength. Additionally, decreased C-terminal telopeptides of type I collagen (CTX-1) and enhanced osteocalcin (OCN) expression were observed in the NG + EX group. The present study demonstrates that the NG + EX may have a therapeutic advantage over each monotherapy for the treatment of osteoporosis. PMID:26260240

Simple Bone Cyst of Metacarpal: Rare Lesion with Unique Treatment

PubMed Central

Patwardhan, Sandeep; Shah, Kunal; Shyam, Ashok; Sancheti, Parag

2014-01-01

Introduction: Simple bone cyst or unicameral bone cyst (UBC) are benign cystic lesions commonly found in femur and humerus. However hand is a very rare site of occurrence. Treatment described for UBC of hand commonly involves curettage and bone grafting. Case Report: A 7 year old right hand dominant girl presented to us with chief complaints of pain and swelling in right 4th metacarpal since 2 month. On imaging, plain radiographs of right hand showed expansile lytic lesion on Metaphyseal-diaphyseal region of 4th metacarpal with pathological fracture. MRI showed cystic lesions with internal loculations and fluid-fluid levels (Fig 2). There was minimal soft tissue extension. We performed aspiration which showed serosanguinous fluid with haemorrhagic tinge. With the diagnosis of unicameral bone cyst in mind we performed and closed intramedullary nail with k wire. The cyst healed up completely within 2 months. There was no recurrence at 18 month follow up. Conclusion: In conclusion simple bone cyst is very rare in metacarpal bone. However it should be considered as important differential since it warrants simple treatment and extensive procedures should be avoided. PMID:27298987

[The use of structural proximal tibial allografts coated with human albumin in treating extensive periprosthetic knee-joint bone deficiency and averting late complications. Case report].

PubMed

Klára, Tamás; Csönge, Lajos; Janositz, Gábor; Pap, Károly; Lacza, Zsombor

2015-01-11

The authors report the history of a 74-year-old patient who underwent surgical treatment for segmental knee-joint periprosthetic bone loss using structural proximal tibial allografts coated with serum albumin. Successful treatment of late complications which occurred in the postoperative period is also described. The authors emphasize that bone replacement with allografts is a physiological process that enables the stable positioning of the implant and the reconstruction of the soft tissues, the replacement of extensive bone loss, and also it is a less expensive operation. It has been already confirmed that treatment of lyophilised allografts with albumin improves the ability of bone marrow-derived mesenchymal stem cells to adhere and proliferate the surface of the allografts, penetrate the pores and reach deeper layers of the graft. Earlier studies have shown osteoblast activity on the surface and interior of the graft.

In vivo and in vitro anti-tumor and anti-metastasis effects of Coriolus versicolor aqueous extract on mouse mammary 4T1 carcinoma.

PubMed

Luo, Ke-Wang; Yue, Grace Gar-Lee; Ko, Chun-Hay; Lee, Julia Kin-Ming; Gao, Si; Li, Long-Fei; Li, Gang; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara Bik-San

2014-01-01

Coriolus versicolor (CV), a medicinal mushroom widely consumed in Asian countries, has been demonstrated to be effective in stimulation of immune system and inhibition of tumor growth. The present study aimed to investigate the anti-tumor and anti-metastasis effects of CV aqueous extract in mouse mammary carcinoma 4T1 cells and in 4T1-tumor bearing mouse model. Our results showed that CV aqueous extract (0.125-2 mg/ml) did not inhibit 4T1 cell proliferation while the non-cytotoxic dose of CV extract (1-2 mg/ml) significantly inhibited cell migration and invasion (p<0.05). Besides, the enzyme activities and protein levels of MMP-9 were suppressed by CV extract significantly. Animal studies showed that CV aqueous extract (1 g/kg, orally-fed daily for 4 weeks) was effective in decreasing the tumor weight by 36%, and decreased the lung metastasis by 70.8% against untreated control. Besides, micro-CT analysis of the tumor-bearing mice tibias indicated that CV extract was effective in bone protection against breast cancer-induced bone destruction as the bone volume was significantly increased. On the other hand, CV aqueous extract treatments resulted in remarkable immunomodulatory effects, which was reflected by the augmentation of IL-2, 6, 12, TNF-α and IFN-γ productions from the spleen lymphocytes of CV-treated tumor-bearing mice. In conclusion, our results demonstrated for the first time that the CV aqueous extract exhibited anti-tumor, anti-metastasis and immunomodulation effects in metastatic breast cancer mouse model, and could protect the bone from breast cancer-induced bone destruction. These findings provided scientific evidences for the clinical application of CV aqueous extract in breast cancer patients. Copyright © 2014 Elsevier GmbH. All rights reserved.

Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells.

PubMed

Falank, Carolyne; Fairfield, Heather; Reagan, Michaela R

2016-01-01

In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutation) (2). In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantly in the bone marrow (BM), it is clear that all these hallmarks and characteristics are in play, contributing to tumor initiation, drug resistance, disease progression, and relapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MM oncogenesis and disease progression, potentially affecting MM cell metabolism, immune action, inflammation, and influences on angiogenesis. In this review, we discuss the confirmed and hypothetical contributions of BMAT to MM development and disease progression. BMAT has been understudied due to technical challenges and a previous lack of appreciation for the endocrine function of this tissue. In this review, we define the dynamic, responsive, metabolically active BM adipocyte. We then describe how BMAT influences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrine signaling, and bone disease. We then discuss the connection between BMAT and systemic inflammation and potential treatments to inhibit the feedback loops between BM adipocytes and MM cells that support MM progression. We aim for researchers to use this review to guide and help prioritize their experiments to develop better treatments or a cure for cancers, such as MM, that associate with and may depend on BMAT.

Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells

PubMed Central

Falank, Carolyne; Fairfield, Heather; Reagan, Michaela R.

2016-01-01

In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutation) (2). In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantly in the bone marrow (BM), it is clear that all these hallmarks and characteristics are in play, contributing to tumor initiation, drug resistance, disease progression, and relapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MM oncogenesis and disease progression, potentially affecting MM cell metabolism, immune action, inflammation, and influences on angiogenesis. In this review, we discuss the confirmed and hypothetical contributions of BMAT to MM development and disease progression. BMAT has been understudied due to technical challenges and a previous lack of appreciation for the endocrine function of this tissue. In this review, we define the dynamic, responsive, metabolically active BM adipocyte. We then describe how BMAT influences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrine signaling, and bone disease. We then discuss the connection between BMAT and systemic inflammation and potential treatments to inhibit the feedback loops between BM adipocytes and MM cells that support MM progression. We aim for researchers to use this review to guide and help prioritize their experiments to develop better treatments or a cure for cancers, such as MM, that associate with and may depend on BMAT. PMID:27379019

Tension degradation of anterior cruciate ligament grafts with dynamic flexion-extension loading: a biomechanical model in porcine knees.

PubMed

Dargel, Jens; Koebke, Jürgen; Brüggemann, Gert-Peter; Pennig, Dietmar; Schmidt-Wiethoff, Rüdiger

2009-10-01

This study investigates the influence of various femoral anterior cruciate ligament graft fixation methods on the amount of tension degradation and the initial fixation strength after cyclic flexion-extension loading in a porcine knee model. One hundred twenty porcine digital extensor tendons, used as 4-stranded free tendon grafts, were fixated within porcine femoral bone tunnels by use of extracortical button, cross-pin, or interference screw fixation. One hundred twenty porcine patellar tendon-bone grafts were fixated by use of cross-pin, interference screw, or press-fit fixation. Each femur-graft complex was submitted to cyclic flexion-extension loading for 1,000 cycles throughout different loading ranges, and the total loss of tension was determined. After cyclic testing, the grafts were loaded to failure, and the data were compared with a pullout series without cyclic loading. Tension degradation after 1,000 cycles of flexion-extension loading averaged 62.6% +/- 10.0% in free tendon grafts and 48.9% +/- 13.35% in patellar tendon-bone grafts. There was no influence of the loading range on the total amount of tension degradation. The total amount of tension degradation was the highest with interference screw fixation of free tendon and patellar tendon-bone grafts. Despite excessive loss of tension, the initial fixation strength of the femur-graft complex was not reduced. The method of femoral graft fixation significantly influenced tension degradation during dynamic flexion-extension loading. Femoral graft fixation methods that secure the graft close to the tunnel entrance and that displace the graft substance from the center of the bone tunnel show the largest amount of tension degradation during cyclic flexion-extension loading. The graft substance, not the fixation site, was the weakest link of the graft complex within this investigation. We believe that the graft fixation method should be considered when aiming to improve the precision of femoral graft placement in anterior cruciate ligament reconstruction.

Evaluation of a Multicomponent Intervention for Diurnal Bruxism in a Young Child with Autism

ERIC Educational Resources Information Center

Barnoy, Emily L.; Najdowski, Adel C.; Tarbox, Jonathan; Wilke, Arthur E.; Nollet, Megan D.

2009-01-01

Bruxism, forceful grinding of one's teeth together, can produce destructive outcomes such as wear on the teeth and damaged gums and bone structures. The current study implemented a multicomponent intervention that consisted of vocal and physical cues to decrease rates of bruxism. A partial component analysis suggested that the vocal cue was only…

Suspected immune-mediated neutropenia and corticosteroid responsive pancytopenia in a Portuguese water dog.

PubMed

Denstedt, Ellen B

2017-01-01

An 8-year-old spayed Portuguese water dog was presented with dysuria, lethargy, and anorexia. A profound neutropenia and pancytopenia were identified. Bone marrow aspirates revealed neutrophilic hyperplasia, a significant left shift, and toxic changes, suggesting immune-mediated destruction as a likely underlying mechanism. Immunosuppressive therapy was instituted and clinical signs improved.

Bone Analyzer

NASA Technical Reports Server (NTRS)

1985-01-01

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

[Differential diagnosis of rheumatic diseases and blood cancers involving the nasal cavity and accessory sinuses].

PubMed

Vasil'ev, V I; Sokol, E V; Sedyshev, S Kh; Gorodetskiĭ, V R; Aleksandrova, E N; Logvinenko, O A; Pal'shina, S G; Rodionova, E B; Radenska-Lopovok, S G; Probatova, N A; Kokosadze, N V; Pavlovskaia, A I; Kovrigina, A M; Varlamova, E Iu; Safonova, T N; Borovskaia, A B; Gaĭduk, I V; Mukhortova, O V; Aslanidi, I P; Nasonov, E L

2014-01-01

To provide the clinical, laboratory, radiological, morphological, and immunomorphological signs that permit the differential diagnosis to be made in patients with involvement of the nasal cavity and accessory sinuses (NCAS). In the period 2009 to 2013, the Laboratory for Intensive Therapy for Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, associated the disease onset with NCAS involvement in 39 (7.6%) of 512 examinees. NCAS involvement was present at disease onset in 100% of the patients with natural killer (NK) cell lymphoma (NK/T lymphoma), in 84.5% of those with Wegener granulomatosis (WG), in 29.5% of those with IgG4-related disease (IgG4-RD), and in 17.5% of those with sarcoidosis. Such an onset could be extremely rarely observed in histiocytosis. Despite the similar clinical manifestations, NCAS involvements in NK/T lymphoma of nasal type and WG at disease onset show clear differences in the laboratory and systemic manifestations of these diseases. The patients with lymphoma have no characteristic laboratory abnormalities at disease onset, except the 100% presence of Epstein-Barr virus (EBV) DNA in blood and, only as a tumor grows, fever appears and there are elevated C-reactive protein and lactate dehydrogenase levels and pronounced destructive changes in the facial bones with mandatory hard palate destruction; at the same time the signs of systemic involvement are virtually absent. The patients with WG at disease onset have fever, high erythrocyte sedimentation rate, elevated C-reactive level, significant anemia, leukocytosis and 90% are found to have anti-neutrophil cytoplasmic antibodies with the rapid development of systemic manifestations: involvements of the lung, kidney, and peripheral nervous system. Destructive changes in the facial bones are minimal and hard palate destructions are absent. The patients with IgG4-RD, sarcoidosis, and juvenile xanthogranuloma have similar clinical and laboratory manifestations in the absence of hemorrhagic nasal discharge, nasal septal perforation, and facial bone destruction, with the practically involvement of the salivary/lacrimal glands and orbital regions. A third of the patients are observed to have different allergic manifestations, moderate eosinophilia, and signs of autoimmune disorders (the presence of rheumatoid and antinuclear factors, hypergammaglobulinemia). Elevated serum IgG4 levels are characteristic of IgG4-RD. Blood anti-neutrophil cytoplasmic antibodies, EBV DNA, and IgG4 levels should be determined in all patients with NCAS involvement. Mini-invasive incision biopsies of the nasal mucosa, orbital regions, and major salivary glands should be done, by morphologically verifying the diagnosis of sarcoidosis, histiocytosis, and WG and by making an immunomorphological examination to diagnose NK/T lymphoma and IgG4-RD.

Identifying Potential Therapeutics for Osteoporosis by Exploiting the Relationship between Mevalonate Pathway and Bone Metabolism.

PubMed

Wan Hasan, Wan Nuraini; Chin, Kok-Yong; Jolly, James Jam; Abd Ghafar, Norzana; Soelaiman, Ima Nirwana

2018-04-23

Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling. This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential. Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans. mevalonate pathway can be exploited to develop effective antiosteoporosis agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Bone-Induced Expression of Tumoral Integrin beta3 Enables Targeted Nanotherapy of Breast Cancer Metastases

NASA Astrophysics Data System (ADS)

Ross, Michael H.

Breast cancer is the most common cancer for women worldwide, representing approximately 25% of all new cancer cases in this population. While early detection and removal of breast cancer still confined to the primary site results in a good prognosis, approximately one- third of patients will develop distant metastases. In these patients, overall survival is markedly reduced. Of the common sites for breast cancer metastasis, the skeletal system is the most frequent. Treating breast cancer bone metastases has proven particularly difficult for several reasons, such as dissemination of metastases throughout the skeleton, poor drug localization to sites of interest, a lack of tumor-specific targets expressed across breast cancer subtypes, and the chemo-protective nature of the bone microenvironment. This dissertation is focused on investigating a potential tumor-target expressed on breast cancer bone metastases, and to improve drug treatment efficacy against tumor cells in the bone microenvironment. Integrins are heterodimeric cell surface receptors, composed of an alpha and beta subunit from a large family of selectively-compatible integrin subunits. As a heterodimeric complex, integrins can bind to components of the extracellular matrix or to other cells. One particular integrin complex, integrin alphavbeta3, is composed of the tightly regulated integrin subunit beta3 and the more widely expressed alphav subunit. I examined the expression of integrin beta3 on primary breast cancer as compared to metastases in murine cancer models, and observed that integrin expression is significantly elevated on bone metastases as compared to the primary tumors or visceral metastases. In addition, I evaluated tumor-associated integrin beta3 expression on a tissue microarray (TMA) composed of primary breast cancer and patient-matched bone metastatic tissue from 42 patients. Across nearly all patients, tumor-associated integrin beta3 expression was significantly elevated on bone metastases as compared to the primary tumor. For the first time, I demonstrate that tumor-associated integrin beta3 is elevated on bone metastases across all breast cancer subtypes, supporting the translational potential of targeting integrin beta3 in breast cancer patients with bone metastases. Integrin beta3 was weakly expressed on tumor cells in vitro and on tumor cells in the primary mammary fat pad (MFP). Additional analysis demonstrated that integrin beta3 on circulating tumor cells is dispensable for strong expression of integrin beta3 on subsequent bone metastases, suggested that integrin beta3 may be induced within the bone microenvironment. I identified transforming growth factor beta (TGF-beta) to be a potent inducer of integrin beta3 in vitro, and further demonstrate canonical TGF-beta signaling through the SMAD2 and SMAD3 (SMAD2/3) pathway is responsible for breast cancer upregulation of integrin beta3 induction on bone metastases, both in vitro and in vivo. Utilizing this information, I sought to evaluate the targeting potential of nanotherapy coated with a targeting ligand specific for integrin alphavbeta3. Nanotherapy has the potential to increase therapeutic efficacy and reduce toxicity versus traditional chemotherapies by enhancing drug delivery to specific targets of interest. I explored the localization potential of two nanoparticles with significantly different sizes: polysorbate (tween) 80 micelle nanoparticles (MPs, 12.5 nm) or perfluorocarbon (PFC) nanoparticles ( 250 nm). The smaller integrin alphavbeta3- targeted micelle nanoparticle (alphavbeta3-MP) could more effectively penetrate breast cancer bone metastases than larger integrin alphavbeta3-targeted PFC nanoparticles (alphavbeta3-PFCs). With these observations, I evaluated whether alphavbeta3-MP-mediated drug delivery could more effectively attenuate bone metastatic tumor burden and bone destruction than free drug delivery. Using the chemotherapeutic agent docetaxel (DTX), a potent microtubule inhibitor that is a first-line therapy for metastatic breast cancer, I observe that DTX is only weakly tumor- suppressive in our mouse model of breast cancer metastases. However, treating mice bearing breast cancer metastases with alphavbeta3-MP-delivery of a docetaxel-prodrug (DTX-PD) significantly reduced bone tumor burden and bone destruction, and with less hepatotoxicity. I observed a significant decrease in bone-residing tumor cell proliferation in mice treated with alphavbeta3-MP- delivery of DTX-PD, without overt osteoclast killing or inhibition of osteoclast formation. Together, these results provide support that nanotherapy-mediated attenuation of bone metastases and bone destruction occurs through enhanced drug efficacy against breast cancer cells within the bone. In this Dissertation, Chapter 1 will provide an overview of breast cancer, bone metastases, integrins, and the therapeutic potential of nanotherapy. In Chapter 2, my work on the expression and physiologic regulation of integrin beta3 on breast cancer during metastases will be explored. In Chapter 3, the role of the cytokine TGF-beta in regulating tumoral expression of integrin beta3 will be discussed. And in Chapter 4, I discuss the use of integrin alphavbeta3-targeted nanotherapy directed against breast cancer metastases. Collectively, I provide evidence that chemotherapeutic efficacy against breast cancer cells within bone can be enhanced by exploiting the expression of tumoral integrin beta3 at that metastatic site.

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.

Prefabricated scalping forehead flap with skeletal support.

PubMed

Fujiwara, Masao; Suzuki, Ayano; Mizukami, Takahide; Terai, Tsutomu; Fukamizu, Hidekazu

2009-07-01

It is difficult to reconstruct a nose with adequate shape, color, and texture in patients who have full-thickness nasal defects with extensive loss of skeletal support. The scalping forehead flap is a reliable technique for nasal reconstruction. To our knowledge, however, there have been no reports about a prefabricated scalping forehead flap with a bone graft as skeletal support. In the case reported here, a prefabricated scalping forehead flap combined with an iliac bone graft as skeletal support was used to successfully reconstruct a full-thickness defect of the nose associated with partial frontal bone loss and complete loss of the nasal bones. Acceptable functional and aesthetic results were achieved. This method may be a good alternative for reconstruction of full-thickness nasal defects with extensive loss of skeletal support.

Predicting Bone Mechanical State During Recovery After Long-Duration Skeletal Unloading Using QCT and Finite Element Modeling

NASA Technical Reports Server (NTRS)

Chang, Katarina L.; Pennline, James A.

2013-01-01

During long-duration missions at the International Space Station, astronauts experience weightlessness leading to skeletal unloading. Unloading causes a lack of a mechanical stimulus that triggers bone cellular units to remove mass from the skeleton. A mathematical system of the cellular dynamics predicts theoretical changes to volume fractions and ash fraction in response to temporal variations in skeletal loading. No current model uses image technology to gather information about a skeletal site s initial properties to calculate bone remodeling changes and then to compare predicted bone strengths with the initial strength. The goal of this study is to use quantitative computed tomography (QCT) in conjunction with a computational model of the bone remodeling process to establish initial bone properties to predict changes in bone mechanics during bone loss and recovery with finite element (FE) modeling. Input parameters for the remodeling model include bone volume fraction and ash fraction, which are both computed from the QCT images. A non-destructive approach to measure ash fraction is also derived. Voxel-based finite element models (FEM) created from QCTs provide initial evaluation of bone strength. Bone volume fraction and ash fraction outputs from the computational model predict changes to the elastic modulus of bone via a two-parameter equation. The modulus captures the effect of bone remodeling and functions as the key to evaluate of changes in strength. Application of this time-dependent modulus to FEMs and composite beam theory enables an assessment of bone mechanics during recovery. Prediction of bone strength is not only important for astronauts, but is also pertinent to millions of patients with osteoporosis and low bone density.

[Toward an anthropometric diagnosis of osteopenia and a biochemical diagnosis of osteoporoses].

PubMed

Cointry, Gustavo R; Capozza, Ricardo F; Ferretti, Jose L; Frost, Harold M

2003-01-01

The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled "mineralized mass" which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their "mass" as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not "intense osteopenias" (as per the current WHO's conception) but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone material's stiffness and distribution by other means ("resistometry"). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between "mechanical" (disuse) and "metabolic" etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.

The response of equine cortical bone to loading at strain rates experienced in vivo by the galloping horse.

PubMed

Evans, G P; Behiri, J C; Vaughan, L C; Bonfield, W

1992-03-01

The behaviour of cortical bone under load is strain rate-dependent, i.e. it is dependent on the rate at which the load is applied. This is particularly relevant in the galloping horse since the strain rates experienced by the bone are far in excess of those recorded for any other species. In this study the effect of strain rates between 0.0001 and 1 sec-1 on the mechanical properties of equine cortical bone were assessed. Initially, increasing strain rates resulted in increased mechanical properties. Beyond a critical value, however, further increases in strain rate resulted in lower strain to failure and energy absorbing capacity. This critical rate occurred around 0.1 sec-1 which is within the in vivo range for a galloping racehorse. Analysis of the stress-strain curves revealed a transition in the type of deformation at this point from pseudo-ductile to brittle. Bones undergoing brittle deformation are more likely to fail under load, leading to catastrophic fracture and destruction of the animal.

Higher Resolution and Faster MRI of 31Phosphorus in Bone

NASA Astrophysics Data System (ADS)

Frey, Merideth; Barrett, Sean; Sethna, Zachary; Insogna, Karl; Vanhouten, Joshua

2013-03-01

Probing the internal composition of bone on the sub-100 μm length scale is important to study normal features and to look for signs of disease. However, few useful non-destructive techniques are available to evaluate changes in the bone mineral chemical structure and functional micro-architecture on the interior of bones. MRI would be an excellent candidate, but bone is a particularly challenging tissue to study given the relatively low water density, wider linewidths of its solid components leading to low spatial resolution, and the long imaging time compared to conventional 1H MRI. Our lab has recently made advances in obtaining high spatial resolution (sub-400 μm)3 three-dimensional 31Phosphorus MRI of bone through use of the quadratic echo line-narrowing sequence (1). In this talk, we describe our current results using proton decoupling to push this technique even further towards the factor of 1000 increase in spatial resolution imposed by fundamental limits. We also discuss our work to speed up imaging through novel, faster reconstruction algorithms that can reconstruct the desired image from very sparse data sets. (1) M. Frey, et al. PNAS 109: 5190 (2012).

Methods: a comparative analysis of radiography, microcomputed tomography, and histology for bone tissue engineering.

PubMed

Hedberg, Elizabeth L; Kroese-Deutman, Henriette C; Shih, Charles K; Lemoine, Jeremy J; Liebschner, Michael A K; Miller, Michael J; Yasko, Alan W; Crowther, Roger S; Carney, Darrell H; Mikos, Antonios G; Jansen, John A

2005-01-01

This study focused on the assessment of radiography, microcomputed tomography, and histology for the evaluation of bone formation in a 15.0-mm defect in the rabbit radius after the implantation of a tissue-engineered construct. Radiography was found to be useful as a noninvasive method for obtaining images of calcified tissue throughout the time course of the experiment. With this method, however, image quality was low, making it difficult to obtain precise information about the location and quantity of the bone formed. Microcomputed tomography was used to create three-dimensional reconstructions of the bone (25-microm resolution). These reconstructions allowed for greater spatial resolution than the radiography, but did not allow for imaging of the implanted scaffold material or the surrounding, nonmineralized tissue. To visualize all materials within the defect area at the cellular level, histology was used. Histological analysis, however, is a destructive technique that did not allow for any further analysis of the samples. Each technique examined here has its own advantages and limitations, but each yields unique information regarding bone regeneration. It is only through the use of all three techniques that complete characterization of the bone growth and tissue/construct responses after implantation in vivo.

Earthquakes, May-June 1981

USGS Publications Warehouse

Person, W.J.

1981-01-01

The months of May and June were somewhat quiet, seismically speaking. There was one major earthquake (7.0-7.9) off the west coast of South Island, New Zealand. The most destructive earthquake during this reporting period was in southern Iran on June 11 which caused fatalities and extensive damage. Peru also experienced a destructive earthquake on June 22 which caused fatalities and damage. In the United States, a number of earthquakes were experienced, but none caused significant damage. 

Boiler-turbine life extension

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

Natzkov, S.; Nikolov, M.

1995-12-01

The design life of the main power equipment-boilers and turbines is about 105 working hours. The possibilities for life extension are after normatively regulated control tests. The diagnostics and methodology for Boilers and Turbines Elements Remaining Life Assessment using up to date computer programs, destructive and nondestructive control of metal of key elements of units equipment, metal creep and low cycle fatigue calculations. As well as data for most common damages and some technical decisions for elements life extension are presented.

A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss

PubMed Central

Lozano, Alysia; Wright, Courtney; Vardanyan, Anna; King, Tamara; Largent-Milnes, Tally M.; Nelson, Mark; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W; Vanderah, Todd W.

2010-01-01

Aims Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side-effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7 day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main Methods A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key Findings Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7 days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain. PMID:20176037

Radiologic Diagnosis of Spondylodiscitis, Role of Magnetic Resonance.

PubMed

Ramadani, Naser; Dedushi, Kreshnike; Kabashi, Serbeze; Mucaj, Sefedin

2017-03-01

Study aim is to report the Magnetic Resonance Imaging (MRI) features of acute and chronic spontaneous spondylodiscitis. 57 year old female, complaining of a fever and longstanding cervical pain worsened during physical therapy. MR images were acquired using superconductive magnet 1.5 T, with the following sequences: sagittal PD and T2 TSE, sagittal T1 SE, axial PD and T2 TSE (lumbar spine), axial T2 GRE (cervical spine). Axial and sagittal T1 SE after administration of (gadolinium DTPA). Examination was reviewed by three radiologists and compared to CT findings. Patient reported cervical pain associated with fever and minimal weight loss. Blood tests were normal except hyperglycemia (DM tip II). X Ray: vertebral destruction localized at C-4 and C-5: NECT: destruction of the C-4/C-5 vertebral bodies (ventral part). MRI: Low signal of the bone marrow on T1l images, which enhanced after Gd-DTPA administration and became intermediate or high on T2 images. The steady high signal intensity of the disk on T2 images and enhancement on T1 images is typical for an acute inflammatory process. Bone Scintigrafi results: Bone changes suspicious for metastasis. Whole body CT results: apart from spine, no other significant changes. MRI is the most sensitive technique for the diagnosis of spondylodiscitis in the acute phase and comparable to CT regarding chronial stage of the disease. The present imagining essay os aimed at showing the main magnetic resonance imaging findings of tuberculous discitis.

An intradural cervical chordoma mimicking schwannoma

PubMed Central

Samadian, Mohammad; Shafizad, Misagh

2012-01-01

Abstract: Chordoma is a relatively rare tumor originating from the embryonic remnants of the notochord. This is an aggressive, slow growing and invasive tumor. It occurs mostly at the two ends of neuroaxis which is more frequent in the sacrococcygeal region. Chordoma in vertebral column is very rare. This tumor is extradural in origin and compresses neural tissues and makes the patient symptomatic. This tumor found extremely rare in the spinal region as an intradural tumor. The present study reports a rare case of intradural chordoma tumor as well as its clinical manifestations and treatment options. Case: The patient was a 50-year-old female presented with 9 months history of progressively worsening neck pain, cervical spine chordoma resembling neurinoma and right arm numbness. Physical examination showed no weakness in her limbs, but she had upward plantar reflex and mild hyperreflexia. In a magnetic resonance imaging (MRI) scan of the cervical spine there was an ill-defined enhancing mass in the posterior aspect of C2-C3 body caused cord compression more severe in right side as well as foraminal scalloping. The patient underwent surgery and after midline posterior cervical incision and paravertebral muscle stripping a laminectomy was performed from C1 through C4 using a high speed drill. Needle biopsy revealed chordoma on frozen section and all of accessible parts of tumor were excised. The gross and microscopic histopathological appearance was consistent with chordoma. Chordomas are malignant tumors that arise from remains of embryonic notochord. These ectopic rests of notochord termed “ecchordosis physaliphora “can be found in approximately 2% of autopsies. These are aggressive, slow growing, locally invasive and destructive tumors those occur in the midline of neuroaxis. They generally thought to account for 2% to 4% of all primary bone neoplasms and 1% to 4% malignant bone neoplasms. They are the most frequent primary malignant spinal tumors after plasmacytomas. The incidence has been estimated to be 0.51 cases per million. The most common location is sacrococcygeal region followed by the clivus. These two locations account for approximately 90% of chordomas. Of the tumors that do not arise in the sacrum or clivus, half occur in the cervical region, with the remainder found in the lumbar or thoracic region, in descending order of frequency. Cervical spine chordomas account for 6% of all cases. Distal metastasis most often occurs in young patients, those with sacrococcygeal or vertebral tumors, and those with atypical histological features. These tumors usually spread to contiguous anatomical structures, but they may be found in distant sites (skin, musculoskeletal system, brain, and other internal organs). Seeding of the tumor has also been reported, and the likely mechanism seems to be tumor cell of contamination during the surgical procedures. The usual radiological findings in chordomas of spine are destructive or lytic lesions with occasional sclerotic changes. They tend to lie anterolateral, rather than dorsal towards the cord, and reportedly known to invade the dura. The midline location, destructive nature, soft tissue mass formation and calcification are the radiological hallmarks of chordomas. Computed Tomography (CT) scan is the best imaging modality to delineate areas of osteolytic, osteosclerotic, or mixed areas of bone destruction.Chordoma is usually known as a hypovascular tumor which grows in a lobulated manner. Septal enhancement which reflects a lobulated growth pattern is seen in both CT and MRI and even in gross examination. Other epidural tumors include neurinoma, neurofibroma, meningioma, neuroblastoma, hemangioma, lymphoma and metastases. Their differentiation from chordoma may be difficult due to the same enhancement pattern on CT and MRI. A dumbbell-shaped chordoma is a rare pathogenic condition. The dumbbell shape is a characteristic finding of neurinomas in spine but in spinal neurinomas extention to transverse foramina has not yet been reported. Although our case mimicked a dumbbell shaped neurogenic tumor, its midline location and destructive pattern were characteristic feature indicating a clue to the diagnosis of chordoma that was already confirmed with histopathology. This unusual behavior of tumor extension can be explained by the soft and gelatinous nature of the tumor enabling the mass to extend or creep into the existing adjacent anatomical structures. Keywords: Cervical Chordoma, Intradural, Computed tomography

Pulse compression favourable aperiodic infrared imaging approach for non-destructive testing and evaluation of bio-materials

NASA Astrophysics Data System (ADS)

Mulaveesala, Ravibabu; Dua, Geetika; Arora, Vanita; Siddiqui, Juned A.; Muniyappa, Amarnath

2017-05-01

In recent years, aperiodic, transient pulse compression favourable infrared imaging methodologies demonstrated as reliable, quantitative, remote characterization and evaluation techniques for testing and evaluation of various biomaterials. This present work demonstrates a pulse compression favourable aperiodic thermal wave imaging technique, frequency modulated thermal wave imaging technique for bone diagnostics, especially by considering the bone with tissue, skin and muscle over layers. In order to find the capabilities of the proposed frequency modulated thermal wave imaging technique to detect the density variations in a multi layered skin-fat-muscle-bone structure, finite element modeling and simulation studies have been carried out. Further, frequency and time domain post processing approaches have been adopted on the temporal temperature data in order to improve the detection capabilities of frequency modulated thermal wave imaging.

[Apical petrositis, osteomyelitis of the base of the skull bones and of the first cervical vertebra in a 5 year-old children following chicken pox].

PubMed

Bogomil'sky, M R; Polunin, M M; Zelikovich, E I; Soldatsky, Yu L; Burova, O V

2016-01-01

This publication was designed to describe a rare case of development of apicalpetrositis in a child presenting with acute otitis mediafollowing chicken pox experienced in the preceding period. We carried out the study with the use of computed tomography (CT) that demonstrated destruction of the temporal bone, bones of the base of the skull and of the first cervical vertebra. The treatment strategy chosen for the management of this condition that included antibiotic therapy and expectant observation proved justified and can be recommended as an algorithm of choice taking into consideration the difficulty of surgical approach to the apex of the petrous pyramid. However, this approach is associated with the high risk of disability arising from the potential injury to the craniocerebral nerves.

Quantitative analysis of the plain radiographic appearance of nonossifying fibroma.

PubMed

Friedland, J A; Reinus, W R; Fisher, A J; Wilson, A J

1995-08-01

To quantitate radiographic features that distinguish the plain radiographic appearance of nonossifying fibroma (NOF) from other solitary lesions of bone. Seven hundred nine cases of focal bone lesions, including 34 NOFs, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of NOF in contrast to other lesions in the data base. The radiographic appearance of NOFs was most consistently a medullary based (97%), lytic lesion (100%) with geographic bone destruction (100%), marginal sclerosis (97%), and well-defined edges (94%). A statistically significant number of lesions were located in the distal aspect of long bones. Unicameral bone cyst shared the most radiographic features with the NOF. Vector analysis showed a large degree of overlap between NOF and other lesions such as aneurysmal bone cyst, chondromyxoid fibroma, and eosinophilic granuloma. The description that optimized sensitivity and prevalence for detection of NOF is a medullary based, ovoid lesion in the distal or proximal portions of a long bone with well-defined edges, a partial or complete rind of sclerosis, and absence of fallen fragment, periosteal reaction, and cortical disruption. The radiographic appearance of NOF is relatively nonspecific but, using vector analysis, can be better elucidated over current textbook descriptions.

HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition

PubMed Central

Gao, Ling; Deng, Hongju; Zhao, Haibo; Hirbe, Angela; Harding, John; Ratner, Lee; Weilbaecher, Katherine

2005-01-01

One in 20 carriers of human T-cell leukemia virus type 1 (HTLV-1) will develop adult T-cell leukemia/lymphoma (ATL), a disease frequently associated with hypercalcemia, bone destruction, and a fatal course refractory to current therapies. Overexpression of the HTLV-1–encoded Tax oncoprotein under the human granzyme B promoter causes large granular lymphocytic leukemia/lymphomas in mice. We found that Tax+ mice spontaneously developed hypercalcemia, high-frequency osteolytic bone metastases, and enhanced osteoclast activity. We evaluated Tax tumors for the production of osteoclast-activating factors. Purification of Tax+ tumor cells and nonmalignant tumor-infiltrating lymphocytes demonstrated that each of these populations expressed transcripts for distinct osteoclast-activating factors. We then evaluated the effect of osteoclast inhibition on tumor formation. Mice doubly transgenic for Tax and the osteoclast inhibitory factor, osteoprotegerin, were protected from osteolytic bone disease and developed fewer soft-tissue tumors. Likewise, osteoclast inhibition with bone-targeted zoledronic acid protected Tax+ mice from bone and soft-tissue tumors and prolonged survival. Tax+ mice represent the first animal model of high-penetrance spontaneous osteolytic bone metastasis and underscore the critical role of nonmalignant host cells recruited by tumor cells in the process of cancer progression and metastasis. PMID:16118323

Phosphorus-31 MRI of bones using quadratic echo line-narrowing

NASA Astrophysics Data System (ADS)

Frey, Merideth; Barrett, Sean; Insogna, Karl; Vanhouten, Joshua

2012-02-01

There is a great need to probe the internal composition of bone on the sub-0.1 mm length scale, both to study normal features and to look for signs of disease. Despite the obvious importance of the mineral fraction to the biomechanical properties of skeletal tissue, few non-destructive techniques are available to evaluate changes in its chemical structure and functional microarchitecture on the interior of bones. MRI would be an excellent candidate, but bone is a particularly challenging tissue to study given the relatively low water density and wider linewidths of its solid components. Recent fundamental research in quantum computing gave rise to a new NMR pulse sequence - the quadratic echo - that can be used to narrow the broad NMR spectrum of solids. This offers a new route to do high spatial resolution, 3D ^31P MRI of bone that complements conventional MRI and x-ray based techniques to study bone physiology and structure. We have used our pulse sequence to do 3D ^31P MRI of ex vivo bones with a spatial resolution of (sub-450 μm)^3, limited only by the specifications of a conventional 4 Tesla liquid-state MRI system. We will describe our plans to push this technique towards the factor of 1000 increase in spatial resolution imposed by fundamental limits.

Mechanical strength of ceramic scaffolds reinforced with biopolymers is comparable to that of human bone.

PubMed

Henriksen, S S; Ding, M; Juhl, M Vinther; Theilgaard, N; Overgaard, S

2011-05-01

Eight groups of calcium-phosphate scaffolds for bone implantation were prepared of which seven were reinforced with biopolymers, poly lactic acid (PLA) or hyaluronic acid in different concentrations in order to increase the mechanical strength, without significantly impairing the microarchitecture. Controls were un-reinforced calcium-phosphate scaffolds. Microarchitectural properties were quantified using micro-CT scanning. Mechanical properties were evaluated by destructive compression testing. Results showed that adding 10 or 15% PLA to the scaffold significantly increased the mechanical strength. The increase in mechanical strength was seen as a result of increased scaffold thickness and changes to plate-like structure. However, the porosity was significantly lowered as a consequence of adding 15% PLA, whereas adding 10% PLA had no significant effect on porosity. Hyaluronic acid had no significant effect on mechanical strength. The novel composite scaffold is comparable to that of human bone which may be suitable for transplantation in specific weight-bearing situations, such as long bone repair.

Optimization of Sample Preparation processes of Bone Material for Raman Spectroscopy.

PubMed

Chikhani, Madelen; Wuhrer, Richard; Green, Hayley

2018-03-30

Raman spectroscopy has recently been investigated for use in the calculation of postmortem interval from skeletal material. The fluorescence generated by samples, which affects the interpretation of Raman data, is a major limitation. This study compares the effectiveness of two sample preparation techniques, chemical bleaching and scraping, in the reduction of fluorescence from bone samples during testing with Raman spectroscopy. Visual assessment of Raman spectra obtained at 1064 nm excitation following the preparation protocols indicates an overall reduction in fluorescence. Results demonstrate that scraping is more effective at resolving fluorescence than chemical bleaching. The scraping of skeletonized remains prior to Raman analysis is a less destructive method and allows for the preservation of a bone sample in a state closest to its original form, which is beneficial in forensic investigations. It is recommended that bone scraping supersedes chemical bleaching as the preferred method for sample preparation prior to Raman spectroscopy. © 2018 American Academy of Forensic Sciences.

Successful subtotal orbitectomy in a cat with osteoma

PubMed Central

Corgozinho, Katia B; Cunha, Simone CS; Siqueira, Ricardo S; Souza, Heloisa JM

2015-01-01

Case summary A 14-year-old Siamese neutered male cat was evaluated for anorexia and a left periorbital mass. Skull radiographic findings showed a well-defined lesion resembling new compact bone formation without destruction. A subtotal orbitectomy was indicated. The tumor was removed intact with a normal tissue margin of at least 1 cm. There were no postsurgical complications. Histopathologic examination revealed an osteoma. The cat returned to normal appetite and activity 15 days after surgery. Six months after surgery, there were no gross signs of recurrence. Relevance and novel information Periorbital tumors are infrequently diagnosed in companion animals and most are malignant. In this case, the diagnosis was orbital osteoma. The most commonly affected bone for osteoma in cats is the mandibular bone; few cases have been identified in orbital bones. Orbital surgery has the potential to be challenging owing to complex anatomy, difficult exposure and the tendency to bleed. Surgical complications are common. In this case, although the disease was advanced, subtotal orbitectomy was successfully performed. PMID:28491397

The Identification of Proteoglycans and Glycosaminoglycans in Archaeological Human Bones and Teeth

PubMed Central

Coulson-Thomas, Yvette M.; Coulson-Thomas, Vivien J.; Norton, Andrew L.; Gesteira, Tarsis F.; Cavalheiro, Renan P.; Meneghetti, Maria Cecília Z.; Martins, João R.; Dixon, Ronald A.; Nader, Helena B.

2015-01-01

Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeletons. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology. PMID:26107959

Reduced mechanical load decreases the density, stiffness, and strength of cancellous bone of the mandibular condyle.

PubMed

Giesen, E B W; Ding, M; Dalstra, M; van Eijden, T M G J

2003-05-01

To investigate the influence of decreased mechanical loading on the density and mechanical properties of the cancellous bone of the human mandibular condyle. Destructive compressive mechanical tests were performed on cancellous bone specimens.Background. Reduced masticatory function in edentate people leads to a reduction of forces acting on the mandible. As bone reacts to its mechanical environment a change in its material properties can be expected. Cylindrical bone specimens were obtained from dentate and edentate embalmed cadavers. Mechanical parameters were determined in the axial and in the transverse directions. Subsequently, density parameters were determined according to a method based on Archimedes' principle. The apparent density and volume fraction of the bone were about 18% lower in the edentate group; no age-related effect on density was found. The decrease of bone in the edentate group was associated with a lower stiffness and strength (about 22% and 28%, respectively). The ultimate strain, however, did not differ between the two groups. Both groups had similar mechanical anisotropy; in axial loading the bone was stiffer and stronger than in transverse loading. Reduced mechanical load had affected the density and herewith the mechanical properties of condylar cancellous bone, but not its anisotropy. The change in material properties of the cancellous bone after loss of teeth indicate that the mandibular condyle is sensitive for changes in its mechanical environment. Therefore, changes in mechanical loading of the condyle have to be accounted for in surgical procedures of the mandible.

Excess TGF-β mediates muscle weakness associated with bone metastases in mice

PubMed Central

Reiken, Steven; Xie, Wenjun; Andersson, Daniel C.; John, Sutha; Chiechi, Antonella; Wright, Laura E.; Umanskaya, Alisa; Niewolna, Maria; Trivedi, Trupti; Charkhzarrin, Sahba; Khatiwada, Pooja; Wronska, Anetta; Haynes, Ashley; Benassi, Maria Serena; Witzmann, Frank A.; Zhen, Gehua; Wang, Xiao; Cao, Xu; Roodman, G. David; Marks, Andrew R.; Guise, Theresa A.

2015-01-01

Cancer-associated muscle weakness is poorly understood and there is no effective treatment. Here, we find that seven different mouse models of human osteolytic bone metastases, representing breast, lung and prostate cancers, as well as multiple myeloma exhibited impaired muscle function, implicating a role for the tumor-bone microenvironment in cancer-associated muscle weakness. We found that TGF-β, released from the bone surface as a result of metastasis-induced bone destruction upregulated NADPH oxidase 4 (Nox4), resulting in elevated oxidization of skeletal muscle proteins, including the ryanodine receptor/calcium (Ca2+) release channel (RyR1). The oxidized RyR1 channels leaked Ca2+, resulting in lower intracellular signaling required for proper muscle contraction. We found that inhibiting RyR1 leak, TGF-β signaling, TGF-β release from bone or Nox4 all improved muscle function in mice with MDA-MB-231 bone metastases. Humans with breast cancer- or lung cancer-associated bone metastases also had oxidized skeletal muscle RyR1 that is not seen in normal muscle. Similarly, skeletal muscle weakness, higher levels of Nox4 protein and Nox4 binding to RyR1, and oxidation of RyR1 were present in a mouse model of Camurati-Engelmann disease, a non-malignant metabolic bone disorder associated with increased TGF-β activity. Thus, metastasis-induced TGF-β release from bone contributes to muscle weakness by decreasing Ca2+-induced muscle force production. PMID:26457758

Fluorosis increases the risk of postmenopausal osteoporosis by stimulating interferon γ.

PubMed

Lv, Yun-Gang; Kang, Li; Wu, Guangyao

2016-10-14

Estrogen deficiency in postmenopausal women frequently activates osteoclasts (OC), accelerates bone resorption, and leads to osteoporosis (OP). Previous studies have demonstrated that interferon γ (IFNγ) could increase bone resorption and may be involved in postmenopausal OP. Fluorosis also increased the risk of fractures and dental fluorosis, and fluoride may enhance osteoclast formation and induce osteoclastic bone destruction in postmenopausal women, but the underlying mechanisms are as yet unknown. Here, we show that serum fluoride and IFNγ levels are negatively correlated with bone mineral density (BMD) in postmenopausal women residing in a fluorotic area. Estrogen suppresses IFNγ, which is elevated by fluoride, playing a pivotal role in triggering bone loss in estrogen-deficient conditions. In vitro, IFNγ is inhibited by estrogen treatment and increased by fluoride in Raw264.7 cell, an osteoclast progenitor cell line. In ovariectomized (Ovx) mice, estrogen loss and IFNγ promote OC activation and subsequent bone loss in vivo. However, IFNγ deficiency prevents bone loss in Ovx mice even in fluoride conditions. Interestingly, fluoride fails to increase IFNγ expression in estrogen receptor α (ERα)-deficient conditions, but not in ERβ-deficient conditions. These findings demonstrate that fluorosis increases the bone loss in postmenopausal OP through an IFNγ-dependent mechanism. IFNγ signaling activates OC and aggravates estrogen deficiency inducing OP. Thus, stimulation of IFNγ production is a pivotal ''upstream'' mechanism by which fluoride promotes bone loss. Suppression of IFNγ levels may constitute a therapeutic approach for preventing bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Suppression of asparaginyl endopeptidase attenuates breast cancer-induced bone pain through inhibition of neurotrophin receptors.

PubMed

Yao, Peng; Ding, Yuanyuan; Han, Zhenkai; Mu, Ying; Hong, Tao; Zhu, Yongqiang; Li, Hongxi

2017-01-01

Objective Cancer-induced bone pain is a common clinical problem in breast cancer patients with bone metastasis. However, the mechanisms driving cancer-induced bone pain are poorly known. Recent studies show that a novel protease, asparaginyl endopeptidase (AEP) plays crucial roles in breast cancer metastasis and progression. We aim to determine the functions and targeted suppress of AEP in a mouse model of breast cancer-induced bone pain. Methods Breast cancer cells with AEP knocked-down or overexpression were constructed and implanted into the intramedullary space of the femur to induce pain-like behavior in mice. AEP-specific inhibitors or purified AEP proteins were further used in animal model. The histological characters of femur and pain ethological changes were measured. The expressions of AEP and neurotrophin receptors (p75NTR and TrkA) in dorsal root ganglion and spinal cord were examined. Results Femur radiographs and histological analysis revealed that cells with AEP knocked-down reduced bone destruction and pain behaviors. However, cells with AEP overexpression elevated bone damage and pain behaviors. Further, Western blot results found that the expressions of p75NTR and TrkA in dorsal root ganglions and spinal cords were reduced in mice inoculated with AEP knocked-down cells. Targeted suppression of AEP with specific small compounds significantly reduced the bone pain while purified recombinant AEP proteins increased bone pain. Conclusions AEP aggravate the development of breast cancer bone metastasis and bone pain by increasing the expression of neurotrophin receptors. AEP might be an effective target for treatment of breast cancerinduced bone pain.

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

PubMed

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

2012-07-01

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

Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.

PubMed

Wehrhan, F; Hyckel, P; Amann, K; Ries, J; Stockmann, P; Schlegel, Ka; Neukam, Fw; Nkenke, E

2011-05-01

Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone. An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels. Labelling indices were significantly lower for Msx-1 (P < 0.03) and RANKL (P < 0.003) and significantly higher (P < 0.02) for BMP-2 in ONJ compared with healthy bone. Expression was sevenfold lower (P < 0.03) for Msx-1, 22-fold lower (P < 0.001) for RANKL and eightfold higher (P < 0.02) for BMP-2 in ONJ bone. Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future. © 2011 John Wiley & Sons A/S.

MR imaging in staging of bone tumors

PubMed Central

Ehara, Shigeru

2006-01-01

For staging of bone tumors, TNM and Enneking’s systems are used with some differences. Magnetic resonance imaging is particularly useful for defining the extent of high-grade tumors, including transcortical and intertrabecular infiltration and periosteal extension. The concepts of compartment and curative surgical margins are important for bone tumor staging. PMID:17098647

Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

PubMed

Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

2016-02-17

Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anterior interbody fusion for cervical osteomyelitis

PubMed Central

Bartal, A. D.; Schiffer, J.; Heilbronn, Y. D.; Yahel, M.

1972-01-01

Interbody fusion for stabilization of the cervical spine after osteomyelitic destruction of the body of C5 vertebra is reported in a patient with quadriplegia and sphincter disturbances secondary to an epidural abscess. The successful union of the bone graft along with complete neurological recovery after anterior decompression and evacuation of the epidural mass seem to justify the procedure. Images PMID:4554587

Acute peg in hole docking in the management of infected non-union of long bones.

PubMed

Dhar, Shabir Ahmed; Mir, Mohammed Ramzan; Ahmed, Molvi Sajjad; Afzal, Suhail; Butt, Mohammed Farooq; Badoo, A R; Dar, Irshad Tabasum; Hussain, Anwar

2008-08-01

The Ilizarov method has been studied extensively in the management of non-union of long bones. In most cases this involves filling of defects present primarily or after débridement by bone transport. Acute docking over gaps longer than 2 cm has not been adequately studied, however. The purpose of this paper is to report the efficacy of acute peg in hole docking as a bone graft-sparing modality in the management of infected non-union of long bones.

Primary paranasal sinus hyalinizing clear cell carcinoma: a case report.

PubMed

AlAli, Batool M; Alyousef, Mohammed J; Kamel, Ahmad Salah; Al Hamad, Mohammad A; Al-Bar, Mohammad H; Algowiez, Roaa M

2017-09-25

Hyalinizing clear cell carcinoma (HCCC) is a rare low-grade tumour of salivary glands that was first described as a distinct entity in 1994 by Milchgrub et al. EWSR1-ATF1 fusion was found to be specific for this tumour. The majority of the reported cases of HCCC arise from minor salivary glands within the oral cavity. Primary HCCC of the paranasal sinus is extremely uncommon. To our knowledge, only three cases have been reported in the English literature. Herein, we present a case of HCCC of the posterior ethmoid/maxillary sinus. A 63-year-old lady who presented with a long history of epistaxis. CT scan revealed a destructive mass in the left ethmoid/posterior maxillary sinus extending to the nasal cavity. Surgical excision was done and microscopic evaluation showed a tumour composed mainly of nests of clear epithelial cells separated by fibrocellular and hyalinized septa with extensive bone destruction. The tumour cells expressed CK5/6, EMA and p63 immunohistochemically but were negative for S100 protein, PAX-8, RCC and CK7. Sinonasal renal cell-like adenocarcinomas, myoepithelial carcinoma and metastatic renal cell carcinoma were excluded by radiological and immunohistochemical studies. Fluorescence in situ hybridization analysis revealed an EWSR1 gene rearrangement. Postoperative radiation was administrated and the patient did not show recurrence or distant metastasis 4 months after the surgery. Head and neck region have many tumours that demonstrate clear cell changes on histology. Thus, the differential diagnosis for HCCC is wide. Awareness of this rare entity and the possibility of it is arising in unusual location is necessary. EWSR1-AFT1 fusion, a consistent finding in HCCC, can be used to confirm the diagnosis.

Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium.

PubMed

Lewis, Rebecca M; Keller, Jesse J; Wan, Liangcai; Stone, Jennifer S

2018-07-01

Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics. In mature basilar papillae, BMP4 mRNA is highly expressed in hair cells, but not in hair cell progenitors (supporting cells). Supporting cells transcribe genes encoding receptors for BMP4 (BMPR1A, BMPR1B, and BMPR2) and effectors of BMP4 signaling (ID transcription factors). Following hair cell destruction, BMP4 transcripts are lost from the sensory epithelium. Using organotypic cultures, we demonstrate that treatments with BMP4 during hair cell destruction prevent supporting cells from upregulating expression of the pro-hair cell transcription factor ATOH1, entering the cell cycle, and fully transdifferentiating into hair cells, but they do not induce cell death. By contrast, noggin, a BMP4 inhibitor, increases numbers of regenerated hair cells. These findings demonstrate that BMP4 antagonizes hair cell regeneration in the chicken basilar papilla, at least in part by preventing accumulation of ATOH1 in hair cell precursors. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of conventional and synchrotron-radiation-based microtomography of bone around dental implants

NASA Astrophysics Data System (ADS)

Cattaneo, Paolo M.; Dalstra, Michel; Beckmann, Felix; Donath, Tilman; Melsen, Birte

2004-10-01

This study explores the application of conventional micro tomography (μCT) and synchrotron radiation (SR) based μCT to evaluate the bone around titanium dental implants. The SR experiment was performed at beamline W2 of HASYLAB at DESY using a monochromatic X-ray beam of 50 keV. The testing material consisted of undecalcified bone segments harvested from the upper jaw of a macaca fascicularis monkey each containing a titanium dental implant. The results from the two different techniques were qualitatively compared with conventional histological sections examined under light microscopy. The SR-based μCT produced images that, especially at the bone-implant interface, are less noisy and sharper than the ones obtained with conventional μCT. For the proper evaluation of the implant-bone interface, only the SR-based μCT technique is able to display the areas of bony contact and visualize the true 3D structure of bone around dental implants correctly. This investigation shows that both conventional and SR-based μCT scanning techniques are non-destructive methods, which provide detailed images of bone. However with SR-based μCT it is possible to obtain an improved image quality of the bone surrounding dental implants, which display a level of detail comparable to histological sections. Therefore, SR-based μCT scanning could represent a valid, unbiased three-dimensional alternative to evaluate osseointegration of dental implants

Blockade of epidermal growth factor receptor signaling leads to inhibition of renal cell carcinoma growth in the bone of nude mice.

PubMed

Weber, Kristy L; Doucet, Michele; Price, Janet E; Baker, Cheryl; Kim, Sun Jin; Fidler, Isaiah J

2003-06-01

Renal cell carcinoma (RCC) frequently produces metastases to the musculoskeletal system that are a major source of morbidity in the form of pain, immobilization, fractures, neurological compromise, and a decreased ability to perform activities of daily living. Patients with metastatic RCC therefore have a dismal prognosis because there is no effective adjuvant treatment for this disease. Because the epidermal growth factor receptor (EGF-R) signaling cascade is important in the growth and metastasis of RCC, its blockade has been hypothesized to inhibit tumor growth and hence prevent resultant bone destruction. We determined whether blockade of EGF-R by the tyrosine kinase inhibitor PKI 166 inhibited the growth of RCC in bone. We use a novel cell line, RBM1-IT4, established from a human RCC bone metastasis. Protein and mRNA expression of the ligands and receptors was assessed by Western and Northern blots. The stimulation of RBM1-IT4 cells with epidermal growth factor or transforming growth factor alpha resulted in increased cellular proliferation and tyrosine kinase autophosphorylation. PKI 166 prevented these effects. First, RBM1-IT4 cells were implanted into the tibia of nude mice, where they established lytic, progressively growing lesions, after which the mice were treated with PKI 166 alone or in combination with paclitaxel (Taxol). Immunohistochemical analysis revealed that tumor cells and tumor-associated endothelial cells in control mice expressed activated EGF-R. Treatment of mice with PKI 166 alone or in combination with Taxol produced a significant decrease in the incidence and size of bone lesions as compared with the results in control or Taxol-treated mice (P < 0.001). Treatment with PKI 166 also decreased the expression of phosphorylated EGF-R by tumor cells and tumor-associated endothelial cells, and this was even more pronounced with PKI 166 plus Taxol treatment. The PKI 166 plus Taxol combination produced apoptosis of tumor cells and tumor-associated endothelial cells. Tumor cell proliferation, shown by proliferating cell nuclear antigen positivity, was decreased in all treatment groups. In addition, the integrity of the bone was maintained in mice treated with PKI 166 or PKI 166 plus Taxol, whereas massive bone destruction was seen in control and Taxol-treated mice. These results suggest that blockade of EGF-R signaling inhibits growth of RCC in the bone by its effect on tumor cells and tumor-associated endothelial cells.

Camp Minden Draft QASP and Work Plan for Public Feedback

EPA Pesticide Factsheets

ESI has developed these operational plans, technical approaches, and related required resources based upon extensive review and planning for material removal, transportation, staging, and Contained Burn Chamber (CBC) destruction of materials.

Mechanical Characterization of Bone: State of the Art in Experimental Approaches-What Types of Experiments Do People Do and How Does One Interpret the Results?

PubMed

Bailey, Stacyann; Vashishth, Deepak

2018-06-18

The mechanical integrity of bone is determined by the direct measurement of bone mechanical properties. This article presents an overview of the current, most common, and new and upcoming experimental approaches for the mechanical characterization of bone. The key outcome variables of mechanical testing, as well as interpretations of the results in the context of bone structure and biology are also discussed. Quasi-static tests are the most commonly used for determining the resistance to structural failure by a single load at the organ (whole bone) level. The resistance to crack initiation or growth by fracture toughness testing and fatigue loading offers additional and more direct characterization of tissue material properties. Non-traditional indentation techniques and in situ testing are being increasingly used to probe the material properties of bone ultrastructure. Destructive ex vivo testing or clinical surrogate measures are considered to be the gold standard for estimating fracture risk. The type of mechanical test used for a particular investigation depends on the length scale of interest, where the outcome variables are influenced by the interrelationship between bone structure and composition. Advancement in the sensitivity of mechanical characterization techniques to detect changes in bone at the levels subjected to modifications by aging, disease, and/or pharmaceutical treatment is required. As such, a number of techniques are now available to aid our understanding of the factors that contribute to fracture risk.

Is cortical bone hip? What determines cortical bone properties?

PubMed

Epstein, Sol

2007-07-01

Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal antibody denosumab binds to RANKL, inhibiting its action and thus improving BMD significantly.

Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway.

PubMed

Mun, Se Hwan; Kim, Hyuk Soon; Kim, Jie Wan; Ko, Na Young; Kim, Do Kyun; Lee, Beob Yi; Kim, Bokyung; Won, Hyung Sik; Shin, Hwa-Sup; Han, Jeung-Whan; Lee, Hoi Young; Kim, Young Mi; Choi, Wahn Soo

2009-09-01

We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway.

Non-Destructive Techniques Based on Eddy Current Testing

PubMed Central

García-Martín, Javier; Gómez-Gil, Jaime; Vázquez-Sánchez, Ernesto

2011-01-01

Non-destructive techniques are used widely in the metal industry in order to control the quality of materials. Eddy current testing is one of the most extensively used non-destructive techniques for inspecting electrically conductive materials at very high speeds that does not require any contact between the test piece and the sensor. This paper includes an overview of the fundamentals and main variables of eddy current testing. It also describes the state-of-the-art sensors and modern techniques such as multi-frequency and pulsed systems. Recent advances in complex models towards solving crack-sensor interaction, developments in instrumentation due to advances in electronic devices, and the evolution of data processing suggest that eddy current testing systems will be increasingly used in the future. PMID:22163754

Non-destructive techniques based on eddy current testing.

PubMed

García-Martín, Javier; Gómez-Gil, Jaime; Vázquez-Sánchez, Ernesto

2011-01-01

Non-destructive techniques are used widely in the metal industry in order to control the quality of materials. Eddy current testing is one of the most extensively used non-destructive techniques for inspecting electrically conductive materials at very high speeds that does not require any contact between the test piece and the sensor. This paper includes an overview of the fundamentals and main variables of eddy current testing. It also describes the state-of-the-art sensors and modern techniques such as multi-frequency and pulsed systems. Recent advances in complex models towards solving crack-sensor interaction, developments in instrumentation due to advances in electronic devices, and the evolution of data processing suggest that eddy current testing systems will be increasingly used in the future.

An Evaluation Method for Suppression of Pathogenic Fusarium oxysporum by Soil Microorganisms Using the Dilution Plate Technique.

PubMed

Mitsuboshi, Masahiro; Kioka, Yuuzou; Noguchi, Katsunori; Asakawa, Susumu

2017-01-01

Volume 31, No. 3, Page 307-313, 2016Page 310, Legend for Fig. 4 IncorrectFig. 4. Growth degree of Fusarium oxysporum f. sp. spinaciae for organic fertilizers at each dilution based on an estimation of the ellipse area (A) and extension length (B) of the colony. Cont, compound inorganic fertilizer; SBM, steamed bone meal; CDC, cow dung compost; MI, microbial inoculant. Values show mean of medians of degrees with SE (n=3). The ellipse area and extension length for control plates were 4,475 mm 2 and 36.5 mm, respectively. CorrectFig. 4. Growth degree of Fusarium oxysporum f. sp. spinaciae for organic fertilizers at each dilution based on an estimation of the ellipse area (A) and extension length (B) of the colony. Cont, compound inorganic fertilizer; SBM, steamed bone meal; CDC, cow dung compost; MI, microbial inoculant. Values show mean of growth degrees with SE (n=3). The ellipse area and extension length for control plates were 4,475 mm 2 and 36.5 mm, respectively. Page 311, Legend for Fig. 5 IncorrectFig. 5. Growth degree of Fusarium oxysporum f. sp. spinaciae for soil applied with organic fertilizers at each dilution based on an estimation of the ellipse area (A) and extension length (B) of the colony. Cont, compound inorganic fertilizer; SBM, steamed bone meal; CDC, cow dung compost; MI, microbial inoculant. Values show the mean of medians of degrees with SE (n=3). The ellipse area and extension length for control plates were 5,473 mm 2 and 40.5 mm, respectively. CorrectFig. 5. Growth degree of Fusarium oxysporum f. sp. spinaciae for soil applied with organic fertilizers at each dilution based on an estimation of the ellipse area (A) and extension length (B) of the colony. Cont, compound inorganic fertilizer; SBM, steamed bone meal; CDC, cow dung compost; MI, microbial inoculant. Values show the mean of growth degrees with SE (n=3). The ellipse area and extension length for control plates were 5,473 mm 2 and 40.5 mm, respectively. Page 312, Legend for Fig. 7 IncorrectFig. 7. Growth degree of Fusarium oxysporum f. sp. spinaciae at each dilution based on an estimation of the ellipse area (A) and extension length (B) of the colony. Cont, compound inorganic fertilizer; SBM, steamed bone meal; CDC, cow dung compost; MI2, microbial inoculant applied with 2,000 kg ha -1 ; MI10, microbial inoculant applied with 10,000 kg ha -1 . Values show the mean of medians of degrees with SE (n=3). The ellipse area and extension length for control plates were 3,404 mm 2 and 29.7 mm, respectively. CorrectFig. 7. Growth degree of Fusarium oxysporum f. sp. spinaciae at each dilution based on an estimation of the ellipse area (A) and extension length (B) of the colony. Cont, compound inorganic fertilizer; SBM, steamed bone meal; CDC, cow dung compost; MI2, microbial inoculant applied with 2,000 kg ha -1 ; MI10, microbial inoculant applied with 10,000 kg ha -1 . Values show the mean of growth degrees with SE (n=3). The ellipse area and extension length for control plates were 3,404 mm 2 and 29.7 mm, respectively. The authors would like to apologize for these corrections and any inconvenience caused.

Hydroxyapatite: Vibrational spectra and monoclinic to hexagonal phase transition

NASA Astrophysics Data System (ADS)

Slepko, Alexander; Demkov, Alexander A.

2015-02-01

Fundamental studies of biomaterials are necessary to deepen our understanding of their degradation and to develop cure for related illnesses. Biomineral hydroxyapatite Ca10(PO4)6(OH)2 is the main mineral constituent of mammal bone, and its synthetic analogues are used in biomedical applications. The mineral can be found in either hexagonal or monoclinic form. The transformation between these two phases is poorly understood, but knowing its mechanism may be critical to reversing processes in bone related to aging. Using density functional theory, we investigate the mechanisms of the phase transformation and estimate the transition temperature to be 680 K in fair agreement with the experimental temperature of 470 K. We also report the heat capacity of hydroxyapatite and a peculiarity in its phonon dispersion that might allow for non-destructive measurements of the crystal composition with applications in preventive medical screening for bone mineral loss.

Osteoimmunology - Unleashing the concepts

PubMed Central

Murthy, M. Bhanu

2011-01-01

Osteoimmunology is an emerging field of research dedicated to the relationship between the immune processes and the bone metabolism of various inflammatory bone diseases. The regulatory mechanisms governing the osteoclast and osteoblast are critical for understanding the health and disease of the skeletal system. These interactions are either by cell to cell contact or by the secretion of immune regulatory mediators like cytokines and chemokines by immune cells that are governed by the RANKL (TRANCE)-RANK- OPG axis. TRANCE-RANK signaling has served as a cornerstone of osteoimmunology research. There is increased recognition of the importance of the inflammatory and immune responses in the pathogenesis of periodontal disease. Thus, this field has provided a framework for studying the mechanisms underlying periodontal destruction. As bone homeostasis is mainly regulated by both the immune and endocrine systems, there emerged osteoimmunoendocrinology where adipokines take the lead. This review focuses on the underlying concepts of osteoimmunology, its relation to Periodontics. PMID:22028503

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

PubMed

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

2018-03-21

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

Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease

PubMed Central

Seeley, Erin H.; Wilson, Kevin J.; Yankeelov, Thomas E.; Johnson, Rachelle W.; Gore, John C.; Caprioli, Richard M.; Matrisian, Lynn M.; Sterling, Julie A.

2014-01-01

Bone metastases are a clinically significant problem that arises in approximately 70% of metastatic breast cancer patients. Once established in bone, tumor cells induce changes in the bone microenvironment that lead to bone destruction, pain, and significant morbidity. While much is known about the later stages of bone disease, less is known about the earlier stages or the changes in protein expression in the tumor micro-environment. Due to promising results of combining magnetic resonance imaging (MRI) and Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI IMS) ion images in the brain, we developed methods for applying these modalities to models of tumor-induced bone disease in order to better understand the changes in protein expression that occur within the tumor-bone microenvironment. Specifically, we integrated three dimensional-volume reconstructions of spatially resolved MALDI IMS with high-resolution anatomical and diffusion weighted MRI data and histology in an intratibial model of breast tumor-induced bone disease. This approach enables us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo imaging and ex vivo histology data. To the best of our knowledge, this is the first time these three modalities have been rigorously registered in the bone. The MALDI mass-to-charge ratio peaks indicate differential expression of calcyclin, ubiquitin, and other proteins within the tumor cells, while peaks corresponding to hemoglobin A and calgranulin A provided molecular information that aided in the identification of areas rich in red and white blood cells, respectively. This multimodality approach will allow us to comprehensively understand the bone-tumor microenvironment and thus may allow us to better develop and test approaches for inhibiting bone metastases. PMID:24487126

Otogenic pneumocephalus as a complication of multiple myeloma.

PubMed

Maguire, Melissa J; Nath, Uma; Bignardi, Guiseppe E

2012-09-01

We report a case of otogenic pneumocephalus in an 80-year-old woman with multiple myeloma. The pneumocephalus was associated with Haemophilus influenzae otitis media and reactive meningitis in the absence of an intracranial brain abscess. Myeloma causes thinning of bone trabeculae and destructive lytic bone lesions. This can predispose to a risk of pathologic fractures and, in patients with skull vault involvement, to the rare complication of pneumocephalus. Therefore, pneumocephalus should be considered in the differential diagnosis of acute headache in patients with multiple myeloma, especially those with skull vault involvement. Prompt computed tomography and liaison between the otolaryngology and neurology teams may assist in making an early diagnosis and preventing life-threatening intracranial complications.

Interleukin-6 from subchondral bone mesenchymal stem cells contributes to the pathological phenotypes of experimental osteoarthritis

PubMed Central

Wu, Xiaofeng; Cao, Lei; Li, Fan; Ma, Chao; Liu, Guangwang; Wang, Qiugen

2018-01-01

As a main cause of morbidity in the aged population, osteoarthritis (OA) is characterized by cartilage destruction, synovium inflammation, osteophytes, and subchondral bone sclerosis. To date its etiology remains elusive. Recent data highlight an important role of subchondral bone in the onset and progression of OA. Therefore, elucidating the mechanisms underlying abnormal subchondral bone could be of importance in the treatment of OA. Interleukin-6 is a proinflammatory cytokine involved in many physiological and pathological processes. Although in vitro and in vivo studies have indicated that IL-6 is an important cytokine in the physiopathogenesis of OA, its effects on subchondral bone have not been studied in OA animal models. In this study, we aimed to i) investigate the role of IL-6 in the pathological phenotypes of OA subchondral bone MSCs including increase in cell numbers, mineralization disorder and abnormal type I collagen production; ii) explore whether the systemic blockade of IL-6 signaling could alleviate the pathological phenotypes of experimental OA. We found that IL-6 was over-secreted by OA subchondral bone MSCs compared with normal MSCs and IL-6/STAT3 signaling was over-activated in subchondral bone MSCs, which contributed to the pathological phenotypes of OA subchondral bone MSCs. More importantly, systemic inhibition of IL-6/STAT3 signaling with IL-6 antibody or STAT3 inhibitor AG490 decreased the severity of pathological phenotypes of OA subchondral bone MSCs and cartilage lesions in OA. Our findings provide strong evidence for a pivotal role for IL-6 signaling in OA and open up new therapeutic perspectives. PMID:29736207

Acute peg in hole docking in the management of infected non-union of long bones

PubMed Central

Mir, Mohammed Ramzan; Ahmed, Molvi Sajjad; Afzal, Suhail; Butt, Mohammed Farooq; Badoo, A. R.; Dar, Irshad Tabasum; Hussain, Anwar

2007-01-01

The Ilizarov method has been studied extensively in the management of non-union of long bones. In most cases this involves filling of defects present primarily or after débridement by bone transport. Acute docking over gaps longer than 2 cm has not been adequately studied, however. The purpose of this paper is to report the efficacy of acute peg in hole docking as a bone graft-sparing modality in the management of infected non-union of long bones. PMID:17387474

Evaluating cochlear implant trauma to the scala vestibuli.

PubMed

Adunka, O; Kiefer, J; Unkelbach, M H; Radeloff, A; Gstoettner, W

2005-04-01

Placement of cochlear implant electrodes into the scala vestibuli may be intentional, e.g. in case of blocked scala tympani or unintentional as a result of trauma to the basilar membrane or erroneous location of the cochieostomy. The aim of this study was to evaluate the morphological consequences and cochlear trauma after implantation of different cochlear implant electrode arrays in the scala vestibuli. Human temporal bone study with histological and radiological evaluation. Twelve human cadaver temporal bones were implanted with different cochlear implant electrodes. Implanted bones were processed using a special method to section undecalcified bone. Cochlear trauma and intracochlear positions. All implanted electrodes were implanted into the scala vestibuli using a special approach that allows direct scala vestibuli insertions. Fractures of the osseous spiral lamina were evaluated in some bones in the basal cochlear regions. In most electrodes, delicate structures of the organ of Corti were left intact, however, Reissner's membrane was destroyed in all specimens and the electrode lay upon the tectorial membrane. In some bones the organ of Corti was destroyed. Scala vestibuli insertions did not cause severe trauma to osseous or neural structures, thus preserving the basis for electrostimulation of the cochlea. However, destruction of Reissner's membrane and impact on the Organ of Corti can be assumed to destroy residual hearing.

Biodegradable hybrid tissue engineering scaffolds for reconstruction of large bone defects

NASA Astrophysics Data System (ADS)

Barati, Danial

Complex skeletal injuries and large bone fractures are still a significant clinical problem in US. Approximately 1.5 million Americans (veterans, their families, and civilians) every year suffer from bone loss due to traumatic skeletal injuries, infection, and resection of primary tumors that require extensive grafting to bridge the gap. The US bone graft market is over $2.2 billion a year. Due to insufficient mechanical stability, lack of vascularity, and inadequate resorption of the graft, patients with traumatic large skeletal injuries undergo multiple costly operations followed by extensive recovery steps to maintain proper bone alignment and length. Current strategies for repairing damaged or diseased bones include autologous or allograft bone transplantations. However, limited availability of autografts and risk of disease transmission associated with allografts have necessitated the search for the development of new bone graft options and strategies. The overall goal of this project is to develop a much-needed bone-mimetic engineered graft as a substitute for current strategies providing required bone grafts for reconstruction of large bone defects. This project will use the structure of natural cortical bone as a guide to produce an engineered bone graft with balanced strength, osteogenesis, vascularization, and resorption. The outcome of this project will be a biodegradable hybrid scaffold system (similar to natural cortical bone) including a mechanically strong scaffold allowing for mechanical stability of the load-bearing defect site and a soft and highly porous structure such as a hydrogel phase which will allow for efficient cell and growth factor delivery into the defect implantation site, cell niche establishment and promotion of mineralization. Successful completion of this project will transform bone graft technology for regeneration of complex bone defects from a frozen or freeze-dried allograft to a safe, infection-free, mechanically-stable, osteoinductive, and vasculogenic graft that is ultimately displaced by the patient's own tissue.

Cervical spine disc prosthesis: radiographic, biomechanical and morphological post mortal findings 12 weeks after implantation. A retrieval example.

PubMed

Pitzen, Tobias; Kettler, Annette; Drumm, Joerg; Nabhan, Abdullah; Steudel, Wolf Ingo; Claes, Lutz; Wilke, Hans Joachim

2007-07-01

There is a gap between in vitro and clinical studies concerning performance of spinal disc prosthesis. Retrieval studies may help to bridge this gap by providing more detailed information about motion characteristics, wear properties and osseous integration. Here, we report on the radiographic, mechanical, histological properties of a cervical spine segment treated with a cervical spine disc prosthesis (Prodisc C, Synthes Spine, Paoli, USA) for 3 months. A 48-year-old male received the device due to symptomatic degenerative disc disease within C5-C6. The patient recovered completely from his symptoms. Twelve weeks later, he died from a subarachnoid hemorrhage. During routine autopsy, C3-T1 was removed with all attached muscles and ligaments and subjected to plain X-rays and computed tomography, three dimensional flexibility tests, shear test as well as histological and electronic microscopic investigations. We detected radiolucencies mainly at the cranial interface between bone and implant. The flexibility of the segment under pure bending moments of +/-2.5 Nm applied in flexion/extension, axial rotation and lateral bending was preserved, with, however, reduced lateral bending and enlarged neutral zone compared to the adjacent segments C4-C5, and C6-C7. Stepwise increase of loading in flexion/extension up to +/-9.5 Nm did not result in segmental destruction. A postero-anterior force of 146 N was necessary to detach the lower half of the prosthesis from the vertebra. At the polyethylene (PE) core, signs of wear were observed compared to an unused core using electronic microscopy. Metal and PE debris without signs of severe inflammatory reaction was found within the surrounding soft tissue shell of the segment. A thin layer of soft connective tissue covered the major part of the implant endplate. Despite the limits of such a case report, the results show: that such implants are able to preserve at least a certain degree of segmental flexibility, that direct bone implant contact is probably rare, and that debris may be found after 12 weeks.

MIF induces osteoclast differentiation and contributes to progression of periodontal disease in mice.

PubMed

Madeira, Mila Fernandes Moreira; Queiroz-Junior, Celso Martins; Costa, Graciela Mitre; Santos, Patrícia Campi; Silveira, Elcia Maria; Garlet, Gustavo Pompermaier; Cisalpino, Patrícia Silva; Teixeira, Mauro Martins; Silva, Tarcília Aparecida; Souza, Daniele da Glória

2012-02-01

Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms from the oral biofilm. Oral inoculation of mice with the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) induces marked alveolar bone loss and local production of inflammatory mediators, including Macrophage Migration Inhibitory Factor (MIF). The role of MIF for alveolar bone resorption during PD is not known. In the present study, experimental PD was induced in BALB/c wild-type mice (WT) and MIF knockout mice (MIF⁻/⁻) through oral inoculation of Aa. Despite enhanced number of bacteria, MIF⁻/⁻ mice had reduced infiltration of TRAP-positive cells and reduced alveolar bone loss. This was associated with decreased neutrophil accumulation and increased levels of IL-10 in periodontal tissues. TNF-α production was similar in both groups. In vitro, LPS from Aa enhanced osteoclastic activity in a MIF-dependent manner. In conclusion, MIF has role in controlling bacterial growth in the context of PD but contributes more significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Phased laser diode array permits selective excitation of ultrasonic guided waves in coated bone-mimicking tubes

NASA Astrophysics Data System (ADS)

Moilanen, Petro; Salmi, Ari; Kilappa, Vantte; Zhao, Zuomin; Timonen, Jussi; Hæggström, Edward

2017-10-01

This paper validates simulation predictions, which state that specific modes could be enhanced in quantitative ultrasonic bone testing. Tunable selection of ultrasonic guided wave excitation is useful in non-destructive testing since it permits the mediation of energy into diagnostically useful modes while reducing the energy mediated into disturbing contributions. For instance, it is often challenging to distinguish and extract the useful modes from ultrasound signals measured in bone covered by a soft tissue. We show that a laser diode array can selectively excite ultrasound in bone mimicking phantoms. A fiber-coupled diode array (4 elements) illuminated two solid tubes (2-3 mm wall thickness) embraced by an opaque soft-tissue mimicking elastomer coating (5 mm thick). A predetermined time delay matching the selected mode and frequency was employed between the outputs of the elements. The generated ultrasound was detected by a 215 kHz piezo receiver. Our results suggest that this array reduces the disturbances caused by the elastomer cover and so pave way to permit non-contacting in vivo guided wave ultrasound assessment of human bones. The implementation is small, inexpensive, and robust in comparison with the conventional pulsed lasers.

Radiologic Diagnosis of Spondylodiscitis, Role of Magnetic Resonance

PubMed Central

Ramadani, Naser; Dedushi, Kreshnike; Kabashi, Serbeze; Mucaj, Sefedin

2017-01-01

Introduction: Study aim is to report the Magnetic Resonance Imaging (MRI) features of acute and chronic spontaneous spondylodiscitis. Case report: 57 year old female, complaining of a fever and longstanding cervical pain worsened during physical therapy. Methods: MR images were acquired using superconductive magnet 1.5 T, with the following sequences: sagittal PD and T2 TSE, sagittal T1 SE, axial PD and T2 TSE (lumbar spine), axial T2 GRE (cervical spine). Axial and sagittal T1 SE after administration of (gadolinium DTPA). Examination was reviewed by three radiologists and compared to CT findings. Results: Patient reported cervical pain associated with fever and minimal weight loss. Blood tests were normal except hyperglycemia (DM tip II). X Ray: vertebral destruction localized at C-4 and C-5: NECT: destruction of the C-4/C-5 vertebral bodies (ventral part). MRI: Low signal of the bone marrow on T1l images, which enhanced after Gd-DTPA administration and became intermediate or high on T2 images. The steady high signal intensity of the disk on T2 images and enhancement on T1 images is typical for an acute inflammatory process. Bone Scintigrafi results: Bone changes suspicious for metastasis. Whole body CT results: apart from spine, no other significant changes. Conclusion: MRI is the most sensitive technique for the diagnosis of spondylodiscitis in the acute phase and comparable to CT regarding chronial stage of the disease. The present imagining essay os aimed at showing the main magnetic resonance imaging findings of tuberculous discitis. PMID:28484299

How do skeletons with HIV present? A study on the identified CAL Milano Cemetery Skeletal Collection.

PubMed

Biehler-Gomez, Lucie; Cabrini, Antonio; De Angelis, Danilo; Cattaneo, Cristina

2018-04-24

With the Human Immunodeficiency Virus (HIV) infection and Acquired Immune Deficiency Syndrome (AIDS) pandemic, the study of HIV/AIDS on bones has become of pivotal interest for research in bone pathologies, forensic applications (especially in the matter of identification when confronted to antemortem data) and medical purposes. In this paper, we document and discuss the macroscopic lesions found on the skeletons of nine individuals with known HIV, including four with known AIDS, coming from the identified CAL Milano Cemetery Skeletal Collection. As a result, several types of lesions were observed on bones: periosteal new bone formation, dental lesions, thickening of the frontal diploë, destructive localized porosity and evidence of trauma. None of the lesions reported can be directly linked to HIV because the virus does not directly affect bones in a macroscopic way. However, HIV/AIDS-induced infections and inflammations and HIV-related risk factors may leave bone markers. The differential diagnosis of each of the lesions noted in this research and its potential link to HIV or AIDS was discussed. Although it is not possible to diagnose HIV on bare bones, this was not the focus of this study. To our knowledge, no anthropological study has ever been performed on known HIV individuals. With this paper, we present for the first time skeletons with known HIV. Copyright © 2018 Elsevier B.V. All rights reserved.

Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion

DTIC Science & Technology

2015-12-01

extensive and painful metastasis of the bone. We proposed compare the impact of exosomes derived from advanced stage prostate cancer on bone stromal cells...The revised report including additional figures, tables, and text, is attached below. 1. INTRODUCTION Bone metastasis is a painful and often lethal...UT) supplemented with 10% fetal bovine serum (Atlanta Biologicals, Lawrenceville, GA) plus penicillin/streptomycin (Gibco, Gaithersburg, MD

Wedelolactone enhances osteoblastogenesis by regulating Wnt/β-catenin signaling pathway but suppresses osteoclastogenesis by NF-κB/c-fos/NFATc1 pathway.

PubMed

Liu, Yan-Qiu; Hong, Zhi-Lai; Zhan, Li-Bin; Chu, Hui-Ying; Zhang, Xiao-Zhe; Li, Guo-Hui

2016-08-25

Bone homeostasis is maintained by formation and destruction of bone, which are two processes tightly coupled and controlled. Targeting both stimulation on bone formation and suppression on bone resorption becomes a promising strategy for treating osteoporosis. In this study, we examined the effect of wedelolactone, a natural product from Ecliptae herba, on osteoblastogenesis as well as osteoclastogenesis. In mouse bone marrow mesenchymal stem cells (BMSC), wedelolactone stimulated osteoblast differentiation and bone mineralization. At the molecular level, wedelolactone directly inhibited GSK3β activity and enhanced the phosphorylation of GSK3β, thereafter stimulated the nuclear translocation of β-catenin and runx2. The expression of osteoblastogenesis-related marker gene including osteorix, osteocalcin and runx2 increased. At the same concentration range, wedelolactone inhibited RANKL-induced preosteoclastic RAW264.7 actin-ring formation and bone resorption pits. Further, wedelolactone blocked NF-kB/p65 phosphorylation and abrogated the NFATc1 nuclear translocation. As a result, osteoclastogenesis-related marker gene expression decreased, including c-src, c-fos, and cathepsin K. In ovariectomized mice, administration of wedelolactone prevented ovariectomy-induced bone loss by enhancing osteoblast activity and inhibiting osteoclast activity. Together, these data demonstrated that wedelolactone facilitated osteoblastogenesis through Wnt/GSK3β/β-catenin signaling pathway and suppressed RANKL-induced osteoclastogenesis through NF-κB/c-fos/NFATc1 pathway. These results suggested that wedelolacone could be a novel dual functional therapeutic agent for osteoporosis.

Combined treatment with a transforming growth factor beta inhibitor (1D11) and bortezomib improves bone architecture in a mouse model of myeloma-induced bone disease

PubMed Central

Nyman, Jeffry S.; Merkel, Alyssa R.; Uppuganti, Sasidhar; Nayak, Bijaya; Rowland, Barbara; Makowski, Alexander J.; Oyajobi, Babatunde O.; Sterling, Julie A.

2016-01-01

Multiplemyeloma (MM) patients frequently develop tumor-induced bone destruction, yet no therapy completely eliminates the tumor or fully reverses bone loss. Transforming growth factor-β (TGF-β) activity often contributes to tumor-induced bone disease, and pre-clinical studies have indicated that TGF-β inhibition improves bone volume and reduces tumor growth in bone metastatic breast cancer. We hypothesized that inhibition of TGF-β signaling also reduces tumor growth, increases bone volume, and improves vertebral body strength in MM-bearing mice. We treated myeloma tumor-bearing (immunocompetent KaLwRij and immunocompromised Rag2 −/−) mice with a TGF-β inhibitory (1D11) or control (13C4) antibody, with or without the anti-myeloma drug bortezomib, for 4 weeks after inoculation of murine 5TGM1 MM cells. TGF-β inhibition increased trabecular bone volume, improved trabecular architecture, increased tissue mineral density of the trabeculae as assessed by ex vivo micro-computed tomography, and was associated with significantly greater vertebral body strength in biomechanical compression tests. Serum monoclonal paraprotein titers and spleen weights showed that 1D11 monotherapy did not reduce overall MM tumor burden. Combination therapy with 1D11 and bortezomib increased vertebral body strength, reduced tumor burden, and reduced cortical lesions in the femoral metaphysis, although it did not significantly improve cortical bone strength in three-point bending tests of the mid-shaft femur. Overall, our data provides rationale for evaluating inhibition of TGF-β signaling in combination with existing anti-myeloma agents as a potential therapeutic strategy to improve outcomes in patients with myeloma bone disease. PMID:27423464

Combined treatment with a transforming growth factor beta inhibitor (1D11) and bortezomib improves bone architecture in a mouse model of myeloma-induced bone disease.

PubMed

Nyman, Jeffry S; Merkel, Alyssa R; Uppuganti, Sasidhar; Nayak, Bijaya; Rowland, Barbara; Makowski, Alexander J; Oyajobi, Babatunde O; Sterling, Julie A

2016-10-01

Multiple myeloma (MM) patients frequently develop tumor-induced bone destruction, yet no therapy completely eliminates the tumor or fully reverses bone loss. Transforming growth factor-β (TGF-β) activity often contributes to tumor-induced bone disease, and pre-clinical studies have indicated that TGF-β inhibition improves bone volume and reduces tumor growth in bone metastatic breast cancer. We hypothesized that inhibition of TGF-β signaling also reduces tumor growth, increases bone volume, and improves vertebral body strength in MM-bearing mice. We treated myeloma tumor-bearing (immunocompetent KaLwRij and immunocompromised Rag2-/-) mice with a TGF-β inhibitory (1D11) or control (13C4) antibody, with or without the anti-myeloma drug bortezomib, for 4weeks after inoculation of murine 5TGM1 MM cells. TGF-β inhibition increased trabecular bone volume, improved trabecular architecture, increased tissue mineral density of the trabeculae as assessed by ex vivo micro-computed tomography, and was associated with significantly greater vertebral body strength in biomechanical compression tests. Serum monoclonal paraprotein titers and spleen weights showed that 1D11 monotherapy did not reduce overall MM tumor burden. Combination therapy with 1D11 and bortezomib increased vertebral body strength, reduced tumor burden, and reduced cortical lesions in the femoral metaphysis, although it did not significantly improve cortical bone strength in three-point bending tests of the mid-shaft femur. Overall, our data provides rationale for evaluating inhibition of TGF-β signaling in combination with existing anti-myeloma agents as a potential therapeutic strategy to improve outcomes in patients with myeloma bone disease. Published by Elsevier Inc.

The electron microscope appearance of the subchondral bone plate in the human femoral head in osteoarthritis and osteoporosis

PubMed Central

LI, BAOHUA; MARSHALL, DEBORAH; ROE, MARTIN; ASPDEN, RICHARD M.

1999-01-01

The subchondral bone plate supports the articular cartilage in diarthrodial joints. It has a significant mechanical function in transmitting loads from the cartilage into the underlying cancellous bone and has been implicated in the destruction of cartilage in osteoarthritis (OA) and its sparing in osteoporosis (OP), but little is known of its composition, structure or material properties. This study investigated the microscopic appearance and mineral composition of the subchondral bone plate in femoral heads from patients with OA or OP to determine how these correspond to changes in composition and stiffness found in other studies. Freeze-fractured full-depth samples of the subchondral bone plate from the femoral heads of patients with osteoarthritis, osteoporosis or a matched control group were examined using back scattered and secondary emission scanning electron microscopy. Other samples were embedded and polished and examined using back-scattered electron microscopy and electron probe microanalysis. The appearances of the samples from the normal and osteoporotic patients were very similar, with the subchondral bone plate overlayed by a layer of calcified cartilage. Osteoporotic samples presented a more uniform fracture surface and the relative thicknesses of the layers appeared to be different. In contrast, the OA bone plate appeared to be porous and have a much more textured surface. There were occasional sites of microtrabecular bone formation between the trabeculae of the underlying cancellous bone, which were not seen in the other groups, and more numerous osteoclast resorption pits. The calcified cartilage layer was almost absent and the bone plate was apparently thickened. The appearance of the osteoarthritic subchondral bone plate was, therefore, considerably different from both the normal and the osteoporotic, strongly indicative of abnormal cellular activity. PMID:10473297

Xanthogranulomatous pyelonephritis with colesional actinomycosis in a 63-year-old man

PubMed Central

Gulwani, Hanni V.

2015-01-01

Xanthogranulomatous pyelonephritis is an uncommon chronic destructive granulomatous disease of the kidney. A rare case of xanthogranulomatous pyelonephritis with extrarenal extension that had coexistence of renal actinomycosis is described in this article. PMID:25878419

Calvarial bone cavernous hemangioma with intradural invasion: An unusual aggressive course-Case report and literature review.

PubMed

Nasi, Davide; Somma, Lucia di; Iacoangeli, Maurizio; Liverotti, Valentina; Zizzi, Antonio; Dobran, Mauro; Gladi, Maurizio; Scerrati, Massimo

2016-01-01

Cavernous hemangioma of the skull is a rare pathological diagnosis, accounting for 0.2% of bone tumors and 7% of skull tumors. Usually calvarial bone cavernous hemangioma are associated with a benign clinical course and, despite their enlargement and subsequent erosion of the surrounding bone, the inner table of the skull remains intact and the lesion is completely extracranial. The authors present the unique case of a huge left frontal bone cavernous malformation with intradural extension and brain compression determining a right hemiparesis. Calvarial cavernous hemangiomas are benign tumors. They arise from vessels in the diploic space and tend to involve the outer table of the skull with relative sparing of the inner table. More extensive involvement of the inner table and extradural space is very unusual and few cases are reported in literature. To the best of our knowledge, intradural invasion of calvarial hemangioma has not been previously reported. Our case highlights the possibility of an aggressive course of this rare benign pathology. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Calvarial bone cavernous hemangioma with intradural invasion: An unusual aggressive course—Case report and literature review

PubMed Central

Nasi, Davide; Somma, Lucia di; Iacoangeli, Maurizio; Liverotti, Valentina; Zizzi, Antonio; Dobran, Mauro; Gladi, Maurizio; Scerrati, Massimo

2016-01-01

Introduction Cavernous hemangioma of the skull is a rare pathological diagnosis, accounting for 0.2% of bone tumors and 7% of skull tumors. Usually calvarial bone cavernous hemangioma are associated with a benign clinical course and, despite their enlargement and subsequent erosion of the surrounding bone, the inner table of the skull remains intact and the lesion is completely extracranial. Presentation of a case The authors present the unique case of a huge left frontal bone cavernous malformation with intradural extension and brain compression determining a right hemiparesis. Discussion Calvarial cavernous hemangiomas are benign tumors. They arise from vessels in the diploic space and tend to involve the outer table of the skull with relative sparing of the inner table. More extensive involvement of the inner table and extradural space is very unusual and few cases are reported in literature. To the best of our knowledge, intradural invasion of calvarial hemangioma has not been previously reported. Conclusion Our case highlights the possibility of an aggressive course of this rare benign pathology. PMID:27061482

Extensive limb lengthening in Ollier's disease: 25-year follow-up.

PubMed

Märtson, Aare; Haviko, Tiit; Kirjanen, Kaur

2005-01-01

A case of extensive lower limb lengthening (32 cm) in a 14-year-old male patient with Ollier's disease is reported. A varus deformity of the femur and a valgus deformity of the tibia were evident. The femur was successfully lengthened 22 cm by metaphyseal distraction, and the tibia was lengthened 10 cm by two-stage distraction-compression method with a cylindrical bone allograft. Ilizarov's distraction device was used. Radiologically, a good bone regenerate was formed. Host bone has incorporated (like sarcophagi) the allograft of tibia. No evidence of vascular or neural disturbances was found. The lengthening indices were counted for femur 22.5 days per centimeter and for tibia 21 days per centimeter, altogether 15.5 days per centimeter. Bone lengthening was performed through the Ollier's disease foci. Fine needle biopsy investigation showed that most embryonic cartilage cells had been replaced with bone tissue. After five years and a 25-year follow-up the patient was satisfied with the result. The function of the knee joint was limited, but the limb was fully weight-bearing. Signs of knee osteoarthritis were found.

Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta-tricalcium phosphate ({beta}-TCP) on the beagle dog 1-wall periodontal defect model

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

Anzai, Jun, E-mail: anzai_jun@kaken.co.jp; Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871; Kitamura, Masahiro, E-mail: kitamura@dent.osaka-u.ac.jp

Research highlights: {yields} Concomitant use of FGF-2 and {beta}-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. {yields} FGF-2 enhanced new bone formation via {beta}-TCP at the defects. {yields} In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. {yields} Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. {yields} This manuscript indicates for the first time that concomitant use of FGF-2 and {beta}-TCP is efficacious in regenerating periodontalmore » tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate ({beta}-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus {beta}-TCP or {beta}-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with {beta}-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and {beta}-TCP as an osteoconductive material for periodontal regeneration following severe destruction by progressive periodontitis.« less

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.

Giant Cell Tumor of Bone - An Overview

PubMed Central

Sobti, Anshul; Agrawal, Pranshu; Agarwala, Sanjay; Agarwal, Manish

2016-01-01

Giant Cell tumors (GCT) are benign tumors with potential for aggressive behavior and capacity to metastasize. Although rarely lethal, benign bone tumors may be associated with a substantial disturbance of the local bony architecture that can be particularly troublesome in peri-articular locations. Its histogenesis remains unclear. It is characterized by a proliferation of mononuclear stromal cells and the presence of many multi- nucleated giant cells with homogenous distribution. There is no widely held consensus regarding the ideal treatment method selection. There are advocates of varying surgical techniques ranging from intra-lesional curettage to wide resection. As most giant cell tumors are benign and are located near a joint in young adults, several authors favor an intralesional approach that preserves anatomy of bone in lieu of resection. Although GCT is classified as a benign lesion, few patients develop progressive lung metastases with poor outcomes. Treatment is mainly surgical. Options of chemotherapy and radiotherapy are reserved for selected cases. Recent advances in the understanding of pathogenesis are essential to develop new treatments for this locally destructive primary bone tumor. PMID:26894211

Mandibular Actinomyces osteomyelitis complicating florid cemento-osseous dysplasia: case report

PubMed Central

2011-01-01

Background Apart from neoplastic processes, chronic disfiguring and destructive diseases of the mandible are uncommon. Case Presentation We report, perhaps for the first time, the simultaneous occurrence of two such conditions in one patient, in a case that emphasizes the importance of bone biopsy in establishing the correct diagnosis. Florid cemento-osseous dysplasia (FCOD) is a chronic, disfiguring condition of the maxillofacial region. This relatively benign disease is primarily observed in middle-aged women of African ancestry. Cervicofacial actinomycosis is an uncommon and progressive infection caused by bacilli of the Actinomyces genus that typically involves intraoral soft tissues but may also involve bone. The accurate diagnosis of actinomycosis is critical for successful treatment. A diagnosis of osteomyelitis caused by Actinomyces bacteria was diagnosed by bone biopsy in a 53 year-old African-American woman with a longstanding history of FCOD after she presented with a new draining ulcer overlying the mandible. Conclusions Clinicians should be aware of the possibility of actinomycosis arising in the setting of FCOD, and the importance of bone biopsy and cultures in arriving at a definitive and timely diagnosis. PMID:21777471

Mandibular Actinomyces osteomyelitis complicating florid cemento-osseous dysplasia: case report.

PubMed

Smith, Miller H; Harms, Paul W; Newton, Duane W; Lebar, Bill; Edwards, Sean P; Aronoff, David M

2011-07-21

Apart from neoplastic processes, chronic disfiguring and destructive diseases of the mandible are uncommon. We report, perhaps for the first time, the simultaneous occurrence of two such conditions in one patient, in a case that emphasizes the importance of bone biopsy in establishing the correct diagnosis. Florid cemento-osseous dysplasia (FCOD) is a chronic, disfiguring condition of the maxillofacial region. This relatively benign disease is primarily observed in middle-aged women of African ancestry. Cervicofacial actinomycosis is an uncommon and progressive infection caused by bacilli of the Actinomyces genus that typically involves intraoral soft tissues but may also involve bone. The accurate diagnosis of actinomycosis is critical for successful treatment. A diagnosis of osteomyelitis caused by Actinomyces bacteria was diagnosed by bone biopsy in a 53 year-old African-American woman with a longstanding history of FCOD after she presented with a new draining ulcer overlying the mandible. Clinicians should be aware of the possibility of actinomycosis arising in the setting of FCOD, and the importance of bone biopsy and cultures in arriving at a definitive and timely diagnosis.

[Multiple sites extrapodal actinomycetoma: Favorable outcome to treatment with a combination of cotrimoxazole and NSAI].

PubMed

Diallo, B; Barro-Traoré, F; Bamba, S; Sanou-Lamien, A; Traoré, S S; Andonaba, J-B; Konaté, I; Niamba, P; Traoré, A; Guiguemdé, T R

2015-12-01

Mycetoma is a bacteriological or fungal infectious disease affecting the skin and/or soft tissues, which can be complicated by bone involvement. The most common feature is a tumor of the foot, but extrapodal localizations have been described. We report one case of a 47-year-old man who presented with tumefaction of a leg with multiple skin fistulae. Histopathological examination permitted to confirm the diagnosis of actinomycetoma and TDM showed the degree of bone and soft tissues involvement. Our case was characterized by the very inflammatory aspect of the tumor, its localization to the leg without foot involvement, the modest functional signs compared to the importance of radiological bone involvements, the deep destruction of the fibula while the tibia was apparently intact and the good response to treatment. In spite of its characteristic features, diagnosis of mycetoma is still late in our country, often with bone and/or articular spread. Priority may be given to measures for reduction of mycetoma diagnosis lateness. Copyright © 2015. Published by Elsevier Masson SAS.

Influence of bone marrow on osseointegration in long bones: an experimental study in sheep.

PubMed

Morelli, Fabrizio; Lang, Niklaus P; Bengazi, Franco; Baffone, Davide; Vila Morales, C Dadonim; Botticelli, Daniele

2015-03-01

To evaluate the influence of yellow bone marrow on osseointegration of titanium oral implants using a long bone model. The two tibiae of eight sheep were used as experimental sites. Two osteotomies for implant installation were prepared in each tibia. At the control sites, no further treatments were performed while, at the test sites, bone marrow was removed from the osteotomy site with a curette to an extent that exceeded the implant dimensions. As a result, the apical portion of the implants at the control sites was in contact with bone marrow while, at the test sites, it was in contact with the blood clot. After 2 months, the same procedures were performed in the contralateral side. After another month, the animal was sacrificed. Ground sections were obtained for histological analysis. After 1 month of healing, no differences between test and control sites were found in the apical extension of osseointegration and the percentage of new bone-to-implant contact. However, after 3 months of healing, a higher percentage of new bone-to-implant contact was found at the test compared to the control sites in the marrow compartment. The apical extension of osseointegration, however, was similar to that found at the 1-month healing period both for test and control sites. Osseointegration appeared to be favored by the presence of a blood clot when compared to the presence of yellow fatty bone marrow. Moreover, the contact with cortical bone appeared to be a prerequisite for the osseointegration process in the long bone model. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bone tissue formation in extraction sockets from sites with advanced periodontal disease: a histomorphometric study in humans.

PubMed

Ahn, Jae-Jin; Shin, Hong-In

2008-01-01

To investigate postextraction bone formation over time in both diseased and healthy sockets. Core specimens of healing tissues following tooth extraction were obtained at the time of implant placement in patients treated between October 2005 and December 2007. A disease group and a control group were classified according to socket examination at the time of extraction. The biopsy specimens were analyzed histomorphometrically to measure the dimensional changes among 3 tissue types: epithelial layer, connective tissue area, and new bone tissue area. Fifty-five specimens from sites of previously advanced periodontal disease from 45 patients were included in the disease group. Another 12 specimens of previously healthy extraction sockets were collected from 12 different patients as a control. The postextraction period of the disease group varied from 2 to 42 weeks. In the disease group, connective tissue occupied most of the socket during the first 4 weeks. New bone area progressively replaced the connective tissue area after the first 4 weeks. The area proportion of new bone tissue exceeded that of connective tissue by 14 weeks. After 20 weeks, most extraction sockets in the disease group demonstrated continuous new bone formation. The control group exhibited almost complete socket healing after 10 weeks, with no more new bone formation after 20 weeks. Osseous regeneration in the diseased sockets developed more slowly than in the disease-free sockets. After 16 weeks, new bone area exceeded 50% of the total newly regenerated tissue in the sockets with severe periodontal destruction. In the control group, after 8 weeks, new bone area exceeded 50% of the total tissue.

Adenosine A2A Receptor Activation Prevents Wear Particle-Induced Osteolysis

PubMed Central

Mediero, Aránzazu; Frenkel, Sally R.; Wilder, Tuere; He, Wenjie; Mazumder, Amitabha; Cronstein, Bruce N.

2012-01-01

Prosthesis loosening, associated with wear-particle–induced inflammation and osteoclast-mediated bone destruction, is a common cause for joint implant failure, leading to revision surgery. Adenosine A2A receptors (A2AR) mediate potent anti-inflammatory effects in many tissues and prevent osteoclast differentiation. We tested the hypothesis that an A2AR agonist could reduce osteoclast-mediated bone resorption in a murine calvaria model of wear-particle–induced bone resorption. C57Bl/6 and A2A knockout (A2ARKO) mice received ultrahigh-molecular weight polyethylene particles (UHMWPE) and were treated daily with either saline or the A2AR agonist CGS21680. After 2 weeks, micro-computed tomography of calvaria demonstrated that CGS21680 reduced particle-induced bone pitting and porosity in a dose-dependent manner, increasing cortical bone and bone volume compared to control mice. Histological examination demonstrated diminished inflammation after treatment with CGS21680. In A2AKO mice, CGS21680 did not affect osteoclast-mediated bone resorption or inflammation. Levels of bone-resorption markers receptor activator of nuclear factor-kB (RANK), RANK ligand (RANKL), cathepsin K, CD163, and osteopontin were reduced following CGS21680 treatment, together with a reduction in osteoclasts. Secretion of interleukin 1β (IL-1β) and TNFα was significantly decreased, whereas IL-10 was markedly increased in bone by CGS21680. These results in mice suggest that site-specific delivery of an adenosine A2AR agonist could enhance implant survival, delaying or eliminating the need for revision arthroplastic surgery. PMID:22623741

Wavelet decomposition of transmitted ultrasound wave through a 1-D muscle-bone system.

PubMed

Buchanan, James L; Gilbert, Robert P; Ou, Miao-jung Y

2011-01-11

In the attempt for using ultrasound as a diagnostic device for osteoporosis, several authors have described the result of the in vitro experiment in which ultrasound is passed through a cancellous bone specimen placed in a water tank. However, in the in vivo setting, a patient's cancellous bone is surrounded by cortical and muscle layers. This paper considers in the one-dimensional case (1) what effect the cortical bone segments surrounding the cancellous segment would have on the received signal and (2) what the received signal would be when a source and receiver are placed on opposite sides of a structure consisting of a cancellous segment surrounded by cortical and muscle layers. Mathematically this is accomplished by representing the received signal as a sum of wavelets which go through different reflection-transmission histories at the muscle-cortical bone and cortical-cancellous bone interfaces. The muscle and cortical bone are modeled as elastic materials and the cancellous bone as a poroelastic material described by the Biot-Johnson-Koplik-Dashen model. The approach presented here permits the assessment of which possible paths of transmission and reflection through the cortical-cancellous or muscle-cortical-cancellous complex will result in significant contributions to the received waveform. This piece of information can be useful for solving the inverse problem of non-destructive assessment of material properties of bone. Our methodology can be generalized to three-dimensional parallelly layered structure by first applying Fourier transform in the directions perpendicular to the transverse direction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Differences of bone healing in metaphyseal defect fractures between osteoporotic and physiological bone in rats.

PubMed

Thormann, Ulrich; El Khawassna, Thaqif; Ray, Seemun; Duerselen, Lutz; Kampschulte, Marian; Lips, Katrin; von Dewitz, Helena; Heinemann, Sascha; Heiss, Christian; Szalay, Gabor; Langheinrich, Alexander C; Ignatius, Anita; Schnettler, Reinhard; Alt, Volker

2014-03-01

Discrepancies in bone healing between osteoporotic and non-osteoporotic bone remain uncertain. The focus of the current work is to evaluate potential healing discrepancies in a metaphyseal defect model in rat femora. Female Sprague-Dawley rats were either ovariectomized (OVX, n=14) and combined with a calcium-, phosphorus- and vitamin D3-, soy- and phytoestrogen-free diet or received SHAM operation with standard diet rat (SHAM, n=14). Three months post-ovariectomy, DEXA measurement showed a reduction of bone mineral density reflecting an osteoporotic bone status in OVX rats. Rats then underwent a 3 mm wedge-shaped osteotomy at the distal metaphyseal area of the left femur stabilized with a T-shaped mini-plate and allowed to heal for 6 weeks. Biomechanical competence by means of a non-destructive three-point bending test showed significant lower flexural rigidity in the OVX rats at 3 mm lever span compared to SHAM animals (p=0.048) but no differences at 10 mm lever span. Microcomputer tomography (μCT) showed bridging cortices and consolidation of the defect in both groups, however, no measurable differences were found in either total ossified tissue or vascular volume fraction. Furthermore, histology showed healing discrepancies that were characterized by cartilaginous remnant and more unmineralized tissue presence in the OVX rats compared to more mature consolidation appearance in the SHAM group. In summary, bone defect healing in metaphyseal bone slightly differs between osteoporotic and non-osteoporotic bone in the current 3 mm defect model in both 3mm lever span biomechanical testing and histology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems.

PubMed

Okamoto, Kazuo; Nakashima, Tomoki; Shinohara, Masahiro; Negishi-Koga, Takako; Komatsu, Noriko; Terashima, Asuka; Sawa, Shinichiro; Nitta, Takeshi; Takayanagi, Hiroshi

2017-10-01

The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems. Here we review the function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions. Osteoimmunology has become indispensable for understanding the pathogenesis of a number of diseases such as rheumatoid arthritis (RA). We review the various osteoimmune pathologies, including the bone destruction in RA, in which pathogenic helper T cell subsets [such as IL-17-expressing helper T (Th17) cells] induce bone erosion through aberrant RANKL expression. We also focus on cellular interactions and the identification of the communication factors in the bone marrow, discussing the contribution of bone cells to the maintenance and regulation of hematopoietic stem and progenitors cells. Thus the time has come for a basic reappraisal of the framework for understanding both the immune and bone systems. The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system. Copyright © 2017 the American Physiological Society.

Characterization of bone-implant fixation using modal analysis: Application to a press-fit implant model

PubMed Central

Swider, P.; Guérin, G.; Baas, Joergen; Søballe, Kjeld; Bechtold, Joan E.

2013-01-01

Orthopaedic implant fixation is strongly dependant upon the effective mechanical properties of newly formed tissue. In this study, we evaluated the potential of modal analysis to derive viscoelastic properties of periprosthetic tissue. We hypothesized that Young's modulus and loss factor could be obtained by a combined theoretical, computational and experimental modal analysis approach. This procedure was applied to ex vivo specimens from a cylindrical experimental implant placed in cancellous bone in an unloaded press-fit configuration, obtained after a four week observation period. Four sections each from seven textured titanium implants were investigated. The first resonant frequency and loss factor were measured. Average experimentally determined loss factor was 2% (SD 0.4%) and average first resonant frequency was 2.1 KHz (SD: 50). A 2D axisymmetric finite element (FE) model identified effective Young's modulus of tissue using experimental resonant frequencies as input. Average value was 42 MPa (SD: 2.4) and no significant difference between specimens was observed. In this pilot study, the non-destructive method allowed accurate measure of dynamic loss factor and resonant frequency and derivation of effective Young's modulus. Prior to implementing this dynamic protocol for broader mechanical evaluation of experimental implant fixation, further work is needed to determine if this affects results from subsequent destructive shear push-out tests. PMID:19464687

Remission of Collagen-Induced Arthritis through Combination Therapy of Microfracture and Transplantation of Thermogel-Encapsulated Bone Marrow Mesenchymal Stem Cells

PubMed Central

Liu, He; Ding, Jianxun; Wang, Jincheng; Wang, Yinan; Yang, Modi; Zhang, Yanbo; Chang, Fei; Chen, Xuesi

2015-01-01

The persistent inflammation of rheumatoid arthritis (RA) always leads to partial synovial hyperplasia and the destruction of articular cartilage. Bone marrow mesenchymal stem cells (BMMSCs) have been proven to possess immunosuppressive effects, and widely explored in the treatment of autoimmune diseases. However, poor inhibitory effect on local inflammatory state and limited capacity of preventing destruction of articular cartilage by systemic BMMSCs transplantation were observed. Herein, toward the classical type II collagen-induced arthritis in rats, the combination treatment of microfracture and in situ transplantation of thermogel-encapsulated BMMSCs was verified to obviously down-regulate the ratio of CD4+ to CD8+ T lymphocytes in peripheral blood. In addition, it resulted in the decreased levels of inflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α and anti-collagen type II antibody, in the serum. Simultaneously, the combination therapy also could inhibit the proliferation of antigen specific lymphocytes and local joint inflammatory condition, and prevent the articular cartilage damage. The results indicated that the treatment programs could effectively stimulate the endogenous and exogenous BMMSCs to exhibit the immunosuppression and cartilage protection capability. This study provided a new therapeutic strategy for autoimmune inflammatory diseases, such as RA. PMID:25774788

Uncovering the molecular networks in periodontitis

PubMed Central

Trindade, Fábio; Oppenheim, Frank G.; Helmerhorst, Eva J.; Amado, Francisco; Gomes, Pedro S.; Vitorino, Rui

2015-01-01

Periodontitis is a complex immune-inflammatory disease that results from a preestablished infection in gingiva, mainly due to Gram-negative bacteria that colonize deeper in gingival sulcus and latter periodontal pocket. Host inflammatory and immune responses have both protective and destructive roles. Although cytokines, prostaglandins, and proteases struggle against microbial burden, these molecules promote connective tissue loss and alveolar bone resorption, leading to several histopathological changes, namely destruction of periodontal ligament, deepening of periodontal pocket, and bone loss, which can converge to attain tooth loss. Despite the efforts of genomics, transcriptomics, proteomics/peptidomics, and metabolomics, there is no available biomarker for periodontitis diagnosis, prognosis, and treatment evaluation, which could assist on the established clinical evaluation. Nevertheless, some genes, transcripts, proteins and metabolites have already shown a different expression in healthy subjects and in patients. Though, so far, ‘omics approaches only disclosed the host inflammatory response as a consequence of microbial invasion in periodontitis and the diagnosis in periodontitis still relies on clinical parameters, thus a molecular tool for assessing periodontitis lacks in current dental medicine paradigm. Saliva and gingival crevicular fluid have been attracting researchers due to their diagnostic potential, ease, and noninvasive nature of collection. Each one of these fluids has some advantages and disadvantages that are discussed in this review. PMID:24828325

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells.

PubMed

Hofemeier, Arne D; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F W; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-05-26

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO4(3-) symmetric stretch vibrations at 959 cm(-1) assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue-implant-interfaces or disease diagnosis.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells

NASA Astrophysics Data System (ADS)

Hofemeier, Arne D.; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F. W.; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-05-01

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO43- symmetric stretch vibrations at 959 cm-1 assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue-implant-interfaces or disease diagnosis.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells

PubMed Central

Hofemeier, Arne D.; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F. W.; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-01-01

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO43− symmetric stretch vibrations at 959 cm−1 assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue–implant-interfaces or disease diagnosis. PMID:27225821

Total knee arthroplasty for the management of joint destruction in tuberculous arthritis.

PubMed

Oztürkmen, Yusuf; Uzümcügil, Onat; Karamehmetoğlu, Mahmut; Leblebici, Cem; Caniklioğlu, Mustafa

2014-05-01

The purpose of this study was to evaluate our experience to clarify the suggestion that there should be a significant disease-free interval before total knee arthroplasty (TKA) and to determine the correct timing of surgery for reconstruction of the joint destruction in patients suffering from tuberculous arthritis. Twelve patients with advanced joint destruction and tuberculous arthritis of the knee with recent onset were reviewed in this study. The time interval from our diagnosis of active infection to arthroplasty averaged 4 ± 1.5 months. Histopathology of the biopsy specimens revealing granulomatous lesions, including epithelioid histiocytes surrounded by lymphocytes, confirmed the diagnosis of each patient. A primary knee prosthesis was performed in seven knees. In five knees, there was severe bone loss after the extensive debridement of the entire joint, and thereafter, revision prosthesis was preferred to preserve the joint line. Patients were given post-operative antituberculous treatment for a total of 1 year, whereas for three patients, whose erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values remained above normal by the sixth month, the chemotherapy was continued for up to 18 months. The Knee Society TKA roentgenographic evaluation and scoring system was used for radiological evaluation of the knees. Clinical evaluation of the knees was done preoperatively and at the time of the most recent follow-up using the American Knee Society Scoring System. Within the average follow-up period of 6.1 ± 1.8 years, no reactivation of tuberculous infection was found in any of the patients. ESR was normal, less than 20 mm/h, after a mean time of 5.5 ± 2.0 months. The CRP was normal, less than 0.8 mg/dl, after a mean time of 4.6 ± 1.3 months. At the most recent follow-up, the average knee score improved from 32.4 ± 19.4 to 83.4 ± 14.0 points (p < 0.05), and the average function score improved from 33.3 ± 11.9 to 86.6 ± 7.7 points (p < 0.05). Ten knees showed good integrity, and no radiolucent lines were found in the bone-prosthesis interface in relation to any component. Radiolucent lines were apparent on the tibial side in two knees. They were less than 1 mm thick and non-progressive, and clinically, there was no evidence of loosening of the component. Culture specimens were positive for five patients. TKA is a safe procedure for tuberculous arthritis with recent onset providing symptomatic relief, functional improvement and early return to activity when performed in correct time. A long disease-free interval should not be a prerequisite for arthroplasty. Wide surgical debridement is the mainstay to eradicate the disease, and post-operative antituberculous chemotherapy controls the residual foci. IV.

[A murder case from 900 years ago? Analysis of extensive cranial trauma observed in a historical skeleton recovered in central Poland].

PubMed

Lorkiewicz, Wiesław; Teul, Iwona; Marchelak, Ireneusz; Tyszler, Lubomira

2011-01-01

This work presents the results of study of a human skeleton from the early Middle Ages recovered in Pecławice (province of Łódź), presenting signs of extensive cranial trauma suffered perimortem. The skeleton belonged to a 20-30 year-old male of sturdy build, with prominent bone processes, marked right-side asymmetry of the bones and joints of the upper extremities, and tallness (stature well above average for early medieval times). Except for the skull, the skeleton lacks any pathologic or traumatic lesions. The right side of the skull bears signs of three extensive injuries involving the frontal and parietal bones and the temporomandibular joint. Two of them penetrated deeply into the cranial cavity. The nature and location of the lesions suggests that the axe was used and that the victim was not confronted face-to-face. None of the lesions show any signs of healing. Fragmentation of the facial bones, which were mostly incomplete except for the well-preserved mandible, suggests additional blows to the face. These massive injuries must have been fatal due to damage to the brain and main blood vessels of the neck and thus they were recognized as the cause of death of the individual.

[Revision hip arthroplasty by Waldemar Link custom-made total hip prosthesis].

PubMed

Medenica, Ivica; Luković, Milan; Radoicić, Dragan

2010-02-01

The number of patients undergoing hip arthroplasty revision is constantly growing. Especially, complex problem is extensive loss of bone stock and pelvic discontinuity that requires reconstruction. The paper presented a 50-year old patient, who ten years ago underwent a total cement artrhroplasty of the left hip. A year after the primary operation the patient had difficulties in walking without crutches. Problems intensified in the last five years, the patient had severe pain, totally limited movement in the left hip and could not walk at all. Radiographically, we found loose femoral component, massive loss of bone stock of proximal femur, acetabular protrusion and a consequent pelvic discontinuity. Clinically, a completely disfunctional left hip joint was registered (Harris hip score--7.1). We performed total rearthroplasty by a custom-made Waldemar Link total hip prosthesis with acetabular antiprotrusio cage and compensation of bone defects with a graft from the bone bank. A year after the operation, we found clinically an extreme improvement in Harris hip score--87.8. Radiographically, we found stability of implanted components, a complete graft integration and bone bridging across the site of pelvic discontinuity. Pelvic discontinuity and massive loss of proximal femoral bone stock is a challenging and complex entity. Conventional prostheses cannot provide an adequate fixation and stability of the hip. Application of custom-made prosthesis (measured specificaly for a patient) and additional alografting bone defects is a good method in revision surgery after unsuccessful hip arthroplasty with extensive bone defects.

Computed tomography as an aid in the diagnosis of chronic nasal disease in dogs.

PubMed

Lefebvre, J; Kuehn, N F; Wortinger, A

2005-06-01

To assess the use of computed tomography (CT) in the diagnosis of chronic nasal disease in dogs. A retrospective study of 85 dogs with chronic nasal discharge due to primary nasal disease, which had undergone nasal CT and biopsy, was carried out. Medical records were reviewed for signalment, clinical signs, CT findings, endoscopic findings and histopathology. The results obtained via CT were correlated with nasal histopathology and gross anatomical observations were recorded at the time of rhinoscopy. Neoplasia was diagnosed in 37 dogs for which CT typically revealed a soft tissue density associated with extensive turbinate destruction. Inflammatory rhinitis was diagnosed in 40 dogs. CT disclosed either normal turbinate structures or mild to moderate turbinate destruction, with or without the presence of soft tissue densities (mucopus) within the nasal passages. Fungal rhinitis was diagnosed in seven dogs for which CT disclosed extensive turbinate destruction with hyperlucency of the nasal passages. One dog had normal CT and histopathology findings. CT greatly enhanced the ability to diagnose chronic nasal disease in dogs, providing detailed Information regarding the extent of the disease, accurate discrimination of neoplastic versus non-neoplastic diseases, and identification of areas of the nose to examine rhinoscopically and suspicious regions to target for biopsy.

Photothermal and infrared thermography characterizations of thermal diffusion in hydroxyapatite materials

NASA Astrophysics Data System (ADS)

Bante-Guerra, J.; Conde-Contreras, M.; Trujillo, S.; Martinez-Torres, P.; Cruz-Jimenez, B.; Quintana, P.; Alvarado-Gil, J. J.

2009-02-01

Non destructive analysis of hydroxyapatite materials is an active research area mainly in the study of dental pieces and bones due to the importance these pieces have in medicine, archeology, dentistry, forensics and anthropology. Infrared thermography and photothermal techniques constitute highly valuable tools in those cases. In this work the quantitative analysis of thermal diffusion in bones is presented. The results obtained using thermographic images are compared with the ones obtained from the photothermal radiometry. Special emphasis is done in the analysis of samples with previous thermal damage. Our results show that the treatments induce changes in the physical properties of the samples. These results could be useful in the identification of the agents that induced modifications of unknown origin in hydroxyapatite structures.

Giant cemento-ossifying fibroma of the maxilla.

PubMed

Unal, Adnan; Yurtsever Kum, Nurcan; Kum, Rauf Oguzhan; Erdogan, Aysun; Ciliz, Deniz Sozmen; Guresci, Servet; Ozcan, Muge

2015-11-14

Fibro-osseous lesions of the skull and facial bones are benign tumors, but they can be mistaken for malignant tumors due to their clinically aggressive behavior. Cemento-ossifying fibroma (COF) is a benign fibro-osseous lesion characterized by slow growth and fibrous and calcified tissue content. COFs are locally destructive lesions causing deformities in the bones. The recurrence risk is high if they are not completely removed. In this case report we describe a giant COF mimicking chondrosarcoma in the oral cavity of a 55-year-old woman causing significant facial deformity and feeding problems. Giant COF occurs rarely in the jaws and given that this lesion has similar imaging and clinical features to several other tumors, the diagnosis is always a challenge for clinicians, radiologists and pathologists.

Skeletal effects of plant products other than soy

USDA-ARS?s Scientific Manuscript database

In addition to the extensive literature on the effects of soy feeding on skeletal parameters and bone turnover, there are a significant number of epidemiological studies suggesting a positive link between bone mineral density (BMD) and overall fruit and vegetable consumption. There is also evidence ...

One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats.

PubMed

Varela, Aurore; Chouinard, Luc; Lesage, Elisabeth; Guldberg, Robert; Smith, Susan Y; Kostenuik, Paul J; Hattersley, Gary

2017-02-01

Abaloparatide is a novel 34 amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor 1 (PTHR1) signaling pathway. The effects of 12months of abaloparatide treatment on bone mass, bone strength and bone quality was assessed in osteopenic ovariectomized (OVX) rats. SD rats were subjected to OVX or sham surgery at 6months of age and left untreated for 3months to allow OVX-induced bone loss. Eighteen OVX rats were sacrificed after this bone depletion period, and the remaining OVX rats received daily s.c. injections of vehicle (n=18) or abaloparatide at 1, 5 or 25μg/kg/d (n=18/dose level) for 12months. Sham controls (n=18) received vehicle daily. Bone changes were assessed by DXA and pQCT after 0, 3, 6 or 12months of treatment, and destructive biomechanical testing was conducted at month 12 to assess bone strength and bone quality. Abaloparatide dose-dependently increased bone mass at the lumbar spine and at the proximal and diaphyseal regions of the tibia and femur. pQCT revealed that increased cortical bone volume at the tibia was a result of periosteal expansion and endocortical bone apposition. Abaloparatide dose-dependently increased structural strength of L4-L5 vertebral bodies, the femur diaphysis, and the femur neck. Increments in peak load for lumbar spine and the femur diaphysis of abaloparatide-treated rats persisted even after adjusting for treatment-related increments in BMC, and estimated material properties were maintained or increased at the femur diaphysis with abaloparatide. The abaloparatide groups also exhibited significant and positive correlations between bone mass and bone strength at these sites. These data indicate that gains in cortical and trabecular bone mass with abaloparatide are accompanied by and correlated with improvements in bone strength, resulting in maintenance or improvement in bone quality. Thus, this study demonstrated that long-term daily administration of abaloparatide to osteopenic OVX rats led to dose-dependent improvements in bone mass, geometry and strength. Copyright © 2016. Published by Elsevier Inc.

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

PubMed

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

2017-09-01

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

Kinetic study of bone ingrowth and ceramic resorption associated with the implantation of different injectable calcium-phosphate bone substitutes.

PubMed

Gauthier, O; Bouler, J M; Weiss, P; Bosco, J; Daculsi, G; Aguado, E

1999-10-01

This study investigated the in vivo performance of two composite injectable bone substitutes (IBS), each with different calcium-phosphate particles granulometries [40-80 (IBS 40-80) and 200-500 microm (IBS 200-500)]. These biomaterials were obtained by associating a biphasic calcium-phosphate (BCP) ceramic mineral phase with a 3% aqueous solution of a cellulosic polymer (hydroxy-propyl-methyl-cellulose). Both materials were injected for periods of 2, 3, 8, or 12 weeks into bone defects at the distal end of rabbit femurs. Quantitative results on new bone formation, BCP resorption, and staining for tartrate-resistant acid phosphatase (TRAP) activity were studied for statistical purposes. Measurements with scanning electron microscopy and image analysis showed that the final rates of newly formed bone were similar for both tested IBS after 12 weeks of implantation. Bone colonization occurred more extensively during early implantation times for IBS 40-80 than for IBS 200-500. For the latter, BCP degradation occurred regularly throughout the implantation period, whereas it was very intensive during the first 2 weeks for IBS 40-80. Positive TRAP-stained degradation cells were significantly more numerous for IBS 40-80 than for IBS 200-500 regardless of implantation time. With the granulometry of either mineral phase, both tested IBS supported extensive bone colonization, which was greater than that previously reported for an equivalent block of macroporous BCP. The resorption-bone substitution process seemed to occur earlier and faster for IBS 40-80 than for IBS 200-500. Both tested IBS expressed similar biological efficiency, with conserved in vivo bioactivity and bone-filling ability. Copyright 1999 John Wiley & Sons, Inc.

Implant preloading in extension reduces spring length change in dynamic intraligamentary stabilization: a biomechanical study on passive kinematics of the knee.

PubMed

Häberli, Janosch; Voumard, Benjamin; Kösters, Clemens; Delfosse, Daniel; Henle, Philipp; Eggli, Stefan; Zysset, Philippe

2018-06-01

Dynamic intraligamentary stabilization (DIS) is a primary repair technique for acute anterior cruciate ligament (ACL) tears. For internal bracing of the sutured ACL, a metal spring with 8 mm maximum length change is preloaded with 60-80 N and fixed to a high-strength polyethylene braid. The bulky tibial hardware results in bone loss and may cause local discomfort with the necessity of hardware removal. The technique has been previously investigated biomechanically; however, the amount of spring shortening during movement of the knee joint is unknown. Spring shortening is a crucial measure, because it defines the necessary dimensions of the spring and, therefore, the overall size of the implant. Seven Thiel-fixated human cadaveric knee joints were subjected to passive range of motion (flexion/extension, internal/external rotation in 90° flexion, and varus/valgus stress in 0° and 20° flexion) and stability tests (Lachman/KT-1000 testing in 0°, 15°, 30°, 60°, and 90° flexion) in the ACL-intact, ACL-transected, and DIS-repaired state. Kinematic data of femur, tibia, and implant spring were recorded with an optical measurement system (Optotrak) and the positions of the bone tunnels were assessed by computed tomography. Length change of bone tunnel distance as a surrogate for spring shortening was then computed from kinematic data. Tunnel positioning in a circular zone with r = 5 mm was simulated to account for surgical precision and its influence on length change was assessed. Over all range of motion and stability tests, spring shortening was highest (5.0 ± 0.2 mm) during varus stress in 0° knee flexion. During flexion/extension, spring shortening was always highest in full extension (3.8 ± 0.3 mm) for all specimens and all simulations of bone tunnels. Tunnel distance shortening was highest (0.15 mm/°) for posterior femoral and posterior tibial tunnel positioning and lowest (0.03 mm/°) for anterior femoral and anterior tibial tunnel positioning. During passive flexion/extension, the highest spring shortening was consistently measured in full extension with a continuous decrease towards flexion. If preloading of the spring is performed in extension, the spring can be downsized to incorporate a maximum length change of 5 mm resulting in a smaller implant with less bone sacrifice and, therefore, improved conditions in case of revision surgery.

Tenuigenin inhibits RANKL-induced osteoclastogenesis by down-regulating NF-κB activation and suppresses bone loss in vivo

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

Yang, Shuo; Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012; Li, Xianan

Tenuigenin, a major active component of polygala tenuifolia root, has been used to treat patients with insomnia, dementia, and neurosis. In this study, we aimed to investigate the effects of tenuigenin on osteoclastogenesis and clarify the possible mechanism. We showed that tenuigenin inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption without cytotoxicity, which was further demonstrated by reduced osteoclast specific gene expression such as TRAP, c-Src, ATP6v0d2, etc. Moreover, the inhibitory effect of tenuigenin was associated with impaired NF-κB activity owing to delayed degradation/regeneration of IkBa and inhibition of p65 nuclear translocation. Consistent with themore » in vitro results, micro-ct scanning and analysis data showed that tenuigenin suppressed RANKL-induced bone loss in an animal model. Taken together, our data demonstrate that tenuigenin inhibit osteoclast formation and bone resorption both in vitro and in vivo, and comprise a potential therapeutic alternative for osteoclast-related disorders such as osteoporosis and cancer-induced bone destruction. - Highlights: • Tenuigenin suppresses osteoclasts formation, survival and function in vitro. • Tenuigenin impairs NF-κB activation. • Tenuigenin suppresses RANKL-induced bone lose in vivo. • Tenuigenin may be used for treating osteoclast related diseases.« less

Mangiferin positively regulates osteoblast differentiation and suppresses osteoclast differentiation

PubMed Central

Sekiguchi, Yuusuke; Mano, Hiroshi; Nakatani, Sachie; Shimizu, Jun; Kataoka, Aya; Ogura, Kana; Kimira, Yoshifumi; Ebata, Midori; Wada, Masahiro

2017-01-01

Mangiferin is a polyphenolic compound present in Salacia reticulata. It has been reported to reduce bone destruction and inhibit osteoclastic differentiation. This study aimed to determine whether mangiferin directly affects osteoblast and osteoclast proliferation and differentiation, and gene expression in MC3T3-E1 osteoblastic cells and osteoclast-like cells derived from primary mouse bone marrow macrophage cells. Mangiferin induced significantly greater WST-1 activity, indicating increased cell proliferation. Mangiferin induced significantly increased alkaline phosphatase staining, indicating greater cell differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that mangiferin significantly increased the mRNA level of runt-related transcription factor 2 (RunX2), but did not affect RunX1 mRNA expression. Mangiferin significantly reduced the formation of tartrate-resistant acid phosphatase-positive multinuclear cells. RT-PCR demonstrated that mangiferin significantly increased the mRNA level of estrogen receptor β (ERβ), but did not affect the expression of other osteoclast-associated genes. Mangiferin may inhibit osteoclastic bone resorption by suppressing differentiation of osteoclasts and promoting expression of ERβ mRNA in mouse bone marrow macrophage cells. It also has potential to promote osteoblastic bone formation by promoting cell proliferation and inducing cell differentiation in preosteoblast MC3T3-E1 cells via RunX2. Mangiferin may therefore be useful in improving bone disease outcomes. PMID:28627701

Mangiferin positively regulates osteoblast differentiation and suppresses osteoclast differentiation.

PubMed

Sekiguchi, Yuusuke; Mano, Hiroshi; Nakatani, Sachie; Shimizu, Jun; Kataoka, Aya; Ogura, Kana; Kimira, Yoshifumi; Ebata, Midori; Wada, Masahiro

2017-08-01

Mangiferin is a polyphenolic compound present in Salacia reticulata. It has been reported to reduce bone destruction and inhibit osteoclastic differentiation. This study aimed to determine whether mangiferin directly affects osteoblast and osteoclast proliferation and differentiation, and gene expression in MC3T3‑E1 osteoblastic cells and osteoclast‑like cells derived from primary mouse bone marrow macrophage cells. Mangiferin induced significantly greater WST‑1 activity, indicating increased cell proliferation. Mangiferin induced significantly increased alkaline phosphatase staining, indicating greater cell differentiation. Reverse transcription‑polymerase chain reaction (RT‑PCR) demonstrated that mangiferin significantly increased the mRNA level of runt‑related transcription factor 2 (RunX2), but did not affect RunX1 mRNA expression. Mangiferin significantly reduced the formation of tartrate‑resistant acid phosphatase‑positive multinuclear cells. RT‑PCR demonstrated that mangiferin significantly increased the mRNA level of estrogen receptor β (ERβ), but did not affect the expression of other osteoclast‑associated genes. Mangiferin may inhibit osteoclastic bone resorption by suppressing differentiation of osteoclasts and promoting expression of ERβ mRNA in mouse bone marrow macrophage cells. It also has potential to promote osteoblastic bone formation by promoting cell proliferation and inducing cell differentiation in preosteoblast MC3T3‑E1 cells via RunX2. Mangiferin may therefore be useful in improving bone disease outcomes.

Inhibition effects of total flavonoids from Scutellaria barbata D. Don on human breast carcinoma bone metastasis via downregulating PTHrP pathway

PubMed Central

Liu, Huihui; Guo, Shanyu

2018-01-01

It is abundantly clear that tumor-derived parathyroid hormone-related protein (PTHrP), receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are central contributors in promoting osteolytic process of breast carcinoma bone metastasis. Forcusing on this molecular basis, the study was undertaken to explore the inhibition effects of total flavonoids from Scutellaria barbata D. Don (TF-SB) on human breast carcinoma bone metastasis. MDA-MB-231 cells and nude mouse models of breast cancer bone metastasis were given TF-SB in different concentrations. The proliferation, migration and invasion potentials of MDA-MB-231 cells were respectively tested. The effects of TF-SB on tumor weights and bone destruction were investigated. The mRNA and protein expression of PTHrP, OPG and RANKL were assessed by qPCR and western blot analysis. In vitro, TF-SB inhibited the proliferation, migration and invasion of MDA-MB-231 cells in a dose-dependent manner. In vivo, TF-SB prevented bone metastasis of breast cancer by decreasing the number of osteoclast cells per field in a dose-dependent manner, but not affecting tumor growth or mouse survival. Molecular analysis revealed that TF-SB controled the secretion of osteolysis-related factors PTHrP and its downstream RANKL/OPG. Together, by controlling the expression of PTHrP and its downstream OPG/RANKL, TF-SB has significant inhibition effects on breast cancer bone metastasis, which indicates a new therapeutic method. PMID:29512770

[NF-κB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-κB].

PubMed

Jimi, Eijiro; Fukushima, Hidefumi

2016-02-01

The transcriptional factor nuclear factor κB(NF-κB)regulates the expression of a wide variety of genes that are involved in immune and inflammatory responses, proliferation, and tumorigenesis. NF-κB consists of five members, such as p65(RelA), RelB, c-Rel, p50/p105(NF-κB1), and p52/p100(NF-κB2). There are two distinct NF-κB activation pathways, termed the classical and alternative NF-κB signaling pathways. Since mice lacking both p50 and p52 subunits developed typical osteopetrosis, due to total lack of osteoclasts, NF-κB is also important osteoclast differentiation. A selective NF-κB inhibitor blocked receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis both in vitro and in vivo. Recent findings have shown that inactivation of NF-κB enhances osteoblast differentiation in vitro and bone formation in vivo. NF-κB is constitutively activated in many cancers including oral squamous cell carcinoma(OSCC), and is involved in the invasive characteristics of OSCC. A selective NF-κB inhibitor also prevented jaw bone destruction by OSCC by reduced osteoclast numbers in animal model. Thus the inhibition of NF-κB might useful for the treatment of bone diseases, such as arthritis, osteoporosis, periodontitis, and bone invasion by OSCC by inhibiting bone resorption and by stimulating bone formation.

Optimizing a micro-computed tomography-based surrogate measurement of bone-implant contact.

PubMed

Meagher, Matthew J; Parwani, Rachna N; Virdi, Amarjit S; Sumner, Dale R

2018-03-01

Histology and backscatter scanning electron microscopy (bSEM) are the current gold standard methods for quantifying bone-implant contact (BIC), but are inherently destructive. Microcomputed tomography (μCT) is a non-destructive alternative, but attempts to validate μCT-based assessment of BIC in animal models have produced conflicting results. We previously showed in a rat model using a 1.5 mm diameter titanium implant that the extent of the metal-induced artefact precluded accurate measurement of bone sufficiently close to the interface to assess BIC. Recently introduced commercial laboratory μCT scanners have smaller voxels and improved imaging capabilities, possibly overcoming this limitation. The goals of the present study were to establish an approach for optimizing μCT imaging parameters and to validate μCT-based assessment of BIC. In an empirical parametric study using a 1.5 mm diameter titanium implant, we determined 90 kVp, 88 µA, 1.5 μm isotropic voxel size, 1600 projections/180°, and 750 ms integration time to be optimal. Using specimens from an in vivo rat experiment, we found significant correlations between bSEM and μCT for BIC with the manufacturer's automated analysis routine (r = 0.716, p = 0.003) or a line-intercept method (r = 0.797, p = 0.010). Thus, this newer generation scanner's improved imaging capability reduced the extent of the metal-induced artefact zone enough to permit assessment of BIC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:979-986, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Association between bacteria occurring in the apical canal system and expression of bone-resorbing mediators and matrix metalloproteinases in apical periodontitis.

PubMed

Takahama, A; Rôças, I N; Faustino, I S P; Alves, F R F; Azevedo, R S; Gomes, C C; Araújo-Filho, W R; Siqueira, J F

2018-07-01

To evaluate the association between the presence of selected bacterial species/groups in the apical root canal and expression of mediators of soft and bone tissue destruction in apical periodontitis lesions. Relationships between bacteria and some other features of apical periodontitis were also investigated. Seventeen freshly extracted teeth with pulp necrosis and apical periodontitis were included. The apical root segment was sectioned and cryopulverized; DNA was extracted and evaluated for the presence of 9 bacterial species/groups using real-time polymerase chain reaction. Lesions were processed for histopathological and immunohistochemical analyses, which targeted matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), receptor activator of NFκB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). Associations of the target bacteria with expression of these mediators, presence of symptoms, lesion size and histopathological diagnosis were evaluated. Data were analysed using the chi-square, Fisher's exact, Mann-Whitney and Pearson tests. P values lower than 0.05 were considered significant. All pulverized apical root samples were positive for bacteria. The most prevalent taxa were Actinobacteria (53%), Streptococcus species (35%), Fusobacterium species and Parvimonas micra (18%). The target mediators exhibited a high mean expression in the lesions (MMP-2: 82%; MMP-9: 73%; RANK: 78%; RANKL; 81%; OPG; 83%). Mean RANKL:OPG ratio was significantly higher in granulomas than cysts (P < 0.05, Mann-Whitney test). Actinobacteria were associated with granulomas, higher MMP-2 expression, lower OPG expression, and higher RANKL:OPG ratio (P < 0.05 for all, Fisher's exact test or Mann-Whitney test). No other significant associations were found. Actinobacteria may play an important role in the active phase of soft and bone tissue destruction in apical periodontitis. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Microbial biofilms are able to destroy hydroxyapatite in the absence of host immunity in vitro.

PubMed

Junka, Adam Feliks; Szymczyk, Patrycja; Smutnicka, Danuta; Kos, Marcin; Smolina, Iryna; Bartoszewicz, Marzenna; Chlebus, Edward; Turniak, Michal; Sedghizadeh, Parish P

2015-03-01

It is widely thought that inflammation and osteoclastogenesis result in hydroxyapatite (HA) resorption and sequestrum formation during osseous infections, and microbial biofilm pathogens induce the inflammatory destruction of HA. We hypothesized that biofilms associated with infectious bone disease can directly resorb HA in the absence of host inflammation or osteoclastogenesis. Therefore we developed an in vitro model to test this hypothesis. Customized HA discs were manufactured as a substrate for growing clinically relevant biofilm pathogens. Single-species biofilms of Streptococcus mutans, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans and mixed-species biofilms of C albicans plus S mutans were incubated on HA discs for 72 hours to grow mature biofilms. Three different non-biofilm control groups also were established for testing. HA discs were then evaluated by means of scanning electron microscopy, micro-computed tomography metrotomography, x-ray spectroscopy, and confocal microscopy with planimetric analysis. In addition, quantitative cultures and pH assessment were performed. Analysis of variance was used to test for significance between treatment and control groups. All investigated biofilms were able to cause significant (P < .05) and morphologically characteristic alterations in HA structure as compared with controls. The highest number of alterations observed was caused by mixed biofilms of C albicans plus S mutans. S mutans biofilm incubated in medium with additional sucrose content was the most detrimental to HA surfaces among single-species biofilms. Our findings suggest that direct microbial resorption of bone is possible in addition to immune-mediated destruction, which has important translational implications for the pathogenesis of chronic bone infections and for targeted antimicrobial therapeutics. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. All rights reserved.

Skeletal muscle metastases on magnetic resonance imaging: analysis of 31 cases.

PubMed

Li, Qi; Wang, Lei; Pan, Shinong; Shu, Hong; Ma, Ying; Lu, Zaiming; Fu, Xihu; Jiang, Bo; Guo, Qiyong

2016-01-01

To investigate the magnetic resonance imaging (MRI) features of skeletal muscle metastases (SMM). The records of 31 patients with proven SMM were retrospectively reviewed. Clinical history, type of primary malignancy, location of metastases, and MRI features of SMM were evaluated. Based on MRI findings, SMM were divided into three MRI types. The correlation between MRI types with ages and pathology category, between MRI types of SMM and ages, as well as MRI types of SMM and pathology category were analysed with Spearman's rho. The most common primary tumour was genital tumour (25.8%) and bronchial carcinoma (19.4%), and the most common cell type was adenocarcinoma (58.1%). SMM were located in the iliopsoas muscle (26.3%), paravertebral muscles (21.1%), and upper extremity muscles (18.4%). MRI features: (1) Type-I localised lesions (12.90%), round-like mass limited to local regions with heterogeneous iso-signal intensity in T1WI and heterogeneous hyper-intensity in T2WI; (2) Type-II diffuse lesions without bone destruction (35.48%), abnormal diffuse swelling of the muscle with irregular boundaries and slightly hypo- to iso-intensity in T1WI and hyper-intensity in T2WI; and (3) Type-III diffuse lesions with bone destruction (51.61%), distinct irregular lump with iso-intensity in T1WI and heterogeneous hyper-intensity in T2WI with adjacent bone invasion. There was positive correlation between MRI types and ages (r = 0.431, p < 0.05). There were no significant differences of MRI types with pathology category (p > 0.05). SMM features on MRI can be broadly used to classify lesions, which is beneficial for SMM diagnosis.

Skeletal muscle metastases on magnetic resonance imaging: analysis of 31 cases

PubMed Central

Li, Qi; Wang, Lei; Shu, Hong; Ma, Ying; Lu, Zaiming; Fu, Xihu; Jiang, Bo; Guo, Qiyong

2016-01-01

Aim of the study To investigate the magnetic resonance imaging (MRI) features of skeletal muscle metastases (SMM). Material and methods The records of 31 patients with proven SMM were retrospectively reviewed. Clinical history, type of primary malignancy, location of metastases, and MRI features of SMM were evaluated. Based on MRI findings, SMM were divided into three MRI types. The correlation between MRI types with ages and pathology category, between MRI types of SMM and ages, as well as MRI types of SMM and pathology category were analysed with Spearman's rho. Results The most common primary tumour was genital tumour (25.8%) and bronchial carcinoma (19.4%), and the most common cell type was adenocarcinoma (58.1%). SMM were located in the iliopsoas muscle (26.3%), paravertebral muscles (21.1%), and upper extremity muscles (18.4%). MRI features: (1) Type-I localised lesions (12.90%), round-like mass limited to local regions with heterogeneous iso-signal intensity in T1WI and heterogeneous hyper-intensity in T2WI; (2) Type-II diffuse lesions without bone destruction (35.48%), abnormal diffuse swelling of the muscle with irregular boundaries and slightly hypo- to iso-intensity in T1WI and hyper-intensity in T2WI; and (3) Type-III diffuse lesions with bone destruction (51.61%), distinct irregular lump with iso-intensity in T1WI and heterogeneous hyper-intensity in T2WI with adjacent bone invasion. There was positive correlation between MRI types and ages (r = 0.431, p < 0.05). There were no significant differences of MRI types with pathology category (p > 0.05). Conclusions SMM features on MRI can be broadly used to classify lesions, which is beneficial for SMM diagnosis. PMID:27647989

The Effect of Different Bone Marrow Stimulation Techniques on Human Talar Subchondral Bone: A Micro-Computed Tomography Evaluation.

PubMed

Gianakos, Arianna L; Yasui, Youichi; Fraser, Ethan J; Ross, Keir A; Prado, Marcelo P; Fortier, Lisa A; Kennedy, John G

2016-10-01

To evaluate morphological alterations, microarchitectural disturbances, and the extent of bone marrow access to the subchondral bone marrow compartment using micro-computed tomography analysis in different bone marrow stimulation (BMS) techniques. Nine zones in a 3 × 3 grid pattern were assigned to 5 cadaveric talar dome articular surfaces. A 1.00-mm microfracture awl (s.MFX), a 2.00-mm standard microfracture awl (l.MFX), or a 1.25-mm Kirschner wire (K-wire) drill hole was used to penetrate the subchondral bone in each grid zone. Subchondral bone holes and adjacent tissue areas were assessed by micro-computed tomography to analyze adjacent bone area destruction and communicating channels to the bone marrow. Grades 1 to 3 were assigned, where 1 = minimal compression/sclerosis; 2 = moderate compression/sclerosis; 3 = severe compression/sclerosis. Bone volume/total tissue volume, bone surface area/bone volume, trabecular thickness, and trabecular number were calculated in the region of interest. Visual assessment revealed that the s.MFX had significantly more grade 1 holes (P < .001) and that the l.MFX had significantly more poor/grade 3 holes (P = .002). Bone marrow channel assessment showed a statistically significant increase in the number of channels in the s.MFX when compared with both K-wire and l.MFX holes (P < .001). Bone volume fraction for the s.MFX was significantly less than that of the l.MFX (P = .029). BMS techniques using instruments with larger diameters resulted in increased trabecular compaction and sclerosis in areas adjacent to the defect. K-wire and l.MFX techniques resulted in less open communicating bone marrow channels, denoting a reduction in bone marrow access. The results of this study indicate that BMS using larger diameter devices results in greater microarchitecture disturbances. The current study suggests that the choice of a BMS technique should be carefully considered as the results indicate that smaller diameter hole sizes may diminish the amount of microarchitectural disturbances in the subchondral bone. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Diagnosing and discriminating between primary and secondary aneurysmal bone cysts

PubMed Central

Sasaki, Hiromi; Nagano, Satoshi; Shimada, Hirofumi; Yokouchi, Masahiro; Setoguchi, Takao; Ishidou, Yasuhiro; Kunigou, Osamu; Maehara, Kosuke; Komiya, Setsuro

2017-01-01

Aneurysmal bone cysts (ABCs) are benign bony lesions frequently accompanied by multiple cystic lesions and aggressive bone destruction. They are relatively rare lesions, representing only 1% of bone tumors. The pathogenesis of ABCs has yet to be elucidated. In the present study, a series of 22 cases of primary and secondary ABC from patients treated in Department of Orthopedic Surgery, Kagoshima University Hospital (Kagoshima, Japan) from 2001–2015 were retrospectively analyzed. The average age at the time of diagnosis of primary ABC was 17.9 years. Intralesional curettage and artificial bone grafting were performed in the majority of the patients with primary ABC. The local recurrence rate following curettage for primary ABC was 18%, and the cause of local recurrence was considered to be insufficient curettage. Although no adjuvant therapy was administered during the surgeries, it may assist the prevention of local recurrence in certain cases. The cases of secondary ABC were preceded by benign bone tumors, including fibrous dysplasia, giant cell tumors, chondroblastoma and non-ossifying fibroma. The features of the secondary ABC typically reflected those of the preceding bone tumor. In the majority of cases, distinguishing the primary ABC from the secondary ABC was possible based on characteristic features, including age of the patient at diagnosis and the tumor location. In cases that exhibit ambiguous features, including a soft tissue mass or a thick septal enhancement on the preoperative magnetic resonance images, a biopsy must be obtained in order to exclude other types of aggressive bone tumors, including giant cell tumor, osteosarcoma and telangiectatic osteosarcoma. PMID:28454393

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection.

PubMed

Inzana, J A; Trombetta, R P; Schwarz, E M; Kates, S L; Awad, H A

2015-11-04

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

Biomechanics and Mechanobiology of Trabecular Bone: A Review

PubMed Central

Oftadeh, Ramin; Perez-Viloria, Miguel; Villa-Camacho, Juan C.; Vaziri, Ashkan; Nazarian, Ara

2015-01-01

Trabecular bone is a highly porous, heterogeneous, and anisotropic material which can be found at the epiphyses of long bones and in the vertebral bodies. Studying the mechanical properties of trabecular bone is important, since trabecular bone is the main load bearing bone in vertebral bodies and also transfers the load from joints to the compact bone of the cortex of long bones. This review article highlights the high dependency of the mechanical properties of trabecular bone on species, age, anatomic site, loading direction, and size of the sample under consideration. In recent years, high resolution micro finite element methods have been extensively used to specifically address the mechanical properties of the trabecular bone and provide unique tools to interpret and model the mechanical testing experiments. The aims of the current work are to first review the mechanobiology of trabecular bone and then present classical and new approaches for modeling and analyzing the trabecular bone microstructure and macrostructure and corresponding mechanical properties such as elastic properties and strength. PMID:25412137

A quantification strategy for missing bone mass in case of osteolytic bone lesions

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

Fränzle, Andrea, E-mail: a.fraenzle@dkfz.de; Giske, Kristina; Bretschi, Maren

Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approachmore » is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean ratiov{sub r}/v{sub m} of the reconstructed bone volume v{sub r} and the healthy model bone volume v{sub m} is 1.07, which indicates a good reconstruction of the modified bone. Conclusions: The qualitative and quantitative comparison of manual and semi-automated segmentation results have shown that comparing a modified bone structure with a healthy model can be used to identify and measure missing bone mass in a reproducible way.« less

[Clinical experience in osteoplastic material Allomatrix-implant and fibrin rich platelets use in surgical treatment of jaw radicular cysts].

PubMed

Kuz'minykh, I A

2009-01-01

Bones forming optimizators applying in surgical dentistry is an important element of jaw destructive processes successful treatment. Today use of osteoplastic materials on the collagen basis is widely spread. One of this challenge solution is FRP and Allomatrix-implant material applying to jaws during surgery operations. We described clinical investigation phase: the estimation of postoperative and remote results of treatment was carried out.

Periodontal aspects of the juvenile form of paracoccidioidomycosis.

PubMed

Migliari, D A; Sugaya, N N; Mimura, M A; Cucé, L C

1998-01-01

Three cases of the juvenile form of paracoccidioidomycosis are reported. Emphasis has been given to the oral manifestations, particularly the periodontal involvement. The main periodontal findings were: generalized and progressive alveolar bone destruction leading to gingival recession with exposure of the tooth roots, and spontaneous tooth losses. The gingival mucosa was predominantly smooth, erythematous and slightly swollen. These aspects, although rare, may be the earliest signs of the disease and sometimes its only manifestations.

Porphyromonas gingivalis sinks teeth into the oral microbiota and periodontal disease.

PubMed

Honda, Kenya

2011-11-17

Periodontitis is linked to polymicrobial interactions and the presence of Porphyromonas gingivalis. In this issue of Cell Host & Microbe, Hajishengallis et al. (2011) demonstrate that P. gingivalis colonization in the oral cavity changes the composition of the oral commensal microbiota and accelerates microbiota-mediated bone-destructive periodontitis, indicating that this single, low-abundance species is a keystone in periodontal disease. Copyright © 2011 Elsevier Inc. All rights reserved.

EVALUATION OF A MULTICOMPONENT INTERVENTION FOR DIURNAL BRUXISM IN A YOUNG CHILD WITH AUTISM

PubMed Central

Barnoy, Emily L; Najdowski, Adel C; Tarbox, Jonathan; Wilke, Arthur E; Nollet, Megan D

2009-01-01

Bruxism, forceful grinding of one's teeth together, can produce destructive outcomes such as wear on the teeth and damaged gums and bone structures. The current study implemented a multicomponent intervention that consisted of vocal and physical cues to decrease rates of bruxism. A partial component analysis suggested that the vocal cue was only effective at decreasing levels of bruxism when paired with a simultaneous physical cue. PMID:20514192

Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering.

PubMed

Wang, Martha O; Vorwald, Charlotte E; Dreher, Maureen L; Mott, Eric J; Cheng, Ming-Huei; Cinar, Ali; Mehdizadeh, Hamidreza; Somo, Sami; Dean, David; Brey, Eric M; Fisher, John P

2015-01-07

There is an unmet need for a consistent set of tools for the evaluation of 3D-printed constructs. A toolbox developed to design, characterize, and evaluate 3D-printed poly(propylene fumarate) scaffolds is proposed for vascularized engineered tissues. This toolbox combines modular design and non-destructive fabricated design evaluation, evaluates biocompatibility and mechanical properties, and models angiogenesis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estrogen related receptor alpha in castration-resistant prostate cancer cells promotes tumor progression in bone

PubMed Central

Delliaux, Carine; Gervais, Manon; Kan, Casina; Benetollo, Claire; Pantano, Francesco; Vargas, Geoffrey; Bouazza, Lamia; Croset, Martine; Bala, Yohann; Leroy, Xavier; Rosol, Thomas J; Rieusset, Jennifer; Bellahcène, Akeila; Castronovo, Vincent; Aubin, Jane E; Clézardin, Philippe; Duterque-Coquillaud, Martine; Bonnelye, Edith

2016-01-01

Bone metastases are one of the main complications of prostate cancer and they are incurable. We investigated whether and how estrogen receptor-related receptor alpha (ERRα) is involved in bone tumor progression associated with advanced prostate cancer. By meta-analysis, we first found that ERRα expression is correlated with castration-resistant prostate cancer (CRPC), the hallmark of progressive disease. We then analyzed tumor cell progression and the associated signaling pathways in gain-of-function/loss-of-function CRPC models in vivo and in vitro. Increased levels of ERRα in tumor cells led to rapid tumor progression, with both bone destruction and formation, and direct impacts on osteoclasts and osteoblasts. VEGF-A, WNT5A and TGFβ1 were upregulated by ERRα in tumor cells and all of these factors also significantly and positively correlated with ERRα expression in CRPC patient specimens. Finally, high levels of ERRα in tumor cells stimulated the pro-metastatic factor periostin expression in the stroma, suggesting that ERRα regulates the tumor stromal cell microenvironment to enhance tumor progression. Taken together, our data demonstrate that ERRα is a regulator of CRPC cell progression in bone. Therefore, inhibiting ERRα may constitute a new therapeutic strategy for prostate cancer skeletal-related events. PMID:27776343

Donor lymphocyte infusions to leukemic bone lesions are therapeutically effective in a Ph+ ALL patient with post-HSCT relapse.

PubMed

Lange, Andrzej; Dlubek, Dorota; Zdziarski, Robert; Chodorowska, Anna; Mordak-Domagala, Monika; Klimczak, Aleksandra; Lange, Janusz; Jaskula, Emilia

2014-10-01

A Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) case was maintained in remission with the use of chemo-immunotherapy. The latter involved sibling bone marrow transplant (BMT) (three procedures) followed by intravenous (IV) donor lymphocyte infusion (DLI). The third relapse responded to routine chemotherapy and again DLI was employed. During hematological and molecular remission verified at the level of iliac crest aspiration, extra-medullary relapse in the bones was apparent. A novel procedure of donor lymphocyte injection to the bone leukemic lesions was developed and employed. A dose of 10(6) donor lymphocytes/kg body weight (BW) of the recipient were each time injected to the plane of the right and left tibia, the head of the humerus, and the calcaneus, which resulted in healing of the destructive process. In consequence of this novel approach, in addition to the healing of bone lesions, an accumulation of cytotoxic activated T-cells in the marrow was documented, which was mirrored by an increase in the number of transcripts for interferon (IFN)-γ, interleukin (IL)-17, as well as RORγt. The local administration of DLI directly to the leukemic lesions requires a lower dose that diminishes the toxicity due to the general immune system activation.

Tooth and bone deformation: structure and material properties by ESPI

NASA Astrophysics Data System (ADS)

Zaslansky, Paul; Shahar, Ron; Barak, Meir M.; Friesem, Asher A.; Weiner, Steve

2006-08-01

In order to understand complex-hierarchical biomaterials such as bones and teeth, it is necessary to relate their structure and mechanical-properties. We have adapted electronic speckle pattern-correlation interferometry (ESPI) to make measurements of deformation of small water-immersed specimens of teeth and bones. By combining full-field ESPI with precision mechanical loading we mapped sub-micron displacements and determined material-properties of the samples. By gradually and elastically compressing the samples, we compensate for poor S/N-ratios and displacement differences of about 100nm were reliably determined along samples just 2~3mm long. We produced stress-strain curves well within the elastic performance range of these materials under biologically relevant conditions. For human tooth-dentin, Young's modulus in inter-dental areas of the root is 40% higher than on the outer sides. For cubic equine bone samples the compression modulus of axial orientations is about double the modulus of radial and tangential orientations (20 GPa versus 10 GPa respectively). Furthermore, we measured and reproduced a surprisingly low Poisson's ratio, which averaged about 0.1. Thus the non-contact and non-destructive measurements by ESPI produce high sensitivity analyses of mechanical properties of mineralized tissues. This paves the way for mapping deformation-differences of various regions of bones, teeth and other biomaterials.

Evaluation of cell sheet application on one wall bone defect in Macaca nemestrina through periostin expression

NASA Astrophysics Data System (ADS)

Tamin, R. Y.; Soeroso, Y.; Amir, L.; Idrus, E.

2017-08-01

Chronic periodontitis is an oral disease in which the destruction of periodontal tissue leads to tooth loss. Regenerative therapy for attachment cannot be applied to one wall bone defects owing to the minimal existing healthy bone. Tissue engineering in the form of cell sheets has been developed to overcome this limitation. In a previous study, cell sheet application to a one wall bone defect in Macaca nemestrina showed good clinical results. To evaluate the effectiveness of cell sheet application histologically, the level of periostin expression in the gingival crevicular fluid (GCF) of M. nemestrina was determined. Periostin is a 90-kDa protein that regulates coordination and interaction for regeneration and tissue repair. A laboratory observation study was performed to see the differences in periostin levels in samples collected from M. nemestrina’s GCF, where a cell sheet was applied to the bone defect. Gel electrophoresis with SDS-PAGE was performed to detect periostin expression based on its molecular weight and to compare the expression band between the cell sheet and the control at 1, 2, and 3 weeks after treatment. The gel electrophoresis result shows different thicknesses of the protein band around the molecular weight of periostin between the cell sheet groups.

Notch signaling drives multiple myeloma induced osteoclastogenesis

PubMed Central

Colombo, Michela; Thümmler, Katja; Mirandola, Leonardo; Garavelli, Silvia; Todoerti, Katia; Apicella, Luana; Lazzari, Elisa; Lancellotti, Marialuigia; Platonova, Natalia; Akbar, Moeed; Chiriva-Internati, Maurizio; Soutar, Richard; Neri, Antonino; Goodyear, Carl S.; Chiaramonte, Raffaella

2014-01-01

Multiple myeloma (MM) is closely associated with bone destruction. Once migrated to the bone marrow, MM cells unbalance bone formation and resorption via the recruitment and maturation of osteoclast precursors. The Notch pathway plays a key role in different types of cancer and drives several biological processes relevant in MM, including cell localization within the bone marrow, proliferation, survival and pharmacological resistance. Here we present evidences that MM can efficiently drive osteoclastogenesis by contemporaneously activating Notch signaling on tumor cells and osteoclasts through the aberrant expression of Notch ligands belonging to the Jagged family. Active Notch signaling in MM cells induces the secretion of the key osteoclastogenic factor, RANKL, which can be boosted in the presence of stromal cells. In turn, MM cells-derived RANKL causes the upregulation of its receptor, RANK, and Notch2 in pre-osteoclasts. Notch2 stimulates osteoclast differentiation by promoting autocrine RANKL signaling. Finally, MM cells through Jagged ligands expression can also activate Notch signaling in pre-osteoclast by direct contact. Such synergism between tumor cells and pre-osteoclasts in MM-induced osteoclastogenesis can be disrupted by silencing tumor-derived Jagged1 and 2. These results make the Jagged ligands new promising therapeutic targets in MM to contrast bone disease and the associated co-morbidities. PMID:25257302

Clinical effectiveness of combining platelet rich fibrin with alloplastic bone substitute for the management of combined endodontic periodontal lesion

PubMed Central

2014-01-01

The term "endo-perio" lesion has been proposed to describe the destructive lesion resulting from inflammatory products found in varying degrees in both the periodontium and the pulpal tissues. In most of the cases, clinical symptoms disappear following successful endodontic therapy. However failure after conventional root canal treatment calls for surgical intervention. A 35 year old male patient with endo-perio lesion in right maxillary lateral incisor was treated with platelet rich fibrin (PRF) and alloplastic bone substitute after conventional endodontic therapy. At the end of 6 months there was gain in clinical attachment, increased radiographic bone fill and reduction in probing depth which was maintained till 18 month follow-up. Present case report aims to evaluate the efficacy of PRF and alloplastic bone substitute in the management of intrabony defect associated with endo-perio lesion in maxillary lateral incisor because the healing potential of PRF and bone graft has not been widely studied in endodontics. The use of PRF allows the clinician to optimize tissue remodelling, wound healing and angiogenesis by the local delivery of growth factors and proteins. The novel technique described here enables the clinician to be benefited from the full regenerative capacity of this autologous biologic material. PMID:24516830

Clinical effectiveness of combining platelet rich fibrin with alloplastic bone substitute for the management of combined endodontic periodontal lesion.

PubMed

Goyal, Lata

2014-02-01

The term "endo-perio" lesion has been proposed to describe the destructive lesion resulting from inflammatory products found in varying degrees in both the periodontium and the pulpal tissues. In most of the cases, clinical symptoms disappear following successful endodontic therapy. However failure after conventional root canal treatment calls for surgical intervention. A 35 year old male patient with endo-perio lesion in right maxillary lateral incisor was treated with platelet rich fibrin (PRF) and alloplastic bone substitute after conventional endodontic therapy. At the end of 6 months there was gain in clinical attachment, increased radiographic bone fill and reduction in probing depth which was maintained till 18 month follow-up. Present case report aims to evaluate the efficacy of PRF and alloplastic bone substitute in the management of intrabony defect associated with endo-perio lesion in maxillary lateral incisor because the healing potential of PRF and bone graft has not been widely studied in endodontics. The use of PRF allows the clinician to optimize tissue remodelling, wound healing and angiogenesis by the local delivery of growth factors and proteins. The novel technique described here enables the clinician to be benefited from the full regenerative capacity of this autologous biologic material.

Aplastic anemia as a feature of systemic lupus erythematosus: a case report and literature review.

PubMed

Chalayer, Émilie; Ffrench, Martine; Cathébras, Pascal

2015-06-01

Peripheral cytopenias are common in systemic lupus erythematosus, but bone marrow involvement is rarely reported. Aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and characterized by an empty bone marrow. This rare but serious disease has been described as an unusual manifestation of systemic lupus erythematosus. We reviewed the 25 cases published in the English language literature and discuss the clinical presentation, outcome, treatment, and pathophysiology of aplastic anemia as a complication of systemic lupus erythematosus. We report here the first case of aplastic anemia associated with systemic lupus erythematosus treated with an allogeneic hematopoietic stem cell transplant. Over one half of patients received concomitantly the diagnoses of systemic lupus erythematosus and aplastic anemia. No clinical or histological features can distinguish primary aplastic anemia from aplastic anemia occurring in systemic lupus erythematosus patients. The overall mortality is about 15% and corticosteroid-based therapy alone or in combination with other immunomodulatory drugs can restore bone marrow function. Systemic lupus erythematosus may be complicated by bone marrow involvement. The diagnosis of peripheral cytopenias should be confirmed by bone marrow aspiration. All these patients should receive cortisone as a first treatment. Plasma exchanges seem to have some efficacy. Other different immunomodulatory therapies were used with variable results.

Neutrophil mobilization by surface-glycan altered Th17-skewing bacteria mitigates periodontal pathogen persistence and associated alveolar bone loss.

PubMed

Settem, Rajendra P; Honma, Kiyonobu; Sharma, Ashu

2014-01-01

Alveolar bone (tooth-supporting bone) erosion is a hallmark of periodontitis, an inflammatory disease that often leads to tooth loss. Periodontitis is caused by a select group of pathogens that form biofilms in subgingival crevices between the gums and teeth. It is well-recognized that the periodontal pathogen Porphyromonas gingivalis in these biofilms is responsible for modeling a microbial dysbiotic state, which then initiates an inflammatory response destructive to the periodontal tissues and bone. Eradication of this pathogen is thus critical for the treatment of periodontitis. Previous studies have shown that oral inoculation in mice with an attenuated strain of the periodontal pathogen Tannerella forsythia altered in O-glycan surface composition induces a Th17-linked mobilization of neutrophils to the gingival tissues. In this study, we sought to determine if immune priming with such a Th17-biasing strain would elicit a productive neutrophil response against P. gingivalis. Our data show that inoculation with a Th17-biasing T. forsythia strain is effective in blocking P. gingivalis-persistence and associated alveolar bone loss in mice. This work demonstrates the potential of O-glycan modified Tannerella strains or their O-glycan components for harnessing Th17-mediated immunity against periodontal and other mucosal pathogens.

In situ hybridization and immunohistochemistry of bone sialoprotein and secreted phosphoprotein 1 (osteopontin) in the developing mouse mandibular condylar cartilage compared with limb bud cartilage

PubMed Central

Shibata, Shunichi; Fukada, Kenji; Suzuki, Shoichi; Ogawa, Takuya; Yamashita, Yasuo

2002-01-01

Mandibular condylar cartilage is often classified as a secondary cartilage, differing from the primary cartilaginous skeleton in its rapid progress from progenitor cells to hypertrophic chondrocytes. In this study we used in situ hybridization and immunohistochemistry to investigate whether the formation of primary (tibial) and secondary (condylar) cartilage also differs with respect to the expression of two major non-collagenous glycoproteins of bone matrix, bone sialoprotein (BSP) and secreted phosphoprotein 1 (Spp1, osteopontin). The mRNAs for both molecules were never expressed until hypertrophic chondrocytes appeared. In the tibial cartilage, hypertrophic chondrocytes first appeared at E14 and the expression of BSP and Spp1 mRNAs was detected in the lower hypertrophic cell zone, but the expression of BSP mRNA was very weak. In the condylar cartilage, hypertrophic chondrocytes appeared at E15 as soon as cartilage tissue appeared. The mRNAs for both molecules were expressed in the newly formed condylar cartilage, although the proteins were not detected by immunostaining; BSP mRNA in the condylar cartilage was more extensively expressed than that in the tibial cartilage at the corresponding stage (first appearance of hypertrophic cell zone). Endochondral bone formation started at E15 in the tibial cartilage and at E16 in the condylar cartilage. At this stage (first appearance of endochondral bone formation), BSP mRNA was also more extensively expressed in the condylar cartilage than in the tibial cartilage. The hypertrophic cell zone in the condylar cartilage rapidly extended during E15–16. These results indicate that the formation process of the mandibular condylar cartilage differs from that of limb bud cartilage with respect to the extensive expression of BSP mRNA and the rapid extension of the hypertrophic cell zone at early stages of cartilage formation. Furthermore, these results support the hypothesis that, in vivo, BSP promotes the initiation of mineralization. PMID:12033735

Carbon Nanostructures in Bone Tissue Engineering

PubMed Central

Perkins, Brian Lee; Naderi, Naghmeh

2016-01-01

Background: Recent advances in developing biocompatible materials for treating bone loss or defects have dramatically changed clinicians’ reconstructive armory. Current clinically available reconstructive options have certain advantages, but also several drawbacks that prevent them from gaining universal acceptance. A wide range of synthetic and natural biomaterials is being used to develop tissue-engineered bone. Many of these materials are currently in the clinical trial stage. Methods: A selective literature review was performed for carbon nanostructure composites in bone tissue engineering. Results: Incorporation of carbon nanostructures significantly improves the mechanical properties of various biomaterials to mimic that of natural bone. Recently, carbon-modified biomaterials for bone tissue engineering have been extensively investigated to potentially revolutionize biomaterials for bone regeneration. Conclusion: This review summarizes the chemical and biophysical properties of carbon nanostructures and discusses their functionality in bone tissue regeneration. PMID:28217212

Bone allografting in children

NASA Astrophysics Data System (ADS)

Sadovoy, M. A.; Kirilova, I. A.; Podorognaya, V. T.; Matsuk, S. A.; Novoselov, V. P.; Moskalev, A. V.; Bondarenko, A. V.; Afanasev, L. M.; Gubina, E. V.

2017-09-01

A total of 522 patients with benign and intermediate bone tumors of various locations, aged 1 to 15 years, were operated in the period from 1996 to 2016. To diagnose skeleton tumors, we used clinical observation, X-ray, and, if indicated, tomography and tumor site biopsy. In the extensive bone resection, we performed bone reconstruction with the replacement of a defect with an allograft (bone strips, deproteinized and spongy grafts), sometimes in the combination with bone autografting. After segmental resection, the defects were filled with bone strips in the form of matchstick grafts; the allografts were received from the Laboratory for Tissue Preparation and Preservation of the Novosibirsk Research Institute of Traumatology and Orthopedics. According to the X-ray data, a complete reorganization of bone grafts occurred within 1.5 to 3 years. The long-term result was assessed as good.

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.

A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis.

PubMed

Jablonski, Heidrun; Polan, Christina; Wedemeyer, Christian; Hilken, Gero; Schlepper, Rüdiger; Bachmann, Hagen Sjard; Grabellus, Florian; Dudda, Marcel; Jäger, Marcus; Kauther, Max Daniel

2017-12-01

Particle-induced osteolysis, which by definition is an aseptic inflammatory reaction to implant-derived wear debris eventually leading to local bone destruction, remains the major reason for long-term failure of orthopedic endoprostheses. Fetuin-A, a 66kDa glycoprotein with diverse functions, is found to be enriched in bone. Besides being an important inhibitor of ectopic calcification, it has been described to influence the production of mediators of inflammation. Furthermore, a regulatory role in bone metabolism has been assigned. In the present study, the influence of a single dose of bovine fetuin-A, intraperitoneally injected in mice subjected to particle-induced osteolysis of the calvaria, was analyzed. Twenty-eight male C57BL/6 mice, twelve weeks of age, were randomly divided into four groups. Groups 2 and 4 were subjected to ultra-high molecular weight polyethylene (UHMWPE) particles placed on their calvariae while groups 1 and 3 were sham-operated. Furthermore, groups 3 and 4 received a single intraperitoneal injection of 20mg bovine fetuin-A while groups 1 and 2 were treated with physiologic saline. After 14days calvarial bone was qualitatively and quantitatively assessed using microcomputed tomography (μCT) and histomorphometrical approaches. Application of fetuin-A led to a reduction of particle-induced osteolysis in terms of visible osteolytic lesions and eroded bone surface. The reduction of bone thickness and bone volume, as elicited by UHMWPE, was alleviated by fetuin-A. In conclusion, fetuin-A was found to exert an anti-resorptive effect on particle-induced osteolysis in-vivo. Thus, fetuin-A could play a potentially osteoprotective role in the treatment of bone metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

The protocol for the isolation and cryopreservation of osteoclast precursors from mouse bone marrow and spleen.

PubMed

Boraschi-Diaz, Iris; Komarova, Svetlana V

2016-01-01

Osteoclasts are responsible for physiological bone remodeling as well as pathological bone destruction in osteoporosis, periodontitis and rheumatoid arthritis, and thus represent a pharmacological target for drug development. We aimed to characterize and compare the cytokine-induced osteoclastogenesis of bone marrow and spleen precursors. Established protocols used to generate osteoclasts from bone marrow were modified to examine osteoclastogenesis of the spleen cells of healthy mice. Osteoclast formation was successfully induced from spleen precursors using receptor activator of nuclear factor κB ligand (50 ng/ml) and macrophage colony stimulating factor (50 ng/ml). Compared to bone marrow cultures, differentiation from spleen required a longer cultivation time (9 days for spleen, as compared to 5 days for marrow cultures) and a higher plating density of non-adherent cells (75,000/cm(2) for spleen, as compared to 50,000/cm(2) for bone marrow). Osteoclasts generated from spleen precursors expressed osteoclast marker genes calcitonin receptor, cathepsin K and matrix metalloproteinase 9 and were capable of resorbing hydroxyapatite. The differentiation capacity of spleen and bone marrow precursors was comparable for BALB/c, C57BL/6 and FVB mice. We also developed and tested a cryopreservation protocol for the osteoclast precursors. While 70-80 % of cells were lost during the first week of freezing, during the subsequent 5 weeks the losses were within 2-5 % per week. Osteoclastogenesis from the recovered bone marrow precursors was successful up to 5 weeks after freezing. Spleen precursors retained their osteoclastogenic capacity for 1 week after freezing, but not thereafter. The described protocol is useful for the studies of genetically modified animals as well as for screening new osteoclast-targeting therapeutics.

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.

MRI differentiation of low-grade from high-grade appendicular chondrosarcoma.

PubMed

Douis, Hassan; Singh, Leanne; Saifuddin, Asif

2014-01-01

To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. • Accurate differentiation of low-grade from high-grade chondrosarcomas is essential before surgery • MRI can reliably differentiate high-grade from low-grade chondrosarcomas of long bone • Differentiating features are bone expansion, periostitis, soft tissue mass and tumour length • Presence of these four MRI features demonstrated a diagnostic accuracy (AUC) of 95.6 % • The findings may result in more accurate diagnosis before definitive surgery.

Spindle Cell Rhabdomyosarcoma of Bone with FUS-TFCP2 Fusion: Confirmation of a Very Recently Described Rhabdomyosarcoma Subtype.

PubMed

Dashti, Nooshin K; Wehrs, Rebecca N; Thomas, Brittany C; Nair, Asha; Davila, Jaime; Buckner, Jan C; Martinez, Anthony P; Sukov, William R; Halling, Kevin C; Howe, Benjamin M; Folpe, Andrew L

2018-05-14

Rhabdomyosarcomas of bone are extremely rare, with fewer than 10 reported cases. A very rare subtype of spindle cell/sclerosing rhabdomyosarcoma harboring a FUS-TFCP2 fusion and involving both soft tissue and bone locations has very recently been reported. We report only the fourth case of this unusual, clinically aggressive rhabdomyosarcoma. A previously-well 72-year old male presented with a destructive lesion of the mandible. Morphological and immunohistochemical study of a needle biopsy and the subsequent resection showed a spindle cell rhabdomyosarcoma. RNA-seq, RT-PCR and FISH confirmed the presence of the FUS-TFCP2 fusion. Spindle cell rhabdomyosarcomas carrying the FUS-TFCP2 fusion are very rare rhabdomyosarcoma variants with osseous predilection. The classification and differential diagnosis of this unusual molecular variant of spindle cell/ sclerosing rhabdomyosarcoma are discussed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Role of Neurokinin 3 Receptor Signaling in Oral Squamous Cell Carcinoma.

PubMed

Obata, Kyoichi; Shimo, Tsuyoshi; Okui, Tatsuo; Matsumoto, Kenichi; Takada, Hiroyuki; Takabatake, Kiyofumi; Kunisada, Yuki; Ibaragi, Soichiro; Yoshioka, Norie; Kishimoto, Koji; Nagatsuka, Hitoshi; Sasaki, Akira

2017-11-01

The neurokinin 3 receptor (NK-3R) is differentially expressed in the central nervous system including cases of human oral squamous cell carcinoma. However, the role of NK-3R signaling in oral squamous cell carcinoma is not well known. NK-3R expression in surgically resected oral squamous cell carcinoma was examined immunohistochemically and the strength of the expression was quantified. We evaluated the function of NK-3R signaling using NK-3R antagonist in human oral squamous cell carcinoma bone invasion mouse model. NK-3R was significantly expressed in tumor cells that had invaded the bone matrix compared to the oral side tumor cells. SB222200, a selective antagonist of NK-3R, significantly suppressed the radiographic osteolytic lesion and tumorigenesis. NK-3R signaling is a potential target for the treatment of oral squamous cell carcinoma in cases of bone destruction. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate suppresses osteoclast maturation and bone resorption by targeting macrophage-colony stimulating factor signaling.

PubMed

Park, So Jeong; Park, Doo Ri; Bhattarai, Deepak; Lee, Kyeong; Kim, Jaesang; Bae, Yun Soo; Lee, Soo Young

2014-08-01

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.

Effect of thermodisinfection on mechanic parameters of cancellous bone.

PubMed

Fölsch, Christian; Kellotat, Andreas; Rickert, Markus; Ishaque, Bernd; Ahmed, Gafar; Pruss, Axel; Jahnke, Alexander

2016-09-01

Revision surgery of joint replacements is increasing and raises the demand for allograft bone since restoration of bone stock is crucial for longevity of implants. Proceedings of bone grafts influence the biological and mechanic properties differently. This study examines the effect of thermodisinfection on mechanic properties of cancellous bone. Bone cylinders from both femoral heads with length 45 mm were taken from twenty-three 6-8 months-old piglets, thermodisinfected at 82.5 °C according to bone bank guidelines and control remained native. The specimens were stored at -20 °C immediately and were put into 21 °C Ringer's solution for 3 h before testing. Shear and pressure modulus were tested since three point bending force was examined until destruction. Statistical analysis was done with non-parametric Wilcoxon, t test and SPSS since p < 0.05 was significant. Shear modulus was significantly reduced by thermodisinfection to 1.02 ± 0.31 GPa from 1.28 ± 0.68 GPa for unprocessed cancellous bone (p = 0.029) since thermodisinfection reduced pressure modulus not significantly from 6.30 ± 4.72 GPa for native specimens to 4.97 ± 2.23 GPa and maximum bending force was 270.03 ± 116.68 N for native and 228.80 ± 70.49 N for thermodisinfected cancellous bone. Shear and pressure modulus were reduced by thermodisinfection around 20 % and maximum bending force was impaired by about 15 % compared with native cancellous bone since only the reduction of shear modulus reached significance. The results suggest that thermodisinfection similarly affects different mechanic properties of cancellous bone and the reduction of mechanic properties should not relevantly impair clinical use of thermodisinfected cancellous bone.

18 F-Fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis

PubMed Central

2014-01-01

Introduction Evaluation of disease severity in experimental models of rheumatoid arthritis is inevitably associated with assessment of structural bone damage. A noninvasive imaging technology allowing objective quantification of pathophysiological alterations of bone structure in rodents could substantially extend the methods used to date in preclinical arthritis research for staging of autoimmune disease severity or efficacy of therapeutical intervention. Sodium 18 F-fluoride (18 F-NaF) is a bone-seeking tracer well-suited for molecular imaging. Therefore, we systematically examined the use of 18 F-NaF positron emission tomography/computed tomography (PET/CT) in mice with glucose-6-phosphate isomerase (G6PI)–induced arthritis for quantification of pathological bone metabolism. Methods F-fluoride was injected into mice before disease onset and at various time points of progressing experimental arthritis. Radioisotope accumulation in joints in the fore- and hindpaws was analyzed by PET measurements. For validation of bone metabolism quantified by 18 F-fluoride PET, bone surface parameters of high-resolution μCT measurements were used. Results Before clinical arthritis onset, no distinct accumulation of 18 F-fluoride was detectable in the fore- and hindlimbs of mice immunized with G6PI. In the course of experimental autoimmune disease, 18 F-fluoride bone uptake was increased at sites of enhanced bone metabolism caused by pathophysiological processes of autoimmune disease. Moreover, 18 F-fluoride signaling at different stages of G6PI-induced arthritis was significantly correlated with the degree of bone destruction. CT enabled identification of exact localization of 18 F-fluoride signaling in bone and soft tissue. Conclusions The results of this study suggest that small-animal PET/CT using 18 F-fluoride as a tracer is a feasible method for quantitative assessment of pathophysiological bone metabolism in experimental arthritis. Furthermore, the possibility to perform repeated noninvasive measurements in vivo allows longitudinal study of therapeutical intervention monitoring. PMID:25053370

Targeted Infrared Photoimmunotherapy for Cancer | Center for Cancer Research

Cancer.gov

A longstanding goal of cancer therapy is the extensive destruction of cancer cells with minimal collateral damage to normal cells. This goal has been very hard to accomplish. Most existing efficacious treatments inevitably inflict collateral damage on nearby normal cells and tissue.

Repair of cocaine-related oronasal fistula with forearm radial free flap.

PubMed

Colletti, Giacomo; Allevi, Fabiana; Valassina, Davide; Bertossi, Dario; Biglioli, Federico

2013-01-01

Cocaine snorting may cause significant local ischemic necrosis and the destruction of nasal and midfacial bones and soft tissues, leading to the development of a syndrome called cocaine-induced midline destructive lesion. A review of the English-language literature reveals only a few articles describing the treatment of hard and/or soft palatal perforation related to cocaine inhalation. Described here are 4 patients with a history of cocaine abuse showing palatal lesions. From 2010 to 2013, a total of 4 patients affected by cocaine-related midline destructive lesions were referred to our department. They all presented signs of a cocaine-induced midline destructive lesion. They showed wide midfacial destruction involving the nasal septum as well as the hard and soft palates causing an ample oronasal communication. In 3 patients, oronasal communication has been treated successfully using a personal technique based on a partially de-epithelialized forearm free flap. The fourth patient had been treated only with local debridement because, when she came to our attention, her abusive habits were still unsolved. Different surgical options have been reported such as local, regional, and free flaps for hard and soft palate reconstruction. However, because of an unpredictable vascularization of the palatal tissues and owing to the scarceness of the local soft tissues, local flaps are at high risk for partial and complete failure. The transfer of free vascularized tissue, however, seems to be the most reliable and logical solution for medium- to large-sized fistulas. Among the various free flaps, we choose the radial forearm type because of the pedicle length and the flap thickness.

Comparisons between two biochemical markers in evaluating periodontal disease severity: a cross-sectional study

PubMed Central

2014-01-01

Background The purpose of this study was to compare two biochemical markers, which have been previously used to determine the degrees of alveolar bone destruction, in evaluating periodontal disease severity. Methods The WF6 epitope of chondroitin sulfate (CS) and the alkaline phosphatase (ALP) levels were determined in gingival crevicular fluid (GCF) samples collected from patients with various degrees of disease severity, including ten patients with gingivitis (50 gingivitis sites) and 33 patients with chronic periodontitis (including gingivitis, slight, moderate, and severe periodontitis sites; n = 50 each), as well as from ten healthy volunteers (50 healthy sites) by Periopaper strips. The levels of CS and ALP were measured by an ELISA and a fluorometric assay, respectively. Results The results demonstrated low levels of CS and ALP in non-destructive and slightly destructive periodontitis sites, whereas significantly high levels of these two biomolecules were shown in moderately and severely destructive sites (p < 0.05). Although a significant difference in CS levels was found between moderate and severe periodontitis sites, no difference in ALP levels was found. Stronger correlations were found between CS levels and periodontal parameters, including probing depth, loss of clinical attachment levels, gingival index and plaque index, than between ALP levels and these parameters. Conclusions It is suggested that the CS level is a better diagnostic marker than the ALP level for evaluating distinct severity of chronic periodontitis. PMID:25174345

Bone cells in birds show exceptional surface area, a characteristic tracing back to saurischian dinosaurs of the late Triassic.

PubMed

Rensberger, John M; Martínez, Ricardo N

2015-01-01

Dinosaurs are unique among terrestrial tetrapods in their body sizes, which range from less than 3 gm in hummingbirds to 70,000 kg or more in sauropods. Studies of the microstructure of bone tissue have indicated that large dinosaurs, once believed to be slow growing, attained maturity at rates comparable to or greater than those of large mammals. A number of structural criteria in bone tissue have been used to assess differences in rates of osteogenesis in extinct taxa, including counts of lines of arrested growth and the density of vascular canals. Here, we examine the density of the cytoplasmic surface of bone-producing cells, a feature which may set an upper limit to the rate of osteogenesis. Osteocyte lacunae and canaliculi, the cavities in bone containing osteocytes and their extensions, were measured in thin-sections of primary (woven and parallel fibered) bone in a diversity of tetrapods. The results indicate that bone cell surfaces are more densely organized in the Saurischia (extant birds, extinct Mesozoic Theropoda and Sauropodomorpha) than in other tetrapods, a result of denser branching of the cell extensions. The highest postnatal growth rates among extant tetrapods occur in modern birds, the only surviving saurischians, and the finding of exceptional cytoplasmic surface area of the cells that produce bone in this group suggests a relationship with bone growth rate. In support of this relationship is finding the lowest cell surface density among the saurischians examined in Dinornis, a member of a group of ratites that evolved in New Zealand in isolation from mammalian predators and show other evidence of lowered maturation rates.

Bone Cells in Birds Show Exceptional Surface Area, a Characteristic Tracing Back to Saurischian Dinosaurs of the Late Triassic

PubMed Central

Rensberger, John M.; Martínez, Ricardo N.

2015-01-01

Background Dinosaurs are unique among terrestrial tetrapods in their body sizes, which range from less than 3 gm in hummingbirds to 70,000 kg or more in sauropods. Studies of the microstructure of bone tissue have indicated that large dinosaurs, once believed to be slow growing, attained maturity at rates comparable to or greater than those of large mammals. A number of structural criteria in bone tissue have been used to assess differences in rates of osteogenesis in extinct taxa, including counts of lines of arrested growth and the density of vascular canals. Methodology/Principal Findings Here, we examine the density of the cytoplasmic surface of bone-producing cells, a feature which may set an upper limit to the rate of osteogenesis. Osteocyte lacunae and canaliculi, the cavities in bone containing osteocytes and their extensions, were measured in thin-sections of primary (woven and parallel fibered) bone in a diversity of tetrapods. The results indicate that bone cell surfaces are more densely organized in the Saurischia (extant birds, extinct Mesozoic Theropoda and Sauropodomorpha) than in other tetrapods, a result of denser branching of the cell extensions. The highest postnatal growth rates among extant tetrapods occur in modern birds, the only surviving saurischians, and the finding of exceptional cytoplasmic surface area of the cells that produce bone in this group suggests a relationship with bone growth rate. In support of this relationship is finding the lowest cell surface density among the saurischians examined in Dinornis, a member of a group of ratites that evolved in New Zealand in isolation from mammalian predators and show other evidence of lowered maturation rates. PMID:25830561

A combined method for DNA analysis and radiocarbon dating from a single sample.

PubMed

Korlević, Petra; Talamo, Sahra; Meyer, Matthias

2018-03-07

Current protocols for ancient DNA and radiocarbon analysis of ancient bones and teeth call for multiple destructive samplings of a given specimen, thereby increasing the extent of undesirable damage to precious archaeological material. Here we present a method that makes it possible to obtain both ancient DNA sequences and radiocarbon dates from the same sample material. This is achieved by releasing DNA from the bone matrix through incubation with either EDTA or phosphate buffer prior to complete demineralization and collagen extraction utilizing the acid-base-acid-gelatinization and ultrafiltration procedure established in most radiocarbon dating laboratories. Using a set of 12 bones of different ages and preservation conditions we demonstrate that on average 89% of the DNA can be released from sample powder with minimal, or 38% without any, detectable collagen loss. We also detect no skews in radiocarbon dates compared to untreated samples. Given the different material demands for radiocarbon dating (500 mg of bone/dentine) and DNA analysis (10-100 mg), combined DNA and collagen extraction not only streamlines the sampling process but also drastically increases the amount of DNA that can be recovered from limited sample material.

Current concepts in periodontal bioengineering

PubMed Central

Taba, M.; Jin, Q.; Sugai, J.V.; Giannobile, W.V.

2008-01-01

Repair of tooth supporting alveolar bone defects caused by periodontal and peri-implant tissue destruction is a major goal of reconstructive therapy. Oral and craniofacial tissue engineering has been achieved with limited success by the utilization of a variety of approaches such as cell-occlusive barrier membranes, bone substitutes and autogenous block grafting techniques. Signaling molecules such as growth factors have been used to restore lost tooth support because of damage by periodontal disease or trauma. This paper will review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Several different polymer delivery systems that aid in the targeting of proteins, genes and cells to periodontal and peri-implant defects will be highlighted. Results from preclinical and clinical trials will be reviewed using the topical application of bone morphogenetic proteins (BMP-2 and BMP-7) and platelet-derived growth factor-BB (PDGF) for periodontal and peri-implant regeneration. The paper concludes with recent research on the use of ex vivo and in vivo gene delivery strategies via gene therapy vectors encoding growth promoting and inhibiting molecules (PDGF, BMP, noggin and others) to regenerate periodontal structures including bone, periodontal ligament and cementum. PMID:16238610

Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement

PubMed Central

Rubin, Mishaela R.; Bilezikian, John P.

2013-01-01

Objective Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder. Subjects and methods Standard histomorphometric and μCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years. Results Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change. Conclusion Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D. PMID:20485912

Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired Aplastic Anemia

PubMed Central

Gonzaga, Vivian Fonseca; Lisboa, Gustavo Sabino; Frare, Eduardo Osório

2017-01-01

Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome characterized by partial or total bone marrow (BM) destruction resulting in peripheral blood (PB) pancytopenia, which is the reduction in the number of red blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The first-line treatment option of AA is given by hematopoietic stem cell (HSCs) transplant and/or immunosuppressive (IS) drug administration. Some patients did not respond to the treatment and remain pancytopenic following IS drugs. The studies are in progress to test the efficacy of adoptive cellular therapies as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe aplastic anemia (SAA) cases. Moreover, bone marrow stromal cells (BMSC) constitute an essential component of the hematopoietic niche, responsible for stimulating and enhancing the proliferation of HSCs by secreting regulatory molecules and cytokines, providing stimulus to natural BM microenvironment for hematopoiesis. This review summarizes scientific evidences of the hematopoiesis improvements after MSC transplant, observed in acquired AA/BMF animal models as well as in patients with acquired AA. Additionally, we discuss the direct and indirect contribution of MSCs to the pathogenesis of acquired AA. PMID:29333168

Steppe lion remains imported by Ice Age spotted hyenas into the Late Pleistocene Perick Caves hyena den in northern Germany

NASA Astrophysics Data System (ADS)

Diedrich, Cajus G.

2009-05-01

Upper Pleistocene remains of the Ice Age steppe lion Panthera leo spelaea (Goldfuss, 1810) have been found in the Perick Caves, Sauerland Karst, NW Germany. Bones from many hyenas and their imported prey dating from the Lower to Middle Weichselian have also been recovered from the Perick Cave hyena den. These are commonly cracked or exhibit deep chew marks. The absence of lion cub bones, in contrast to hyena and cave bear cub remains in the Perick Caves, and other caves of northern Germany, excludes the possibility that P. leo spelaea used the cave for raising cubs. Only in the Wilhelms Cave was a single skeleton of a cub found in a hyena den. Evidence of the chewing, nibbling and cracking of lion bones and crania must have resulted from the importation and destruction of lion carcasses (4% of the prey fauna). Similar evidence was preserved at other hyena den caves and open air sites in Germany. The bone material from the Perick and other Central European caves points to antagonistic hyena and lion conflicts, similar to clashes of their modern African relatives.

Effect of Ultraviolet Irradiation of the Implant Surface on Progression of Periimplantitis--A Pilot Study in Dogs.

PubMed

Ishii, Kouken; Matsuo, Masato; Hoshi, Noriyuki; Takahashi, Shun-Suke; Kawamata, Ryota; Kimoto, Katsuhiko

2016-02-01

The objective of this study was to investigate morphologically the progression of periimplantitis around an ultraviolet (UV)-light-irradiated implant in dogs. Pure titanium implants (3.3 mm in diameter and 8 mm long) were placed into dog jawbone bilaterally. Implants on one side were irradiated with UV light for 15 minutes using a photodevice immediately before placement (UV group), whereas those on the other side were not irradiated (non-UV group). Osseointegration was confirmed 90 days after implant placement by radiography. Experimental periimplantitis was induced by the application of dental floss over 90 days. Clinical and radiographic examination and micro-computed tomography (micro-CT) were performed after 90 and 180 days, and bone resorption was measured. The bone-implant interface in tissue sections was examined by light microscopy. Bone resorption around the UV-irradiated implant was less pronounced than around the non-UV-irradiated implant in the ligature-induced periimplantitis model. Tissue section images revealed no contact and partial destruction at the bone-implant interface. Within the limitations of this preliminary investigation, it is suggested that UV-light-irradiated implants suppress spontaneous progression of periimplantitis.

Mineral trioxide aggregate repair of a perforating internal resorption in a mandibular molar.

PubMed

Meire, Maarten; De Moor, Roeland

2008-02-01

Internal resorption is a rare condition in permanent teeth that poses difficulties for treatment. The challenge is complicated further if the resorption extends beyond the confines of the root. This article describes treatment of a perforating internal resorption in the mesial root of a second lower molar, with adjacent destruction of the alveolar bone. After cleaning the root canal space and the resorption lacuna by mechanical instrumentation, irrigation, and interim calcium hydroxide dressing, the defect was filled with mineral trioxide aggregate, and the canals were obturated conventionally with gutta percha and epoxy resin sealer. At a 2-year follow-up examination, no clinical abnormalities were found, and complete resolution of the alveolar bone lesion and establishment of a new periodontal ligament were observed.

The use of microtomography in bone tissue and biomaterial three-dimensional analysis.

PubMed

Bedini, Rossella; Meleo, Deborah; Pecci, Raffaella; Pacifici, Luciano

2009-01-01

X-ray computed microtomography (micro-CT, microComputerised Tomography) is a miniaturized form of conventional computerized axial tomography (CAT ). This sophisticated technology enables 3D riconstruction of the internal structure of small X-ray opaque objects without sample destruction or preparation. The aim of this study is to show the possible applications of micro-CT in the analysis of bone graft materials of different origins (i.e. homologous, heterologous, alloplastic) in order to define their morphometric properties by means of SkyScan 1072 3D microtomography system. Since there is a close relationship between the properties of the materials and their microstructure, it is necessary to examine them using the highest levels of resolution before being able to improve existing materials or create new products.

Network-Based Method for Identifying Co-Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues

PubMed Central

Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Cai, Yu-Dong

2017-01-01

Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein–protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method. PMID:28974058

Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

PubMed

Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

2017-10-02

Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

Reconstruction of Extensive Soft-Tissue Defects with Concomitant Bone Defects in the Lower Extremity with the Latissimus Dorsi-Serratus Anterior-Rib Free Flap.

PubMed

Sia, Wei Tee; Xu, Germaine Guiqin; Puhaindran, Mark Edward; Tan, Bien Keem; Cheng, Mathew Hern Wang; Chew, Winston Yoon Chong

2015-07-01

The combined latissimus dorsi-serratus anterior-rib (LD-SA-rib) free flap provides a large soft-tissue flap with a vascularized bone flap through a solitary vascular pedicle in a one-stage reconstruction. Seven LD-SA-rib free flaps were performed in seven patients to reconstruct concomitant bone and extensive soft-tissue defects in the lower extremity (tibia, five; femur, one; foot, one). The patients were all male, with an average age of 34 years (range, 20-48 years). These defects were secondary to trauma in five patients and posttraumatic osteomyelitis in two patients. All flaps survived and achieved bony union. The average time to bony union was 9.4 months. Bone hypertrophy of at least 20% occurred in all flaps. All patients achieved full weight-bearing ambulation without aid at an average duration of 23.7 months. Two patients developed stress fractures of the rib flap. There was no significant donor site morbidity, except for two patients who had pleural tears during harvesting of the flap. The LD-SA-rib flap provides a large soft-tissue component and a vascularized bone flap for reconstruction of composite large soft-tissue defects with concomitant bone defects of the lower extremity in a one-stage procedure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Electrospun Gelatin/β-TCP Composite Nanofibers Enhance Osteogenic Differentiation of BMSCs and In Vivo Bone Formation by Activating Ca (2+) -Sensing Receptor Signaling.

PubMed

Zhang, Xuehui; Meng, Song; Huang, Ying; Xu, Mingming; He, Ying; Lin, Hong; Han, Jianmin; Chai, Yuan; Wei, Yan; Deng, Xuliang

2015-01-01

Calcium phosphate- (CaP-) based composite scaffolds have been used extensively for the bone regeneration in bone tissue engineering. Previously, we developed a biomimetic composite nanofibrous membrane of gelatin/β-tricalcium phosphate (TCP) and confirmed their biological activity in vitro and bone regeneration in vivo. However, how these composite nanofibers promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unknown. Here, gelatin/β-TCP composite nanofibers were fabricated by incorporating 20 wt% β-TCP nanoparticles into electrospun gelatin nanofibers. Electron microscopy showed that the composite β-TCP nanofibers had a nonwoven structure with a porous network and a rough surface. Spectral analyses confirmed the presence and chemical stability of the β-TCP and gelatin components. Compared with pure gelatin nanofibers, gelatin/β-TCP composite nanofibers caused increased cell attachment, proliferation, alkaline phosphatase activity, and osteogenic gene expression in rat BMSCs. Interestingly, the expression level of the calcium-sensing receptor (CaSR) was significantly higher on the composite nanofibrous scaffolds than on pure gelatin. For rat calvarial critical sized defects, more extensive osteogenesis and neovascularization occurred in the composite scaffolds group compared with the gelatin group. Thus, gelatin/β-TCP composite scaffolds promote osteogenic differentiation of BMSCs in vitro and bone regeneration in vivo by activating Ca(2+)-sensing receptor signaling.

Enhancement of tissue engineered bone formation by a low pressure system improving cell seeding and medium perfusion into a porous scaffold.

PubMed

Wang, Juyong; Asou, Yoshinori; Sekiya, Ichiro; Sotome, Shinichi; Orii, Hisaya; Shinomiya, Kenichi

2006-05-01

To obtain more extensive bone formation in composites of porous ceramics and bone marrow stromal cells (BMSCs), we hypothesized that a low-pressure system would serve to facilitate the perfusion of larger number of BMSCs into the porous scaffold, enhancing bone formation within the composites. After culturing BMSCs in osteogenic medium, porous blocks of beta-tricalcium phosphate (beta-TCP) were soaked in the cell suspension. Composites of the block and BMSCs were put immediately into a vacuum desiccator. Low pressure was applied to the low pressure group, while controls were left at atmospheric pressure. Composites were incubated in vitro or subcutaneously implanted into syngeneic rats, then analyzed biologically and histologically. In the in vitro group, cell suspension volume, cell seeding efficiency, alkaline phosphatase (ALP) activity, and DNA content in the beta-TCP blocks were significantly higher in low pressure group than in the controls. Scanning electron microscopy (SEM) demonstrated that a greater number of cells covered the central parts of the composites in the low pressure group. ALP activity in the composites was increased at 3 and 6 weeks after implantation into rats. Histomorphometric analysis revealed more uniform and extensive bone formation in the low pressure group than in the controls. The application of low pressure during the seeding of BMSCs in perfusing medium into a porous scaffold is useful for tissue-engineered bone formation.

Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging

PubMed Central

Batey, Michael A.; Almeida, Gilberto S.; Wilson, Ian; Dildey, Petra; Sharma, Abhishek; Blair, Helen; Hide, I. Geoff; Heidenreich, Olaf; Vormoor, Josef; Maxwell, Ross J.; Bacon, Chris M.

2014-01-01

Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2−/−/γc−/− mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which resemble the human disease. We have shown the utility of small animal bioimaging for tracking disease progression, making this model a useful assay for preclinical drug testing. PMID:24409320

Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

PubMed

Hayami, Tadashi; Pickarski, Maureen; Zhuo, Ya; Wesolowski, Gregg A; Rodan, Gideon A; Duong, Le T

2006-02-01

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction, subchondral bone sclerosis, and osteophyte formation. Subchondral bone stiffness has been proposed to initiate and/or contribute to cartilage deterioration in OA. The purpose of this study was to characterize subchondral bone remodeling, cartilage damage, and osteophytosis during the disease progression in two models of surgically induced OA. Rat knee joints were subjected either to anterior cruciate ligament transection (ACLT) alone or in combination with resection of medial menisci (ACLT + MMx). Histopathological changes in the surgical joints were compared with sham at 1, 2, 4, 6, and 10 weeks post-surgery. Using a modified Mankin scoring system, we demonstrate that articular cartilage damage occurs within 2 weeks post-surgery in both surgical models. Detectable cartilage surface damage and proteoglycan loss were observed as early as 1 week post-surgery. These were followed by the increases in vascular invasion into cartilage, in loss of chondrocyte number and in cell clustering. Histomorphometric analysis revealed subchondral bone loss in both models within 2 weeks post-surgery followed by significant increases in subchondral bone volume relative to sham up to 10 weeks post-surgery. Incidence of osteophyte formation was optimally observed in ACLT joints at 10 weeks and in ACLT + MMx joints at 6 weeks post-surgery. In summary, the two surgically induced rat OA models share many characteristics seen in human and other animal models of OA, including progressive articular cartilage degradation, subchondral bone sclerosis, and osteophyte formation. Moreover, increased subchondral bone resorption is associated with early development of cartilage lesions, which precedes significant cartilage thinning and subchondral bone sclerosis. Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone resorption inhibitors as potential disease-modifying pharmaco-therapies.

CALCIUM-47 IN THE STUDY OF BONE PHYSIOLOGY AND PATHOLOGY

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

Guerin, R.A.

1962-06-01

The use of Ca/sup 45/, Ca/sup 47/, Ga/sup 67/, and Sr/sup 85/ in the study of Ca metabolism of bone in human subjects is discussed. Ca/sup 47/ is considered to be most suitable because of its short half-life ( approximates 5 days) and high specific activity (10 mc/mg for Ca/sup 47/ Cl/sub 2/). Studies were conducted in 28 patients injected intravenously with Ca/sup 47/; uptake in various bones was followed by external scintillometry for periods up to 11 days later. In healthy subjects the distribution of activity was symmetrical, with highest uptake in sternum and manubrium and lower uptake inmore » cranium (particularly the occipital region), clavicle, and iliac crest. Epiphyses of the long bones showed less avidity for Ca/sup 47/, that in tibia being highest. Sternum fixed 2 to 21/2 more Ca/sup 47/ than the upper tibial epiphysis. This indicates that in the normal adult more Ca is taken up by spongy than compact bone. The Ca/sup 47/ content of bone increased rapidly, reaching a plateau by the 5th or 6th day in most bones and by the 10th day in some, such as clavicle. Studies in pathologic cases showed the very high, but transient, uptake by callus in fractures and and uptake in Paget's disease of bone that was 3 times normal. Higher than normal uptake was also noted in bone lesions in lymphogranulomatosis, where osteogenesis compensating for increased bone destruction could be detected. Pathologic states could also be detected by following the disappearance of Ca/sup 47/ from plasma, it being delayed by hypercalcemia associated with multiple cancer metastases in bone or accelerated by hypocalcemia, such as in Paget's disease. The rate of urinary excretion of radioactivity was also of diagnostic value. (H.H.D.)« less

Long bone reconstruction using multilevel lengthening of bone defect fragments.

PubMed

Borzunov, Dmitry Y

2012-08-01

This paper presents experimental findings to substantiate the use of multilevel bone fragment lengthening for managing extensive long bone defects caused by diverse aetiologies and shows its clinical introduction which could provide a solution for the problem of reducing the total treatment time. Both experimental and clinical multilevel lengthening to bridge bone defect gaps was performed with the use of the Ilizarov method only. The experimental findings and clinical outcomes showed that multilevel defect fragment lengthening could provide sufficient bone formation and reduction of the total osteosynthesis time in one stage as compared to traditional Ilizarov bone transport. The method of multilevel regeneration enabled management of critical-size defects that measured on average 13.5 ± 0.7 cm in 78 patients. The experimental and clinical results proved the efficiency of the Ilizarov non-free multilevel bone plasty that can be recommended for practical use.

Radionuclide bone scanning of osteosarcoma: falsely extended uptake patterns.

PubMed

Chew, F S; Hudson, T M

1982-07-01

The pathologic specimens of 18 osteosarcomas of long bones were examined to correlate histologic abnormalities with abnormalities seen on preoperative 99mTc pyrophosphate or methylene diphosphonate bone scans. Seven scans accurately represented the extent of the tumor. Eleven scans disclosed increased activity extending beyond the radiographic abnormalities. In eight of these, there was no occult tumor extension and in the other three, the scan activity did not accurately portray the skip metastases that were present. Therefore, these 11 scans demonstrated the falsely extended pattern of uptake beyond the true limits of the tumors. Pathologic slides were available for 10 of the 11 areas of bone that exhibited extended uptake. In two instances, there was no pathologic abnormality. In the other eight cases we found marrow hyperemia, medullary reactive bone, or periosteal new bone. This is the first description of these histologic abnormalities of medullary bone in areas of extended uptake on radionuclide bone scans.

Cavernous hemangioma of the rib: a rare diagnosis.

PubMed

Gourgiotis, Stavros; Piyis, Anastasios; Panagiotopoulos, Nikolaos; Panayotopoulos, Panayotis; Salemis, Nikolaos S

2010-01-01

Hemangioma of the rib is an uncommon benign vascular tumour. A case of rib hemangioma in a 29-year-old woman is presented. Chest roentgenogram and computed tomography revealed a mass along the inner surface of the 7th left rib with bone destruction. She underwent resection of the 7th rib. The pathologic diagnosis was cavernous hemangioma. Hemangiomas of the rib are rare tumours but should be kept in mind in the differential diagnosis of rib tumours.

Fourier transform Raman spectroscopy and archaeology: a preliminary study of human teeth

NASA Astrophysics Data System (ADS)

Edwards, Howell G.; Farwell, Dennis W.; Roberts, Charlotte A.; Williams, Adrian C.

1994-01-01

The FT-Raman spectra of human bones and teeth in archaeological specimens dating to the 4th and 10th centuries AD from Romano-British and Anglo-Saxon burial sites in the U.K. have been recorded successfully using microscopic and remote sensing techniques. The samples exhibit fluorescence ascribed to mineral absorption from the grave soils but, nevertheless, good quality spectra are obtained. The versatility of the technique for non destructive sampling is demonstrated.

Laser-induced propagation and destruction of amyloid beta fibrils.

PubMed

Yagi, Hisashi; Ozawa, Daisaku; Sakurai, Kazumasa; Kawakami, Toru; Kuyama, Hiroki; Nishimura, Osamu; Shimanouchi, Toshinori; Kuboi, Ryoichi; Naiki, Hironobu; Goto, Yuji

2010-06-18

The amyloid deposition of amyloid beta (Abeta) peptides is a critical pathological event in Alzheimer disease (AD). Preventing the formation of amyloid deposits and removing preformed fibrils in tissues are important therapeutic strategies against AD. Previously, we reported the destruction of amyloid fibrils of beta(2)-microglobulin K3 fragments by laser irradiation coupled with the binding of amyloid-specific thioflavin T. Here, we studied the effects of a laser beam on Abeta fibrils. As was the case for K3 fibrils, extensive irradiation destroyed the preformed Abeta fibrils. However, irradiation during spontaneous fibril formation resulted in only the partial destruction of growing fibrils and a subsequent explosive propagation of fibrils. The explosive propagation was caused by an increase in the number of active ends due to breakage. The results not only reveal a case of fragmentation-induced propagation of fibrils but also provide insights into therapeutic strategies for AD.

Use of a CO{sub 2} pellet non-destructive cleaning system to decontaminate radiological waste and equipment in shielded hot cells at the Bettis Atomic Power Laboratory

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

Bench, T.R.

1997-05-01

This paper details how the Bettis Atomic Power Laboratory modified and utilized a commercially available, solid carbon dioxide (CO{sub 2}) pellet, non-destructive cleaning system to support the disposition and disposal of radioactive waste from shielded hot cells. Some waste materials and equipment accumulated in the shielded hot cells cannot be disposed directly because they are contaminated with transuranic materials (elements with atomic numbers greater than that of uranium) above waste disposal site regulatory limits. A commercially available CO{sub 2} pellet non-destructive cleaning system was extensively modified for remote operation inside a shielded hot cell to remove the transuranic contaminants frommore » the waste and equipment without generating any secondary waste in the process. The removed transuranic contaminants are simultaneously captured, consolidated, and retained for later disposal at a transuranic waste facility.« less

Development and validation of a canine radius replica for mechanical testing of orthopedic implants.

PubMed

Little, Jeffrey P; Horn, Timothy J; Marcellin-Little, Denis J; Harrysson, Ola L A; West, Harvey A

2012-01-01

To design and fabricate fiberglass-reinforced composite (FRC) replicas of a canine radius and compare their mechanical properties with those of radii from dog cadavers. Replicas based on 3 FRC formulations with 33%, 50%, or 60% short-length discontinuous fiberglass by weight (7 replicas/group) and 5 radii from large (> 30-kg) dog cadavers. Bones and FRC replicas underwent nondestructive mechanical testing including 4-point bending, axial loading, and torsion and destructive testing to failure during 4-point bending. Axial, internal and external torsional, and bending stiffnesses were calculated. Axial pullout loads for bone screws placed in the replicas and cadaveric radii were also assessed. Axial, internal and external torsional, and 4-point bending stiffnesses of FRC replicas increased significantly with increasing fiberglass content. The 4-point bending stiffness of 33% and 50% FRC replicas and axial and internal torsional stiffnesses of 33% FRC replicas were equivalent to the cadaveric bone stiffnesses. Ultimate 4-point bending loads did not differ significantly between FRC replicas and bones. Ultimate screw pullout loads did not differ significantly between 33% or 50% FRC replicas and bones. Mechanical property variability (coefficient of variation) of cadaveric radii was approximately 2 to 19 times that of FRC replicas, depending on loading protocols. Within the range of properties tested, FRC replicas had mechanical properties equivalent to and mechanical property variability less than those of radii from dog cadavers. Results indicated that FRC replicas may be a useful alternative to cadaveric bones for biomechanical testing of canine bone constructs.

Whole body vibration during fracture healing intensifies the effects of estradiol and raloxifene in estrogen-deficient rats.

PubMed

Stuermer, Ewa K; Komrakova, Marina; Sehmisch, Stephan; Tezval, Mohammad; Dullin, Christian; Schaefer, Nadine; Hallecker, Jan; Stuermer, Klaus M

2014-07-01

Current osteoporosis therapies aim to delay bone destruction and have additional anabolic effects. While they have demonstrated some positive effects on bone healing, more progress is needed in this area. This study used the well-known osteoporotic agents estrogen (E) and raloxifene (R) in conjunction with biomechanical whole body vibration (WBV) at a frequency of 70 Hz twice daily for six weeks to stimulate bone healing. Eighty-four 3-month old female Sprague-Dawley rats (12 per group) were bilaterally ovariectomized to develop osteopenia within eight weeks. Osteotomy of the metaphyseal tibiae was performed and fracture healing was then studied using mechanical tests, histomorphometry, computed tomography (μCT), and gene analysis. We found that E and R improved the structure of osteopenic bones as did WBV alone, although significant levels for WBV were seldom reached. Combination treatments significantly enhanced stiffness (R+WBV; p<0.05), endosteal bone (R+WBV; p<0.01), and trabecular density (E+WBV; p<0.05, R+WBV; p<0.05). In addition, the expression of osteoclast-specific Trap was significantly reduced after treatment with E, R, or their combination with WBV (p<0.01). The effects were additive and not inhibitory, leading us to conclude that the combined applications of WBV with E or R may improve the healing of osteopenic bones. The therapies studied are all currently approved for human use, suggesting ready applicability to clinical practice. To better understand the effects of WBV on osteopenic bones, the ideal vibration regime will require further study. Copyright © 2014 Elsevier Inc. All rights reserved.

Ebselen Is a Potential Anti-Osteoporosis Agent by Suppressing Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclast Differentiation In vitro and Lipopolysaccharide-Induced Inflammatory Bone Destruction In vivo.

PubMed

Baek, Jong Min; Kim, Ju-Young; Yoon, Kwon-Ha; Oh, Jaemin; Lee, Myeung Su

2016-01-01

Ebselen is a non-toxic seleno-organic drug with anti-inflammatory and antioxidant properties that is currently being examined in clinical trials to prevent and treat various diseases, including atherosclerosis, stroke, and cancer. However, no reports are available for verifying the pharmacological effects of ebselen on major metabolic bone diseases such as osteoporosis. In this study, we observed that ebselen suppressed the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in an osteoblast/osteoclast co-culture by regulating the ratio of receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin secreted by osteoblasts. In addition, ebselen treatment in the early stage of osteoclast differentiation inhibited RANKL-dependent osteoclastogenesis by decreasing the phosphorylation of IκB, PI3K, and Akt in early signaling pathways and by subsequently inducing c-Fos and nuclear factor of activated T-cells c1. Further, ebselen induced apoptosis of osteoclasts in the late stage of osteoclast differentiation. In addition, ebselen treatment suppressed filamentous actin ring formation and bone resorption activity of mature osteoclasts. Reflecting these in vitro effects, administration of ebselen recovered bone loss and its µ-CT parameters in lipopolysaccharide-mediated mouse model. Histological analysis confirmed that ebselen prevented trabecular bone matrix degradation and osteoclast formation in the bone tissues. Finally, it was proved that the anti-osteoclastogenic action of ebselen is achieved through targeting N-methyl-D-aspartate (NMDA) receptor. These results indicate that ebselen is a potentially safe drug for treating metabolic bone diseases such as osteoporosis.

Ontogeny of the maxilla in Neanderthals and their ancestors

PubMed Central

Lacruz, Rodrigo S.; Bromage, Timothy G.; O'Higgins, Paul; Arsuaga, Juan-Luis; Stringer, Chris; Godinho, Ricardo Miguel; Warshaw, Johanna; Martínez, Ignacio; Gracia-Tellez, Ana; de Castro, José María Bermúdez; Carbonell, Eudald

2015-01-01

Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived. PMID:26639346

Systemic rhabdomyosarcoma presenting as leukemia: case report with ultrastructural study and reviews.

PubMed

Huntrakoon, M; Callaway, L A; Vergara, G G

1987-08-01

A 20-year-old white male was initially suspected clinically and pathologically of having an acute lymphoblastic leukemic process because of fatigue, severe anemia, thrombocytopenia, a leuko-erythroblastic peripheral blood picture, and a diffusely infiltrated bone marrow. Subsequent review of the bone marrow material indicated cytologic features consistent with either an embryonal, undifferentiated small cell mesenchymal malignancy or reticulo-endothelial malignancy. Ultimately, the electron microscopic (EM) study of the tumor proved to be diagnostic of rhabdomyosarcoma. An extensive search for a primary site of rhabdomyosarcoma did not show any lesion, although the genitourinary region was clinically suspected. The clinical course was a rapidly downhill one with extensive bone and CNS involvement. The patient died 5 months later. An autopsy permit was not obtained. This case emphasizes the occasional tendency of rhabdomyosarcoma to masquerade as a hematopoietic malignancy at the time of presentation and the usefulness of EM study in confirming a diagnosis.

Ontogeny of the maxilla in Neanderthals and their ancestors.

PubMed

Lacruz, Rodrigo S; Bromage, Timothy G; O'Higgins, Paul; Arsuaga, Juan-Luis; Stringer, Chris; Godinho, Ricardo Miguel; Warshaw, Johanna; Martínez, Ignacio; Gracia-Tellez, Ana; de Castro, José María Bermúdez; Carbonell, Eudald

2015-12-07

Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived.

Cervical Spine pain as a presenting complaint in metastatic pancreatic cancer: a case report.

PubMed

Rosenberg, Emily; Buchtel, Lindsey

2016-01-01

A 48 year-old female presented to her primary care physician with a two-month history of neck pain with negative cervical spine x-rays. During that office visit, the patient was noted to be tachycardic with EKG revealing ST depressions, which led to hospital admission. Acute coronary syndrome was ruled out, however, persistent neck pain warranted inpatient MRI of the cervical spine, which revealed a cervical spine lesion. Extensive investigation and biopsy ultimately confirmed stage IV pancreatic adenocarcinoma with metastases to the bone, liver, and likely lung. In the literature, the findings of a primary metastatic site being bone is rare with only a few case reports showing vertebral or sternal metastasis as the first clinical manifestation of pancreatic cancer. The uniqueness of this case lies in the only presenting complaint being cervical spine pain in the setting of extensive metastases to the liver, bone, and likely lung.

Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis.

PubMed

Javaheri, Behzad; Poulet, Blandine; Aljazzar, Ahmed; de Souza, Roberto; Piles, Miriam; Hopkinson, Mark; Shervill, Elaine; Pollard, Andrea; Chan, Boris; Chang, Yu-Mei; Orriss, Isabel R; Lee, Peter D; Pitsillides, Andrew A

2017-10-01

Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in protecting against such chronic disorders have been examined previously. Sulforaphane is a naturally occurring antioxidant. Herein, we explore whether SFX-01®, a stable synthetic form of sulforaphane, modifies gait, bone architecture and slows/reverses articular cartilage destruction in a spontaneous OA model in STR/Ort mice. Sixteen mice (n=8/group) were orally treated for 3months with either 100mg/kg SFX-01® or vehicle. Gait was recorded, tibiae were microCT scanned and analysed. OA lesion severity was graded histologically. The effect of SFX-01® on bone turnover markers in vivo was complemented by in vitro bone formation and resorption assays. Analysis revealed development of OA-related gait asymmetry in vehicle-treated STR/Ort mice, which did not emerge in SFX-01®-treated mice. We found significant improvements in trabecular and cortical bone. Despite these marked improvements, we found that histologically-graded OA severity in articular cartilage was unmodified in treated mice. These changes are also reflected in anabolic and anti-catabolic actions of SFX-01® treatment as reflected by alteration in serum markers as well as changes in primary osteoblast and osteoclast-like cells in vitro. We report that SFX-01® improves bone microarchitecture in vivo, produces corresponding changes in bone cell behaviour in vitro and leads to greater symmetry in gait, without marked effects on cartilage lesion severity in STR/Ort osteoarthritic mice. Our findings support both osteotrophic roles and novel beneficial gait effects for SFX-01® in this model of spontaneous OA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

3D analysis of bone formation around titanium implants using micro-computed tomography (μCT)

NASA Astrophysics Data System (ADS)

Bernhardt, Ricardo; Scharnweber, Dieter; Müller, Bert; Beckmann, Felix; Goebbels, Jürgen; Jansen, John; Schliephake, Henning; Worch, Hartmut

2006-08-01

The quantitative analysis of bone formation around biofunctionalised metallic implants is an important tool for the further development of implants with higher success rates. This is, nowadays, especially important in cases of additional diseases like diabetes or osteoporosis. Micro computed tomography (μCT), as non-destructive technique, offers the possibility for quantitative three-dimensional recording of bone close to the implant's surface with micrometer resolution, which is the range of the relevant bony structures. Within different animal models using cylindrical and screw-shaped Ti6Al4V implants we have compared visualization and quantitative analysis of newly formed bone by the use of synchrotron-radiation-based CT-systems in comparison with histological findings. The SRμCT experiments were performed at the beamline BW 5 (HASYLAB at DESY, Hamburg, Germany; at the BAMline (BESSY, Berlin, Germany). For the experiments, PMMA-embedded samples were prepared with diameters of about 8 mm, which contain in the center the implant surrounded by the bony tissue. To (locally) quantify the bone formation, models were developed and optimized. The comparison of the results obtained by SRμCT and histology demonstrates the advantages and disadvantages of both approaches, although the bone formation values for the different biofunctionalized implants are identical within the error bars. SRμCT allows the clear identification of fully mineralized bone around the different titanium implants. As hundreds of virtual slices were easily generated for the individual samples, the quantification and interactive bone detection led to conclusions of high precision and statistical relevance. In this way, SRμCT in combination with interactive data analysis is proven to be more significant with respect to classical histology.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection

PubMed Central

Inzana, Jason A.; Trombetta, Ryan P.; Schwarz, Edward M.; Kates, Stephen L.; Awad, Hani A.

2015-01-01

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site via poly(methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerization. To examine the efficacy of localized, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50% of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100% of the bones treated with vancomycin monotherapy via PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics. PMID:26535494

Ectopic bone formation cannot occur by hydroxyapatite/β-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice

NASA Astrophysics Data System (ADS)

Cheng, Lijia; Duan, Xin; Xiang, Zhou; Shi, Yujun; Lu, Xiaofeng; Ye, Feng; Bu, Hong

2012-12-01

Many studies have shown that calcium phosphate ceramics (CP) have osteoconductive and osteoinductive properties; however, the exact mechanism of bone induction has not yet been reported. This study was performed to investigate if destroying immunological function will influence osteogenesis, to explain the mechanism which is unclear. In this study, twenty C57BL/6 mice were divided into two groups (n = 10), in group 1, a hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramic was implanted into both the left and right leg muscles of each mouse; in group 2, ten mice experienced lethal irradiation, then were injected bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice by tail veil, after bone marrow transplantation (BMT), heart, liver, spleen, lung, kidney, and muscle were harvested for biological analysis, after the GFP chimera model was established successfully, the same HA/β-TCP ceramic was implanted into both leg muscles of each mouse immediately after irradiation. 45 and 90 days after implantation, the ceramics of the two groups were harvested to perform with hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining; the results showed that there was no bone formation in group 2, while new bone tissues were detected in group 1. Our findings suggest that the BM cell from GFP transgenic mice is a good biomarker and it could set a good platform for chimera model; it also shows that BM cell is one of cell resources of bone induction, and destruction of immune function will impede osteoinduction by CP. Overall, our results may shed light on clear mechanism study of bone induction in the future.

Novel method for in vitro depletion of T cells by monoclonal antibody-targeted photosensitization.

PubMed

Berki, T; Németh, P

1998-02-01

An immunotargeting method (called photo-immunotargeting) has been developed for selective in vitro cell destruction. The procedure combines the photosensitizing (toxic) effect of light-induced dye-molecules, e.g., hematoporphyrin (HP) and the selective binding ability of monoclonal antibodies (mAb) to cell surface molecules. The photosensitizer HP molecules were covalently attached to monoclonal antibodies (a-Thy-1) recognizing an antigen on the surface of T lymphocytes, and used for T cell destruction. To increase the selectivity of the conventional targeting methods, a physical activation step (local light irradiation) as a second degree of specificity was employed. The HP in conjugated form was sufficient to induce T cell (thymocytes, EL-4 cell line) death after irradiation at 400 nm, at tenfold lower concentration compared to the photosensitizing effect of unbound HP. The selective killing of T lymphocytes (bearing the Thy-1 antigen) in a mixed cell population was demonstrated after a treatment with the phototoxic conjugate and light irradiation. This method can be useful for selective destruction of one population (target cell) in an in vitro heterogeneous cell mixture, e.g., in bone marrow transplants for T cell depletion to avoid graft vs. host reaction.

The effect of an inhibitor of gut serotonin (LP533401) during the induction of periodontal disease.

PubMed

Lima, G M G; Corazza, B J M; Moraes, R M; de Oliveira, F E; de Oliveira, L D; Franco, G C N; Perrien, D S; Elefteriou, F; Anbinder, A L

2016-10-01

LP533401 is an inhibitor of tryptophan hydroxylase 1, which regulates serotonin production in the gut. Previous work indicates that LP533401 has an anabolic effect in bone. Thus, we hypothesized that inhibition of gut serotonin production may modulate the host response in periodontal disease. In this study, we aimed to analyze the effects of LP533401 in a rat periodontitis model to evaluate the role of gut serotonin in periodontitis pathophysiology. Twenty-four rats were divided into three groups: treated group (T: ligature-induced periodontal disease and LP533401, 25 mg/kg/d) by gavage; ligature group (L: ligature-induced periodontal disease only); and control group (C: without ligature-induced periodontal disease). After 28 d, radiographic alveolar bone support was measured on digital radiographs, and alveolar bone volume fraction, tissue mineral density and trabeculae characteristics were quantified by microcomputed tomography in the right hemi-mandible. Left hemi-mandibles were decalcified and alveolar bone loss, attachment loss and area of collagen in the gingiva were histologically analyzed. Significant difference between the L and C groups was found, confirming that periodontal disease was induced. We observed no difference between the T and L groups regarding alveolar bone destruction and area of collagen. LP533401 (25 mg/kg/d) for 28 d does not prevent bone loss and does not modulate host response in a rat model of induced periodontal disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IL-17A GENE TRANSFER INDUCES BONE LOSS AND EPIDERMAL HYPERPLASIA ASSOCIATED WITH PSORIATIC ARTHRITIS

PubMed Central

ADAMOPOULOS, IANNIS E.; SUZUKI, ERIKA; CHAO, CHENG-CHI; GORMAN, DAN; ADDA, SARVESH; MAVERAKIS, EMANUAL; ZARBALIS, KONSTANTINOS; GEISSLER, RICHARD; ASIO, AGELIO; BLUMENSCHEIN, WENDY M; McCLANAHAN, TERRILL; DE WAAL MALEFYT, RENE; GERSHWIN, M. ERIC; BOWMAN, EDWARD P.

2014-01-01

Background Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. IL-17A participates in many pathologic immune responses; however, its role in PsA has not been fully elucidated. Objective To determine the role of IL-17A in epidermal hyperplasia and bone destruction associated with psoriatic arthritis. Design An in vivo gene transfer approach was used to investigate the role of IL-17A in animal models of inflammatory (Collagen-induced arthritis) and non-inflammatory (RANKL-gene transfer) bone loss. Results IL-17A gene transfer induced the expansion of IL-17RA+CD11b+Gr1low osteoclast precursors and a concomitant elevation of biomarkers indicative of bone resorption. This occurred at a time preceding noticeable joint inflammation suggesting that IL-17A is critical for the induction of pathological bone resorption through direct activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid population CD11b+Gr1high neutrophil-like cells which was associated with cutaneous pathology including epidermal hyperplasia, parakeratosis, and Munro’s microabscesses formation. Conclusion Collectively, these data support that IL-17A can play a key role in the pathogenesis of inflammation-associated arthritis and/or skin disease, as observed in PsA. PMID:24567524

EFFECT OF USE OF BONE-MARROW CENTRIFUGATE ON MUSCLE INJURY TREATMENT: EXPERIMENTAL STUDY ON RABBITS

PubMed Central

Vieira, Daniel Ferreira Fernandes; Guarniero, Roberto; Vaz, Carlos Eduardo Sanches; de Santana, Paulo José

2015-01-01

Objective: The objective of this study was to evaluate the effect of bone-marrow centrifugate on the healing of muscle injuries in rabbits. Methods: This experimental study involved use of fifteen adult male New Zealand White rabbits. Each animal received a transverse lesion in the middle of the right tibialis anterior muscle, to which an absorbable collagen sponge, soaked in a centrifugate of bone marrow aspirate from the ipsilateral iliac bone, was added. The left hind limb was used as a control and underwent the same injury, but in this case only the absorbable collagen sponge. Thirty days later, the animals were sacrificed to study the muscle healing. These muscle areas were subjected to histological analysis with histomorphometry, with the aim of measuring the number of muscle cells per square micrometer undergoing regeneration and the proportion of resultant fibrosis. Results: The centrifugation method used in this study resulted in an average concentration of nucleated cells greater than the number of these cells in original aspirates, without causing significant cell destruction. Addition of the bone marrow centrifugate did not result in any significant increase in the number of muscle cells undergoing regeneration, in relation to the control group. There was also no significant difference in the proportion of resultant fibrosis, compared with the control group. Conclusion: Administration of the bone marrow centrifugate used in this study did not favor healing of muscle injuries in rabbits. PMID:27047832

Craton destruction by subduction, collision or plume impingement? Comparisons of some representative cratons in the world

NASA Astrophysics Data System (ADS)

Wang, Zhensheng; Kusky, Timothy; Li, Xiaoyong; Wang, Xu; Fu, Jianmin; Yuan, Yuefeng; Zhu, Peimin

2015-04-01

The fact that cratonic lithosphere can be destructed has been demonstrated by numerous studies. However, the driving force of craton destruction and its mechanism are still unclear1,2. Subduction, collision and mantle plumes, the most important driving forces for most geological events, may also be responsible for craton destruction. However, their relationship in the destruction process including which of them is the major driving force and how they interact with each other is not understood sufficiently1,2. In this article, the North China Craton, North Atlantic Craton, Tanzania Craton, Wyoming Craton, Kaapvaal Craton, Yangtze Craton, Yilgarn Craton and Superior Craton are used as examples to study their difference and similarities during subduction, collision, or mantle plume impingement. The work is mainly based on comparison of their tectonic history, geophysical data, as well as xenolith chronology. It is suggested that large-scale craton destruction can be influenced by the interaction of subduction, collision and mantle plumes, acting to different degrees in different examples. Mantle plume related thermal action enhances the chemical stratification or layering of subcontinental lithospheric mantle (SCLM), which can form a weak-coupling mid lithosphere discontinuity (MLD) 3,4,5 and a lower denser SCLM below the MLD. Convergence (subduction and collision), especially when associated with slab rollback 6, leads to the regional thinning of the cratonic margin, which is subsequently linked by extension (mantle plume or slab rollback) related discontinuities. Continuous extension-related discontinuities extend upward to the MLD depth and cut off the shearing resistance from adjacent blocks. Next, the lower part of the chemically stratified SCLM in the cratonic interior is decoupled along the weakly coupled MLD and founders into the deep asthenosphere 7. Then the destruction of the rest of the lithosphere can be affected by upwelling related decompression melting and subduction related hydroweakening. Additionally, if the craton is surrounded by orogenic (mobile) belts, these, can absorb tectonic energy from collisions, may be aid in the preservation of the cratonic root 8. Kusky T., et al. (2007). Geological Society, London, Special Publications, 280(1): 331-343. Gao, S., et al. (2009). Chinese Science Bulletin, 54(19): 3367-3378. Thybo H., et al. (1997). Science, 275(5306): 1626-1629. Thybo H. (2006). Tectonophysics, 416(1): 53-79. Rader E. Et al. (2013). AGU Fall Meeting Abstracts, 2013, 8. Kusky T., et al. (2014). Tectonophysics, 3(630): 208-221. Chen L., et al. (2014). Geology, 42(3): 223-226. Lenardic, A. et al. (2000). Geophysical Research Letters, 27(8): 1235-1238.

Development of a greenhouse-based inoculation protocol for the fungus Colletotrichum cereale pathogenic to annual bluegrass (Poa annua)

USDA-ARS?s Scientific Manuscript database

The fungus Colletotrichum cereale incites anthracnose disease on Poa annua (annual bluegrass) turfgrass. Anthracnose disease is geographically widespread highly destructive, with infections by C. cereale resulting in extensive turfgrass loss. Comprehensive research aimed at controlling turfgrass a...

The aircraft as an instrument of self destruction.

DOT National Transportation Integrated Search

1973-03-01

Often the relationship between the pilot and his aircraft is such that the aircraft may be thought of as an extension of the pilot himself during the act of flight. If this pilot accumulates stress in his life with which he can no longer adequately c...

36 CFR 1226.18 - When may agencies temporarily extend retention periods?

Code of Federal Regulations, 2012 CFR

2012-07-01

... extend retention periods? 1226.18 Section 1226.18 Parks, Forests, and Public Property NATIONAL ARCHIVES... temporarily extend retention periods? (a) Agencies may temporarily retain records approved for destruction... or not to temporarily extend the retention period of records, agencies must ensure that the extension...

36 CFR 1226.18 - When may agencies temporarily extend retention periods?

Code of Federal Regulations, 2011 CFR

2011-07-01

... extend retention periods? 1226.18 Section 1226.18 Parks, Forests, and Public Property NATIONAL ARCHIVES... temporarily extend retention periods? (a) Agencies may temporarily retain records approved for destruction... or not to temporarily extend the retention period of records, agencies must ensure that the extension...

36 CFR 1226.18 - When may agencies temporarily extend retention periods?

Code of Federal Regulations, 2010 CFR

2010-07-01

... extend retention periods? 1226.18 Section 1226.18 Parks, Forests, and Public Property NATIONAL ARCHIVES... temporarily extend retention periods? (a) Agencies may temporarily retain records approved for destruction... or not to temporarily extend the retention period of records, agencies must ensure that the extension...

36 CFR 1226.18 - When may agencies temporarily extend retention periods?

Code of Federal Regulations, 2014 CFR

2014-07-01

... extend retention periods? 1226.18 Section 1226.18 Parks, Forests, and Public Property NATIONAL ARCHIVES... temporarily extend retention periods? (a) Agencies may temporarily retain records approved for destruction... or not to temporarily extend the retention period of records, agencies must ensure that the extension...

Gross, computed tomographic and histological findings in mandibular cheek teeth extracted from horses with clinical signs of pulpitis due to apical infection.

PubMed

Casey, M B; Pearson, G R; Perkins, J D; Tremaine, W H

2015-09-01

The most prevalent type of equine dental pulpitis due to apical infection is not associated with coronal fractures or periodontal disease. The pathogenesis of this type of pulpitis is not fully understood. Computed tomography (CT) is increasingly used to investigate equine dental disorders. However, gross, tomographic and histopathological changes in equine dental pulpitis have not been compared previously. To compare gross, CT and histological appearances of sectioned mandibular cheek teeth extracted from horses with clinical signs of pulpitis without coronal fractures or periodontal disease. To contribute to understanding the pathogenesis of equine dental pulpitis. Descriptive study using diseased and healthy teeth. Mandibular cheek teeth extracted from horses with clinical signs of pulpitis (cases), and from cadavers with no history of dental disease (controls), were compared using CT in the transverse plane at 1 mm intervals. Teeth were then sectioned transversely, photographed and processed for histopathological examination. Tomographs were compared with corresponding gross and histological sections. Cement, dentine and bone had similar ranges of attenuation (550-2000 Hounsfield Units, HU) in tomographs but could be differentiated from pulp (-400 to 500 HU) and enamel (> 2500 HU). Twelve discrete dental lesions were identified grossly, 10 of which were characterised histologically. Reactive and reparative dentinogenesis and extensive pulpar mineralisation, previously undescribed, were identified. Pulpar oedema, neutrophilic inflammation, cement and enamel defects, and reactive cemental deposition were also observed. The CT and pathological findings corresponded well where there was mineralised tissue deposited, defects in mineralised tissue, or food material in the pulpar area. Pulpar and dentinal necrosis and cement destruction, evident grossly and histologically, did not correspond to CT changes. Computed tomography is useful for identifying deposition and defects of mineralised material but less useful for identifying inflammation and tissue destruction. The equine dentine-pulp complex responds to insult with reactive and reparative changes. © 2014 EVJ Ltd.

Ketosteroid Standardized Cissus quadrangularis L. Extract and its Anabolic Activity: Time to Look Beyond Ketosteroid?

PubMed

Jadhav, Atul N; Rafiq, Mohammed; Devanathan, Rajendran; Azeemuddin, Mohammed; Anturlikar, Suryakanth D; Ahmed, Akhil; Sundaram, Ramchandran; Babu, U V; Paramesh, Rangesh

2016-05-01

Cissus quadrangularis (CQ) L. reported to contain 3-ketosteroids and have bone health benefits. This study aimed at establishing the relationship between the ketosteroid content and anabolic as well as bone health-promoting activities of various Cissus extracts in well-established orchidectomized (ORX) rat model. Supercritical carbon dioxide, ethyl acetate, and aqueous extracts (AE) of CQ L. were prepared and standardized for ketosteroid content by two methods used in commerce. Moreover, ketosteroid standardized extracts of this plant were evaluated for anabolic activity in rats in well-established ORX rat model. The increase in the absolute weight was appreciable in the CQ-AE treated group. Similarly, with respect to bone parameters, a similar trend was seen. The mean bone density, strength, and calcium content were found to be highest in the group treated with CQ-AE compared to groups treated with other extracts. This study reveals for the first time that 3-ketosteroids are not linked to the beneficial activities on bone and highlights the need for extensive characterization of biological active principles from CQ L. In light of the above estimation studies, we believe that current standardization of Cissus extraction "3-ketosteroids" is incorrect. We also did not find any report suggesting the presence of androgenic steroids in this plant and hence the characterization based on "3-ketosteroids" is scientifically incorrect. This study highlights the insufficient understanding of biological active principles from CQ L. and underlines the need for extensive bioactivity guided studies. Cissus quadrangularis (CQ) L. reported to contain 3.ketosteroids and have bone health benefitsWe did not find correlation between ketosteroid content obtained by conventional methods and its biological effectStudies indicate that claims of ketosteroid content need not necessarily correlate to biological effects and hence warrants extensive phytochemical characterization of biological active principles from CQ L. Abbreviations used: CQ: Cissus quadrangularis, ORX: Orchidectomized, AE: Aqueous extract, EE: Ethyl acetate extract, SFE: Supercritical fluid extract.

Matrix Metalloproteinases as Regulators of Periodontal Inflammation

PubMed Central

Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández

2017-01-01

Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation. PMID:28218665

Matrix Metalloproteinases as Regulators of Periodontal Inflammation.

PubMed

Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández

2017-02-17

Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the 'protease web' is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules-such as cytokines, chemokines, and growth factors, among others-regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation.

Benefits of additional courses of systemic azithromycin in periodontal disease case report.

PubMed

Schmidt, Edgard F; Bretz, Walter A

2007-01-01

The strong association of subgingival anaerobic bacteria, such as Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, with destructive periodontal disease has been well documented in the literature. Several double-blind studies have also shown the beneficial use of systemic antimicrobials that are active against these microorganisms in conjunction with conventional periodontal treatment, especially when periodontal abscesses and/or suppuration upon probing are present. Four cases with periodontal abscesses were treated with scaling/root planing in conjunction with systemic azithromycin. Partial improvement led to retreatment with two additional courses of azithromycin. Bone formation was noted on periapical radiographs after the patients took additional courses of azithromycin. In view of the benefits of using additional courses of azithromycin in the treatment of destructive periodontal disease, we conclude that the single course of systemic antimicrobials currently used in periodontal therapy may be insufficient to reach necessary therapeutic levels in infected sites.

[Clinical and pathogenetic aspects of the chronic occupational intoxication with fluorine compounds in modern reality].

PubMed

Roslaia, N A; Likhacheva, E I; Oranskiĭ, I E; Odinokaia, V A; Plotko, É G; Zhovtiak, E P; Fedorov, A A; Riabko, E V

2012-01-01

Multi-year follow-up of 358 workers of aluminum pot rooms, including 165 individuals suffering from fluorosis, has shown significant changes in the clinical picture of the chronic occupational fluorine intoxication, developed under modern conditions of production, at lower concentrations of fluorine compounds in the air of working area. In this connection, the pathology of the musculoskeletal system plays the dominating role in this clinical picture and has the large variability of combinations of the individual sections destructions of the bone tissue. The main criterion to establish the phase of the disease is still the number and severity of the signs of this destruction. The visceral pathology in contemporary production circumstances is registered with less frequency and loses a number of the previously described clinical manifestations, however, is still of some importance to identify the early signs of the disease and to prevent the dental fluorosis on time.

Streptococcus pyogenes degrades extracellular matrix in chondrocytes via MMP-13

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

Sakurai, Atsuo; Okahashi, Nobuo; Maruyama, Fumito

2008-08-29

Group A streptococcus (GAS) causes a wide range of human diseases, including bacterial arthritis. The pathogenesis of arthritis is characterized by synovial proliferation and the destruction of cartilage and subchondral bone in joints. We report here that GAS strain JRS4 invaded a chondrogenic cell line ATDC5 and induced the degradation of the extracellular matrix (ECM), whereas an isogenic mutant of JRS4 lacking a fibronectin-binding protein, SAM1, failed to invade the chondrocytes or degrade the ECM. Reverse transcription-PCR and Western blot analysis revealed that the expression of matrix metalloproteinase (MMP)-13 was strongly elevated during the infection with GAS. A reporter assaymore » revealed that the activation of the AP-1 transcription factor and the phosphorylation of c-Jun terminal kinase participated in MMP-13 expression. These results suggest that MMP-13 plays an important role in the destruction of infected joints during the development of septic arthritis.« less

Towards Large-Scale, Non-Destructive Inspection of Concrete Bridges

NASA Astrophysics Data System (ADS)

Mahmoud, A.; Shah, A. H.; Popplewell, N.

2005-04-01

It is estimated that the rehabilitation of deteriorating engineering infrastructure in the harsh North American environment could cost billions of dollars. Bridges are key infrastructure components for surface transportation. Steel-free and fibre-reinforced concrete is used increasingly nowadays to circumvent the vulnerability of steel rebar to corrosion. Existing steel-free and fibre-reinforced bridges may experience extensive surface-breaking cracks that need to be characterized without incurring further damage. In the present study, a method that uses Lamb elastic wave propagation to non-destructively characterize cracks in plain as well as fibre-reinforced concrete is investigated both numerically and experimentally. Numerical and experimental data are corroborated with good agreement.

Simple (unicameral) bone cyst of the calcaneus: a pathologic variant revisited.

PubMed

Thomas, L Brannon; Steffensen, Thora; Walling, Arthur K; Gilbert-Barness, Enid

2008-01-01

A 17-year-old girl was admitted to the hospital for surgery of an enlarging, painful mass of the left calcaneus. Preoperative imaging studies suggested either a simple (unicameral) or aneurysmal bone cyst. Intraoperative biopsy of the lesion revealed a simple bone cyst with extensive cholesterol clefts. Such cysts are not uncommon in the calcaneus. However, the pathology of this case is unusual and often overlooked. The typical presentation, treatment, and pathology of these lesions are reviewed.

Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standarizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

DTIC Science & Technology

2008-08-01

To better understand the cellular basis of a long bone defect, we have utilized the GFP reporters in the closed tibial fracture. The surprise finding...callus. In the coming year we will apply the information learned from the calvarial defect to a non-union extension of the tibial fracture model...initiated a comprehensive examination of the tibial fracture model in mice bearing GFP reporters of lineage progression. This project has been assumed